mocetinostat and Chronic-Disease

Myeloperoxidase (MPO) is an immune enzyme found in neutrophils and macrophages. It produces the highly oxidative compound HOCl from H. This article covers the patent literature published on MPO inhibitors from 2013 to 2019, as well as the potential use of these compounds as therapeutics for inflammatory syndromes, especially that plays an important role in the initiation and progression of atherosclerosis.. To date, many MPO inhibitors with different structures have been studied, many of which have prominent inhibitory activities. Furthermore, the specificity of these drugs offers hope for the targeted therapy of inflammatory syndromes. Although many data have proved that MPO can contribute to several chronic inflammatory syndromes, the usefulness of MPO inhibitors in preventing and treating inflammatory disorders is still under investigation.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cardiovascular Diseases; Chronic Disease; Drug Development; Enzyme Inhibitors; Humans; Inflammation; Patents as Topic; Peroxidase

In this review, we present recent insights on chronic heart failure (CHF) and the potential role of tumor necrosis factor (TNF)-alpha, interleukins, myeloperoxidase (MPO), and nitrosative stress in the progression of this disease process. Reactive oxygen species (ROS) are produced as a consequence of aerobic metabolism. Under physiologic conditions, their unfavourable effect in causing oxidative damage is counteracted by antioxidants. An imbalance in favour of oxidants leads to oxidative stress, and contributes to myocyte apoptosis, direct negative inotropic effects, and reduced bioavailability of nitric oxide (NO). Together, these effects lead to impaired vasodilatation of the coronary, pulmonary and peripheral vascular beds. In patients with moderate to severe forms of CHF, TNF-alpha leads to the formation of nitrotyrosine and consumption of nitric oxide by virtue of activation of myeloperoxidase. Further studies are required to better elucidate the complex interaction of oxidative stress, endothelial dysfunction and inflammatory activation in CHF. Such insights would likely lead to development of better strategies for the assessment of the disease severity by monitoring of new bio-humoral indices and better treatment approaches.

Topics: Biomarkers; Chronic Disease; Endothelium, Vascular; Heart Failure; Humans; Natriuretic Peptide, Brain; Nitrosation; Oxidative Stress; Peroxidase

Endothelial cells are key modulators of diverse physiological processes, and their impaired function is a cause of numerous cardiovascular diseases. Under physiologic condition, the reactive oxygen and nitrogen mediators in endothelia lead to the signal propagation of the initial stimulus, by forming molecules with a longer half-life like hydrogen peroxide. Hydrogen peroxide is the focus of growing attention in endothelial biology, and consequently the enzymes involved in its generation and clearance are viewed as novel mediators of great importance. In particular, among peroxidases, myeloperoxidase is recognized as a key enzyme, capable of impairing intracellular NO reservoirs as well as producing oxidized amino acids such as 3-chlorotyrosine or 3-nitrotyrosine. This process switches the functional pathways from normal signalling to a condition characterized by oxidative and/or nitrosative stress. Understanding the molecular mechanisms involved in these stress responses in endothelium will lead to better therapeutic strategies for oxidative stress-driven cardiovascular diseases.

Topics: Chronic Disease; Endothelium, Vascular; Heart Failure; Humans; Oxidative Stress; Peroxidase; Reactive Oxygen Species

There is an emerging and significant body of research that suggests that MPO (myeloperoxidase) may be a critical mediator in dysfunctional lipoprotein formation and, hence, atherogenic initiation and progression. MPO is a haem peroxidase found in leucocytes and is abundant in macrophages surrounding atherosclerotic lesions. Several lines of evidence support the role of MPO-mediated carbamylation of proteins in atherogenesis. The generic mechanism of MPO-mediated protein carbamylation has been elucidated recently and has been identified as a potentially crucial pathway that links smoking, inflammation and atherogenesis. HDL (high-density lipoprotein) exerts a physiologically beneficial effect of reducing arterial cholesterol deposition; however, there are considerable gaps in current understanding of the molecular basis of dysfunctional HDL formation. Especially deserving of attention is a contextual understanding of dysfunctional pro-atherogenic HDL formation in light of inflammatory changes in atheroma. The present review is especially timely in light of the solved structures of nascent and discoidal HDL and integrates the biochemical significance of MPO carbamylation in the context of these structures. Various avenues of experimental investigation are explored which will be crucial in understanding the vascular consequences of dysfunctional HDL formation and the identification of novel mechanistic pathways in vascular disease. It is anticipated that further knowledge on the intricacies of dysfunctional HDL formation, potentially by an MPO-driven pathway, will lead to considerable progress in identifying novel drug targets for atherosclerosis and characterization of the primary atherogenic process.

Topics: Atherosclerosis; Chronic Disease; Diet; Humans; Kidney Diseases; Lipoproteins; Peroxidase; Protein Processing, Post-Translational; Proteins; Signal Transduction; Smoking

The etiology of sarcoidosis remains uncertain. The hallmark of sarcoidosis is the epithelioid granuloma, which serves as a necessary starting point for considering disease etiology. Any etiologic agent of sarcoidosis must also explain the typical clinical behaviors and characteristic immunopathologic features of the disease. One clinical observation that serves as a bridge to the etiology of sarcoidosis is the Kveim reaction. In this reaction, local epithelioid granulomas develop several weeks after the intradermal injection of homogenates of sarcoidosis tissue. Our group capitalized on the known properties of the Kveim reagent to search for candidate pathogenic tissue antigens in sarcoidosis without other a priori hypotheses regarding possible microbial or autoimmune etiologies. Using a limited proteomics approach based on the physicochemical properties of Kveim reagent, we detected a limited number of poorly soluble antigenic proteins in sarcoidosis tissues by protein immunoblotting, using sarcoidosis sera. Matrix-associated laser desorption/ionization-time of flight mass spectrometry identified one of these antigens to be the Mycobacterium tuberculosis catalase-peroxidase protein (mKatG). We found IgG responses to recombinant mKatG in more than 50% of patients with sarcoidosis but rarely in purified protein derivative (PPD)-negative control subjects. These findings support the conclusion that mKatG is a tissue antigen and target of the adaptive immune response in sarcoidosis, providing further evidence of a mycobacterial etiology in a subset of sarcoidosis. More generally, the approach used in these studies might be employed to discover and validate other candidate pathogenic antigens in sarcoidosis or other granulomatous disorders.

Topics: Bacterial Proteins; Catalase; Chronic Disease; Disease Progression; Humans; Kveim Test; Mycobacterium tuberculosis; Peroxidase; Remission, Spontaneous; Sarcoidosis, Pulmonary; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

We report a 54-year-old woman with systemic sclerosis who presented alveolar hemorrhage. She noticed shortness of breath in May 1997. She was diagnosed having interstitial pneumonitis and systemic sclerosis with sclerodactylia of bilateral fingers in December. She developed bloody sputum and dyspnea suddenly on March 12, 1999. Bloody lavage fluid with hemosiderin-laden macropharge was observed by bronchial fiber scopic examination. The elevated level of MPO-ANCA was detected without anti-DNA antibody. Administration of intravenous methylprednisolone(1g per day, 3 days) followed by 40 mg per day of prednisolone achieved complete response, and MPO-ANCA level was decreased. Mild proteinuria and microhematuria was detected on admission, but renal biopsy revealed no findings of crescent formation or angiitis. With coadministration of oral cyclophosphamide she doesn't have any renal involvement or recurrence of alveolar hemorrhage during these four years. MPO-ANCA level remains negative. Alveolar hemorrhage, which is uncommon pulmonary event in systemic sclerosis, is often coexist with renal angiitis in the context of "pulmo-renal syndrome". MPO-ANCA is said to be related to pulmo-renal syndrome and is sometimes induced by D-penicillamine. This patient is really important in considering the pathogenesis of alveolar hemorrhage because she had no renal vasculitic lesions or D-penicillamine intake.

Topics: Antibodies, Antineutrophil Cytoplasmic; Biomarkers; Chronic Disease; Female; Hemorrhage; Humans; Kidney Diseases; Lung Diseases; Lung Diseases, Interstitial; Middle Aged; Peroxidase; Prednisolone; Pulmonary Alveoli; Scleroderma, Systemic; Treatment Outcome

The functional activity of peripheral phagocytes were comparatively studied in 14 HIV-infected patients and 28 patients with chronic Herpes simplex viral infection. The two groups exhibited lowered adhesive capacity of phagocytes, impaired production and excretion of active oxygen metabolites. In addition, the patients with chronic Herpes simplex infection showed much elevated levels of myeloperoxidase and acid phosphatase, which indicated its compensatory pattern. The HIV infected had no enhanced enzymatic activity. One cannot rule out that these differences in the functional activity of phagocytes are associated with different effects of viral peptides on the cellular wall of phagocytes.

Topics: Acid Phosphatase; Acquired Immunodeficiency Syndrome; Adult; Cell Adhesion; Chemotaxis, Leukocyte; Chronic Disease; Enzyme Activation; Female; Herpes Simplex; Humans; Male; Neutrophils; Peroxidase; Phagocytosis; Recurrence

Infants, children, and young adults who suffer chronic and recurrent bacterial or fungal infection despite adequate numbers of circulating granulocytes and normal or elevated levels of immunoglobulins should be suspected of having fundamental defects in granulocyte functioning. This article considers clinical disorders for which there is evidence for associated defects of polymorphonuclear leukocytes.

Topics: Adolescent; Animals; Cell Adhesion; Chediak-Higashi Syndrome; Chemotactic Factors; Chemotaxis, Leukocyte; Child; Child, Preschool; Chronic Disease; Female; Glucosephosphate Dehydrogenase Deficiency; Granulomatous Disease, Chronic; Hematologic Diseases; Humans; Hypergammaglobulinemia; Ichthyosis; Immunoglobulin E; Infant, Newborn; Infections; Lymphatic Diseases; Male; Neutrophils; Oxidoreductases; Oxygen Consumption; Peroxidase; Phagocyte Bactericidal Dysfunction; Rabbits; Staphylococcal Infections

The mechanisms underlying increased thrombotic risk in chronic myeloproliferative neoplasms (MPN) are incompletely understood. We assessed whether neutrophil extracellular traps (NETs), which promote thrombosis, contribute to the procoagulant state in essential thrombocythemia, polycythemia vera and myelofibrosis (MF) patients. Although MPN neutrophils showed increased basal reactive oxygen species (ROS), enhanced NETosis by unstimulated neutrophils was an infrequent finding, whereas PMA-triggered NETosis was impaired, particularly in MF, due to decreased PMA-triggered ROS production. Elevated circulating nucleosomes were a prominent finding and were higher in patients with advanced disease, which may have potential prognostic implication. Histone-MPO complexes, proposed as specific NET biomarker, were seldomly detected, suggesting NETs may not be the main source of nucleosomes in most patients, whereas their correlation with high LDH points to increased cell turn-over as a plausible origin. Lack of association of nucleosomes or NETs with thrombosis or activation markers does not support their use as predictors of thrombosis although prospective studies in a larger cohort may help define their potential contribution to MPN thrombosis. These results do not provide evidence for relevant in vivo NETosis in MPN patients under steady state conditions, although availability of standardized NET biomarkers may contribute to further research in this field.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Chronic Disease; Extracellular Traps; Female; Hematologic Neoplasms; Humans; Male; Middle Aged; Myeloproliferative Disorders; Neutrophils; Nucleosomes; Peroxidase; Reactive Oxygen Species

Studies indicate that myeloperoxidase (MPO) is associated with disease progression and severity in heart failure (HF), while it may provide a mechanistic link between inflammation and adverse cardiac remodeling. The mechanisms that regulate MPO are unclear, while it is unknown whether specific treatments such as HMG-CoA reductase inhibitors and xanthine oxidase inhibitors may modify MPO. Therefore in the present study we examined the effects of rosuvastatin and allopurinol on MPO levels in patients HF.. Sixty clinically stable patients with systolic HF were randomized to receive rosuvastatin 10mg/day, allopurinol 300mg/day or placebo and followed up for 1 month. Plasma levels of MPO and serum levels of soluble CD40 ligand, interleukin-6, and oxidized LDL were determined using ELISA. All measurements were made before and after 1-month treatment.. Rosuvastatin significantly reduced plasma levels of MPO (p=0.003), which remained unchanged in the other groups. Furthermore, the change of MPO levels in the rosuvastatin-treated group was significantly different compared with the other groups (p<0.05). Rosuvastatin administration also led to a significant decrease in oxidized LDL (p=0.009), while the other inflammatory markers remained unchanged in all groups. In the total population, a significant correlation was observed between the baseline levels of MPO and hsCRP (r=0.275, p=0.027), fibrinogen (r=0.278, p=0.025), and sCD40L (r=0.288, p=0.021).. Short-term treatment with rosuvastatin regulates inflammatory process in patients with heart failure by significantly reducing plasma levels of MPO. This finding reveals a novel pleiotropic effect of statins in patients with heart failure, and provides further insights into the pathophysiological mechanisms of MPO in heart failure.

Topics: Aged; Allopurinol; Biomarkers; Cholesterol; Cholesterol, LDL; Chronic Disease; Female; Fluorobenzenes; Heart Failure; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Inflammation; Male; Peroxidase; Pyrimidines; Rosuvastatin Calcium; Sulfonamides; Triglycerides

In the present prospective trial, the PMN response following resorbable GTR barrier placement was evaluated in mandibular class II furcation lesions.. In 10 patients with treated chronic periodontitis, we randomly selected the 1st molars in the mandible with buccal degree II furcation involvement for either polylactic-citric-acid-ester (PLA) or glycolide-lactic-copolymer (PGL) GTR membrane therapy. We examined contralateral healthy molar sites as untreated controls. We then evaluated the PMN-derived inflammatory tissue response at baseline, weekly up to 6 weeks post-therapy and at 12 and 24 weeks using GCF myeloperoxidase (MPO), beta-glucuronidase (betaG) and beta-N-acetyl-hexosaminidase (betaNAH).. The enzyme levels increased from baseline to the 6-week examination. After the 6-week reappointment, enzyme levels dropped reaching the baseline scores at both the 12- and 24-week visit. At PGL sites, the enzyme levels decreased earlier. Compared with healthy control sites, the MPO, betaNAH and betaG tests revealed different maximum levels at week 2 and 3 (PGL) and week 4, 5 and 6 (PLA). For both of the barriers the clinical parameters revealed a sustained improvement following therapy.. The release of PMN enzymes following placement of bioabsorbable membranes reflects the early soft tissue healing process. Our results suggest that the PMN response is barrier-dependent with the maximum response occuring at different times. However, the host response did not measureably affect the course of clinical healing.

Topics: Absorbable Implants; beta-N-Acetylhexosaminidases; Chronic Disease; Dental Plaque Index; Female; Follow-Up Studies; Furcation Defects; Gingival Crevicular Fluid; Glucuronidase; Guided Tissue Regeneration, Periodontal; Humans; Lactic Acid; Male; Mandibular Diseases; Membranes, Artificial; Middle Aged; Neutrophils; Periodontal Attachment Loss; Periodontal Index; Periodontal Pocket; Periodontitis; Peroxidase; Polyesters; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Polymers; Prospective Studies; Statistics, Nonparametric; Wound Healing

Many studies have demonstrated that, in asthma, serum levels of eosinophil cationic protein (ECP) are related to the activity and severity of the disease and can be used to evaluate the response to steroid treatment. During exacerbations of chronic bronchitis, airway inflammation shows some features of asthmatic inflammatory processes, with recruitment of eosinophils and recovery of significant amounts of ECP in bronchial lavage fluid (BAL). Involvement of neutrophils, with high levels of myeloperoxidase (MPO), is, on the contrary, typical of this latter disease, and not shared with asthma. In spite of the information collected with BAL and bronchial biopsy studies, few data still exist on serum levels of these proteins in chronic bronchitis. The objective of this study was to assess if serum levels of ECP and MPO are specifically increased in exacerbations of chronic bronchitis, as compared to other non-asthmatic acute respiratory disturbances. Serum ECP, MPO and immunoglobulin E (IgE) levels were measured in 17 non-atopic patients with exacerbation of chronic bronchitis with airway obstruction (COPD) and in 11 control subjects seeking emergency medical treatment for unrelated acute respiratory problems. Spirometry was performed in patients able to give the necessary collaboration. All the subjects of this study were recruited from the emergency department. Both ECP and MPO were significantly increased in serum from patients with exacerbated COPD (22.2 +/- 4.1 vs 9.5 +/- 1.4 mcg/L and 853 +/- 168 vs 375 +/- 41 mcg/L) and a strong correlation existed between these two variables (r = 0.782). A further control group was made of 11 patients with stable COPD. These subjects had levels of both ECP (13.1 +/- 2.7 mcg/L) and MPO (469 +/- 71) significantly lower than patients with exacerbated disease and higher than those without COPD. We conclude that serum ECP and MPO are increased during the exacerbations of COPD. These observations can give a basis for further studies aimed to evaluate the utility of these two proteins as markers of activity and severity of COPD.

Topics: Aged; Airway Obstruction; Blood Proteins; Bronchitis; Chronic Disease; Eosinophil Granule Proteins; Female; Humans; Immunoglobulin E; Lung Diseases, Obstructive; Male; Neutrophils; Peroxidase; Respiratory Insufficiency; Ribonucleases; Spirometry

Viable bacteria are often isolated from airway secretions in clinically stable patients with chronic bronchitis. We hypothesized that the number of organisms and bacterial species might be important modulators of airway inflammation.. We performed quantitative sputum cultures in 160 stable patients [55 with chronic obstructive pulmonary disease (COPD) and normal serum alpha(1)-antitrypsin levels, 62 with COPD and severe alpha(1)-antitrypsin deficiency (PiZ), and 43 with idiopathic bronchiectasis]. The results were related to several indicators of the mechanisms and severity of airway inflammation.. Airway bacterial load correlated with sputum myeloperoxidase level, an indirect measure of neutrophil activation and number (r = 0.50, P<0. 001); sputum neutrophil chemoattractants [interleukin-8 level (r = 0. 68, P<0.001) and leukotriene B4 level (r = 0.53, P<0.001)]; sputum leukocyte elastase activity (r = 0.55, P<0.001); and albumin leakage from serum to sputum (r = 0.26, P<0.01). Markers of inflammation increased at bacterial loads of 10(6) to 10(7) colony-forming units per milliliter, and increased progressively with increasing bacterial load. For example, the median (interquartile range) sputum myeloperoxidase level was 0.3 U/mL (0.1 to 0.5 U/mL) for patients who were not colonized or who had mixed normal oropharyngeal flora alone; 0.5 U/mL (0.2 to 0.7 U/mL) for patients with 10(5) to 10(6) colony-forming units per milliliter (P = 0.07); 0.5 U/mL (0.3 to 1.2 U/mL) for patients with 10(6) to 10(7) colony-forming units per milliliter (P<0.01); 0.7 U/mL (0.3 to 1.2 U/mL) for patients with 10(7) to 10(8) colony-forming units per milliliter (P <0.005); and 2.4 U/mL (0.7 to 4.8 U/mL) for patients with 10(8) or greater colony-forming units per milliliter (P<0.0001). The bacterial species influenced airway inflammation; for example, sputum myeloperoxidase activity was greater (P<0.005) in patients colonized with Pseudomonas aeruginosa [median 32 U/mL (interquartile range, 20 to 65 U/mL)] than those colonized with nontypeable Hemophilus influenzae [4 U/mL (2 to 31 U/mL)], which in turn was greater (P = 0.01) than among those colonized with Moraxella catarrhalis [1.1 U/mL (0.6 to 1.8 U/mL)]. We did not find a relation between bacterial load and lung function.. The bacterial load and species contribute to airway inflammation in patients with stable chronic bronchitis. Further studies are required to determine the consequences of bacterial colonization on patient morbidity and decline in lung function.

Topics: Aged; Bacteria; Biomarkers; Bronchitis; Bronchoalveolar Lavage Fluid; Chi-Square Distribution; Chronic Disease; Colony Count, Microbial; Female; Humans; Inflammation Mediators; Interleukin-8; Leukotriene B4; Lung Diseases, Obstructive; Male; Middle Aged; Peroxidase; Prognosis; Reference Values; Severity of Illness Index; Sputum; Statistics, Nonparametric; Stem Cells

Twenty eight adult patients of both sexes with chronic bronchitis participated in an open study to determine the effect of intranasal treatment with IRS-19, an immunomodulating agent, on the number of polymorphonuclear leukocytes (PMNL), H2O2 concentration and myeloperoxidase (MPO) activity in nasal washings. The number of PMNL recovered from nasal spaces increased from 4460 +/- 3960 to 10,490 +/- 10,950 cells/ml (p < 0.02) after two month administration of IRS-19. It was accompanied by 2.6- and 1.4-fold increase (p < 0.001) in MPO activity and H2O2 concentration, respectively. However, no correlation was found between increments in these three variables. Since PMNL and MPO-H2O2-Cl- system are involved in the first line of defense against invading pathogens it is suggested that above mentioned changes may represent one among mechanisms leading to enhancement of antibacterial defence in the airways in response to treatment with IRS-19.

Topics: Adjuvants, Immunologic; Adult; Bacteria; Bronchitis; Chronic Disease; Female; Humans; Hydrogen Peroxide; Immunity, Innate; Leukocyte Count; Male; Middle Aged; Nasal Lavage Fluid; Neutrophils; Peroxidase

The effects of fluticasone propionate (FP) on sputum chemotactic activity, elastase inhibitory potential, albumin concentrations, and peripheral neutrophil function were studied in a group of patients with clinically stable, smoking-related chronic bronchitis and emphysema. Seventeen patients (50 to 75 yr of age) were entered into a double-blind, placebo-controlled study of 1.5 mg inhaled FP/d for 8 wk. Following treatment with FP the chemotactic activity of the sputum sol phase was lower than the corresponding values for the placebo group (p < 0.01). Values fell from a mean of 21.75 (+/- 1.58) during the run-in period to 18.37 (+/- 1.46; p < 0.01) after 4 wk and 17.63 (+/- 1.86; p < 0.05) after 8 wk treatment returning to 22.08 (+/- 1.26) cell/field after the washout period. The neutrophil elastase inhibitory capacity of the sputum sol phase increased (p < 0.025) with treatment from a mean of 0.177 microM elastase inhibited/L (+/- 0.05) pretreatment to 0.413 microM (+/- 0.054) after 4 wk and 0.415 microM (+/- 0.054) after 8 wk returning to 0.270 microM (+/- 0.07) after the washout period. Treatment with FP did not result in a change in the peripheral neutrophil functions studied or sputum albumin and myeloperoxidase concentrations. The results suggest that FP may play a protective role in these patients through a reduction in the chemotactic activity of lung secretions and potentially a reduction in the recruitment of neutrophils to the lung, and also by directly affecting the proteinase/antiproteinase balance, in favor of antiproteinases, within lung secretions.

Topics: Administration, Inhalation; Aged; Albumins; Androstadienes; Bronchitis; Chemotaxis, Leukocyte; Chronic Disease; Double-Blind Method; Female; Fibronectins; Fluticasone; Glucocorticoids; Humans; Leukocyte Elastase; Male; Middle Aged; Neutrophils; Pancreatic Elastase; Peroxidase; Pulmonary Emphysema; Sputum; Superoxides

The mechanisms explaining the beneficial effects of glucocorticoid in ventilator-dependent preterm infants are not known. In the present randomized trial, we evaluated the hypothesis that dexamethasone (DEX) treatment of small, preterm infants at risk for chronic lung disease favorably affects the surfactant system. Twenty-three ventilator-dependent infants, with a mean +/- SD gestational age of 26 +/- 2 wk and a mean birth weight of 836 +/- 173 g, received 1 wk of treatment with either DEX (dose 0.5 mg/kg/d) or placebo beginning at 2 wk of age. The airway specimens were analyzed for surfactant components, surface activity, surfactant inhibitors, and inflammatory mediators. The concentrations of these parameters in epithelial lining fluid were calculated using the urea method. DEX treatment decreased the concentration of nonsedimentable protein in epithelial lining fluid within 3 d (p < 0.05). The nonsedimentable fraction of airway specimens decreased the surface activity of surfactant as a function of protein concentration. At a constant protein concentration, the protein from placebo-treated infants inhibited the surface activity of human surfactant in vitro more than protein from DEX-treated infants (p < 0.05). DEX transiently increased the concentration of surfactant protein-A in epithelial lining fluid but had no effect on surface activity of the sedimentable surfactant complex or on concentrations of phosphatidylcholine, IL-1 beta, lactoferrin, or myeloperoxidase. We conclude that the acute beneficial effect of DEX treatment in preterm ventilator-dependent infants may in part be mediated through a decrease in the concentration of non-sedimentable protein and a decrease in the capacity of this protein to inhibit surface activity.

Topics: Blood Proteins; Chronic Disease; Dexamethasone; Female; Humans; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature, Diseases; Inflammation; Interleukin-1; Lactoferrin; Lung Diseases; Male; Peroxidase; Pulmonary Surfactants; Risk Factors; Trachea; Treatment Outcome

In 34 patients with non-A non-B, 28 with type B and 11 with autoimmune chronic hepatitis, anti-neutrophil antibodies were investigated using indirect immunofluorescence and anti-myeloperoxidase antibodies by enzyme-linked immunosorbent assay. Granulocyte-specific antinuclear antibodies, were detected in 14 patients with advanced stages of non-A, non-B hepatitis (41%). Their presence correlated with histological features of disease activity but not with response to interferon therapy. Within 24 h after the first dose of interferon, 9 of these became negative and 3 more became negative after 1, 3 and 5 months. Myeloperoxidase-positive perinuclear neutrophil cytoplasmic antibodies were detected in a single patient and increased reaching a peak level after 8 weeks of interferon, decreasing thereafter. In type B, all were negative before and during the 6 months of therapy. In 6 patients with autoimmune hepatitis (55%), myeloperoxidase-negative perinuclear neutrophil cytoplasmic antibodies were detected in high titers. The association of granulocyte-specific anti-nuclear antibodies with non-A, non-B hepatitis support the hypothesis that hepatitis C virus infection might trigger humoral autoimmune response. In chronic autoimmune hepatitis, perinuclear neutrophil cytoplasmic antibodies appear as another marker of autoimmunity.

Topics: Adult; Antibody Specificity; Autoantibodies; Chronic Disease; Female; Hepatitis; Hepatitis Antibodies; Humans; Interferon-alpha; Male; Middle Aged; Neutrophils; Peroxidase; Prospective Studies

Anti-neutrophil cytoplasmic antibody (ANCA) kinetic in ANCA-associated vasculitis with glomerulonephritis (AAV-GN) has been suggested to be associated with AAV relapse. Few studies have focused on its association with renal prognosis. Thus we aimed to investigate the relationship between ANCA specificity and the evolutive profile and renal outcomes.. This multicentric retrospective study included patients diagnosed with ANCA-GN since 1 January 2000. Patients without ANCA at diagnosis and with fewer than three ANCA determinations during follow-up were excluded. We analysed estimated glomerular filtration rate (eGFR) variation, renal-free survival and relapse-free survival according to three ANCA profiles (negative, recurrent and persistent) and to ANCA specificity [myeloperoxidase (MPO) or proteinase 3 (PR3)].. Over a follow-up of 56 months [interquartile range (IQR) 34-101], a median of 19 (IQR 13-25) ANCA determinations were performed for the 134 included patients. Patients with a recurrent/persistent ANCA profile had a lower relapse-free survival (P = .019) and tended to have a lower renal survival (P = .053) compared with those with a negative ANCA profile. Patients with a recurrent/persistent MPO-ANCA profile had the shortest renal survival (P = .015) and those with a recurrent/persistent PR3-ANCA profile had the worst relapse-free survival (P = .013) compared with other profiles. The negative ANCA profile was associated with a greater eGFR recovery. In multivariate regression analysis, it was an independent predictor of a 2-fold increase in eGFR at 2 years [odds ratio 6.79 (95% confidence interval 1.78-31.4), P = .008]).. ANCA kinetic after an ANCA-GN diagnosis is associated with outcomes. MPO-ANCA recurrence/persistence identifies patients with a lower potential of renal recovery and a higher risk of kidney failure, while PR3-ANCA recurrence/persistence identifies patients with a greater relapse risk. Thus ANCA kinetics may help identify patients with a smouldering disease.

Topics: Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Antineutrophil Cytoplasmic; Chronic Disease; Glomerulonephritis; Humans; Kidney; Myeloblastin; Peroxidase; Retrospective Studies

The optimal strategy for remission-maintenance therapy in patients with myeloperoxidase-ANCA (MPO-ANCA)-associated vasculitis is not established. Defining parameters to guide maintenance therapy is required.. This was a retrospective cohort study of all patients with MPO-ANCA-associated vasculitis (microscopic with polyangiitis and granulomatosis with polyangiitis) and GN followed at the Mayo Clinic between 1996 and 2015. Relapse rate, MPO-ANCA status, and remission-maintenance therapies were reviewed. Logistic regression models, Kaplan-Meier method, and Cox proportional hazards regression models were applied.. We analyzed 159 patients with active MPO-ANCA-associated vasculitis with GN. Sixty-six (42%) patients had at least one relapse, and 52 (33%) relapsed before 60 months. Patients with MPO-ANCA who became persistently negative did not relapse (hazard ratio [HR], 0.03; 95% confidence interval [95% CI], 0.002 to 0.431; P =0.01). The reappearance of MPO-ANCA was associated with a higher risk of relapse (HR, 1.91; 95% CI, 1.109 to 3.293; P =0.02). Immunosuppression was withdrawn in 80 (50%) patients, and this was less likely in those who received cyclophosphamide for remission induction or in patients with persistently positive MPO-ANCA (odds ratio [OR], 0.44; 95% CI, 0.228 to 0.861; P =0.02 and OR, 0.42; 95% CI, 0.213 to 0.820; P =0.01, respectively). Relapse frequency was not different between patients with persistently positive MPO-ANCA and patients with MPO-ANCA reappearance (44% versus 39%, P =0.49), irrespective of remission-maintenance treatment. Ear, nose, and throat involvement (OR, 6.10; 95% CI, 1.280 to 29.010; P =0.02) and MPO-ANCA reappearance (OR, 9.25; 95% CI, 3.126 to 27.361; P <0.001) were independently associated with relapse after treatment withdrawal.. Patients persistently MPO-ANCA negative are at low risk for relapse even without remission-maintenance therapy. Persistence or subsequent reappearance of MPO-ANCA is associated with a higher risk of relapse.. This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast.aspx?p=CJASN&e=2023_01_10_CJN06460622.mp3.

Topics: Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Antineutrophil Cytoplasmic; Chronic Disease; Granulomatosis with Polyangiitis; Humans; Kidney; Peroxidase; Recurrence; Retrospective Studies

In anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV), relapses are cause of concern as they are unpredictable and predictors of poor prognosis. We aimed to assess the characteristic and predictors of clinical relapse in AAV.. This retrospective study included 132 cases of AAV newly diagnosed from January 2016 through November 2021 in the Affiliated Hospital of Qingdao University. We reviewed clinical data of patients and analysed the risk factors for clinical relapse of overall population and subgroups by univariate and multivariate regression models and the K-M survival curve was plotted.. The rate of relapse was highest in the positive conversion group than the others significantly (p<0.001). In overall population, ANCA patterns (p<0.001; persistent positive pattern: HR=3.352, 95%CI 1.463~7.678, p=0.004; positive conversion pattern: HR=4.760, 95%CI 2.094~10.820, p<0.001) and infections (HR =4.684, 95%CI 1.980~11.079, p<0.001) were significantly associated with clinical relapse. In myeloperoxidase (MPO)-AAV patients, ANCA patterns (p=0.001; persistent positive pattern: HR=4.495, 95%CI 1.508~13.396, p=0.007; positive conversion pattern: HR=7.404, 95%CI 2.652~20.671, p<0.001) and infections (HR=3.594, 95%CI 1.511~8.547, p=0.004) were significantly associated with clinical relapse. In renal involvement patients, ANCA patterns (p=0.004; persistent positive pattern: HR=3.618, 95%CI 1.364~9.592, p=0.01; positive conversion pattern: HR=4.492, 95%CI 1.778~11.352, p<0.001) and infections (HR=7.791, 95%CI 2.511~24.174, p<0.001) were significantly associated with clinical relapse, but were not in patients without renal involvement.. Persistently positive and re-positive ANCA and infections predict clinical relapse in AAV, especially in patients with MPO-AAV and renal involvement. Regular ANCA monitoring should be carried out in high-risk populations.

Topics: Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Antineutrophil Cytoplasmic; Chronic Disease; Humans; Myeloblastin; Peroxidase; Recurrence; Retrospective Studies

Topics: Child; Chronic Disease; Exanthema; Humans; Mutation; Peroxidase; Psoriasis

To explore associations between inflammatory endotypes and clinical presentations in CRS. To investigate the value of secretions myeloperoxidase (MPO) and eosinophilic cationic protein (ECP) detections in the diagnosis of endotypes of chronic rhinosinusitis (CRS), so as to provide guidance for the clinical application of MPO and ECP detection in secretions.. We collected clinical symptom scores from patients with CRS and examined the differences between endotypes in clinical features. Patients' nasal secretions and polyps (or middle turbinate for control) were collected and their NEU number, EOS%, MPO and ECP levels were measured. Correlation analysis was performed for these biomarkers in secretions and tissues, respectively. Receiver operating characteristic curves were used to assess the predictive potential of the biomarkers mentioned above in nasal secretions.. Patients with Eos+Neu+ and Eos+Neu-CRS scored highest in most clinical symptom scores, while Eos-Neu+ and Eos-Neu-CRS scored lowest. Correlation analysis showed that tissues NEU number was correlated with NEU number and MPO level in nasal secretions (R = 0.4088; 0.6613); tissues EOS % was correlated with EOS% and ECP level in nasal secretions (R = 0.2344; 0.5774). To diagnose Neu+CRS, the highest area under the curve (AUC) (0.8961) was determined for MPO in secretions; the highest AUC (0.7400) was determined for NEU number in secretions. To diagnose Eos+Neu-CRS from Eos-Neu-CRS in Neu-CRS, the highest AUC (0.8801) was determined for ECP in secretions.. Clinical presentations are directly associated with CRS endotypes. Measurement of MPO and ECP in nasal secretions is useful for the endotypes diagnosis of CRS.

Topics: Biomarkers; Chronic Disease; Eosinophil Cationic Protein; Humans; Nasal Polyps; Peroxidase; Rhinitis; Sinusitis

Pathogenic variants in MPO, which encodes the myeloperoxidase, were reported as causative genetic defects in several cases of generalised pustular psoriasis (GPP) in addition to patients with myeloperoxidase deficiency in 2020. However, which clinical subtypes of GPP patients have pathogenic variants in MPO remains largely undetermined, and elucidating this is clinically important. The present report outlines a mild case of GPP with a rare missense heterozygous variant, c.1810C>T p.(Arg604Cys), in MPO. Our structural analysis and functional assays to measure myeloperoxidase activity suggest that the present MPO substitution is a hypomorphic variant in MPO. Thus, the mild phenotype of the present GPP patient might be associated with an incomplete hypomorphic loss-of-function variant in MPO. Additionally, the severe intractable edematous pustules and erythema improved dramatically after five rounds of granulocyte and monocyte adsorption apheresis (GMA) therapy. This is the first report of GMA treatment for GPP associated with a pathogenic variant in MPO, as far as we know. Our findings suggest that GMA might be a useful and powerful tool for controlling GPP in patients with myeloperoxidase deficiency.

Topics: Adsorption; Blood Component Removal; Chronic Disease; Granulocytes; Humans; Interleukins; Monocytes; Peroxidase; Psoriasis; Skin Diseases, Vesiculobullous

Generalized pustular psoriasis is a severe psoriatic subtype characterized by epidermal neutrophil infiltration. Although variants in IL36RN and MPO have been shown to affect immune cells, a systematic analysis of neutrophils and PBMC subsets and their differential gene expression dependent on MPO genotypes was not performed yet. We assessed the transcriptomes of MPO-deficient patients using single-cell RNA sequencing of PBMCs and RNA sequencing of neutrophils in a stable disease state. Cell-type annotation by multimodal reference mapping of single-cell RNA-sequencing data was verified by flow cytometry of surface and intracellular markers; the proportions of CD4

Topics: Acute Disease; CD4-Positive T-Lymphocytes; Chronic Disease; Humans; Leukocytes, Mononuclear; Peroxidase; Psoriasis; Skin Diseases, Vesiculobullous; T-Lymphocytes, Cytotoxic; Transcriptome

Inflammatory bowel disease [IBD], consisting of Crohn's disease [CD] and ulcerative colitis [UC], is a relapsing-remitting illness. Treat-to-target IBD management strategies require monitoring of gastrointestinal inflammation. This study aimed to investigate faecal myeloperoxidase [fMPO], a neutrophil granule enzyme, as a biomarker of IBD activity.. Prospectively recruited participants with IBD, undergoing ileocolonoscopy for disease assessment, provided biological samples and completed symptom questionnaires prior to endoscopy. fMPO, C-reactive protein [CRP], and faecal calprotectin [fCal] were compared with validated endoscopic indices [simple endoscopic score for CD and UC endoscopic index of severity]. Receiver operating characteristic [ROC] curves assessed the performance of fMPO, CRP, and fCal in predicting endoscopic disease activity. Baseline biomarkers were used to predict a composite endpoint of complicated disease at 12 months [need for escalation of biologic/immunomodulator due to relapse, steroid use, IBD-related hospitalisation, and surgery].. A total of 172 participants were recruited [91 female, 100 with CD]. fMPO was significantly correlated with endoscopic activity in both CD [r = 0.53, p < 0.01] and UC [r = 0.63, p < 0.01], and with fCal in all patients with IBD [r = 0.82, p < 0.01]. fMPO was effective in predicting moderate-to-severely active CD [AUROC 0.86, p < 0.01] and UC [AUROC 0.92, p < 0.01]. Individuals with a baseline fMPO > 26 µg/g were significantly more likely to reach the composite outcome at 12 months (hazard ratio [HR] 3.71, 95% confidence interval [CI] 2.07-6.64, p < 0.01).. Faecal myeloperoxidase is an accurate biomarker of endoscopic activity in IBD and predicted a more complicated IBD course during follow-up.

Topics: Biomarkers; C-Reactive Protein; Chronic Disease; Colitis, Ulcerative; Crohn Disease; Endoscopy, Gastrointestinal; Feces; Female; Humans; Inflammatory Bowel Diseases; Leukocyte L1 Antigen Complex; Male; Peroxidase; Severity of Illness Index

Myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) is often positive in patients with interstitial lung disease (ILD), which is also often present in patients with microscopic polyangiitis (MPA). A possible association between MPO-ANCA, MPA, and idiopathic ILD remains unclear. The objective of this study was to determine whether high-resolution computed tomography (HRCT) classification based on recent idiopathic pulmonary fibrosis guideline and specific CT findings can obtain new knowledge of prognostic factors in all MPO-ANCA-positive patients with ILD including both idiopathic ILD and MPA-ILD.. We analyzed 101 consecutive MPO-ANCA-positive patients with respiratory disease. We assessed the diagnostic accuracy of CT findings, HRCT pattern, and specific radiological signs. Prognostic predictors were determined using Cox regression models.. Subjects with chronic ILD included 22 patients with MPA-ILD and 39 patients with ILD but without MPA. A quarter of the patients were radiological indeterminate for usual interstitial pneumonia (UIP) pattern, which resulted in a better prognosis than that for UIP pattern. "Increased attenuation around honeycomb and traction bronchiectasis" and "anterior upper lobe honeycomb-like lesion" were found to be highly frequent radiological findings (39% and 30%, respectively). In addition, the latter finding was a significant negative prognostic factor.. Radiological indeterminate for UIP was a useful HRCT classification in MPO-ANCA-positive patients with ILD. In addition, anterior upper lobe honeycomb-like lesion was found to be specific radiological finding that was a significant prognostic factor. The present results might aid in the assessment of appropriate strategies of diagnosis in these patients.

Topics: Aged; Aged, 80 and over; Antibodies, Antineutrophil Cytoplasmic; Chronic Disease; Female; Humans; Idiopathic Pulmonary Fibrosis; Japan; Lung Diseases, Interstitial; Male; Middle Aged; Peroxidase; Prognosis

Long-term observation of patients with ANCA-associated vasculitis (AAV) allows the identification of different longitudinal patterns of ANCA levels during follow-up. This study aimed to characterize these patterns and to determine their prognostic significance. All ANCA determinations performed in two university hospitals during a 2-year period were retrospectively reviewed. Patients were included in the analysis if they had high titers of anti-myeloperoxidase (anti-MPO) or anti-proteinase 3 (anti-PR3) antibodies at least once, ≥ 5 serial ANCA determinations and AAV diagnosed by biopsy or American College of Rheumatology (ACR) classification criteria. Patients' time-course ANCA patterns were classified as monophasic, remitting, recurrent or persistent. Associations between ANCA patterns and prognostic variables (relapse rate and renal outcome) were analysed by univariate and multivariate statistics. A total of 99 patients [55 with microscopic polyangiitis (MPA), 36 with granulomatosis with polyangiitis (GPA) and eight with eosinophilic granulomatosis with polyangiitis (EGPA)] were included. Median follow-up was 9 years. Among patients diagnosed with MPA or GPA, recurrent or persistent ANCA patterns were associated with a higher risk of clinical relapse [hazard ratio (HR) = 3·7, 95% confidence interval (CI) = 1·5-9·1 and HR = 2·9, 95% CI = 1·1-8·0, respectively], independently of clinical diagnosis or ANCA specificity. In patients with anti-MPO antibodies, the recurrent ANCA pattern was associated with worsening renal function [odds ratio (OR) = 5·7, 95% CI = 1·2-26·0]. Recurrent or persistent ANCA patterns are associated with a higher risk of clinical relapse. A recurrent ANCA pattern was associated with worsening renal function in anti-MPO-associated vasculitis.

Topics: Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Antineutrophil Cytoplasmic; Biopsy; Chronic Disease; Churg-Strauss Syndrome; Female; Follow-Up Studies; Granulomatosis with Polyangiitis; Humans; Kidney; Male; Microscopic Polyangiitis; Middle Aged; Myeloblastin; Peroxidase; Prognosis; Recurrence; Retrospective Studies

This study evaluated the gastric healing activity of eugenol, the main bioactive compound from clove (Syzygium aromaticun) essential oil. Five groups of female Wistar rats were submitted to acetic acid-induced ulcer model and treated with Vehicle (1 mL/kg, p.o.), eugenol (1, 10 or 100 mg/kg, p.o) or omeprazole (20 mg/kg, p.o), twice a day, by seven or fourteen days. Macroscopic, microscopic and biochemical analyses were performed in the ulcerated site. Eugenol (1 mg/kg, p.o) administered by 7 or 14 days accelerated the gastric healing process by 33% and 52%, respectively. The healing actions of eugenol were accompanied by the rescue on the histological architecture and the normalization of the superoxide dismutase and catalase activity. Moreover, eugenol (1 mg/kg, p.o) reduced the gastric mucosal myeloperoxidase activity and increased the mucin secretion. In contrast, eugenol at a dose of 100 mg/kg administered by 7 days enhanced 49% the ulcerated area, but at 10 mg/kg did not change the ulcer area after 7 or 14 days of treatment. Thus, despite the undesirable results due to the worsening of the gastric lesion with the use of eugenol in high doses, the antiulcer potential of this compound is evident and manageable in an adequate dose.

Topics: Animals; Catalase; Chronic Disease; Eugenol; Female; Glutathione; Hormesis; Mice; Peroxidase; Rats; Stomach Ulcer; Superoxide Dismutase

Brain natriuretic peptide is an established, surrogate follow-up marker, strongly correlated with heart failure severity. Several other biomarkers and tests are useful for assessing the prognosis of patients with HF, such as oxidized low-density lipoprotein antibodies and C-reactive protein. Some inflammatory cells, including monocytes, lymphocytes, and neutrophils, are involved in coronary heart disease and may be useful for prognosis also. This study assessed the potential usefulness of various laboratory biomarkers in predicting long-term outcomes and hospitalization among a cohort of outpatients with chronic, advanced HF.This retrospective, 18-year follow-up study included all patients admitted to the Heart Failure Outpatient Unit in our tertiary care medical center from 2000 through 2001 due to chronic HF. Excluded were patients with malignant disease, severe stroke, active inflammatory disease, or infection. At the first visit, blood was sampled for routine analysis and biomarkers NT-proBNP, C-reactive protein, myeloperoxidase, heat shock protein, and antibodies to oxidized low density lipoprotein. left ventricular ejection fraction and New York Heart Association class class were also established. Patients were followed every 3 months. Study endpoints were mortality or first hospitalization.Among 305 study patients, HF duration ranged from 2 months to 18 years. Mean follow-up was 9.1 ± 6 years. Mean time to first hospitalization was 60 ± 58.1 months, median = 38 (range 0-179). Mortality rate was 41%. Regression analysis showed New York Heart Association class, lymphocyte count and alkaline phosphatase were independent predictors of survival, with hazard ratios of 1.0, 0.973, and 1.006, respectively (P < .05).N-terminal pro-B-type natriuretic peptide, alkaline phosphatase, and lymphocyte count are important prognostic predictors for very long-term follow-up among patients with chronic HF.

Topics: Age Factors; Aged; Aged, 80 and over; Biomarkers; Blood Pressure; Body Weight; C-Reactive Protein; Chronic Disease; Comorbidity; Female; Follow-Up Studies; Heart Failure; Heart Rate; Heat-Shock Proteins; Hematologic Tests; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Peroxidase; Retrospective Studies; Sex Factors; Ventricular Function, Left

Topics: Animals; Cannabinoid Receptor Agonists; Carbon Tetrachloride; Chemotaxis; Chronic Disease; Cytoskeleton; GTP-Binding Protein alpha Subunits, Gi-Go; Liver; MAP Kinase Signaling System; Mice, Inbred ICR; Neutrophil Activation; Neutrophils; p38 Mitogen-Activated Protein Kinases; Peroxidase; Phosphorylation; Reactive Oxygen Species; Receptors, Cannabinoid

Ping weisan (PWS), a complex formulation used in traditional Chinese medicine, is first described in 1107 AD and published in the Prescriptions of Taiping Benevolent Dispensary. We have previously confirmed that PWS has the effect of alleviating DSS-induced chronic ulcerative colitis (UC) in mice.. We aimed to examine whether PWS protects mice from chronic UC by regulating intestinal microbiota composition.. Chronic colitis was induced in C57BL/6 mice with 2.5% DSS in drinking water. PWS (8 g/kg) was orally administered throughout the experiment. Body weight changes, stool consistency and myeloperoxidase (MPO) activity were measured in these mice. Interleukin-17A (IL-17A) and interferon gamma (IFN-γ) mRNA levels were detected by qRT-PCR. The alterations of fecal microflora were investigated by 16S rRNA sequencing. Furthermore, intestinal tight junction protein including occludin, and serum lipopolysaccharide (LPS) level were also detected.. PWS relieved DSS-induced loss of body weight, and improved stool consistency and MPO activity in mice. The levels of IL-17A and IFN-γ mRNA were also reduced after treatment with PWS. PWS not only regulated occludin level but also decreased serum LPS. We further showed DSS-induced changes in intestinal microbial composition and richness are significantly regulated by PWS. PWS treatment significantly decreased the abundance of Bacteroidetes, but increased the abundance of Firmicutes in chronic UC mice induced by DSS.. Combining with our previous results, we found that PWS could exert anti-UC role by rebalancing intestinal bacteria.

Topics: Animals; Chronic Disease; Colitis; Colon; Dextran Sulfate; Disease Models, Animal; Drugs, Chinese Herbal; Dysbiosis; Gastrointestinal Agents; Gastrointestinal Microbiome; Interferon-gamma; Interleukin-17; Lipopolysaccharides; Male; Mice, Inbred C57BL; Occludin; Peroxidase; Weight Loss

Mastitis is the most common health concern plaguing the modern dairy cow and costs dairy producers estimates of two billion dollars annually. Staphylococcus aureus infections are prevalent, displaying varied disease presentation and markedly low cure rates. Neutrophils are considered the first line of defense against mastitis causing bacteria and are frequently targeted in the development of treatment and prevention technologies. We describe a case of naturally occurring, chronic mastitis in a Holstein cow (1428), caused by a novel strain of S. aureus that was not able to be cleared by antibiotic treatment.. The infection was identified in a single quarter, 2 months into the cow's first lactation. The infection persisted for the following 20 months, including through dry off, and a second calving and lactation. This case of mastitis was associated with a consistently high somatic cell count, however presented with no other clinical signs. This cow was unsuccessfully treated with antibiotics commonly used to treat mastitis, consisting of two rounds of treatment during lactation and an additional round at the beginning of dry off. The chronic infection was also unchanged through an experimental mid-lactation treatment with pegylated granulocyte-colony stimulating factor (PEG-gCSF) and an additional periparturient treatment with PEG-gCSF. We isolated milk neutrophils from 1428 and compared them to two cows challenged with experimental S. aureus, strain Newbould 305. Neutrophils from 1428's milk had higher surface expression of myeloperoxidase compared to experimental Newbould challenged animals, as well as increased presence of Neutrophil Extracellular Traps. This suggests a heightened activation state of neutrophils sourced from 1428's naturally occurring infection. Upon postmortem examination, the affected quarter revealed multifocal abscesses separated by fibrous connective tissues. Abscesses were most common in the gland cistern and collecting duct region. Microscopically, the inflammatory reaction was pyogranulomatous to granulomatous and consistent with botryomycosis. Colonies of Gram-positive cocci were found within the eosinophilic matrix of the Splendore-Hoeppli reaction within granulomas and intracellularly within the acinar epithelium.. Collectively, we describe a unique case of chronic mastitis, the characterization of which provides valuable insight into the mechanics of S. aureus treatment resistance and immune escape.

Topics: Abscess; Animals; Anti-Bacterial Agents; Cattle; Chronic Disease; Female; Granulocyte Colony-Stimulating Factor; Mastitis, Bovine; Milk; Neutrophils; Peroxidase; Polyethylene Glycols; Recombinant Proteins; Staphylococcal Infections; Staphylococcus aureus

Previous studies have evaluated the risk factors for relapse of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and the biomarkers of AAV for predicting relapse. However, little is known about the association between the presence of sinusitis and relapse and changes in the ANCA levels in AAV. This single-center, retrospective cohort study included 104 consecutive patients who were newly diagnosed with myeloperoxidase (MPO)-ANCA-positive microscopic polyangiitis (MPA) between 2006 and 2018 and were treated at the Aichi Medical University Hospital in Japan. The relationships between sinusitis and relapse of vasculitis and elevated MPO-ANCA levels were assessed using multivariate Cox proportional hazards models that were adjusted for clinically relevant factors. During the entire follow-up period (median, 24 months; interquartile range, 7-54 months), 93 (89.4%) patients achieved remission. After achieving remission, 38 (40.9%) patients experienced at least one relapse (13 [65.0%] in the sinusitis group; 25 [34.3%] in the non-sinusitis group). Sinusitis was identified as a significant predictor of relapse (adjusted hazard ratio: 2.41, 95% confidence interval [CI]: 1.19-4.88; P = 0.015). Furthermore, sinusitis was more likely to be associated with elevated MPO-ANCA levels (adjusted hazard ratio: 2.59, 95% CI: 1.14-5.92; P = 0.024). In conclusion, sinusitis was associated with a higher risk of relapse and elevated MPO-ANCA levels in MPA patients, suggesting that careful management may be required to reduce the risk of relapse in patients with sinusitis. Further studies are needed to elucidate the optimal treatment strategy for these patients.

Topics: Aged; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Antineutrophil Cytoplasmic; Biomarkers; Chronic Disease; Cohort Studies; Female; Granulomatosis with Polyangiitis; Humans; Japan; Male; Microscopic Polyangiitis; Middle Aged; Myeloblastin; Peroxidase; Proportional Hazards Models; Recurrence; Retrospective Studies; Risk Factors; Sinusitis

The aim of this study was to investigate the effect of oxidative stress and antioxidant situation on chronic otitis media with effusions (COME) and acute otitis media (AOM) in children.. A total of 107 children aged 2 to 13 years were examined. The study included 31 patients with AOM, 39 with COME, and 37 as control subjects. Venous blood samples were collected from all patients and control group. Myeloperoxidase (MPO), glutathione peroxidase (GPx), catalase (CAT), nitric oxide (NO), malondialdehyde (MDA), and superoxide dismutase (SOD) activities were investigated in the blood samples.. The mean age was found as 7.3 ± 3.3 in the AOM group, 6.2 ± 3.0 in the COME group, and 6 ± 2.4 in the control group. MPO, NO, and CAT were found to be significantly higher in the AOM and COME groups than the control groups (P = 0.040, P = 0.001, and P = 0.044).. In this study, we observed activity of antioxidant and oxidative stress in children with COME and AOM. These results may be important in the diagnosis of these diseases and may affect the theurapeutic approach to the patients with COME and AOM.

Topics: Acute Disease; Adolescent; Antioxidants; Catalase; Child; Child, Preschool; Chronic Disease; Female; Glutathione Peroxidase; Humans; Male; Malondialdehyde; Nitric Oxide; Otitis Media; Otitis Media with Effusion; Oxidative Stress; Peroxidase; Superoxide Dismutase

Despite increasing evidence that adults with long-standing atopic dermatitis (AD) have systemic inflammation, little is known about systemic inflammation in recent-onset early pediatric AD.. To analyze blood inflammatory proteins of early pediatric AD.. Using high-throughput proteomics (proximity extension assay), we assessed 257 inflammatory and cardiovascular risk proteins in the blood of 30 children with moderate to severe AD younger than 5 years of age (within 6 months of onset) compared with age-matched pediatric control individuals and adult patients with AD.. In pediatric AD blood, T helper (Th) type 2 (CCL13, CCL22) and Th17 (peptidase inhibitor-3/elafin) markers were increased, together with markers of tissue remodeling (matrix metalloproteinases 3/9/10, urokinase receptor), endothelial activation (E-selectin), T-cell activation (IL2RA), neutrophil activation (myeloperoxidase), lipid metabolism (FABP4), and growth factors (FGF21, transforming growth factor-α). Total numbers of dysregulated proteins were smaller in pediatric AD (n = 22) than in adult AD (n = 61). Clinical severity scores were positively correlated with receptors for interleukins 33 and 36 and inversely correlated with some Th1 markers (interferon gamma, CXCL11).. Different baseline expression levels in healthy pediatric vs adult samples.. Within months of pediatric AD onset, systemic immune activation is present, with Th2/Th17 skewing but otherwise different proteomic patterns from adult AD. Future correlation of proteomic patterns with disease course, comorbidity development, and drug response may yield predictive biomarkers.

Topics: Age Factors; Biomarkers; Case-Control Studies; Chemokines; Child, Preschool; Chronic Disease; Dermatitis, Atopic; E-Selectin; Elafin; Fatty Acid-Binding Proteins; Female; Fibroblast Growth Factors; Humans; Infant; Inflammation; Interleukin-2 Receptor alpha Subunit; Male; Matrix Metalloproteinases; Peroxidase; Proteome; Receptors, Interleukin; RNA, Messenger; Severity of Illness Index; Transforming Growth Factor alpha

Topics: Animals; Chronic Disease; Colitis; Colon; Dextran Sulfate; Gene Expression; Immunity, Humoral; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Lymph Nodes; Lymphocyte Count; Male; Mesentery; Mice; Mice, Inbred C57BL; Peroxidase; Probiotics; T-Lymphocytes, Helper-Inducer; Treatment Outcome

Sepsis is a severe, life-threatening condition primarily caused by the cellular response to infection. Sepsis leads to increased tissue damage and mortality in patients in the intensive care unit. L-Lysine is an essential amino acid required for protein biosynthesis and is abundant in lamb, pork, eggs, red meat, fish oil, cheese, beans, peas, and soy. Male albino rats were divided into sham, control, 10-mg/kg bwt L-lysine, and 20-mg/kg bwt L-lysine groups. At the end of treatment, we determined the levels of oxidative and inflammatory markers, myeloperoxidase (MPO) and catalase activities, total cell count, the wet/dry ratio of lung tissue, and total protein content. Furthermore, the effect of L-lysine on the cellular architecture of lung tissue was evaluated. L-Lysine significantly reduced the magnitude of lipid peroxidation; total protein content; wet/dry ratio of lung tissue; tumor necrosis factor-alpha, interleukin-8, and macrophage inhibitory factor levels; MPO activity; and total cell, neutrophil, and lymphocyte counts, and it increased the reduced glutathione levels and the glutathione peroxidase, superoxide dismutase, and catalase activities. A normal cellular architecture was noted in rats in the sham group, whereas proinflammatory changes, such as edema and neutrophilic infiltration, were detected in rats in the control group. L-lysine significantly ameliorated these proinflammatory changes. Thus, L-lysine has the potential for the treatment of sepsis-induced CLI.

Topics: Animals; Antioxidants; Biomarkers; Cell Count; Chronic Disease; Glutathione; Glutathione Peroxidase; Inflammation Mediators; Lipid Peroxidation; Lung; Lung Injury; Lysine; Male; Peroxidase; Protective Agents; Rats; Sepsis; Superoxide Dismutase

Cyanogenic glycosides are found in a diverse group of plants and are metabolized into thiocyanate by the intestines and liver. Conversion of plant derived thiocyanates into cyanide and isocyanic acid occurs by the activity of neutrophil-derived enzyme myeloperoxidase. Therefore, increased intake of cyanogenic glycoside rich plant based diet may lead to increased isocyanic acid induced protein carbamylation in chronic inflammatory states (increased myeloperoxidase activity). As there is a close relationship between non-enzymatic post-translational modification and protein function, carbamylation induced structural changes also affect the functions of proteins. Carbamylation induced structural alterations of proteins have recently drawn a great attention in the current literature, especially regarding the alterations of proteins with long half-life such as type I collagen, elastin, α-crystallin. We hypothesize that a plant-based natural diet, rich in cyanogenic glycosides, may have unintended consequences on native protein structure/function in individuals with chronic inflammatory diseases such as chronic kidney and rheumatological diseases because of the higher rate of transformation of plant derived thiocyanates into isocyanic acid by the increased activity of neutrophil-derived enzyme myeloperoxidase. Regulation of myeloperoxidase activity or moderation of cyanogenic glycoside rich diet might be important in the prevention/modulation of dangerous protein carbamylation process, especially in this patient group.

Topics: Chronic Disease; Collagen; Cyanates; Cyanides; Diet; Elastin; Glycosides; Humans; Inflammation; Intestines; Liver; Models, Theoretical; Neutrophils; Peroxidase; Protein Carbamylation; Proteins; Risk; Up-Regulation

Intestinal mucosal S100A12 and myeloperoxidase (MPO) are inflammatory biomarkers in humans with inflammatory bowel disease (IBD). However, these biomarkers have not been studied in the intestinal mucosa of dogs with chronic enteropathies (CE), even though dogs with CE have increased S100A12 concentrations in feces and serum. This study investigated mucosal S100A12 concentrations and MPO activities in both dogs with CE and healthy Beagles. ELISA (S100A12 concentrations) and spectrophotometric methods (MPO activity) were used. The associations of both biomarkers with canine IBD activity index (CIBDAI), histopathologic findings, clinical outcome, and serum albumin concentrations were also investigated. We studied intestinal mucosal samples originating from different intestinal regions of 40 dogs with CE and 18 healthy Beagle dogs (duodenum, ileum, colon, and cecum).. Compared with healthy Beagles, mucosal S100A12 concentrations in dogs with CE were significantly higher in the duodenum (p < 0.0001) and colon (p = 0.0011), but not in the ileum (p = 0.2725) and cecum (p = 0.2194). Mucosal MPO activity of dogs with CE was significantly higher in the duodenum (p < 0.0001), ileum (p = 0.0083), colon (p < 0.0001), and cecum (p = 0.0474). Mucosal S100A12 concentrations in the duodenum were significantly higher if the inflammatory infiltrate consisted mainly of neutrophils (p = 0.0439) or macrophages (p = 0.037). Mucosal S100A12 concentrations also showed a significant association with the severity of total histopathological injury and epithelial injury in the colon (p < 0.05). Mucosal MPO activity showed a significant association (p < 0.05) with the severity of total histopathological injury, epithelial injury, and eosinophil infiltration in the duodenum. There was no significant association of both biomarkers with CIBDAI or clinical outcome.. This study showed that both mucosal S100A12 concentrations and MPO activities are significantly increased in the duodenum and colon of dogs with CE; mucosal MPO was also increased in the ileum and cecum. Future research should focus on assessing the clinical utility of S100A12 and MPO as diagnostic markers in dogs with CE.

Topics: Animals; Biomarkers; Chronic Disease; Dog Diseases; Dogs; Female; Intestinal Diseases; Intestinal Mucosa; Male; Peroxidase; S100A12 Protein

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by cellular infiltration into the joints and cartilage destruction. Neutrophils play a crucial role in the pathogenesis of RA. Triptolide (TP) is a bioactive compound derived from Tripterygium wilfordii Hook F, which has been used in folk medicine as a treatment for a variety of inflammatory disorders, including RA, for many centuries. Previous studies have shown that TP possesses anti-arthritic activity. However, the anti-arthritic mechanism of TP remains to be fully defined. In the present study, we used the adjuvant-induced arthritis (AA) murine model of RA to investigate the impact of TP on RA and neutrophil function. TP alleviated AA by reducing neutrophil recruitment and suppressing the expression of interleukin-6 and tumour necrosis factor-α in vivo. TP also suppressed the expression of pro-inflammatory cytokines in neutrophils, promoted neutrophil apoptosis and inhibited the migration, NETosis and autophagy of neutrophils in vitro. Based on our findings, TP effectively ameliorates RA by down-regulating neutrophil inflammatory functions, indicating that TP represents a potential therapeutic agent for RA.

Topics: Animals; Apoptosis; Arthritis, Experimental; Arthritis, Rheumatoid; Autophagy; Chronic Disease; Cytokines; Diterpenes; Epoxy Compounds; Extracellular Traps; Inflammation; Leukocyte Elastase; Lipopolysaccharides; Male; Mice, Inbred C57BL; Neutrophil Infiltration; Neutrophils; Peroxidase; Phenanthrenes

To investigate the role of local allergic inflammation and Staphylococcus aureus enterotoxins in chronic rhinosinusitis with nasal polyps.. This study included 36 patients with chronic rhinosinusitis with nasal polyps and 18 controls. Total immunoglobulin E, eosinophil cationic protein, staphylococcal enterotoxin types A and B specific immunoglobulin E, staphylococcal enterotoxin types A and B, and myeloperoxidase levels were determined.. Four patients with chronic rhinosinusitis with nasal polyps had a local allergy. All chronic rhinosinusitis with nasal polyps patients tested negative for staphylococcal enterotoxin types A and B specific immunoglobulin E. The chronic rhinosinusitis with nasal polyps group had significantly elevated staphylococcal enterotoxin types A and B levels in the supernatant. Fourteen patients belonged to the eosinophilic chronic rhinosinusitis with nasal polyps group and the others were characterised as having non-eosinophilic chronic rhinosinusitis with nasal polyps.. Local allergy may play a role in chronic rhinosinusitis with nasal polyps, independent of staphylococcal enterotoxin superantigens. Staphylococcal enterotoxins may be important in the pathogenesis of chronic rhinosinusitis with nasal polyps; however, their roles as superantigens were not confirmed in this study. In Chinese subjects, chronic rhinosinusitis with nasal polyps usually manifests as a neutrophilic inflammation.

Topics: Adult; Case-Control Studies; China; Chronic Disease; Enterotoxins; Eosinophil Cationic Protein; Female; Humans; Hypersensitivity; Immunoglobulin E; Male; Middle Aged; Nasal Polyps; Peroxidase; Rhinitis; Sinusitis; Staphylococcus aureus; Superantigens

Moringa (Moringa oleifera Lam.) seed extract (MSE) has anti-inflammatory and antioxidant activities. We investigated the effects of MSE enriched in moringa isothiocyanate-1 (MIC-1), its putative bioactive, on ulcerative colitis (UC) and its anti-inflammatory/antioxidant mechanism likely mediated through Nrf2-signaling pathway. Dextran sulfate sodium (DSS)-induced acute (n = 8/group; 3% DSS for 5 d) and chronic (n = 6/group; cyclic rotations of 2.5% DSS/water for 30 d) UC was induced in mice that were assigned to 4 experimental groups: healthy control (water/vehicle), disease control (DSS/vehicle), MSE treatment (DSS/MSE), or 5-aminosalicyic acid (5-ASA) treatment (positive control; DSS/5-ASA). Following UC induction, water (vehicle), 150 mg/kg MSE, or 50 mg/kg 5-ASA were orally administered for 1 or 2 wks. Disease activity index (DAI), spleen/colon sizes, and colonic histopathology were measured. From colon and/or fecal samples, pro-inflammatory biomarkers, tight-junction proteins, and Nrf2-mediated enzymes were analyzed at protein and/or gene expression levels. Compared to disease control, MSE decreased DAI scores, and showed an increase in colon lengths and decrease in colon weight/length ratios in both UC models. MSE also reduced colonic inflammation/damage and histopathological scores (modestly) in acute UC. MSE decreased colonic secretions of pro-inflammatory keratinocyte-derived cytokine (KC), tumor necrosis factor (TNF)-α, nitric oxide (NO), and myeloperoxidase (MPO) in acute and chronic UC; reduced fecal lipocalin-2 in acute UC; downregulated gene expression of pro-inflammatory interleukin (IL)-1, IL-6, TNF-α, and inducible nitric oxide synthase (iNOS) in acute UC; upregulated expression of claudin-1 and ZO-1 in acute and chronic UC; and upregulated GSTP1, an Nrf2-mediated phase II detoxifying enzyme, in chronic UC. MSE was effective in mitigating UC symptoms and reducing UC-induced colonic pathologies, likely by suppressing pro-inflammatory biomarkers and increasing tight-junction proteins. This effect is consistent with Nrf2-mediated anti-inflammatory/antioxidant signaling pathway documented for other isothiocyanates similar to MIC-1. Therefore, MSE, enriched with MIC-1, may be useful in prevention and treatment of UC.

Topics: Animals; Chronic Disease; Claudin-1; Colitis, Ulcerative; Colon; Cytokines; Dextran Sulfate; Isothiocyanates; Lipocalin-2; Male; Mice; Moringa; NF-E2-Related Factor 2; Nitric Oxide; Nitric Oxide Synthase Type II; Peroxidase; Plant Extracts; Seeds; Spleen; Tight Junctions; Zonula Occludens-1 Protein

To correlate the serotype specificity to myeloperoxidase (MPO) and proteinase-3 (PR3) with clinical characteristics in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).. Clinical characteristics and outcomes of patients with AAV in our division from 2005 to 2014 were retrospectively compared on the basis of ANCA subtype.. We collected the data from 88 patients with MPO-ANCA vasculitis, and 17 with PR3-ANCA vasculitis. Patients with PR3-ANCA vasculitis were younger, and had higher involvement-rates in the eye, nose, and ear. In both MPO- and PR3-ANCA vasculitis, the most frequently involved organ was the respiratory system. Interstitial pneumonia was more frequent in MPO-ANCA vasculitis (52.3% versus 5.9%, p < 0.01), whereas nodular shadow was more frequent in PR3-ANCA vasculitis (9.1% versus 58.8%, p < 0.01). Multivariable Cox proportional hazard regression analysis showed that the hazard ratio of PR3-ANCA for relapse was 2.48 (95% confidence interval 1.14-5.42, p = 0.02). There was no difference in the survival and the progression to end-stage kidney disease and respiratory failure between the two vasculitides.. MPO-ANCA vasculitis was a predominant form of AAV in Japan. Classification based on ANCA subtype would be clinically relevant in the prediction of organ involvement and relapse.

Topics: Adult; Age Factors; Aged; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Antineutrophil Cytoplasmic; Autoantibodies; Chronic Disease; Female; Humans; Japan; Male; Middle Aged; Myeloblastin; Peroxidase; Phenotype; Recurrence; Retrospective Studies; Risk Factors; Sex Factors

The transcription factor Nrf2 is a major modulator of the cellular antioxidant response. Oxidative burst of infiltrating macrophages leads to a massive production of reactive oxygen species in inflamed tissue of inflammatory bowel disease patients. This oxidative burst contributes to tissue destruction and epithelial permeability, but it is also an essential part of the antibacterial defence. We therefore investigated the impact of the Nrf2 orchestrated antioxidant response in both acute and chronic intestinal inflammation.. To study the role of Nrf2 overexpression in mucosal inflammation, we used transgenic mice conditionally expressing a constitutively active form of Nrf2 [caNrf2] either in epithelial cells or in the myeloid cell lineage. Acute colitis was induced by dextran sulphate sodium [DSS] in transgenic and control animals, and changes in gene expression were evaluated by genome-wide expression studies. Long-term effects of Nrf2 activation were studied in mice with an IL-10-/- background.. Expression of caNrf2 either in epithelial cells or myeloid cells resulted in aggravation of DSS-induced acute colitis. Aggravation of inflammation by caNrf2 was not observed in the IL-10-/- model of spontaneous chronic colitis, where even a trend towards reduced prolapse rate was observed.. Our findings show that a well-balanced redox homeostasis is as important in epithelial cells as in myeloid cells during induction of colitis. Aggravation of acute DSS colitis in response to constitutive Nrf2 expression emphasises the importance of tight regulation of Nrf2 during the onset of intestinal inflammation.

Topics: Acute Disease; Animals; Chronic Disease; Colitis; Cytokines; Dextran Sulfate; Disease Models, Animal; Female; Interleukin-10; Intestinal Mucosa; Macrophages; Male; Mice; Mice, Transgenic; Myeloid Cells; NF-E2-Related Factor 2; Peroxidase; Respiratory Burst

An imbalance between cellular antioxidant defence system[s] and reactive oxygen species [ROS]-driven oxidative stress has been implicated in the pathogenesis of inflammatory bowel disease. Peroxiredoxin [PRDX] 6 contributes to an appropriate redox balance by clearing ROS and reducing peroxidized membrane phospholipids. We here studied the role of PRDX6 in acute and chronic dextran sodium sulphate [DSS]-induced colitis.. To investigate the impact of PRDX6 on intestinal inflammation, we used wild type [WT], Prdx6 knock-out mice [Prdx6-/-] and transgenic mice [Prdx6tg/tg], overexpressing Prdx6. Acute and chronic colitis was induced by DSS in WT, Prdx6-/- and Prdx6tg/tg mice. Colitis was evaluated by endoscopy, colon length, histopathological assessment and myeloperoxidase [MPO] activity. Changes in mRNA and protein expression of pro-inflammatory cytokines and antioxidant enzymes were evaluated by real-time quantitative polymerase chain reaction [RT-qPCR] and western blot. Total glutathione [GSH] levels in colon samples were determined.. Prdx6-/- mice exposed to acute and chronic DSS showed a significant decrease in the clinical parameters and in colonic expression of pro-inflammatory cytokines compared with WT mice. mRNA expression of antioxidant enzymes in colon samples was significantly increased in Prdx6-/- compared with WT mice exposed to acute and chronic DSS. In addition, total GSH levels were increased in Prdx6-/- mice treated with DSS in comparison with WT. Overexpression of Prdx6 did not significantly influence acute and chronic colitis.. Our data indicate that a lack of the antioxidant enzyme PRDX6 protects against the development of acute and chronic experimental colitis and is associated with increased expression and function of other antioxidant enzymes, suggesting effective compensatory mechanisms.

Topics: Acute Disease; Animals; Chronic Disease; Colitis; Colon; Cytokines; Dextran Sulfate; Endoscopy, Gastrointestinal; Epithelial Cells; Female; Glutamate-Cysteine Ligase; Glutathione; Glutathione Synthase; Humans; Inflammatory Bowel Diseases; Interferon-gamma; Interleukin-1beta; Interleukin-6; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; NF-E2-Related Factor 2; Nitric Oxide Synthase Type II; Peroxidase; Peroxiredoxin III; Peroxiredoxin VI; Peroxiredoxins; RNA, Messenger; Tumor Necrosis Factor-alpha

The purpose of this study was to assess the effect of an enriched C-glycosyl flavonoids fraction (EFF-Cp) from Cecropia Pachystachya leaves on behavior, mitochondrial chain function, and oxidative balance in the brain of rats subjected to chronic mild stress. Male Wistar rats were divided into experimental groups (saline/no stress, saline/stress, EFF-Cp/no stress, and EFF-Cp/stress). ECM groups were submitted to stress for 40 days. On the 35th ECM day, EFF-Cp (50 mg/kg) or saline was administrated and the treatments lasted until the 42nd day. On the 41st and 42nd days, the animals were submitted to the splash test and the forced swim test. After these behavioral tests, the enzymatic activity of mitochondrial chain complexes and oxidative stress were analyzed. EFF-Cp reversed the depressive-like behavior induced by ECM. It also reversed the increase in thiobarbituric acid reactive species, myeloperoxidase activity, and nitrite/nitrate concentrations in some brain regions. The reduced activities of the antioxidants superoxide dismutase and catalase in some brain regions were also reversed by EFF-Cp. The most pronounced effect of EFF-Cp on mitochondrial complexes was an increase in complex IV activity in all studied regions. Thus, it is can be concluded that EFF-Cp exerts an antidepressant-like effect and that oxidative balance may be an important physiological process underlying these effects.

Topics: Animals; Antidepressive Agents; Chronic Disease; Creatine Kinase; Disease Models, Animal; Exploratory Behavior; Flavonoids; Grooming; Male; Nitrites; Oxidative Stress; Oxidoreductases; Peroxidase; Plant Extracts; Plant Leaves; Protein Carbonylation; Rats; Rats, Wistar; Stress, Psychological; Swimming; Thiobarbituric Acid Reactive Substances

Current phenotyping of chronic rhinosinusitis (CRS) into chronic rhinosinusitis with nasal polyps (CRSwNP) and chronic rhinosinusitis without nasal polyps (CRSsNP) might not adequately reflect the pathophysiologic diversity within patients with CRS.. We sought to identify inflammatory endotypes of CRS. Therefore we aimed to cluster patients with CRS based solely on immune markers in a phenotype-free approach. Secondarily, we aimed to match clusters to phenotypes.. In this multicenter case-control study patients with CRS and control subjects underwent surgery, and tissue was analyzed for IL-5, IFN-γ, IL-17A, TNF-α, IL-22, IL-1β, IL-6, IL-8, eosinophilic cationic protein, myeloperoxidase, TGF-β1, IgE, Staphylococcus aureus enterotoxin-specific IgE, and albumin. We used partition-based clustering.. Clustering of 173 cases resulted in 10 clusters, of which 4 clusters with low or undetectable IL-5, eosinophilic cationic protein, IgE, and albumin concentrations, and 6 clusters with high concentrations of those markers. The group of IL-5-negative clusters, 3 clusters clinically resembled a predominant chronic rhinosinusitis without nasal polyps (CRSsNP) phenotype without increased asthma prevalence, and 1 cluster had a TH17 profile and had mixed CRSsNP/CRSwNP. The IL-5-positive clusters were divided into a group with moderate IL-5 concentrations, a mixed CRSsNP/CRSwNP and increased asthma phenotype, and a group with high IL-5 levels, an almost exclusive nasal polyp phenotype with strongly increased asthma prevalence. In the latter group, 2 clusters demonstrated the highest concentrations of IgE and asthma prevalence, with all samples expressing Staphylococcus aureus enterotoxin-specific IgE.. Distinct CRS clusters with diverse inflammatory mechanisms largely correlated with phenotypes and further differentiated them and provided a more accurate description of the inflammatory mechanisms involved than phenotype information only.

Topics: Adult; Bacterial Toxins; Biomarkers; Case-Control Studies; Chronic Disease; Cluster Analysis; Cytokines; Enterotoxins; Female; Humans; Immunoglobulin E; Male; Peroxidase; Principal Component Analysis; Rhinitis; Sinusitis; Staphylococcus aureus

Rheumatoid arthritis (RA)--a widespread chronic inflammatory disease in industrialized countries--is characterized by a persistent and progressive joint destruction. The chronic pro-inflammatory state results from a mutual activation of the innate and the adaptive immune system, while the exact pathogenesis mechanism is still under discussion. New data suggest a role of the innate immune system and especially polymorphonuclear granulocytes (PMNs, neutrophils) not only during onset and the destructive phase of RA but also at the chronification of the disease. Thereby the enzymatic activity of myeloperoxidase (MPO), a peroxidase strongly abundant in neutrophils, may be important: While its peroxidase activity is known to contribute to cartilage destruction at later stages of RA the almost MPO-specific oxidant hypochlorous acid (HOCl) is also discussed for certain anti-inflammatory effects. In this study we used pristane-induced arthritis (PIA) in Dark Agouti rats as a model for the chronic course of RA in man. We were able to shown that a specific detection of the HOCl-producing MPO activity provides a sensitive new marker to evaluate the actual systemic inflammatory status which is only partially detectable by the evaluation of clinical symptoms (joint swelling and redness measurements). Moreover, we evaluated the long-term pharmacological effect of the well-known anti-inflammatory flavonoid epigallocatechin gallate (EGCG). Thereby only upon early and continuous oral application of this polyphenol the arthritic symptoms were considerably diminished both in the acute and in the chronic phase of the disease. The obtained results were comparable to the treatment control (application of methotrexate, MTX). As revealed by stopped-flow kinetic measurements, EGCG may regenerate the HOCl-production of MPO which is known to be impaired at chronic inflammatory diseases like RA. It can be speculated that this MPO activity-promoting effect of EGCG may contribute to the pharmacological mode of action of this polyphenol.

Topics: Animals; Arthritis; Biomarkers; Catechin; Chronic Disease; Female; Inflammation; Methotrexate; Orosomucoid; Peroxidase; Rats; Terpenes

Our aim was to investigate the possible relationship between myeloperoxidase (MPO) and myocardial damage markers such as heart-type fatty acid-binding protein (H-FABP) and troponin T (TnT) in patients with chronic heart failure (HF).. Forty-two consecutive patients (age range: 27-80 years) with chronic HF were enrolled in the study. Serum H-FABP, TnT and MPO levels were measured. Routine biochemical and clinical parameters were recorded. Echocardiographic examinations were performed on all patients. A linear regression analysis was performed to determine the correlates of serum H-FABP.. The MPO, H-FABP and TnT levels were 255 ± 227, 60.6 ± 48.5 and 0.07 ± 0.15 ng/ml, respectively. In multiple linear regression analysis, age (β = -0.36, p = 0.006), creatinine level (β = 0.3, p = 0.024) and serum MPO level (β = 0.41, p = 0.009) were significant determinants of H-FABP levels. Bivariate predictors were not significantly associated with TnT levels in linear regression analyses.. The MPO was significantly associated with serum H-FABP levels but not with TnT.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Blood Urea Nitrogen; Chronic Disease; Echocardiography; Fatty Acid-Binding Proteins; Female; Heart Failure; Humans; Linear Models; Male; Middle Aged; Outpatients; Peroxidase; Troponin T; Turkey

To test if MPO-Gd, a gadolinium-based magnetic resonance (MR) imaging probe that is sensitive and specific for the proinflammatory and oxidative enzyme myeloperoxidase (MPO), which is secreted by certain inflammatory cells, is more sensitive than diethylenetriaminepentaacetic acid (DTPA)-Gd in revealing early subclinical and chronic disease activity in the brain in experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis.. The protocol for animal experiments was approved by the institutional animal care committee. A total of 61 female SJL mice were induced with EAE. Mice underwent MPO-Gd- or DTPA-Gd-enhanced MR imaging on days 6, 8, and 10 after induction, before clinical disease develops, and during chronic disease at remission and the first relapse. Brains were harvested at these time points for flow cytometric evaluation of immune cell subtypes and immunohistochemistry. Statistical analysis was performed, and P < .05 was considered to indicate a significant difference.. MPO-Gd helps detect earlier (5.2 vs 2.3 days before symptom onset, P = .004) and more (3.1 vs 0.3, P = .008) subclinical inflammatory lesions compared with DTPA-Gd, including in cases in which there was no evidence of overt blood-brain barrier (BBB) breakdown detected with DTPA-Gd enhancement. The number of MPO-Gd-enhancing lesions correlated with early infiltration of MPO-secreting monocytes and neutrophils into the brain (r = 0.91). MPO-Gd also helped detect more lesions during subclinical disease at remission (5.5 vs 1.3, P = .006) and at the first relapse (9.0 vs 2.7, P = .03) than DTPA-Gd, which also correlated well with the presence and accumulation of MPO-secreting inflammatory cells in the brain (r = 0.93).. MPO-Gd specifically reveals lesions with inflammatory monocytes and neutrophils, which actively secrete MPO. These results demonstrate the feasibility of detection of subclinical inflammatory disease activity in vivo, which is different from overt BBB breakdown.

Topics: Acute Disease; Animals; Chronic Disease; Contrast Media; Disease Models, Animal; Encephalomyelitis, Autoimmune, Experimental; Female; Gadolinium DTPA; Mice; Multiple Sclerosis; Peroxidase; Radionuclide Imaging

T helper (Th)1 and Th17 cells play a critical role in inflammatory bowel disease (IBD). 1,25-dihydroxyvitamin D3 (1,25(OH)2 D3 ) has emerged as a direct regulator of immune system function. Mice were grouped as follows: Control group (received PBS, n = 10), DSS group (received 2% DSS and PBS, n = 10), and DSS+VD group (received 2% DSS and 1,25(OH)2 D3 , n = 10). The disease activity index (DAI), colon length, and damage store of the mice were observed; the spleen length, weight, spleen index, and mononuclear cells of spleen were measured; mononuclear cells from mesenteric lymph nodes (MLN) were measured, and the levels of Th 1 and Th17 cytokines in the colon mucosa and spleen were measured. Mice in the DSS group developed severe diarrhea, rectal bleeding, and marked BW loss. Histological examination revealed extensive ulceration and inflammatory cell infiltration in the colon, and the structure of the spleen was disordered, infiltrated with inflammatory cytokines in red pulp. In the DSS group, mononuclear cell numbers from MLN and spleen were increased, and enhanced proteins and mRNA levels of Th 1 and Th17 cytokines were detected. In the DSS+VD group, 1,25(OH)2 D3 ameliorated the inflammation of the colon and spleen. In addition, 1,25(OH)2 D3 down-regulated the levels of Th 1 and Th17 cytokines. 1,25(OH)2 D3 represents a novel therapeutic drug for UC, which may correlate to inhibit the activation of Th1 and Th17 cells.

Topics: Animals; Calcitriol; Calcium; Chronic Disease; Colitis; Colon; Dextran Sulfate; Disease Models, Animal; Down-Regulation; Inflammation; Interferon-gamma; Interleukin-17; Interleukin-6; Intestinal Mucosa; Male; Mice; Mice, Inbred C57BL; Peroxidase; RNA, Messenger; Spleen; Th1 Cells; Th17 Cells; Tumor Necrosis Factor-alpha

Topics: Aged; Biomarkers; Case-Control Studies; Chronic Disease; Female; Humans; Leukocyte Elastase; Male; Muramidase; Peroxidase; Prospective Studies; Wound Infection

Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome is a newly characterized autoinflammatory disorder, caused by mutations in PSMB8. It is characterized by early-onset fevers, accompanied by a widespread, violaceous, and often annular cutaneous eruption. Although the exact pathogenesis of this syndrome is still obscure, it is postulated that the inflammatory disease manifestations stem from excess secretion of interferons. Based on preliminary blood cytokine and gene expression studies, the signature seems to come mostly from type I interferons, which are proposed to lead to the recruitment of immature myeloid cells into the dermis and subcutis. In this study, we systematically analyzed skin biopsies from 6 patients with CANDLE syndrome by routine histopathology and immunohistochemistry methods. Skin lesions showed the presence of extensive mixed dermal and subcutaneous inflammatory infiltrate, composed of mononuclear cells, atypical myeloid cells, neutrophils, eosinophils, and some mature lymphocytes. Positive LEDER and myeloperoxidase staining supported the presence of myeloid cells. Positive CD68/PMG1 and CD163 staining confirmed the existence of histiocytes and monocytic macrophages in the inflammatory infiltrate. CD123 staining was positive, demonstrating the presence of plasmacytoid dendritic cells. Uncovering the unique histopathological and immunohistochemical features of CANDLE syndrome provides tools for rapid and specific diagnosis of this disorder and further insight into the pathogenesis of this severe life-threatening condition.

Topics: Antigens, CD; Antigens, Differentiation, Myelomonocytic; Chronic Disease; Dendritic Cells; Eosinophils; Fever; Histiocytes; Humans; Immunohistochemistry; Interleukin-3 Receptor alpha Subunit; Lipodystrophy; Lymphocytes; Macrophages; Myeloid Cells; Neutrophils; Peroxidase; Receptors, Cell Surface; Skin Diseases; Syndrome

Based on the notion that inflammation favors tumorigenesis, our experiments comparatively assessed the influence of acute and chronic inflammation on the development of a murine mammary tumor (4T1). In addition, we characterized angiogenic and inflammatory markers in the tumor tissue and systemically. Subcutaneous implantation of polyether-polyurethane sponge discs in Balb/c mice was used to host 4T1 tumor cells (1x10(6)), which were inoculated intraimplant 24 h or 10 days post implantation. Flow cytometric analysis of enzyme-digested implants revealed that, after 24 hours, the population of leukocytes was primarily characterized by neutrophils (42.53% +/- 8.45) and monocytes (37.53% +/- 7.48), with some lymphocytes (16.27% +/- 4.0) and a few dendritic cells (1.82% +/- 0.36). At 10 days, macrophages were predominant (37.10% +/- 4.54), followed by lymphocytes (28.1% +/- 4.77), and monocytes (22.33% +/- 3.05), with some dendritic cells (13.60% +/- 0.55) and neutrophils (11.07% +/- 2.27). A mammary tumor grown in a chronic inflammatory environment was 2-fold when compared with one grown in acute inflammation and 5-fold when compared with tumor alone. The levels of pro-angiogenic cytokine (VEGF-Vascular Endothelial Growth Factor) were higher in implant-bearing tumor when 4T1 cells were grown in 10-day old implants as compared to the VEGF levels of the two other groups. Overall, the levels of the inflammatory markers evaluated (NAG -N-acetylglucosaminidase, TNF-α-Tumor Necrosis Factor-α) were higher in both groups of implant-bearing tumors and in serum from those animals when compared with the tumor alone levels. This inflammation-related difference in tumor growth may provide new insights into the contribution of different inflammatory cell populations to cancer progression.

Topics: Acetylglucosaminidase; Acute Disease; Animals; Biomarkers, Tumor; Chronic Disease; Disease Progression; Flow Cytometry; Inflammation; Lymphocytes; Macrophages; Male; Mammary Neoplasms, Experimental; Mice, Inbred BALB C; Monocytes; Neovascularization, Pathologic; Neutrophils; Peroxidase; Time Factors; Tumor Burden; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor A

Heart failure (HF) is accompanied by the development of an imbalance between oxygen- and nitric oxide-derived free radical production leading to protein nitration. Both chlorinating and peroxidase cycle of Myeloperoxidase (MPO) contribute to oxidative and nitrosative stress and are involved in tyrosine nitration of protein. Ceruloplasmin (Cp) has antioxidant function through its ferroxidase I (FeOxI) activity and has recently been proposed as a physiological defense mechanism against MPO inappropriate actions.. We investigated the relationship between plasma MPO-related chlorinating activity, Cp and FeOxI, and nitrosative stress, inflammatory, neurohormonal, and nutritional biomarkers in HF patients.. In chronic HF patients (n = 81, 76 ± 9 years, NYHA Class II (26); Class III (29); Class IV (26)) and age-matched controls (n = 17, 75 ± 11 years, CTR), plasma MPO chlorinating activity, Cp, FeOxI, nitrated protein, free Malondialdehyde, BNP, norepinephrine, hsCRP, albumin, and prealbumin were measured. Plasma MPO chlorinating activity, Cp, BNP, norepinephrine, and hsCRP were increased in HF versus CTR. FeOxI, albumin, and prealbumin were decreased in HF. MPO-related chlorinating activity was positively related to Cp (r = 0.363, P < 0.001), nitrated protein, hsCRP, and BNP and inversely to albumin.. Plasma MPO chlorinated activity is increased in elderly chronic HF patients and positively associated with Cp, inflammatory, neurohormonal, and nitrosative parameters suggesting a role in HF progression.

Topics: Aged; Aged, 80 and over; Albumins; Biomarkers; C-Reactive Protein; Ceruloplasmin; Chronic Disease; Cross-Sectional Studies; Female; Halogenation; Heart Failure; Humans; Inflammation; Male; Natriuretic Peptide, Brain; Peroxidase

A key role of bacterial biofilm in the pathogenesis of chronic rhinosinusitis (CRS) with (CRSwNP) and without nasal polyps (CRSsNP) is commonly accepted. However, the impact of some bacterial species isolated from inflamed sinus mucosa on biofilm formation is unclear. In particular, the role of Staphylococcus epidermidis as aetiological agents of CRS is controversial. Moreover, the effect of biofilm formation on neutrophil infiltration and activity in CRSwNP calls for explanation. In this study, biofilms were found in three of 10 patients (mean age = 46 ± 14) with CRS undergoing endoscopic sinus surgery by means of scanning electron microscopy. Unexpectedly, S. epidermidis was the primary isolated bacteria and was also found to be present in all biofilm-positive mucosa specimens, indicating its pivotal role in the pathogenesis of severe chronic infections associated with biofilm formation. We have also measured the activity of myeloperoxidase (MPO), the most abundant neutrophil enzyme, to demonstrate the presence of neutrophils in the samples tested. Our present results show that the level of MPO in CRS associated with biofilm is lower than that without biofilm. It may suggest either a low number of neutrophils or the presence of a type of neutrophils with compromised antimicrobial activity, described as biofilm-associated neutrophils (BAN). Finally, we conclude that further studies with a large number of CRS cases should be performed to establish the association between S. epidermidis and other frequently isolated bacterial species from paranasal sinuses, with the severity of CRS, biofilm formation and the infiltration of BAN.

Topics: Adult; Biofilms; Biomarkers; Chronic Disease; Colony Count, Microbial; Double-Blind Method; Female; Humans; Male; Microscopy, Electrochemical, Scanning; Middle Aged; Nasal Mucosa; Neutrophil Infiltration; Neutrophils; Peroxidase; Prospective Studies; Rhinitis; Severity of Illness Index; Sinusitis; Staphylococcal Infections; Staphylococcus epidermidis

The abundance of Faecalibacterium prausnitzii, an abundant and representative bacterium of Firmicutes phylum, has consistently been observed to be lower in patients with Crohn's disease than in healthy individuals. We have shown that both F. prausnitzii and its culture supernatant (SN) have anti-inflammatory and protective effects in a TNBS-induced acute colitis mouse model. Here, we tested the effects of both F. prausnitzii and its SN in moderate and severe DNBS-induced chronic colitis mouse models.. Colitis was induced by intrarectal administration of DNBS. After either 4 or 10 days of recovery (severe and moderate protocols, respectively), groups of mice were intragastrically administered either with F. prausnitzii A2-165 or with its culture SN for 7 or 10 days. Three days before being sacrificed, colitis was reactivated by administration of a lower dose of DNBS. The severity of colitis at the time of being sacrificed was assessed by weight loss and macroscopic and microscopic scores. Myeloperoxidase (MPO) activity, cytokine levels, lymphocyte populations, and changes in microbiota were studied.. Intragastric administration of either F. prausnitzii or its SN led to a significant decrease in colitis severity in both severe and moderate chronic colitis models. The lower severity of colitis was associated with down-regulation of MPO, pro-inflammatory cytokines, and T-cell levels.. We show, for the first time, protective effects of both F. prausnitzii and its SN during both the period of recovery from chronic colitis and colitis reactivation. These results provide further evidence that F. prausnitzii is an anti-inflammatory bacterium with therapeutic potential for patients with inflammatory bowel disease.

Topics: Animals; Chronic Disease; Colitis; Dinitrofluorobenzene; Disease Models, Animal; Lactococcus lactis; Male; Mice; Mice, Inbred C57BL; Peroxidase; Probiotics; Prognosis; Ruminococcus

Lipoxins (LXs) are proresolving and anti-inflammatory eicosanoids whose role in chronic heart failure (CHF) pathogenesis has never been investigated. This study evaluated levels of LXs in CHF patients, its relationship with disease severity and correlation with established CHF biomarkers. The effect of low-dose aspirin [acetylsalicylic acid (ASA)] on the levels of LXs was also studied.. Lipoxin A4 (LXA4 ), 15-epi-lipoxin A4 (15-epi-LXA4 ) and myeloperoxidase (MPO) concentration and activity were evaluated by immunoenzymatic and spectrophotometric assays in 34 CHF patients [New York Heart Association (NYHA) functional class I to IV]. B-type natriuretic peptide (BNP), troponin, myoglobin, C-reactive protein (CRP) and uric acid (UA) were also analyzed.. Patients were stratified into mild-to-moderate CHF (NYHA, classes I and II) and severe CHF (NYHA classes III and IV). Severe patients had lower plasma LXA4 (0·262 ± 0·034 vs. 0·362 ± 0·039 ng/mL, P < 0·05) and decreased urinary 15-epi-LXA4 levels (2·28 ± 0·44 vs. 4·88 ± 1·03 μg/day, P < 0·05) besides exhibiting increased plasma BNP (1464 ± 442 vs. 555 ± 162 pg/mL, P < 0·05) and MPO activity (45·15 ± 11·56 vs. 15·90 ± 2·80 μmol/min/mg protein, P < 0·05). Plasma LXA4 was inversely correlated with BNP, troponin, myoglobin, CRP, UA and MPO activity. ASA treatment was associated with higher urinary excretion of 15-epi-LXA4 (7·70 ± 1·48 vs. 2·06 ± 0·30 μg/day, P < 0·05) in mild-to-moderate CHF patients and lower BNP levels in both groups.. Higher severity of CHF is associated with reduced levels of LXs. Plasma LXA4 appears to be a valuable marker for risk stratification in CHF. Furthermore, the ASA-related increase in urinary 15-epi-LXA4 suggests enhanced renal synthesis of this eicosanoid and may represent a disregarded benefit of ASA.

Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Biomarkers; Cardiovascular Diseases; Chronic Disease; Female; Glomerular Filtration Rate; Heart Failure; Humans; Inflammation; Leukocyte Count; Lipoxins; Male; Peroxidase; Risk Factors

Crohn's disease (CD) and ulcerative colitis are two main clinically defined forms of chronic inflammatory bowel disease (IBD). Our understanding of IBD depends largely on rodent models. DSS-induced intestinal inflammation in mice and T cell transfer colitis in SCID mice are most widely used and accepted models that can recapitulate the human diseases. Here, we provide detailed protocols of these two mouse models of experimentally induced intestinal inflammation. We also discuss the protocols for the isolation and analysis of inflammatory T cell from the colon.

Topics: Acute Disease; Animals; CD4-Positive T-Lymphocytes; Chronic Disease; Colitis, Ulcerative; Colon; Disease Models, Animal; Enzyme Assays; Homeodomain Proteins; Humans; Leukocyte Common Antigens; Lymph Nodes; Male; Mice; Peroxidase; Staining and Labeling; Tissue and Organ Harvesting; Tissue Culture Techniques

In chronic kidney disease (CKD) cardiovascular risk is increased. Oxidative stress is strictly involved in the pathophysiology of this enhanced risk as well as leukocytes' activation. To better elucidate these phaenomena we evaluated some parameters of leukocyte activation and oxidative state on fasting blood samples obtained from CKD patients on conservative or hemodialysis (HD) treatment, compared to those obtained from control subjects.. We enrolled 41 patients (25 men and 16 women, mean age 64.7 ± 11.1 years) with CKD and 42 patients (21 men and 21 women, mean age 66.83 ± 14.8 years) with CKD on hemodialysis (HD) treatment. Hemodialyzed patients were evaluated before and after a standard HD session. Leukocyte activation was evaluated by determining plasma elastase and myeloperoxidase level employing ELISA methods. Lipid peroxidation was evaluated as thiobarbituric acid-reactive substances (TBARS), total antioxidant status using spectrophotometry.. Elastase was higher in CKD on conservative and on HD treatment and its value increased after the HD session. Myeloperoxidase did not show any variation in CKD on conservative and HD treatment while after HD its value was increased. Lipid peroxidation was increased in CKD on conservative and on HD therapy and its value after dialysis showed no significant variation. Total antioxidant status was increased in CKD on HD treatment and significantly decreased after the HD session; no variation between normal controls and CKD subjects on conservative therapy was observed.. Several aspects derive from these data considering the role of oxidative stress in the cardiovascular events that accompany CKD.

Topics: Adult; Aged; Antioxidants; Chronic Disease; Enzyme-Linked Immunosorbent Assay; Female; Humans; Kidney Diseases; Leukocyte Elastase; Lipid Peroxidation; Male; Middle Aged; Neutrophil Activation; Oxidative Stress; Peroxidase; Renal Dialysis; Thiobarbituric Acid Reactive Substances; Young Adult

It has been suggested that oxidative stress may play an important role in the pathogenesis of chronic otitis media (COM), but the role of oxidative stress in the pathogenesis of COM has not yet been fully explored. Therefore, the aim of this study was to investigate serum myeloperoxidase (MPO) activity, 4-hydroxynonenal (4-HNE), malondialdehyde (MDA), total antioxidant capacity (TAC) and nitric oxide (NO) in patients with COM. Sixty-one patients with COM and 30 controls were enrolled in the present study. Patients were divided into two groups according to the presence (n = 21) or absence (n = 40) of cholesteatoma. Serum MPO activity and 4-HNE, MDA and NO levels were significantly higher in patients with COM than controls (for all, p < 0.001), while TAC levels were significantly lower (for all, p < 0.001). Serum MPO activity and MDA, 4-HNE and NO levels were significantly higher in patients with cholesteatoma than in those without cholesteatoma, while TAC levels were significantly lower; but the difference between groups was not statistically significant (p > 0.05). Increased oxidative stress seems to be associated with decreased antioxidant levels in patients with COM. Thus, increased oxidative stress may play a role in the pathogenesis of COM. It is believed that the administration of antioxidant vitamins such as A, C and E may be useful in preventing and treating COM.

Topics: Adolescent; Adult; Aldehydes; Antioxidants; Case-Control Studies; Child; Chronic Disease; Female; Humans; Lipid Peroxidation; Male; Nitric Oxide; Otitis Media; Oxidants; Oxidation-Reduction; Oxidative Stress; Peroxidase; Young Adult

Inflammation is a fundamental aspect of many human diseases. In this video report, we demonstrate non-invasive bioluminescence imaging techniques that distinguish acute and chronic inflammation in mouse models. With tissue damage or pathogen invasion, neutrophils are the first line of defense, playing a major role in mediating the acute inflammatory response. As the inflammatory reaction progresses, circulating monocytes gradually migrate into the site of injury and differentiate into mature macrophages, which mediate chronic inflammation and promote tissue repair by removing tissue debris and producing anti-inflammatory cytokines. Intraperitoneal injection of luminol (5-amino-2,3-dihydro-1,4-phthalazinedione, sodium salt) enables detection of acute inflammation largely mediated by tissue-infiltrating neutrophils. Luminol specifically reacts with the superoxide generated within the phagosomes of neutrophils since bioluminescence results from a myeloperoxidase (MPO) mediated reaction. Lucigenin (bis-N-methylacridinium nitrate) also reacts with superoxide in order to generate bioluminescence. However, lucigenin bioluminescence is independent of MPO and it solely relies on phagocyte NADPH oxidase (Phox) in macrophages during chronic inflammation. Together, luminol and lucigenin allow non-invasive visualization and longitudinal assessment of different phagocyte populations across both acute and chronic inflammatory phases. Given the important role of inflammation in a variety of human diseases, we believe this non-invasive imaging method can help investigate the differential roles of neutrophils and macrophages in a variety of pathological conditions.

Topics: Acute Disease; Animals; Chronic Disease; Disease Models, Animal; Inflammation; Luminescent Measurements; Luminol; Mice; Mice, Inbred C57BL; Mice, Nude; Neutrophils; Peroxidase; Superoxides

There is a strong male predominance of oesophageal adenocarcinoma, which might be related to the higher prevalence of precursor lesions such as erosive reflux oesophagitis in men compared with women. This experiment investigated the gender difference in a reflux oesophagitis model of rats and explored the potential role of oestrogen in controlling oesophageal tissue damage.. An acid-reflux oesophagitis model was surgically produced in male and female rats, and ascorbic acid in the diet and sodium nitrite in the drinking water were administered to half of either group to provoke luminal exogenous nitric oxide (NO) as an exacerbating agent. Seven days after the surgery, the oesophagus was excised, and the injury area, myeloperoxidase activity and pro-inflammatory cytokine levels were measured. Furthermore, 17β-oestradiol was administered to ovariectomised female rats or male rats, which then underwent reflux oesophagitis surgery.. While there was no gender difference in oesophageal damage in the baseline model, oesophageal damage was more intensively observed in males than in females in the presence of exogenous NO administration. While oesophageal damage was increased in ovariectomised rats compared with sham ovariectomised, exacerbated oesophageal damage was attenuated by the replacement of 17β-oestradiol. In addition, exacerbated oesophageal damage in male rats was suppressed by 17β-oestradiol.. This is the first study showing the prominent gender difference in the severity of oesophageal tissue damage in a gastro-oesophageal reflux disease-related animal model, highlighting the critical involvement of oestrogen in controlling gastro-oesophageal reflux disease-related oesophageal epithelial injury.

Topics: Animals; Ascorbic Acid; Biomarkers; Chronic Disease; Cytokines; Disease Models, Animal; Esophagitis, Peptic; Esophagus; Estradiol; Estrogens; Female; Gastroesophageal Reflux; Male; Mucous Membrane; Nitric Oxide; Ovariectomy; Peroxidase; Random Allocation; Rats; Rats, Wistar; Severity of Illness Index; Sex Factors; Sodium Nitrite; Stomach

Chronic venous insufficiency (CVI) represents a social and health care problem because it affects working age populations, particularly in jobs requiring orthostasis, has no effective pharmacologic treatment, and requires surgery. Oxidative stress is present in varicose veins, but whether this is reflected in the plasma is controversial. We aimed to quantify plasma oxidative stress biomarkers in the early stages of CVI and calculate a global index of oxidative stress representative of the disease.. Plasma was obtained from blood samples of nine patients with CEAP C2 stage CVI and 10 healthy controls. Biomarkers related to antioxidant defense systems (total thiols, reduced glutathione, uric acid, total antioxidant capacity, catalase), oxidative damage (malondialdehyde-bound protein, protein carbonyls, advanced oxidation products, and 3-nitrotyrosine), and activity of enzymes producing key free radicals (xanthine oxidase and myeloperoxidase) were assessed.. Compared with the controls, CVI patients exhibited decreased catalase activity and thiol levels and increased malondialdehyde-bound protein and protein carbonyls. These parameters were used to calculate the global index of oxidative stress in CVI, which was significantly different between groups.. It is possible to detect significant changes in plasma oxidative stress biomarkers in early stages of CVI and to calculate a global index representative of the oxidative status in an individual. This index, with the appropriate validation in a larger population, could be used for early detection or progression of CVI.

Topics: Adult; Advanced Oxidation Protein Products; Biomarkers; Case-Control Studies; Catalase; Chronic Disease; Disease Progression; Early Diagnosis; Female; Glutathione; Humans; Male; Malondialdehyde; Middle Aged; Oxidative Stress; Peroxidase; Predictive Value of Tests; Protein Carbonylation; Sulfhydryl Compounds; Tyrosine; Ultrasonography, Doppler, Color; Uric Acid; Veins; Venous Insufficiency; Xanthine Oxidase

The expression and regulation of serum amyloid A (SAA) in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) have not been well documented. This study enrolled 24 CRSwNP patients and 19 controls to evaluate the expression of SAA in polyp tissues in Chinese adult patients and investigate underlying mechanism. The levels of SAA and interleukin (IL)-17A and myeloperoxidase (MPO) in nasal tissues were detected using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. In addition, the mRNA expression of SAA was examined in cultured polyp epithelial cells (PECs) in the presence of various cytokines (IFN-γ, IL-4, IL-5 and IL-17A) using qRT-PCR, and the role of extracellular signal-related kinase (ERK) signalling in SAA expression was evaluated by western blot analysis. We found the levels of SAA, IL-17A and MPO were significantly upregulated in polyp tissues compared with the controls (p < 0.05), and significant correlations between SAA and IL-17A mRNA levels, as well as between SAA and MPO protein levels, were observed in polyp tissues (p < 0.05). In the in vitro culture system, IL-17A was found to significantly increase SAA mRNA expression in PECs via ERK signaling pathway, in a time- and dose-dependent manner (p < 0.05). Our results suggested a regulatory mechanism underlying excessive SAA production in polyp tissues, which might gain more insights into the pathophysiology of CRSwNP in Chinese adult patients.

Topics: Adult; Blotting, Western; Case-Control Studies; China; Chronic Disease; Cytokines; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interleukin-17; Male; Middle Aged; Nasal Polyps; Peroxidase; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Serum Amyloid A Protein; Signal Transduction; Sinusitis; Up-Regulation

Pharmacologic inhibition or genetic ablation of phosphoinositide 3-kinase gamma (PI3Kγ) has been shown to be protective against experimental colitis. However, the role of PI3Kγ in the resolution phase of colitis remains unexplored. In this study, we assess the effects of genetic knockout of PI3Kγ on the induction and resolution of colitis induced by the hapten trinitrobenzene sulfonic acid (TNBS).. Colitis was induced in wild-type C57/Bl6 or PI3Kγ-/- mice by intrarectal administration of 2.5 mg of TNBS in 50% ethanol. Body weights were monitored daily, and colon tissues were collected at days 3, 7, or 14 after treatment, and colitis was assessed using disease activity and histologic damage scores, measurement of tissue myeloperoxidase and neutrophil infiltration, and local cytokine production.. Mice lacking PI3Kγ were significantly protected from disease during the acute phase (day 3) of TNBS colitis. However, PI3Kγ-/- mice have difficulty resolving acute inflammation because they failed to restore lost weight and had significantly elevated histologic damage scores and tissue myeloperoxidase levels at days 7 and 14 after TNBS administration compared with wild-type controls. This phenomenon was dependent on presensitization with TNBS and seems to involve an inability to clear invading bacteria, resulting in the generation of a persistent inflammatory cytokine response.. This study confirms that PI3Kγ plays a role in the induction of colitis. However, PI3Kγ is also required for the resolution of intestinal damage following acute inflammation. This must be taken into consideration before the inhibition of PI3Kγ can be used as a treatment for disorders such as inflammatory bowel disease.

Topics: Acute Disease; Animals; Bacterial Translocation; Biomarkers; Chronic Disease; Class Ib Phosphatidylinositol 3-Kinase; Colitis; Cytokines; Fluorescent Antibody Technique; Mice; Mice, Inbred C57BL; Mice, Knockout; Neutrophil Infiltration; Peroxidase; Phagocytosis; Real-Time Polymerase Chain Reaction; Severity of Illness Index; Trinitrobenzenesulfonic Acid; Weight Loss

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is characterized by systemic necrotizing vasculitis, and patients fall into 2 groups: those with proteinase 3-ANCA and those with myeloperoxidase-ANCA. As infections are a trigger of ANCA-associated vasculitis, this disease tends to localize in areas around the upper airway. In this study, the authors compared ear and nasal symptoms between patients with proteinase 3-ANCA and those with myeloperoxidase-ANCA. We undertook a retrospective case series study of 34 patients diagnosed with ANCA-associated vasculitis. The otologic symptoms were divided into 3 types: chronic otitis media, secretory otitis media, and sensorineural hearing loss. Chronic otitis media was more common in patients with proteinase 3-ANCA (P = .001), whereas secretory otitis media was more frequently found in patients with myeloperoxidase-ANCA (P = .007). Crust formation (P = .001), saddle nose (P = .024), and sinusitis (P = .001) were more common in patients with proteinase 3-ANCA than in those with myeloperoxidase-ANCA. Marked differences were observed in the disease spectrum between the 2 ANCA groups.

Topics: Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Antineutrophil Cytoplasmic; Chronic Disease; Disease Progression; Follow-Up Studies; Hearing Loss, Sensorineural; Humans; Myeloblastin; Otitis Media; Peroxidase; Prognosis; Retrospective Studies

Intestinal fibrostenosis is a hallmark of severe Crohn's disease and can lead to multiple surgeries. Patients with certain TNFSF15 variants overexpress TL1A. The aim of this study was to determine the effect of TL1A overexpression on intestinal inflammation and the development of fibrostenosis. We assessed the in vivo consequences of constitutive TL1A expression on gut mucosal inflammation and fibrostenosis using two murine models of chronic colitis. In the dextran sodium sulfate (DSS) and adoptive T-cell transfer models, there was proximal migration of colonic inflammation, worsened patchy intestinal inflammation, and long gross intestinal strictures in Tl1a transgenic compared to wild-type littermates. In the DSS model, myeloid- and T-cell-expressing Tl1a transgenic mice had increased T-cell activation markers and interleukin-17 expression compared to wild-type mice. In the T-cell transfer model, Rag1(-/-) mice receiving Tl1a transgenic T cells had increased interferon-γ expression but reduced T-helper 17 cells and IL-17 production. Narrowed ureters with hydronephrosis were found only in the Tl1a transgenic mice in all chronic colitis models. In human translational studies, Crohn's disease patients with higher peripheral TL1A expression also exhibited intestinal fibrostenosis and worsened ileocecal inflammation with relative sparing of rectosigmoid inflammation. These data show that TL1A is an important cytokine that not only modulates the location and severity of mucosal inflammation, but also induces fibrostenosis.

Topics: Adoptive Transfer; Animals; Chronic Disease; Colitis; Colon; Constriction, Pathologic; Fibrosis; Humans; Interleukin-17; Intestinal Mucosa; Lymphocyte Activation; Mice; Mice, Transgenic; Peroxidase; T-Lymphocytes; Tumor Necrosis Factor Ligand Superfamily Member 15

Topics: Aged; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antirheumatic Agents; Chronic Disease; Cyclophosphamide; Dermatitis, Atopic; Eosinophilia; Female; Glomerulonephritis; Glucocorticoids; Heart Failure; Hemorrhage; Humans; Lung Diseases; Methylprednisolone; Peroxidase; Prednisone; Tomography, X-Ray Computed

Statins represent a class of drugs that effectively lowers cholesterol, however they also possess pleiotropic effects, like promotion of angiogenesis, prevention of bone loss, immunomodulatory and anti-inflammatory effects.. Thus, the aim of this study was to investigate the activity of simvastatin topically applied in mice in acute and chronic skin inflammation models.. Skin inflammation was induced in mice ears by topical application of 12-O-tetradecanoylphorbol acetate (TPA). In the acute model, ear oedema was measured by the increase of ear thickness 6h after TPA (2.5μg/ear). The chronic inflammatory process was induced by multiple applications of TPA (2.0μg/ear) for nine alternate days, and the oedema was measured daily as the increase in ear thickness.. Topical treatment was applied immediately after TPA in acute model or started at 5th day of chronic experiment. For acute model treatment was simvastatin (0.24, 0.71 and 2.40μM), dexamethasone (0.13μM), both in acetone or vehicle alone (acetone). In chronic model simvastatin (1% and 3%) and dexamethasone (0.5%) were incorporated in ointment preparations, and a group received ointment alone (vehicle). Samples of ear tissue (6mm) were taken from acute and chronic models, weighted and prepared for histological analysis and myeloperoxidase (MPO) enzymatic activity evaluation. Application of simvastatin in acetone reduced the ear oedema after a single TPA application in a dose dependent manner [ID(50) of 0.47 (0.22-1.13) μM], and the MPO enzymatic activity up to 61±10%. Also, both simvastatin ointment preparations 1% and 3% reduced acute TPA-induced ear oedema in 55±7% and 65±8%, respectively. In the chronic model, simvastatin ointment 1% was able to reduce ear oedema (25±3%) and ear weight (10±1%), though 3% formulation augmented both parameters. Histological analysis revealed a reduction of swelling and leukocyte migration in the acute model for both the formulations of simvastatin (1% and 3%), while in chronic model simvastatin 1% decreased ear swelling and epidermal thickness, but simvastatin 3% increased both parameters.. The results confirm the anti-inflammatory activity of simvastatin when applied topically in both acute and chronic models of skin inflammation. Besides, the formulation of simvastatin ointment 1% shows to be a very effective formulation for a chronic usage.

Topics: Acute Disease; Administration, Topical; Animals; Anti-Inflammatory Agents, Non-Steroidal; Chronic Disease; Dermatitis, Irritant; Disease Models, Animal; Female; Mice; Ointments; Peroxidase; Proliferating Cell Nuclear Antigen; Simvastatin; Tetradecanoylphorbol Acetate

Interleukin-33 (IL-33) is a member of the IL-1 family. Recent evidence shows the importance of IL-33 in autoimmune and inflammatory diseases. To elucidate its impact on inflammatory bowel disease we studied the effects of exogenous IL-33 during the induction of acute dextran sodium sulfate (DSS)-induced colitis, the induction period of chronic DSS colitis, and after establishment of chronic inflammation.. For induction of acute colitis mice received DSS in their drinking water for 7 days and were killed at day 8 or 14 after first DSS administration. Chronic colitis was induced by four cycles of DSS. Animals were treated with IL-33 between the DSS cycles (intermediate treatment) or after onset of chronic disease (posttreatment). Colons and mesenteric lymph nodes were isolated for histology and cytokine secretion, flow cytometric analysis, determination of myeloperoxidase, and transcription factor activity.. While IL-33 in acute colitis led to slight aggravation of inflammation, both chronic colitis approaches resulted in a significant reduction of inflammatory colon contraction, amelioration of disease scores, suppression of interferon-gamma (IFN-γ), and a shift to T helper (Th)2-associated cytokines. Examination of colon tissue revealed increased Ly6g-mRNA levels and myeloperoxidase (MPO) activity in IL-33-treated animals. Evaluation of bacterial translocation revealed decreased translocation incidence in IL-33-treated mice.. In summary, IL-33 has extenuating effects in chronic DSS-induced colitis: Excessive Th1-directed cytokine responses are shifted toward Th2-like immune reactions and general inflammation parameters are reduced. IL-33-induced neutrophil influx during chronic inflammation reduced translocation of pathogenic bacteria across damaged epithelium.

Topics: Acute Disease; Animals; Bacterial Translocation; Cell Movement; Chronic Disease; Colitis; Dextran Sulfate; Disease Models, Animal; Female; Flow Cytometry; Interferon-gamma; Interleukin-33; Interleukins; Liver; Lymph Nodes; Mice; Mice, Inbred BALB C; Neutrophils; Peroxidase; Recombinant Proteins; Spleen

The brush border enzyme intestinal alkaline phosphatase (IAP) functions as a gut mucosal defense factor and is protective against dextran sulfate sodium (DSS)-induced acute injury in rats. The present study evaluated the potential therapeutic role for orally administered calf IAP (cIAP) in two independent mouse models of chronic colitis: 1) DSS-induced chronic colitis, and 2) chronic spontaneous colitis in Wiskott-Aldrich Syndrome protein (WASP)-deficient (knockout) mice that is accelerated by irradiation.. The wildtype (WT) and IAP knockout (IAP-KO) mice received four cycles of 2% DSS ad libitum for 7 days. Each cycle was followed by a 7-day DSS-free interval during which mice received either cIAP or vehicle in the drinking water. The WASP-KO mice received either vehicle or cIAP for 6 weeks beginning on the day of irradiation.. Microscopic colitis scores of DSS-treated IAP-KO mice were higher than DSS-treated WT mice (52±3.8 versus 28.8±6.6, respectively, P<0.0001). cIAP treatment attenuated the disease in both groups (KO=30.7±6.01, WT=18.7±5.0, P<0.05). In irradiated WASP-KO mice cIAP also attenuated colitis compared to control groups (3.3±0.52 versus 6.2±0.34, respectively, P<0.001). Tissue myeloperoxidase activity and proinflammatory cytokines were significantly decreased by cIAP treatment.. Endogenous IAP appears to play a role in protecting the host against chronic colitis. Orally administered cIAP exerts a protective effect in two independent mouse models of chronic colitis and may represent a novel therapy for human IBD.

Topics: Alkaline Phosphatase; Animals; Chronic Disease; Colitis; Cytokines; Dextran Sulfate; Disease Models, Animal; Intestinal Mucosa; Mice; Mice, Inbred C57BL; Mice, Knockout; Peroxidase; Wiskott-Aldrich Syndrome; Wiskott-Aldrich Syndrome Protein

The contribution of infections to the mortality of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis patients is important and should induce early and careful control of these events. However, the differentiation of infection from active vasculitis is often difficult. The usefulness of serum-soluble triggering receptor expressed on myeloid cells-1 (TREM-1) for detecting the presence of infectious complications regardless of disease activity was investigated.. Soluble TREM-1 in serum obtained from 41 patients with myeloperoxidase (MPO)-ANCA-associated vasculitis was measured by an enzyme-linked immunosorbent assay. Twenty-nine samples were from active vasculitis patients, 27 samples from inactive vasculitis patients without infection and 17 samples from inactive vasculitis patients with infectious complications. Serum-soluble TREM-1 was also measured in 10 patients with acute pyelonephritis and 30 patients with chronic kidney disease (CKD).. There was a significant correlation between serum levels of soluble TREM-1 and serum creatinine levels among all patients (r = 0.554, P < 0.0001). The serum-soluble TREM-1/creatinine ratio was higher in inactive vasculitis patients with infectious complications than in active vasculitis, inactive vasculitis without infection and CKD patients (P = 0.0005, P < 0.0001 and P < 0.0001, respectively), but not significantly different to that in acute pyelonephritis patients. On receiver-operating-characteristic curve analysis, a lower-limit value of 9.40 ng/mg for this ratio had a sensitivity of 84.6% and a specificity of 90.8% in differentiating patients with infection from those without infection.. The serum ratio of soluble TREM-1 to creatinine may be a useful marker for detection of infectious complications in MPO-ANCA-associated vasculitis.

Topics: Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Bacterial Infections; Biomarkers; Chronic Disease; Creatinine; Enzyme-Linked Immunosorbent Assay; Humans; Kidney Diseases; Kidney Failure, Chronic; Membrane Glycoproteins; Peroxidase; Receptors, Immunologic; ROC Curve; Sensitivity and Specificity; Triggering Receptor Expressed on Myeloid Cells-1

MEP1A, which encodes the α subunit of meprin metalloproteinases, is a susceptibility gene for inflammatory bowel disease (IBD), and decreased intestinal meprin-α expression is associated with enhanced IBD in humans. Mice lacking meprin α (α knockout, αKO) have more severe colitis induced by dextran sulfate sodium (DSS) than wild-type (WT) mice, indicating an anti-inflammatory role for meprin A. Previous studies and those herein indicate the meprin B has proinflammatory activities. Therefore, mice lacking both meprin A and B (dKO mice) were generated to determine how their combined absence alters the inflammatory response to DSS. Unchallenged dKO mice grow and reproduce normally and have no obvious abnormal phenotype, except for a slightly elevated plasma albumin in both males and females and a lower urine creatinine level in dKO males. Upon oral administration of 3.5% DSS, the dKO mice have more severe colitis than the WT and βKO mice but significantly less than the αKO mice. The dKO mice lose more weight and have elevated MPO and IL-6 activities in the colon compared with WT mice. Systemic inflammation, monitored by plasma nitric oxide levels, is absent in DSS-treated dKO mice, unlike WT mice. The severity of experimental IBD in dKO mice is intermediate between αKO and WT mice. The data indicate that the absence of meprin A aggravates chronic inflammation and the lack of meprin B affords some protection from injury. Manipulation of the expression of meprin gene products may have therapeutic potential.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents; Chronic Disease; Colitis; Dextran Sulfate; Disease Progression; Female; Genetic Predisposition to Disease; Inflammation Mediators; Inflammatory Bowel Diseases; Interleukin-6; Intestinal Mucosa; Male; Metalloendopeptidases; Mice; Mice, Knockout; Permeability; Peroxidase; Severity of Illness Index

Collagen sponges loaded with polyphenols from Hamamelis virginiana were investigated as active materials for chronic wound dressings, evaluating in vitro the inhibition of two major enzymes that impair the wound healing process - myeloperoxidase (MPO) and collagenase. Prior to polyphenols loading, collagen was cross-linked with genipin to improve its biostability. The effect of genipin cross-linking and polyphenol concentration in the development of mechanically and enzymatically stable sponges was studied. The tensile strength of the cross-linked collagen increased with the increase of the cross-linking degree, coupled to decrease in the elongation and the swelling capacity of the sponges. The stability of the sponges to collagenase digestion reached maximum when 1 mM genipin was used. However, the biostability decreased more than 10-fold after loading the sponges with polyphenols (0.5 mg/mL), nevertheless, this effect was partially overcome using higher concentration of polyphenols (1 and 2 mg/mL) to inhibit collagenase. Moreover, the polyphenols released from the sponges were sufficient for complete inhibition of MPO activity. No considerable cytotoxicity of the genipin cross-linked collagen loaded with polyphenols was observed evaluating the NIH 3T3 fibroblasts viability.

Topics: Animals; Bandages; Biocompatible Materials; Chronic Disease; Collagen Type I; Cross-Linking Reagents; Drug Stability; Hamamelis; Iridoid Glycosides; Iridoids; Matrix Metalloproteinase Inhibitors; Mice; Microscopy, Electron, Scanning; NIH 3T3 Cells; Particle Size; Peroxidase; Plant Extracts; Plant Stems; Polyphenols; Wound Healing

We investigated whether eosinophil degranulation is a distinctive feature of asthma and can distinguish between chronic cough patients with asthma and those without.. Thirty-seven patients, with a chronic cough for more than 1 month, and nine normal individuals (controls) were enrolled. Subjects were divided into two groups: one group with asthma and positive bronchial hyperresponsiveness (BHR) (Asthma group, n = 18) and the other group without asthma and negative BHR (Non-Asthma group, n = 19). From induced sputum, total cell counts and differentials were determined. Myeloperoxidase levels were measured by Enzyme-Linked Immunosorbent Assay (ELISA), and eosinophil-derived neurotoxin (EDN) and major basic protein (MBP) levels were measured by radioimmunoassay.. The percentage of sputum eosinophils was increased in the Asthma (p < .001) and Non-Asthma (p < .05) groups compared with the Control group and when comparing the Asthma and Non-Asthma (p < .001) groups. Sputum EDN and MBP levels were increased in the Asthma group compared with the Non-Asthma (p < .05 and p < .05, respectively) and Control groups (p < .05 and p = .055, respectively). However, EDN and MBP levels were not increased in the Non-Asthma group compared with the Control group. The percentage of sputum eosinophils in the Asthma group correlated positively with sputum EDN (Rs = 0.921, p < .001) and MBP (Rs = 0.882, p < .0001) levels and negatively with maxΔFEV(1) (Rs = -0.501, p < .05) (FEV(1), forced expiratory volume in 1 second). Unexpectedly, the percentage of eosinophils in the Non-Asthma group did not correlate significantly with any of these markers. Increased EDN and MBP levels and significant correlations between the percentage of eosinophils and EDN and MBP were only observed in asthma patients.. These findings suggest that eosinophil degranulation is more important than eosinophilia in identifying asthma.

Topics: Adolescent; Adult; Aged; Asthma; Bronchial Provocation Tests; Cell Count; Cell Degranulation; Chemokine CCL24; Chronic Disease; Cough; Eosinophil Major Basic Protein; Eosinophil-Derived Neurotoxin; Eosinophilia; Eosinophils; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Peroxidase; Sputum; Young Adult

Ruta graveolens L. (Rutaceae) are traditionally used for the treatment of rheumatism, arthritis and other inflammatory conditions in the traditional medicine of India, were evaluated for their protective effect in acute and chronic models of inflammation. Carrageenan induced rat paw edema and adjuvant induced arthritis were employed as the experimental models of acute and chronic inflammation respectively. Isolated polyphenolic and alkaloid fraction (AFR) from Ruta graveolens and evaluated its anti inflammatory activity in carrageenan induced acute model. AFR with a dose 10 mg/kg showed higher anti inflammatory effect than polyphenols and standard drug diclofenec. AFR significantly decreased the paw edema in arthritic rats. TBARS, COX-2, 5-LOX and MPO level were decreased and the levels of antioxidant enzymes and GSH level were increased on treatment with AFR. The increment in CRP level and ceruloplasmin level observed in arthritic animals were also found to be significantly restored in AFR treated rats. The results demonstrated the potential beneficiary effect of isolated polyphenolic and alkaloid fraction of Ruta graveolens L. on acute and chronic models of inflammation in rats.

Topics: Acute Disease; Alkaloids; Animals; Anti-Inflammatory Agents; Antioxidants; Arachidonate 5-Lipoxygenase; Arthritis, Experimental; Carrageenan; Catalase; Ceruloplasmin; Chronic Disease; Cyclooxygenase 2; Edema; Flavonoids; Freund's Adjuvant; Glutathione; Glutathione Peroxidase; Inflammation; Lipid Peroxidation; Male; Oxidative Stress; Peroxidase; Phenols; Plant Components, Aerial; Polyphenols; Rats; Rats, Wistar; Ruta; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances

Cyclooxygenase (COX)-derived prostaglandin E(2) (PGE(2)) is a prevalent and established mediator of inflammation and pain in numerous tissues and diseases. Distribution and expression of the four PGE(2) receptors (EP1-EP4) can dictate whether PGE(2) exerts an anti-inflammatory or a proinflammatory and/or a proangiogenic effect. The role and mechanism of endogenous PGE(2) in the cornea, and the regulation of EP expression during a dynamic and complex inflammatory/reparative response remain to be clearly defined.. Chronic or acute self-resolving inflammation was induced in mice by corneal suture or epithelial abrasion, respectively. Reepithelialization was monitored by fluorescein staining and neovascularization quantified by CD31/PECAM-1 immunofluorescence. PGE(2) formation was analyzed by lipidomics and polymorphonuclear leukocyte (PMN) infiltration quantified by myeloperoxidase activity. Expression of EPs and inflammatory/angiogenic mediators was assessed by real-time PCR and immunohistochemistry. Mice eyes were treated with PGE(2) (100 ng topically, three times a day) for up to 7 days.. COX-2, EP-2, and EP-4 expression was upregulated with chronic inflammation that correlated with increased corneal PGE(2) formation and marked neovascularization. In contrast, acute abrasion injury did not alter PGE(2) or EP levels. PGE(2) treatment amplified PMN infiltration and the angiogenic response to chronic inflammation but did not affect wound healing or PMN infiltration after epithelial abrasion. Exacerbated inflammatory neovascularization with PGE(2) treatment was independent of the VEGF circuit but was associated with a significant induction of the eotaxin-CCR3 axis.. These findings place the corneal PGE(2) circuit as an endogenous mediator of inflammatory neovascularization rather than general inflammation and demonstrate that chronic inflammation selectively regulates this circuit at the level of biosynthetic enzyme and receptor expression.

Topics: Animals; Cell Migration Assays, Leukocyte; Chromatography, High Pressure Liquid; Chronic Disease; Corneal Injuries; Corneal Neovascularization; Cyclooxygenase 2; Dinoprostone; Disease Models, Animal; Epithelium, Corneal; Eye Injuries; Female; Fluorescent Antibody Technique, Indirect; Keratitis; Mice; Mice, Inbred C57BL; Neutrophils; Peroxidase; Platelet Endothelial Cell Adhesion Molecule-1; Receptors, Prostaglandin E; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Tandem Mass Spectrometry; Wound Healing; Wounds, Nonpenetrating

Irritable bowel syndrome (IBS) is common in countries where chronic parasitic infestations are endemic. However, the relationship between parasitic infection and IBS is not clear. The aim of this study was to examine whether chronic parasitic infection is accompanied by gut dysfunction and whether the continued presence of the parasite is required for the maintenance of the dysfunction. We used chronic Trichuris muris infection in Th1-biased susceptible AKR mice to evaluate this relationship. AKR mice were infected with T. muris and were euthanized on various days postinfection (pi) to examine worm burden, muscle function, and immune and inflammatory responses. Mice were treated with the anthelmintic oxantel pamoate to assess the effect of eradication of infection on muscle function. Infection resulted in persistence of the parasite, elevated IFN-γ, and increased MPO activity evident at 45 days pi. This was accompanied by a reduction in muscle contractility and excitatory innervation. Whereas parasite eradication at 7 days pi normalized IFN-γ and muscle contractility, eradication at 28 days pi failed to normalize muscle contractility. Administration of dexamethasone after parasite eradication normalized all parameters. Anthelmintic treatment improved histology except for eosinophils, which were normalized by subsequent dexamethasone therapy. Persistent gut dysfunction is independent of the continued presence of the parasite and is maintained by inflammatory process that includes eosinophils. Thus data in this preclinical model suggest that parasitic infection could be a cause of IBS, and the lack of symptomatic improvement following eradication is insufficient evidence to refute a causal relationship between the infection and IBS.

Topics: Adrenal Cortex Hormones; Animals; Anthelmintics; Anti-Inflammatory Agents; Chronic Disease; Colon; Dexamethasone; Gastrointestinal Diseases; Interferon-gamma; Male; Mice; Mice, Inbred AKR; Muscle Contraction; Muscle, Smooth; Peroxidase; Pyrantel Pamoate; Trichuriasis; Trichuris

Although Asparagus cochinchinensis Merrill (Liliaceae) has long been used in traditional Korean and Chinese medicine to treat inflammatory diseases, the underlying mechanism(s) by which these effects are induced remains to be defined. We investigated the effects of 70% ethanolic extract from Asparagus cochinchinensis Merrill (ACE) on skin inflammation in mice.. Production of pro-inflammatory cytokines (tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta), activation of myeloperoxidase, and histological assessment were examined in acute and chronic skin inflammation using 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced mouse ear edema. We also performed acetic acid-induced vascular permeability test.. ACE inhibited topical edema in the mouse ear, following administration at 200mg/kg (i.p.), leading to substantial reductions in skin thickness and tissue weight, inflammatory cytokine production, neutrophil-mediated myeloperoxidase (MPO) activity, and various histopathological indicators. Furthermore, ACE was effective at reducing inflammatory damage induced by chronic TPA exposure and evoked a significant inhibition of vascular permeability induced by acetic acid in mice.. These results demonstrate that ACE is an effective anti-inflammatory agent in murine phorbol ester-induced dermatitis, and suggest that the compound may have therapeutic potential in a variety of immune-related cutaneous diseases.

Topics: Acetic Acid; Acute Disease; Animals; Anti-Inflammatory Agents; Asparagus Plant; Capillary Permeability; Chronic Disease; Cytokines; Dermatitis; Ear, External; Edema; Enzyme Activation; Injections, Intraperitoneal; Interleukin-1; Male; Mice; Mice, Inbred C57BL; Neutrophils; Peroxidase; Phytotherapy; Plant Extracts; Plant Roots; Tetradecanoylphorbol Acetate; Tumor Necrosis Factor-alpha

The cytokine network in inflammatory bowel disease (IBD) is a complex, dynamic system that plays an important role in regulating mucosal innate and adaptive immune responses. While several studies have been done to evaluate immunomodulatory profiles in murine IBD, they have been limited to a relatively small number of cytokines that do not take into account its dependency of the interplay of multiple factors, and therefore the diagnostic potential of their cytokine profiles have been inconclusive.. A novel approach of comprehensive serum multiplex cytokine profiling with biometric immunosandwich ELISA's was used to describe the modulation of 16 Th1, Th2, Th17 cytokines and chemokines in both acute and chronic murine models of DSS and TNBS-induced colitis. Advanced multivariate discriminant functional analyses (DFA) was used to identify statistically interrelated sets of variables with the most significant power to discriminate among the groups. Profiles of multiple cytokines seen systemically were also validated locally in colonic mucosa using Western blot analysis and fluorescent immunohistochemistry.. Distinctive disease-specific cytokine profiles were identified with significant correlations to disease activity and duration of disease. TNBS colitis exhibits heightened Th1-Th17 response (increased IL-12 and IL-17) as the disease becomes chronic. In contrast, DSS colitis switches from a Th1-Th17-mediated acute inflammation (increased TNF-alpha, IL6, IL-17, and KC) to a predominant Th2-mediated inflammatory response (increase in IL-4 and IL-10 and concomitant decrease in TNF-alpha, IL6, IL-17, and KC) in the chronic state. Moreover, DFA identified discriminatory cytokine profiles that can be sufficiently used to distinguish unaffected controls from diseases, and one disease type from another. IL-6 and IL-12 stratified gender-associated disease activity in chronic colitis.. Our studies provide insight into disease immunopathogenesis and illustrate the significant potential of utilizing multiplex cytokine profiles and bioinformatics as diagnostic tools in IBD.

Topics: Animals; Blotting, Western; Chronic Disease; Colitis; Cytokines; Dextran Sulfate; Disease Models, Animal; Disease Progression; Electrophoresis, Polyacrylamide Gel; Enzyme-Linked Immunosorbent Assay; Female; Immunohistochemistry; Intestinal Mucosa; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Peroxidase; Trinitrobenzenesulfonic Acid

Topics: Acute Disease; Biomarkers; Chronic Disease; Heart Failure; Humans; Immunoassay; Peroxidase; Sensitivity and Specificity

Increased oxidative stress has been implicated in the pathogenesis of a number of cardiovascular diseases. Recent findings suggest that myeloperoxidase (MPO) may play a key role in the initiation and maintenance of chronic heart failure (CHF) by contributing to the depletion of the intracellular reservoir of nitric oxide (NO). NO consumption through MPO activity may lead to protein chlorination or nitration, leading to tissue damage. Primary cultures of human endocardial endothelial cells (EEC) obtained at heart transplantation of patients with CHF and human umbilical vein endothelial cells (HUVEC) were subjected to oxidative stress by incubation with hydrogen peroxide at non lethal (60 microM) dose for different exposure times (3 and 6 h). Treated and control cells were tested by immunohistochemistry and RT-PCR for MPO and 3-chlorotyrosine expression. Both endothelial cell types expressed myeloperoxidase following oxidative stress, with higher levels in EEC. Moreover, 3-chlorotyrosine accumulation in treated cells alone indicated the presence of MPO-derived hypochlorous acid. Immunohistochemistry on sections from post-infarcted heart confirmed in vivo the endothelial positivity to MPO, 3-chlorotyrosine and, to a minor extent, nitrotyrosine. Immunohistochemical observations were confirmed by detection of MPO mRNA in both stimulated EEC and HUVEC cells. This study demonstrates for the first time that EEC can express MPO after oxidative stress, both in vitro and in vivo, followed by accumulation of 3-chlorotyrosine, an end product of oxidative stress. Deregulation of endothelial functions may contribute to the development of a number of cardiovascular diseases, including CHF. The results also highlight the notion that endothelium is not only a target but also a key player in oxidative-driven cardiovascular stress.

Topics: Cells, Cultured; Chronic Disease; Endothelial Cells; Gene Expression; Heart Failure; Humans; Hydrogen Peroxide; Immunohistochemistry; Myocardium; Oxidants; Oxidative Stress; Peroxidase; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Tyrosine; Umbilical Veins

The presence of a reciprocal link between inflammation and oxidative/nitrosative stress has been postulated in chronic heart failure (CHF). We aimed to determine signs of nitrosative stress in serum/plasma of CHF patients. ELISA tests were used for quantification of serum/plasma levels of Nitrotyrosine (NT), H(2)O(2), total NO, nitrite (NO(2)(-)), myeloperoxidase (MPO), Tumor Necrosis Factor-alpha (TNFalpha) and pro-Brain Natriuretic Peptide (proBNP) in 66 CHF patients (9 in NYHA I, 34 NYHA II, 23 NYHA III) and in 14 age-matched healthy subjects. NT levels were higher in NYHA III CHF patients compared to NYHA II (p<0.05), NYHA I (p<0.03) and controls (p<0.02), whereas NO(2)(-) and total NO were higher in NYHA III compared to I (p<0.05 and p<0.04, respectively) and controls (p<0.004 and 0.002) and in NYHA II compared to controls (p<0.04 and p<0.009). NT levels correlated significantly with MPO (r=0.37, p<0.003), TNFalpha (r=0.32, p<0.01) and proBNP (r=0.32, p<0.01). These data demonstrate an increased NT plasma level in patients with moderate/severe CHF which is associated to increased levels of markers of systemic inflammation.

Topics: Aged; Biomarkers; Chronic Disease; Cohort Studies; Female; Heart Failure; Humans; Inflammation Mediators; Male; Middle Aged; Peroxidase; Tyrosine

Previous investigation demonstrated predominantly lymphocytic inflammation in sinus mucosa of young children with chronic rhinosinusitis (CRS) rather than eosinophilic inflammation typical of adult CRS. Immunohistopathological study was undertaken to define further the cellular response in pediatric CRS.. Maxillary mucosal biopsies from children and adults with CRS were stained for CD3 (T lymphocytes), CD4 (helper T lymphocytes), CD8 (cytotoxic T lymphocytes), CD20 (B lymphocytes), CD68 (monocytes/macrophages), CD56 (natural killer cells), kappa and lambda (plasma cells), and myeloperoxidase (MPO; neutrophils).. Nineteen children with CRS (median age, 3.0 years; range, 1.4-8.2 years) had more CD8+, MPO+, and CD68+ cells (P < or = .03) and a trend toward more CD3+ and CD4+ cells (P = .06) in their epithelium and more CD20+, kappa+ and lambda+, MPO+, and CD68+ cells (P < or = .05) and a trend toward more CD4+ cells (P = .06) in their submucosa compared with adult control subjects. Immunostains from children with positive sinus cultures were similar to those with negative cultures except for more MPO+ cells in the submucosa (P = .04).. The inflammatory response of young children with CRS is characterized by a mixed lymphocyte population, macrophages, and neutrophils. Differences between pediatric and adult CRS suggest differing pathogenic mechanisms or progression in the inflammatory response with protracted disease.

Topics: Adult; Antigens, CD; B-Lymphocytes; Biopsy; Case-Control Studies; Child; Child, Preschool; Chronic Disease; Humans; Infant; Macrophages; Maxillary Sinus; Nasal Mucosa; Natural Killer T-Cells; Neutrophils; Peroxidase; Plasma Cells; Rhinitis; Sinusitis; Staining and Labeling; T-Lymphocytes

We recently showed that patients with inflammatory bowel disease (IBD) report significantly more sleep disturbances. To determine whether disrupted sleep can affect the severity of inflammation and the course of IBD, we used an animal model of colonic inflammation to determine the effects of acute and chronic intermittent sleep deprivation on the severity of colonic inflammation and tissue damage in colitis and recovery from this damage.. Acute sleep deprivation (ASD) consisted of 24h of forced locomotor activity in a mechanical wheel rotating at a constant speed. Chronic intermittent sleep deprivation (CISD) consisted of an acute sleep deprivation episode, followed by additional sleep deprivation periods in the wheel for 6h every other day throughout the 10day study period. To induce colitis, mice were given 2% dextran sodium sulfate (DSS) in their daily drinking water for 7days. The development and severity of colitis were monitored by measuring weight loss and tissue myeloperoxidase (MPO) activity daily and colon histology scores 10days after initiation of colitis.. ASD or CISD did not cause colonic inflammation in vehicle-treated mice. Changes in daily body weight, tissue MPO levels and colon histopathology score were similar between mice that were sleep deprived and controls. Daily DSS ingestion caused colitis in mice. ASD worsened colonic inflammation: tissue MPO levels in ASD/DSS-treated mice were significantly higher than in DSS-treated mice that were not sleep deprived. However, the worsening of colonic inflammation by ASD was not enough to exacerbate clinical manifestations of colitis such as weight loss. In contrast, the deleterious effects of CISD were severe enough to cause worsening of histological and clinical manifestations of colitis. The deleterious effects of sleep deprivation on severity of colitis appeared to be due to both increased colonic inflammation and a decrease in the ability of mice to recover from DSS-induced colonic injury.. Both acute and chronic intermittent sleep deprivation exacerbate colonic inflammation. Thus, sleep deprivation could be an environmental trigger that predisposes IBD patients to develop flare ups and a more severe disease course. These results provide a scientific rationale to conduct an interventional trial to determine whether improvement in sleep patterns will prevent IBD flare ups, modify the disease course, and improve quality of life.

Topics: Acute Disease; Animals; Body Weight; Chronic Disease; Colitis; Colon; Dextran Sulfate; Diarrhea; Disease Models, Animal; Gastrointestinal Hemorrhage; Male; Mice; Mice, Inbred C57BL; Organ Size; Peroxidase; Rectal Diseases; Sleep Deprivation

Although Chrysanthemum indicum Linné (Compositae) has long been used in traditional Korean, Chinese, Japanese medicine to treat various immune-related diseases the underlying mechanism(s) by which these effects are induced remains to be defined in vivo model system. We investigated the effects of 70% ethanolic extract from Chrysanthemum indicum Linné (CIE) on skin inflammation in mice.. Production of pro-inflammatory cytokines (TNF-alpha and IL-1 beta), activation of myeloperoxidase, and histological assessment were examined in acute and chronic skin inflammation using 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced mouse ear edema.. CIE inhibited topical edema in the mouse ear, following administration at 200mg/kg (i.p.), leading to substantial reductions in skin thickness and tissue weight, inflammatory cytokine production, neutrophil-mediated myeloperoxidase activity, and various histopathological indicators. Furthermore, CIE was effective at reducing inflammatory damage induced by chronic TPA exposure.. These results demonstrate that CIE is an effective anti-inflammatory agent in murine phorbol ester-induced dermatitis, and suggest that the extract may have therapeutic potential in a variety of immune-related cutaneous diseases.

Topics: Acute Disease; Animals; Anti-Inflammatory Agents; Chronic Disease; Chrysanthemum; Dermatitis; Enzyme Activation; Inflammation Mediators; Interleukin-1beta; Male; Mice; Mice, Inbred C57BL; Peroxidase; Plant Extracts; Tetradecanoylphorbol Acetate; Tumor Necrosis Factor-alpha

To study the effect of melatonin, a potent antioxidant both in vitro and in vivo, on hyperoxia-induced oxidant/antioxidant imbalance in the lung of neonatal rats with chronic lung disease (CLD).. Ninety neonatal rats were randomly divided into three groups (n=30 each): air-exposed, hyperoxia-exposed, melatonin-treated (4 mg/kg melatonin was administered 30 minutes before hyperoxia exposure and once daily after exposure). CLD was induced by hyperoxia exposure (FiO2=0.85). Lung specimens were obtained 3, 7, and 14 days after exposure (n=10 each) for histopathologic examination. The levels of total antioxydase capacity (T-AOC), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), myeloperoxidase (MPO), catalase (CAT), nitrite/nitrate, and malondialdehyde (MDA) in the lung were assayed by the spectrophotometer.. The histopathologic examination showed that lung damage was obviously alleviated in the melatonin-treated group. The levels of T-AOC, GSH-Px, SOD and CAT in the lung were significantly higher in the melatonin-treated group than those in the other two groups at all time points (p<0.05). The levels of MPO, nitrite/nitrate and MDA in the lung increased significantly in the untreated hypoxia-exposed group compared with those in the air-exposed group at all time points (p<0.05 or 0.01), while the levels of MPO, nitrite/nitrate and MDA in the melatonin-treated group were significantly reduced as compared with the untreated hypoxia-exposed group (p<0.05).. Melatonin may reverse oxidant/antioxidant imbalance in hyperoxia-induced lung disease, thus providing a protective effect against CLD in neonatal rats.

Topics: Animals; Animals, Newborn; Antioxidants; Chronic Disease; Female; Hyperoxia; Lung; Lung Diseases; Male; Malondialdehyde; Melatonin; Nitric Oxide; Peroxidase; Rats; Rats, Wistar

Anti-neutrophil cytoplasmic autoantibodies (ANCA)-associated disease among other manifestations can underlie rapidly progressive glomerulonephritis (RPGN), with crescentic and necrotizing GN. Differences in pathogenic immune mechanisms in RPGN may provide differences in the renal expression of adhesion molecules mediating these lesions.. Renal intercellular adhesion molecule 1 (ICAM-1; CD54) and vascular cell adhesion molecule 1 (VCAM-1; CD106) were assessed in 40 patients with type I RPGN (anti-glomerular basement membrane antibodies, n = 4), type II (immune complexes, n = 17), and type III (ANCA, n = 19). Enzyme-linked immunosorbent assay (ELISA) for detection of immunoglobulin G antibodies against the Goodpasture's antigen and indirect immunofluorescence and ELISA for myeloperoxidase (MPO) and proteinase 3 (PR3) were performed for ANCA testing. Ten normal renal tissues were used as controls. Relationships between ICAM-1 and VCAM-1, histopathologic features, and CD18, CD14, and CD3 cells were analyzed.. Abnormal ICAM-1 and VCAM-1 in tubule was seen in >80% of biopsies with RPGN. Abnormal VCAM-1 in glomerular tuft was seen in >60% of biopsies with RPGN. Glomerular ICAM-1 was associated with less glomerulosclerosis (chi (2) = 6.719, p = 0.01), less interstitial fibrosis (chi (2) = 4.322, p < 0.05), and less tubular atrophy (chi (2) = 8.547, p < 0.005). Glomerular VCAM-1 was associated with glomerular leukocyte infiltration (chi (2) = 4.698, p < 0.05). Glomerular tuft stains of ++/+++ for VCAM-1 was observed in 10% from MPO-ANCA-GN patients but in 60% from PR3-ANCA-GN (Fi = 8.538, p = 0.03).. The following conclusions can be made from this study. (1) The renal expression of ICAM-1 and VCAM-1 is upregulated in RPGN, and this is associated with the histological activity. (2) De novo expression of VCAM-1 on glomerular tuft suggests that endothelial cells play a role in RPGN. (3) De novo tubular expression of ICAM-1 and VCAM-1 suggests that epithelial cells may participate in adhesive interactions in RPGN. (4) De novo expression of VCAM-1 at the glomerular tuft in PR3-ANCA positive patients seems greater than in MPO-ANCA positive patients, which suggests that testing specific immune activation mechanisms may play a role in ANCA-associated GN.

Topics: Acute Disease; Adult; Aged; Antibodies, Antineutrophil Cytoplasmic; Autoimmune Diseases; Autoimmunity; Chronic Disease; Female; Glomerulonephritis; Humans; Intercellular Adhesion Molecule-1; Kidney; Male; Middle Aged; Myeloblastin; Peroxidase; Vascular Cell Adhesion Molecule-1

During periodontitis, an innate immune response to bacterial challenge is primarily mediated by neutrophils. We compared neutrophilic content and the level of neutrophil-derived antimicrobial peptides in gingival crevicular fluid (GCF) in two clinical forms of severe periodontitis.. GCF was collected from 14 patients with aggressive periodontitis, 17 patients with chronic periodontitis, and nine healthy subjects. Samples were analyzed for periodontopathogen load using real-time polymerase chain reactions. The amounts of myeloperoxidase and alpha-defensins (HNP1-3) were determined by enzyme-linked immunosorbent assay, and the level of cathelicidin (hCAP18/LL-37) was assayed by Western blot.. Myeloperoxidase concentration was not correlated with levels of LL-37 and HNP1-3 in samples from patients, compared to controls. The amount of HNP1-3 was twofold and fourfold higher in patients with aggressive and chronic periodontitis, respectively. Those with chronic disease had significantly elevated amounts of mature LL-37. The increased concentration of both peptides in chronic periodontitis correlated with the load of Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola.. The lack of a correlation between LL-37, HNP1-3, and myeloperoxidase content suggests that neutrophils are not the sole source of these bactericidal peptides in the GCF of patients with periodontitis; and that other cells contribute to their local production. The bacterial proteases of P. gingivalis, T. forsythia, and T. denticola might degrade hCAP18/LL-37, because the 11-kDa cathelicidin-derived fragment was present in GCF collected from pockets infected with these bacteria. Collectively, it appears that a local deficiency in LL-37 can be considered as a supporting factor in the pathogenesis of severe cases of periodontitis.

Topics: Adult; Aggregatibacter actinomycetemcomitans; alpha-Defensins; Alveolar Bone Loss; Anti-Infective Agents; Antimicrobial Cationic Peptides; Bacteroides; Cathelicidins; Chronic Disease; Female; Gingival Crevicular Fluid; Humans; Lipopolysaccharides; Male; Middle Aged; Periodontal Attachment Loss; Periodontal Pocket; Periodontitis; Peroxidase; Porphyromonas gingivalis; Prevotella intermedia; Treponema denticola

Coumarins represent an important class of phenolic compounds with multiple biological activities, including inhibition of lipidic peroxidation and neutrophil-dependent anion superoxide generation, anti-inflammatory and immunosuppressor actions. All of these proprieties are essential for that a drug may be used in the treatment of inflammatory bowel disease. The present study examined intestinal anti-inflammatory activity of coumarin and its derivative, the 4-hydroxycoumarin on experimental ulcerative colitis in rats. This was performed in two different experimental settings, i.e. when the colonic mucosa is intact or when the mucosa is in process of recovery after an initial insult. The results obtained revealed that the coumarin and 4-hydroxycoumarin, at doses of 5 and 25 mg/kg, significantly attenuated the colonic damage induced by trinitrobenzenesulphonic acid (TNBS) in both situations, as evidenced macroscopically, microscopically and biochemically. This effect was related to an improvement in the colonic oxidative status, since coumarin and 4-hydroxycoumarin prevented the glutathione depletion that occurred as a consequence of the colonic inflammation.

Topics: 4-Hydroxycoumarins; Acute Disease; Alkaline Phosphatase; Animals; Anti-Inflammatory Agents; Chronic Disease; Colitis; Colon; Coumarins; Diarrhea; Gastrointestinal Agents; Glutathione; Male; Organ Size; Peroxidase; Rats; Rats, Wistar; Secondary Prevention; Sulfasalazine; Trinitrobenzenesulfonic Acid

The vagus nerve is an important pathway signaling immune activation of the gastrointestinal tract to the brain. Probiotics are live organisms that may engage signaling pathways of the brain-gut axis to modulate inflammation. The protective effects of Lactobacillus rhamnosus [corrected] (LR) and Bifidobacterium infantis (BI) during intestinal inflammation were studied after subdiaphragmatic vagotomy in acute dextran sulfate sodium (DSS) colitis in BALB/c mice and chronic colitis induced by transfer of CD4(+) CD62L(+) T lymphocytes from BALB/c into SCID mice. LR and BI (1 x 10(9)) were given daily. Clinical score, myeloperoxidase (MPO) levels, and in vivo and in vitro secreted inflammatory cytokine levels were found to be more severe in mice that were vagotomized compared with sham-operated animals. LR in the acute DSS model was effective in decreasing the MPO and cytokine levels in the tissue in sham and vagotomized mice. BI had a strong downregulatory effect on secreted in vitro cytokine levels and had a greater anti-inflammatory effect in vagotomized- compared with sham-operated mice. Both LR and BI retained anti-inflammatory effects in vagotomized mice. In SCID mice, vagotomy did not enhance inflammation, but BI was more effective in vagotomized mice than shams. Taken together, the intact vagus has a protective role in acute DSS-induced colitis in mice but not in the chronic T cell transfer model of colitis. Furthermore, LR and BI do not seem to engage their protective effects via this cholinergic anti-inflammatory pathway, but the results interestingly show that, in the T cell, transfer model vagotomy had a biological effect, since it increased the effectiveness of the BI in downregulation of colonic inflammation.

Topics: Acute Disease; Administration, Oral; Animals; Bifidobacterium; Body Weight; CD4-Positive T-Lymphocytes; Chronic Disease; Colitis; Colon; Dextran Sulfate; Interleukin-6; Limosilactobacillus reuteri; Male; Mice; Mice, Inbred BALB C; Mice, SCID; Peroxidase; Probiotics; Spleen; T-Lymphocytes; Tumor Necrosis Factor-alpha; Vagotomy; Vagus Nerve

The diterpene compounds, centipedic acid (CA) and 12-acetoxyhawtriwaic acid lactone (AHAL, tanabalin) isolated from the flower buds of Egletes viscosa LESS. (Asteraceae) were evaluated on acute and chronic models of mouse ear dermatitis. A single topical application of CA (0.125; 0.25 and 0.5 mg/ear) or AHAL (0.125, 0.25, 0.5 mg/ear) immediately before 12-O-tetradecanoylphorbol-13-acetate (TPA, 2.5 mug/ear) caused a dose-related significant inhibition of ear inflammatory edema and influx of polymorphonuclear cells, as evidenced by a decrease in ear thickness and reduced myeloperoxidase (MPO) activity and tumor necrosis factor-alpha (TNF-alpha) in ear tissue homogenates. The maximal obtained inhibition for both ear edema and neutrophil influx were almost similar to that of topically applied dexamethasone (0.05 mg/ear). The extent of inhibitions for the respective treatments of CA (0.5 mg/ear), AHAL (0.5 mg/ear), or dexamethasone (0.05 mg/ear) were in the order of 63%, 61% and 81% for the ear edema, and 90%, 95% and 95% for the neutrophil influx. Also, at similar doses, both diterpenes and dexamethasone effectively inhibited the delayed-type hypersensitivity reaction induced by repeated topical application of 1% oxazolone (OXA, 20 microl/ear), as evidenced by significant decreases in ear thickness and interferon-gamma (INF-gamma) levels in ear tissue. Histopathological analysis revealed a marked decrease in epidermal hyperplasia and neutrophil infiltration in animals pretreated with CA or AHAL, in a manner similar to dexamethasone. These data provide evidence for the anti-dermatitis effect of Egletes viscosa diterpenes, by mechanisms that involve a reduced neutrophil influx and decreased production of inflammatory cytokines, TNF-alpha and IFN-gamma.

Topics: Acute Disease; Administration, Topical; Animals; Anti-Inflammatory Agents; Asteraceae; Chronic Disease; Dermatitis, Contact; Diterpenes; Ear, External; Fatty Acids, Unsaturated; Flowers; Furans; Interferon-gamma; Lactones; Male; Mice; Oxazolone; Peroxidase; Skin; Tetradecanoylphorbol Acetate; Tumor Necrosis Factor-alpha

Adrenomedullin (AM) is a 52 amino acid peptide and member of the calcitonin gene-related peptide (CGRP) super family. Given that AM has emerged as a potential immuno-regulatory and anti-inflammatory agent in various experimental models, this study has deepened into its possible therapeutic effect in intestinal inflammation analyzing the responses in both acute and chronic (14 and 21 days) phases of TNBS-induced colitis in rats. In the acute model, AM treatment reduced the incidence of diarrhea and the severity of colonic damage, and improved the survival rate at the three doses assayed (50, 100, and 200ng/kg animal). AM administration was able to reduce the early production of TNF-alpha and collaborated to maintaining basal levels of IFN-gamma and IL-10. In the chronic studies the peptide attenuated the extent of the damage with lesser incidence of weight loss and diarrhea (50 and 100ng/kg animal). Cellular neutrophil infiltration, with the subsequent increase in myeloperoxidase (MPO) levels caused by TNBS, was reduced after chronic AM administration. The peptide played a role in the evolution of Th1/Th2 cytokines balance and chronic disease recuperation: levels of proinflammatory TNF-alpha and IFN-gamma decreased and anti-inflammatory IL-10 increased significantly. Cyclooxygenase-2 (COX-2) and nitric oxide synthase (iNOS) protein expression were not modified by AM administration, although a reduction of nitric oxide (NO) production could be detected in the chronic model. These results support a role of AM as an anti-inflammatory factor with beneficial effects in intestinal inflammatory colitis.

Topics: Acute Disease; Adrenomedullin; Animals; Anti-Inflammatory Agents; Chronic Disease; Colitis; Colon; Female; Interferon-gamma; Interleukin-10; Male; Peroxidase; Rats; Rats, Wistar; Trinitrobenzenesulfonic Acid; Tumor Necrosis Factor-alpha

Continuous disruption of circadian rhythms, as seen in human shift workers, has been associated with the development of a number of adverse mental and physiological conditions. However, scientific evidence linking circadian disruption to overall health, particularly in animal models, is not well documented. In this study, we have demonstrated that exposing C57BL/6J mice to 12-h phase shifts every 5 days for 3 mo had no effect on body weight or intestinal physiology. However, when animals were further challenged with dextran sodium sulfate to induce colitis, chronic shifting of the light-dark cycle led to a dramatic increase in the progression of the colitis as indicated by reduced body weight, abnormal intestinal histopathology, and an exacerbated inflammatory response. These data indicate that circadian disruption is an important predisposing factor that may provoke the onset or worsening of various disease states such as inflammatory disorders. This study provides further evidence for continued investigations using animal models of circadian disruption to examine the consequences of circadian disruption on health when organisms are faced with a "challenging" environment.

Topics: Adaptation, Physiological; Animals; Body Weight; Chronic Disease; Chronobiology Disorders; Circadian Rhythm; Colitis; Colon; Dextran Sulfate; Environment; Male; Mice; Mice, Inbred C57BL; Peroxidase; Photoperiod; Risk Factors

Reactive oxygen metabolites (ROMs) and inducible nitric oxide synthase (iNOS) are involved in pathogenesis of inflammatory bowel disease. In this study, we examined the effects of 2,3,5,4'-tetrahydroxystilbene-2-O-beta-D-glucoside (THSG), an active component extracted from Polygonum multiflorum Thunb, on acetic acid-induced acute colitis and mitomycin C-induced chronic colitis. The inflammatory degree was assessed by histology and myeloperoxidase (MPO) activity. Nitric oxide (NO), malondialdehyde (MDA) and superoxide dismutase (SOD) levels were determined with biochemical methods. In addition, inducible nitric oxide synthase (iNOS) expression was immunohistochemically studied. In acetic acid-induced acute model, THSG (60 and 120 mg/kg) significantly ameliorated colon damage, inhibited the increase of acetic acid-induced MPO activity, depressed MDA and NO level, and enhanced SOD activity. Moreover, the effects of 120 mg/kg THSG were better than that of positive control drug, 5-aminosalicylic acid (5-ASA). In mitomycin C-induced model, THSG (60 mg/kg) administered for 7 days and 24 days, significantly improved colon damage and inhibited MPO activity and MDA content while increased SOD activity only on the 7th day and debased NO level on the 24th day. Furthermore, on the 24th day, the effects of THSG were prior to that of 5-ASA. Additionally, THSG (60 mg/kg) could inhibit iNOS expression in both models. In conclusion, THSG exerts protective effects on experimental colitis through alleviating oxygen and nitrogen free radicals level and down-regulating iNOS expression.

Topics: Acetic Acid; Acute Disease; Animals; Anti-Inflammatory Agents; Antioxidants; Chronic Disease; Colitis; Colon; Disease Models, Animal; Dose-Response Relationship, Drug; Gastrointestinal Agents; Glucosides; Malondialdehyde; Mesalamine; Mice; Mitomycin; Nitric Oxide; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; Peroxidase; Polygonum; Stilbenes; Superoxide Dismutase; Time Factors

The pathogenic mechanism of acetyl salicylic acid (ASA)-induced urticaria (AIU) is not fully understood. We compared the levels of neutrophil activation and related cytokines in patients with ASA-intolerant acute urticaria (AIAU) and ASA-intolerant chronic urticaria (AICU). A total of 51 patients with AIAU, 88 patients with AICU, and 102 normal controls (NC) were enrolled in this study. The serum levels of myeloperoxidase (MPO), interleukin-8 (IL-8), and IL-18 were compared among the three groups. The serum levels of MPO were highest in the AIAU group, followed by the AICU and NC groups, and the serum levels of IL-18 were significantly higher in the AIAU and AICU groups than in NC group. Within the AIU groups, significant correlations were noted between the levels of MPO and IL-8, and IL-8 and IL-18. In conclusion, neutrophil activation, which was associated with the levels of IL-8 and IL-18 in the AIAU group, may be involved in the pathogenic mechanism of AIU. A role for IL-18 in the pathogenesis of AIU is also suggested.

Topics: Acute Disease; Administration, Oral; Adult; Angioedema; Aspirin; Chronic Disease; Cytokines; Drug Hypersensitivity; Female; Humans; Hypersensitivity, Immediate; Male; Neutrophil Activation; Neutrophils; Peroxidase; Urticaria

The aim of the study was to show the difference in the pattern of inflammation, and Th1/Th2 polarization between asthmatic and non-asthmatic patients with CRS, specifically eosinophil activation, local IgE levels in the sinus fluid and tissue, and the severity of inflammation were measured. The maxillary sinus lavages, mucosal biopsies and bacteriological swabs were taken in 17 asthmatic and 36 non-asthmatic adult patients with CRS. The concentrations of IgE, eosinophil cationic protein (ECP), myeloperoxidase (MPO), and tryptase were analyzed and IgE+ cells, eosinophils, lymphocytes and plasma cells were counted. The granulocyte activation markers and IgE in sinus lavages, and the inflammatory and IgE+ cells counts were significantly higher in the asthmatics with the greatest difference in ECP and IgE concentrations. The tryptase concentrations did not differ, but only in the asthmatics they correlated significantly with the IgE concentrations and IgE+ cells count. Asthmatic patients present a distinct subgroup among the patients with chronic rhinosinusitis (CRS). The levels of the cellular markers and IgE in the sinus fluid differ from those of non-asthmatic patients with CRS. The activation of granulocytes (especially eosinophils), local IgE concentrations and the inflammatory cells infiltration are significantly higher in the asthmatics.

Topics: Adolescent; Adult; Aged; Asthma; Biomarkers; Chronic Disease; Eosinophil Cationic Protein; Female; Fluorescence Polarization Immunoassay; Follow-Up Studies; Granulocytes; Humans; Immunoglobulin E; Male; Middle Aged; Peroxidase; Prognosis; Radioimmunoassay; Rhinitis; Severity of Illness Index; Sinusitis; Young Adult

Infiltration of inflammatory cells into the colon plays an important role in the onset and course of inflammatory bowel disease. G-protein-coupled receptor kinase 6 (GRK6) is an intracellular kinase that regulates the sensitivity of certain G-protein-coupled receptors, including those involved in the migration of inflammatory cells. Therefore, it is hypothesised that GRK6 plays a role in determining the course of inflammation.. To analyse the role of GRK6 in the course of dextran sodium sulphate (DSS)-induced colitis.. Colitis was induced by administering 1% DSS in drinking water to GRK6(-/-), GRK6(+/-) and wild-type (WT) mice for 6 days. The severity of colitis was assessed on the basis of clinical signs, colon length and histology. Moreover, keratinocyte-derived chemokine (KC) levels, granulocyte infiltration, interleukin 1beta (IL1beta), CD4, CD8 and forkhead box protein P3 (FoxP3) expression in the colon were determined. In addition, regulatory T cell function in WT and GRK6(-/-) mice was analysed. The chemotactic response of granulocytes to colon culture supernatants was assessed using a transendothelial migration assay.. The severity of colitis was increased in GRK6(-/-) and GRK6(+/-) mice and was accompanied by increased KC levels and increased granulocyte infiltration. Moreover, the chemotactic response of GRK6(-/-) granulocytes to supernatants of colon cultures was enhanced. Interestingly, the WT mice completely recovered from colitis, whereas the GRK6(-/-) and GRK6(+/-) mice developed chronic colitis, which was accompanied by increased IL1beta and CD4 expression and decreased FoxP3 expression. Moreover, regulatory T cell function was impaired in the GRK6(-/-) mice.. The intracellular level of GRK6 is an important factor in determining the onset, severity and chronicity of DSS-induced colitis.

Topics: Acute Disease; Animals; Chemotaxis, Leukocyte; Chronic Disease; Colitis; Dextran Sulfate; Disease Models, Animal; Eosinophil Peroxidase; Forkhead Transcription Factors; G-Protein-Coupled Receptor Kinases; Granulocytes; Male; Mice; Mice, Inbred C57BL; Peroxidase; Protein Serine-Threonine Kinases; Reverse Transcriptase Polymerase Chain Reaction; Severity of Illness Index; T-Lymphocytes, Regulatory; Tissue Culture Techniques

Oxidative stress is common in inflammatory processes of many diseases, including the Chagas' disease, which is characterized by chronic inflammation. The present study is a sequence of a related publication [Oliveira TB, Pedrosa RC, Wilhelm Filho D. Oxidative stress in chronic cardiopathy associated with Chagas' disease. Int J Cardiol in press.] on the same subjects, which showed an increase in oxidative stress associated with the progression of the severity of the disease. Components of the antioxidant system and oxidative biomarkers present in the blood were measured in the same chronic chagasic patients (n=40), before and after vitamin E (800 IU/day) and vitamin C (500 mg/day) supplementation for 6 months. Antioxidant enzymes and contents of reduced glutathione in erythrocytes and plasma TBARS contents were analyzed in four groups of patients in different stages of chronic Chagas heart disease (n=10 each group, groups I, II, III, and IV) according to the Los Andes classification. After the combined vitamin supplementation, TBARS and protein carbonyl levels were decreased in plasma, whilst red cell GSH contents were increased in group I. The vitamin E contents found in the plasma were inversely related to the severity of the disease. No differences in gamma-glutamiltransferase activities were detected but the myeloperoxidase levels were decreased in patients at the initial stages, whilst seric nitric oxide levels were increased in groups II and III. After the antioxidant supplementation, CAT activity was increased in group II, GPx activity was increased in group I, GR activity was increased in groups I and II, whilst the GST activity was decreased in groups II, III and IV. The results clearly indicate that the antioxidant supplementation was able to counteract the progressive oxidative stress associated with the disease. New perspectives for the treatment of Chagas' disease might include an antioxidant therapy in order to attenuate the consequences of oxidative insult related to this disease.

Topics: Antioxidants; Biomarkers; Catalase; Chagas Cardiomyopathy; Chromatography, High Pressure Liquid; Chronic Disease; Follow-Up Studies; Glutathione; Humans; Nitric Oxide; Oxidative Stress; Peroxidase; Severity of Illness Index; Thiobarbituric Acid Reactive Substances; Treatment Outcome

Solid organ transplant recipients have a 60-250-fold increased likelihood of developing sunlight-induced squamous cell carcinoma (SCC) compared with the general population. This increased risk is linked to the immunosuppressive drugs taken by these patients to modulate T cell function, thus preventing organ rejection. To determine the importance of T cells in the development of cutaneous SCC, we examined the effects of selectively depleting Skh-1 mice of systemic CD4+ or CD8+ T cells, using monoclonal antibodies, on ultraviolet B (UVB) radiation-induced inflammation and tumor development. Decreases in systemic CD4+ but not CD8+ T cells significantly increased and prolonged the acute UVB-induced cutaneous inflammatory response, as measured by neutrophil influx, myeloperoxidase activity, and prostaglandin E2 levels. Significantly more p53+ keratinocytes were observed in UVB-exposed CD4-depleted than in CD4-replete mice, and this difference was abrogated in mice depleted of neutrophils before UVB exposure. Increased acute inflammation was associated with significantly increased tumor numbers in CD4-depleted mice chronically exposed to UVB. Furthermore, topical treatment with the anti-inflammatory drug celecoxib significantly decreased tumor numbers in both CD4-replete and CD4-depleted mice. Our findings suggest that CD4+ T cells play an important role in modulating both the acute inflammatory and the chronic carcinogenic response of the skin to UVB.

Topics: Acute Disease; Animals; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Chronic Disease; Dermatitis; Dinoprostone; Female; Immunocompromised Host; Keratinocytes; Mice; Mice, Hairless; Neutrophils; Peroxidase; Risk Factors; Skin; Skin Neoplasms; Tumor Suppressor Protein p53; Ultraviolet Rays

Recently we demonstrated that in inflammatory bowel disease (IBD) macrophage-oxidative burst activity is increased and NADPH oxidase mRNA is induced. The herbal phenylethanoid acteoside isolated from Plantago lanceolata L. was shown to exhibit anti-oxidative potential. Using the dextran sulphate sodium (DSS)-induced colitis model, in this study we have assessed whether systemic application of acteoside affects colitis. Colitis was induced by DSS in Balb/c mice. Treatment with acteoside (120, 600 microg/mouse/day) was performed intraperitoneally. The colon lengths were determined. Colonic tissue was scored histologically (max. score 8) by a blinded investigator. T cells isolated from mesenteric lymph nodes (MLN) were stimulated with anti-CD3 antibody in the presence of interleukin (IL)-2 (final concentration 10 U/ml). After incubation for 24 h, IL-1beta, IL-6, IL-12 tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma levels in supernatants were analysed by the beadlyte cytokine detection system. Histological scoring of colonic tissue revealed that application of acteoside was followed by a significantly improved histological score. In acute colitis the histological score was 3.2 with acteoside versus 5.2 with phosphate-buffered saline (PBS) (P < 0.02). In chronic colitis both 120 microg (3.3 versus 5.2) or 600 microg acteoside (3.0 versus 5.2) significantly ameliorated colitis (both P < 0.02). Stimulated MLN from mice with chronic DSS-induced colitis treated with acteoside showed a significant down-regulation of IFN-gamma secretion (195 pg/ml with 600 microg acteoside versus 612 pg/ml with PBS, P < 0.02). Inhibition of oxidative burst activity with acteoside reduced mucosal tissue damage in DSS colitis and could be a therapeutic alternative for IBD treatment. Further studies of this agent are warranted.

Topics: Acute Disease; Animals; Antioxidants; Chronic Disease; Colitis; Colon; Cytokines; Dextran Sulfate; Enzyme-Linked Immunosorbent Assay; Female; Glucosides; Inflammation Mediators; Intestinal Mucosa; Lymph Nodes; Macrophages; Mice; Mice, Inbred BALB C; Peroxidase; Phenols; Respiratory Burst; Weight Loss

Transendothelial migration of circulating leukocytes into the colonic wall is a key step in the development of the inflammatory infiltrate in inflammatory bowel disease (IBD). The platelet-endothelial cell adhesion molecule-1 PECAM-1 (CD31) is expressed in the tight junction area of endothelial cells, where it is supposed to support the transmigration process. The aim of this study was to determine the role of PECAM-1 in experimental IBD and to show whether blockade of PECAM-1 has therapeutic effects. Chronic colitis was induced in female BALB/c mice by cyclic oral administration of dextran sodium sulfate (DSS) 3% (wt/vol). Expression of PECAM-1 was visualized by immunohistochemistry. In the treatment group animals received 1 mg/kg anti-PECAM-1 (2H8) ip daily starting on day 26. On day 30 leukocyte adhesion and migration was measured during N(2)O-isoflurane anesthesia in the distal colon by intravital microscopy. Disease activity index (DAI), histology, and MPO levels were compared with healthy and diseased controls. PECAM-1 was expressed in colitic mice. Chronic DSS colitis was characterized by a marked increase in rolling, adherent, and transmigrated leukocytes compared with healthy controls. Immunoblockade of PECAM-1 reduced leukocyte transmigration significantly and also diminished leukocyte rolling and sticking in an indirect manner. It also resulted in a significantly diminished DAI and MPO levels, as well as an amelioration of the histological inflammation score. PECAM-1 plays an important role in transendothelial leukocyte migration in DSS colitis. PECAM-1 could be a novel target for antibody-based treatment in IBD.

Topics: Animals; Anti-Inflammatory Agents; Antibodies, Monoclonal; Chronic Disease; Colitis; Dextran Sulfate; Disease Models, Animal; Endothelial Cells; Female; Gastrointestinal Agents; Leukocyte Rolling; Leukocytes; Mice; Mice, Inbred BALB C; Microscopy, Video; Peroxidase; Platelet Endothelial Cell Adhesion Molecule-1

To investigate the effect of hemodilution with high-concentration human serum albumin (HSA) on brain injury in a rat model of chronic cerebral hypoperfusion associated with arteriovenous malformations.. The animal model was established by creating a fistula through an end-to-side anastomosis between the right distal external jugular vein and the ipsilateral common carotid artery, followed by ligation of the left vein draining the transverse sinus and bilateral external carotid arteries. The agent (20% HSA) or control solution (0.9% sodium chloride) was administered intravenously at a dosage of 1% body weight 24 hours before ligation of the fistula. Blood-brain barrier (BBB) disruption was judged by extravasation of Evans blue (EB) dye. EB, water content and the changes of myeloperoxidase (MPO) activity and superoxide dismutase (SOD) activity in rat brains 24 hours after ligation of the fistula were determined.. EB and water content in rat brains of the pre-treated group were significantly decreased compared with the control group accompanied by reduction of MPO activity and enhancement of SOD activity.. Hemodilution with high-concentration HSA has a certain pre-treatment effect on brain injury after ligation of the fistula in rat model of chronic cerebral hypoperfusion, which may be resulted from improved microcirculation, decrease in inflammatory cell infiltration and inactivation of oxygen free radicals.

Topics: Animals; Blood Pressure; Blood-Brain Barrier; Brain Edema; Brain Injuries; Cerebrovascular Circulation; Chronic Disease; Disease Models, Animal; Hemodilution; Male; Peroxidase; Rats; Rats, Sprague-Dawley; Recovery of Function; Reperfusion Injury; Superoxide Dismutase

The purpose of this study was to explore the relationship between myeloperoxidase (MPO) and cardiac structure, performance, and prognosis.. Myeloperoxidase is an inflammatory marker that is elevated in patients with heart failure (HF) and cardiac dysfunction, with mechanistic links to plaque vulnerability and left ventricular (LV) remodeling.. We evaluated plasma MPO levels (CardioMPO, PrognostiX, Inc., Cleveland, Ohio) in 140 patients with chronic systolic HF (LV ejection fraction <35%) and examined the plasma MPO levels' relationships with echocardiographic indexes of systolic and diastolic performance, as well as long-term clinical outcomes (death, cardiac transplantation, or HF hospitalization).. Within the overall cohort, increasing plasma MPO levels were associated with increasing likelihood of more advanced HF (restrictive diastolic stage, right ventricular systolic dysfunction > or =3+, and tricuspid regurgitation area > or =1.8 cm2). Plasma MPO levels were predictive of long-term clinical outcomes (risk ratio [95% confidence interval] = 3.35 [1.52 to 8.86]), even after adjustment for age, LV ejection fraction, plasma B-type natriuretic peptide (BNP), creatinine clearance, or diastolic stage. In receiver-operator characteristic curve analyses, addition of MPO to BNP testing augmented the predictive accuracy of future adverse clinical events (area under the curve 0.66 for BNP only [chi-square test = 12.9, p = 0.0003], and 0.70 for BNP plus MPO [chi-square test = 15.87, p = 0.0004]).. In chronic systolic HF, elevated plasma MPO levels are associated with an increased likelihood of more advanced HF. Moreover, elevated plasma MPO levels within a HF subject seem to be predictive of increased adverse clinical outcomes.

Topics: Aged; Arabidopsis Proteins; Chronic Disease; Creatinine; Cyclophilins; Female; Heart Failure; Humans; Leukocyte Count; Male; Middle Aged; Neutrophils; Peroxidase; Prognosis; Proportional Hazards Models; Stroke Volume; Ultrasonography; Ventricular Dysfunction, Left; Ventricular Dysfunction, Right

Polymorphonuclear leukocyte infiltration and activation into colonic mucosa are believed to play a pivotal role in mediating tissue damage in human ulcerative colitis (UC). Ligands of human CXC chemokine receptor 1 and 2 (CXCR1/R2) are chemoattractants of PMN, and high levels were found in the mucosa of UC patients. To investigate the pathophysiological role played by CXCR2 in experimental UC, we induced chronic experimental colitis in WT and CXCR2(-/-) mice by two consecutive cycles of 4% dextran sulfate sodium administration in drinking water. In wild-type (WT) mice, the chronic relapsing of DSS-induced colitis was characterized by clinical signs and histopathological findings that closely resemble human disease. CXCR2(-/-) mice failed to show PMN infiltration into the mucosa and, consistently with a key role of PMN in mediating tissue damage in UC, showed limited signs of mucosal damage and reduced clinical symptoms. Our data demonstrate that CXCR2 plays a key pathophysiological role in experimental UC, suggesting that CXCR2 activation may represent a relevant pharmacological target for the design of novel pharmacological treatments in human UC.

Topics: Animals; Chemokine CXCL1; Chemokine CXCL2; Chronic Disease; Colitis, Ulcerative; Dextran Sulfate; Disease Models, Animal; Fluorescent Antibody Technique; Incidence; Male; Mice; Mice, Inbred BALB C; Mice, Knockout; Neutrophils; Peroxidase; Receptors, Interleukin-8B

Smoking is the major cause of airway inflammation in chronic obstructive pulmonary disease (COPD), and smoking cessation is regarded as one of the important strategies for prevention and treatment of the inflammation. The inflammation of the chronic airway may be present and deteriorated even if the COPD patients stop smoking. Whether and how early smoking cessation affects the progress of inflammation is still obscure. This study was conducted to find the appropriate time for smoking cessation to terminate the airway inflammation in rats with smoke-induced chronic bronchitis.. A rat model of COPD was established by passively inhaling smoke mixture. Fifty-four young male Sprague-Dawley rats were randomly divided into 9 groups with different periods of smoke exposure and different time points of cessation. The inflammation markers to be detected included inflammatory cells in the bronchoalveolar lavage fluid (BALF), the myeloperoxidose (MPO) activity, the morphologic changes and the expression of ICAM-1 on the airway epithelium.. When smoking was terminated at early stage, the inflammatory markers and related indexes were different from those of the typical chronic bronchitis group (group M7) (P < 0.01). The pathologic score of group SC7 (2 weeks of smoking cessation after occurrence of typical chronic bronchitis) was not different from that of group M7, and the level of ICAM-1 was still up-regulated (compared to group M7, P > 0.05). Meanwhile, most of inflammatory cells in BALF were neutrophils compared to other groups (P < 0.01). When smoking was terminated, the MPO activity was significantly lower than that of group M7 (P < 0.01).. Smoking cessation at early stage can effectively inhibit the inflammatory reaction of COPD. Once chronic bronchitis occurs, little could be improved by smoking cessation.

Topics: Animals; Bronchitis; Chronic Disease; Inflammation; Intercellular Adhesion Molecule-1; Lung; Male; Neutrophils; Peroxidase; Rats; Rats, Sprague-Dawley; Smoking Cessation

The phosphodiesterase-4 (PDE4) inhibitors may be an important target in the treatment of several inflammatory conditions. The anti-inflammatory effect of PDE4 inhibitors bears similarities with that of steroids, without interfering with the hypophysary-adrenal-axis. We compared the effect of rolipram, a selective PDE4 inhibitor, with steroids on the clinical course of experimental colitis induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS). Three groups of rats (n = 20) received TNBS. One group received methylprednisolone from day 7, another group received rolipram from the same day, and control group received no further treatment. On days 14 and 21 after TNBS instillation, sets of 10 rats underwent colonic dialysis to measure eicosanoid release. Colonic lesions were blindly scored, and colons were homogenized for quantification of myeloperoxidase (MPO) activity and collagen content. Concentration of tumor necrosis factor alpha (TNF-alpha) and transforming growth factor beta1 (TGF-beta1) in colonic tissue was also measured. Both treatments reduced significantly the eicosanoid release and MPO activity. On day 14, both rolipram and methylprednisolone significantly reduced TNF-alpha content, but TGF-beta1 was only inhibited by rolipram. On day 21, lesion scores and collagen content were significantly reduced only in rolipram-treated group. In conclusion, PDE4 inhibition by rolipram markedly ameliorates the course of chronic colitis and it is superior to methylprednisolone in preventing late collagen deposition.

Topics: 3',5'-Cyclic-AMP Phosphodiesterases; Animals; Chronic Disease; Colitis; Colon; Cyclic Nucleotide Phosphodiesterases, Type 4; Disease Models, Animal; Fibrosis; Male; Methylprednisolone; Peroxidase; Phosphodiesterase Inhibitors; Rats; Rats, Sprague-Dawley; Rolipram; Transforming Growth Factor beta; Transforming Growth Factor beta1; Tumor Necrosis Factor-alpha

Systemic vasculitis may, at times, be drug-induced and associated with antineutrophil cytoplasmic antibodies (ANCA). However, pantoprazole, a commonly used and well-tolerated proton pump inhibitor, has not previously been reported to cause ANCA-associated syndromes. We describe a patient who developed interstitial nephritis, cutaneous vasculitis, a perinuclear ANCA staining pattern (pANCA) on immunofluorescence, and anti-myeloperoxidase antibodies (MPO-ANCA) in association with pantoprazole. We review various immune-mediated syndromes reported in association with proton pump inhibitors, including one report of omeprazole associated with interstitial nephritis and the development of ANCA.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Acute Disease; Aged; Anti-Ulcer Agents; Antibodies, Antineutrophil Cytoplasmic; Benzimidazoles; Cell Nucleus; Chronic Disease; Exanthema; Female; Humans; Methylprednisolone; Nephritis, Interstitial; Omeprazole; Pantoprazole; Peroxidase; Renal Dialysis; Sulfoxides; Treatment Outcome; Vasculitis, Leukocytoclastic, Cutaneous

Radiation therapy is a widely used adjuvant therapy for various abdominal and pelvic cancers. On the other hand, it is not a benign treatment modality, as most radiation patients suffer from some kind of radiation enteritis. Currently available treatments are only palliative and no ideal compound has as yet been discovered. The aim of this study was to evaluate cyclooxygenase-2 (COX-2) expression, and to investigate the possible protective effect of the selective COX-2 inhibitor, Rofecoxib, in acute and late stages of radiation-induced intestinal injury in rats.. Forty-eight male Sprague-Dawley rats were randomly divided into eight groups. After abdominal irradiation of all of the animals except the six in the control group, the expression of the enzyme cyclooxygenase-2 (COX-2) was evaluated in different cell types present in the intestinal wall 2 h post exposure (study day 0) and again on study days 4, 14, and 60. The effects of Rofecoxib on histological damage, intestinal myeloperoxidase (MPO) activity, and malondialdehyde (MDA) levels were also measured.. Expression of COX-2 in vascular endothelial cells was found to be significantly increased on post exposure days 4 and 14 (2.4 and 2.9 stained vessels/high power field [hpf] respectively compared to 1.3 vessels/hpf for controls) (P = 0.002). Expression of COX-2 in fibroblasts increased immediately after irradiation (29 cells/hpf 2 h after irradiation compared to 12 cells/hpf for non-irradiated control animals) and remained high during the entire study period (P < 0.001), whereas there was a peak COX-2 expression (54.9 cells/hpf) on day 14 that was similar to what was observed in endothelial cells. Irradiation of rats significantly increased intestinal epithelial damage, MPO activity, and MDA levels in comparison to the control group in a time-dependent fashion. Treatment with rofecoxib significantly decreased these elevations except on day 4 of the study.. The current study suggests that the COX-2 pathway is involved in radiation induced intestinal injury and that targeting COX-2 may be useful in limiting radiation enteritis.

Topics: Acute Disease; Animals; Apoptosis; Chronic Disease; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Disease Models, Animal; Enteritis; Intestine, Small; Lactones; Male; Malondialdehyde; Peroxidase; Radiation Injuries, Experimental; Rats; Rats, Sprague-Dawley; Sulfones

During inflammation, myeloperoxidase (MPO) is released, for which its measurement in systemic circulation may be used as an index of leukocyte activation and oxidant stress. MPO levels correlate with angiographic evidence of coronary atherosclerosis and cardiovascular events in subjects with chest pain within the general population. We hypothesized that serum MPO levels are associated with adverse clinical outcomes in maintenance hemodialysis (MHD) patients.. MPO levels were determined in serum samples from 356 MHD patients at the start of a 3-year cohort.. Patients (46% women, 28% blacks, 54% with diabetes) were 54.6 +/- 14.6 (SD) years old and had undergone MHD for a median period of 26 months. Measured serum MPO level was 2,005 +/- 1,877 pmol/L (median, 1,444 pmol/L; interquartile range, 861 to 2,490 pmol/L). MHD patients with greater total body fat had greater MPO levels. MPO level had statistically significant (P < 0.01) and positive correlations with values for serum C-reactive protein (CRP; r = +0.15), interleukin 6 (IL-6; r = +0.23), tumor necrosis factor alpha (TNF-alpha; r = +0.21), and white blood cell count (r = +0.21). A death hazard ratio for each 1,000-pmol/L increase in serum MPO level was 1.14 (95% confidence interval [CI], 1.03 to 1.26; P = 0.01) after controlling for age, race (black), diabetes mellitus, dialysis vintage, Charlson comorbidity score, history of previous cardiovascular disease, blood hemoglobin level, and serum concentrations of albumin, CRP, IL-6, and TNF-alpha. After dividing MPO values into 3 equal groups (tertiles), the death hazard ratio of the highest tertile (versus the middle tertile) was 1.82 (95% CI, 1.07 to 3.10; P = 0.03).. Serum MPO levels correlate with levels of markers of inflammation and prospective mortality risk in MHD patients.

Topics: Adult; Aged; Biomarkers; Chronic Disease; Cohort Studies; Cytokines; Female; Humans; Inflammation; Kidney Diseases; Male; Malnutrition; Middle Aged; Oxidative Stress; Peroxidase; Prognosis; Renal Dialysis; Survival Analysis; Syndrome

We recently demonstrated that both lisinopril and candesartan, an angiotensin-converting enzyme inhibitor and angiotensin II type 1 receptor blocker, respectively, attenuate pancreatic inflammation and fibrosis in male Wistar Bonn/Kobori (WBN/Kob) rats. The purpose of the present study was to assess whether combination therapy with low doses of both, ineffective when given alone, might synergistically exert protective effects. Lisinopril, candesartan, or a combination of both in drinking water was administered to 10-week-old male WBN/Kob rats for 10 weeks. Parameters of inflammation and fibrosis, positive immunostaining for alpha-smooth muscle actin, and gene expression of cytokine and growth factors were assessed, as well as circulating renin-angiotensin system components. Dose-dependent effects of combination therapy were also investigated. Only combination therapy attenuated gross alterations in the pancreas, as quantitatively confirmed by increases in pancreatic weights and decreases in myeloperoxidase activity, hydroxyproline content, histologic scores, relative fibrosis area, and relative area of alpha-smooth muscle actin-positive cells. Combination therapy suppressed up-regulation of tumor necrosis factor-alpha, platelet-derived growth factor-receptor beta, and transforming growth factor-beta1 mRNA in the pancreas. Dose dependence of combination therapy was recognized with reference to improvement in these parameters. The conclusions are that combination therapy synergistically alleviated pancreatic inflammation and fibrosis in male WBN/Kob rats. This effect may be related to suppression of tumor necrosis factor-alpha, platelet-derived growth factor-receptor beta, and transforming growth factor-beta1 mRNA. Compared with the either therapy alone, combination therapy with an angiotensin-converting enzyme inhibitor and an angiotensin II type 1 receptor blocker may be more beneficial for treating chronic pancreatitis.

Topics: Actins; Aldosterone; Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Animals; Benzimidazoles; Biphenyl Compounds; Body Weight; Chronic Disease; Cytokines; Dose-Response Relationship, Drug; Drug Synergism; Fibrosis; Genes, ras; Hydroxyproline; Immunohistochemistry; Lisinopril; Male; Organ Size; Pancreatitis; Peptidyl-Dipeptidase A; Peroxidase; Rats; Rats, Wistar; Receptor, Angiotensin, Type 1; RNA, Messenger; Tetrazoles

To examine the effect of eradication of Helicobacter pylori prior to usage of NSAIDs, by investigating gastric inflammatory activity, myeloperoxidase (MPO) activity, prostaglandin (PG) E2 synthesis in H pylori-infected, and H pylori-eradicated gerbils followed by administration of indomethacin and rofecoxib.. Six-week-old male gerbils were orally inoculated with H pylori. Seven weeks later, anti-H pylori triple therapy and vehicle were given to gerbils respectively and followed by oral indomethacin (2 mg/kg.d) or rofecoxib (10 mg/kg.d) for 2 wk. We examined the area of lesions, gastric inflammatory activity, PGE2 synthesis and MPO activity in the stomach.. In indomethacin and rofecoxib-treated gerbils, the following results were obtained in H pylori-infected group vs H pylori-eradicated group respectively: hyperplasia area of the stomach (mm2): 82.4+/-9.2 vs 13.9+/-3.5 (P<0.05), 30.5+/-5.1 vs 1.3+/-0.6 (P<0.05); erosion and ulcer area (mm2): 14.4+/-4.9 vs 0.86+/-0.5 (P<0.05), 1.3+/-0.6 vs 0.4+/-0.3 (P<0.05); score of gastritis: 7.0+/-0.0 vs 3.6+/-0.5 (P<0.05), 7.0+/-0.0 vs 2.7+/-0.5 (P<0.05); MPO activity (micromol H2O2/min/g tissue): 104.7+/-9.2 vs 9.0+/-2.3 (P<0.05), 133.5+/-15.0 vs 2.9+/-0.7 (P<0.05); PGE2 synthesis (pg/mg wet weight/min): 299.2+/-81.5 vs 102.8+/-26.2 (P<0.05), 321.4+/-30.3 vs 11.9+/-4.8 (P<0.05).. Eradication of H pylori reduced gastric damage of NSAID-treated Mongolian gerbils. Rofecoxib caused less severe gastric damage than indomethacin in H pylori-eradicated gerbils.

Topics: Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Body Weight; Chronic Disease; Dinoprostone; Gastritis; Gerbillinae; Helicobacter Infections; Helicobacter pylori; Indomethacin; Lactones; Male; Organ Size; Peroxidase; Stomach; Stomach Ulcer; Sulfones

Clinical examination and laboratory tests performed on 708 patients with chronic obstructive and non-obstructive bronchitis (COB and CNB), demonstrated heterogeneous character of the group of these patients in clinical remission. This suggests that it is appropriate to distinguish between the stages of complete and partial remission, implying different tasks concerning treatment and rehabilitation. Remission of CNB is characterized by minimal deviation of clinical and laboratory parameters; functional balance between the lipid peroxidation-antioxidative activity (LP-AA) system and immunity is preserved. At the stage of rehabilitation of these patients the major attention is paid to the general sanitary measures (physiotherapy exercises, climate therapy). The stage of partial remission in COB and CNB is characterized by residual activity of the inflammatory process, a disbalance between the LP-AA system and immunity, most prominent in partial remission of COB. Rehabilitation of these patients, in addition to physiotherapy exercises and tempering of the organism, should include special activity, directed towards the normalization of LP and immunity parameters.

Topics: Adult; Biomarkers; Bronchitis; Catalase; Ceruloplasmin; Chronic Disease; Disease-Free Survival; Erythrocytes; Female; Fibrinogen; Haptoglobins; Humans; Immunoglobulins; Lipid Peroxidation; Male; Malondialdehyde; Neutrophils; Peroxidase; Phagocytosis; Physical Therapy Modalities; Sialic Acids; Superoxide Dismutase; T-Lymphocytes

Prostaglandin, a key molecule that stimulates the complex array of ulcer healing mechanism, gets synthesized in the mucosal cells by cyclooxygenase (COX) enzymes: COX-1 and COX-2. High expression level of COX-2 protein at healing ulcer margins highlights its role in ulcer healing and hypothesized to be an important contributing factor in healing mechanism of anti-ulcer drugs. In the present study we have compared the expression profile of COX-2 protein, prostaglandin E2 (PGE2) levels and myeloperoxidase activity in acetic acid induced chronic gastric ulcer model in rats treated with omeprazole, misoprostol and COX-2 selective nonsteroidal anti-inflammatory drug (NSAID) celecoxib. Both COX-2 expression and PGE2 level have shown differential pattern in different treated groups parallel to the differential effects of these drugs on ulcer healing. Omeprazole has significantly elevated the expression level of COX-2 protein, PGE2 level (19.37%), and decreased myeloperoxidase activity (81.92%), thereby causing the most effective ulcer healing (89.74%). Similar trend was observed with misoprostol, but with relatively less pronounced ulcer healing and COX-2 expression. Celecoxib has retarded COX-2 expression and delayed ulcer healing. Therefore, induction of COX-2 expression leading to higher level of prostaglandin appears to be an important contributing factor in drug mediated ulcer healing apart from the respective mechanisms of different drugs.

Topics: Animals; Anti-Ulcer Agents; Blotting, Western; Celecoxib; Chronic Disease; Cyclooxygenase 2; Dinoprostone; Female; Gastric Mucosa; Male; Misoprostol; Omeprazole; Peroxidase; Prostaglandin-Endoperoxide Synthases; Pyrazoles; Rats; Rats, Sprague-Dawley; Stomach Ulcer; Sulfonamides; Wound Healing

Increased expression of CD44 variant isoforms have been shown on the inflammatory infiltrates in human and mouse colitis and blockade or deletion of CD44 isoforms inhibit experimental colitis. The objective of this study was to find out if short-term treatment of CD44 antibodies specific to CD44v7, but not to other variant isoforms, suppresses leucocyte-endothelial interaction in chronic dextran sodium sulphate (DSS)-induced colitis in mice. Chronic colitis was induced by oral administration of four cycles of 5% DSS in BALB/c mice. Expression of CD44 was investigated on isolated mononuclear cells of the gut immune system. In established colitis, mice were treated with antibodies against CD44v7 or CD44v4 three times in 7 days. Intravital microscopy was used to study leucocyte-endothelial interactions and leucocyte extravasation. As a marker of inflammatory infiltrates myeloperoxidase was quantified in gut tissue. CD44-induced apoptosis was determined by fluorescence staining of hypodiploidic cell nuclei. In chronic DSS-induced colitis both CD44 variant isoforms, v4 and v7 were significantly up-regulated on mononuclear cells. However, whereas anti-CD44v7 antibody treatment induced a marked restoration of the gut mucosa and significantly reduced endothelial sticking and extravasation of circulating leucocyte in vivo (P < 0.01), application of anti-CD44v4 or an isotype control antibody had no anti-inflammatory effect. A significant reduction of myeloperoxidase activity was detected after blockade of CD44v7, but not v4. Short-term treatment with anti-CD44v7 antibody blocks T cell extravasation and recruitment to the intestinal mucosa and cures established experimental colitis.

Topics: Animals; Antibodies, Monoclonal; Cell Adhesion; Chronic Disease; Colitis; Dextran Sulfate; Disease Models, Animal; Down-Regulation; Endothelial Cells; Female; Hyaluronan Receptors; Immunity, Mucosal; Intestinal Mucosa; Leukocytes; Lymph Nodes; Lymphocyte Activation; Mesentery; Mice; Mice, Inbred BALB C; Peroxidase; Protein Isoforms

To assess the synergistic action of famotidine (FMD) and chlorpheniramine (CPA) on acetic acid-induced chronic gastric ulcer in rats.. Chronic gastric lesions were induced in male Sprague-Dawley (SD) rats by serosal application of the acetic acid. Forty SD rats were randomly divided into blank group (n = 8), control group (n = 8), FMD group (n = 8), CPA group (n = 8), and FMD+CPA group (n = 8). Each group was given intraperitoneally (i.p.) 0.5 mL/100 g distilled water, 9 g/L NaCl saline, 4 mg/kg FMD, 10 mg/kg CPA, 4 mg/kg FMD+10 mg/kg CPA, respectively, daily for 10 d. On d 10, ulcer area was determined by planimetry. The level of myeloperoxidase (MPO) in the liver homogenization was determined by biochemical methods and the plasma levels of 6-ketoprostaglandin F1 alpha (6-keto-PGF(1a)) and IL-8 were determined by radioimmunoassay.. The synergistic effects of FMD+CPA group on the lesion, IL-8, 6-keto-PGF(1a) and MPO were confirmed. The effect of FMD+CPA group was significantly different as compared to the control and FMD groups. The lesion (mm(2)) was reduced from 40.18+/-2.6 in control group to 6.83+/-2.97 in PMD+CPA group, P<0.01, and from 32.9+/-3.27 in FMD group to 6.83+/-2.97 in PMD+CPA group, P<0.01. The plasma levels of IL-8 decreased from 0.69+/-0.11 ng/L in control group to 0.4+/-0.04 ng/L in PMD+CPA group, P<0.01, and from 0.51+/-0.08 ng/L in FMD group to 0.4+/-0.04 ng/L in PMD+CPA group, P<0.05. The level of 6-keto-PGF(1a) increased from 7.55+/-1.65 ng/L in control group to 16.62+/-0.97 ng/L in PMD+CPA group, P<0.01, and from 13.15+/-1.48 ng/L in FMD group to 16.62+/-0.97 ng/L in PMD+CPA group, P<0.05. The levels of MPO in the liver homogenate decreased from 9.12+/-2.05 u/L in control group to 4.33+/-0.95 u/L in PMD+CPA group, P<0.01, and from 8.3+/-1.29 u/L in FMD group to 4.33+/-0.95 u/L, P<0.01.. The synergistic action of FMD and CPA on acetic acid-induced chronic gastric ulcer in rats decreases the incidence of ulcer and also enhances the healing of ulcer.

Topics: 6-Ketoprostaglandin F1 alpha; Acetic Acid; Animals; Chlorpheniramine; Chronic Disease; Drug Synergism; Famotidine; Histamine H1 Antagonists; Histamine H2 Antagonists; Interleukin-8; Liver; Male; Peroxidase; Rats; Rats, Sprague-Dawley; Stomach Ulcer

It has been reported that alveolar hemorrhage caused by ANCA-associated vasculitis occurs in the seriously acute stage. However, we report a rare case of chronic alveolar hemorrhage in a 26-year-old woman who had been on maintenance hemodialysis because of rapidly progressive glomerulonephritis (RPGN) since the age of 17. On a regular checkup at her clinic, chest radiographs revealed diffuse micronodular opacities in both lung fields when she was 22 years of age, and anemia was identified at 24. Before the patient was referred to our hospital, the shadows on the radiographs remained almost unchanged, whereas the anemia, for reasons unknown, slowly deteriorated. She was referred to our hospital because of micronodular opacities detected on a chest radiogram in an annual health check at the age of 26. She was asymptomatic, but her laboratory data showed a normochromic anemia (hemoglobin 6.3 g/dl), and the serum level of MPO-ANCA was 195 EU. Bronchoalveolar lavage at bronchoscopy macroscopically revealed bloody fluids containing hemosiderin-laden macrophages. Histological examination of the biopsy specimen by video-assisted thoracoscopic lung biopsy revealed pauci-immune pulmonary capillaritis and alveolar hemorrhage. She was diagnosed as having MPO-ANCA-related vasculitis, especially microscopic polyangiitis preceding RPGN, and the clinical course suggesting alveolar hemorrhage was progressing slowly. The diagnosis was therefore "chronic alveolar hemorrhage". We emphasize that it is necessary to consider alveolar hemorrhage when a patient who has been on maintenance hemodialysis for RPGN has a combination of anemia and diffuse micronodular opacities, even if the condition is not accompanied with any respiratory symptoms.

Topics: Adult; Anemia; Antibodies, Antineutrophil Cytoplasmic; Chronic Disease; Disease Progression; Female; Glomerulonephritis; Hemorrhage; Humans; Lung Diseases; Peroxidase; Pulmonary Alveoli; Renal Dialysis; Thoracic Surgery, Video-Assisted; Vasculitis

The aim of the study was to verify (i) if crevicular fluid defence variables reflect the changes after surgical periodontal treatment and (ii) if they are in correspondence with changes of these variables in the unstimulated and stimulated whole saliva.. For 12 male and 13 female volunteers with chronic periodontitis lactoferrin concentration as well as the lysozyme and peroxidase activities were determined in crevicular fluid as well as in unstimulated and stimulated saliva before and 14 days after surgical periodontal treatment by a minimal invasive flap technique.. The lactoferrin concentrations decreased significantly in the crevicular fluid eluting solution from 1.63 to 1.23 mg/l reflecting a decrease in the total amount collected, in unstimulated saliva from 10.54 to 8.96 mg/l, and in stimulated saliva from 9.00 to 7.11 mg/l after treatment. No significant change could be found for lysozyme. Peroxidase activity was significantly reduced from 269.06 to 186.15 U/l only in the crevicular fluid.. The results of this study suggest that (i) the defence factor lactoferrin is suitable for monitoring of periodontal treatment results and (ii) changes of the lactoferrin concentration in crevicular fluid are related with significant changes in unstimulated and stimulated saliva.

Topics: Biomarkers; Chronic Disease; Female; Gingival Crevicular Fluid; Humans; Immunoenzyme Techniques; Lactoferrin; Male; Middle Aged; Muramidase; Periodontitis; Peroxidase; Saliva; Statistics, Nonparametric

We established a mouse model in which fatal pneumonia was induced by pneumococcal superinfection following influenza virus infection in chronic Pseudomonas aeruginosa infected mice. In this mouse model, influenza virus infection caused a significant increase in inflammatory cells, cytokines and severe tissue damage in the lungs of these P. aeruginosa infected mice, before pneumococcal infection. Intrapulmonary virus titres were significantly increased in mice with chronic P. aeruginosa infection, compared with control mice. Neutrophil function analysis showed significant reduction of myeloperoxidase (MPO) activity and lysozyme secretion by influenza virus infection in these mice. Our results suggest that influenza virus infection may play an important role in inducing pneumococcal pneumonia in chronic P. aeruginosa infected mice. Our results suggested that our mouse model is useful for investigating the pathogenesis of influenza virus infection in patients with chronic lung infection.

Topics: Acute Disease; Animals; Chronic Disease; Colony Count, Microbial; Cytokines; Disease Models, Animal; Disease Susceptibility; Lung; Lung Diseases, Parasitic; Male; Mice; Mice, Inbred Strains; Muramidase; Orthomyxoviridae Infections; Peroxidase; Pneumococcal Infections; Pneumonia, Pneumococcal; Pseudomonas Infections; Superinfection

Oxidative injury is implicated in the development of chronic lung disease in preterm infants with respiratory distress. However, direct evidence of a causal role is limited and the source of reactive oxidants has not been identified. We have previously shown that protein carbonyl levels in tracheal aspirates correlate positively with myeloperoxidase, suggesting that neutrophil oxidants could be the source of this protein injury. We have extended these observations by measuring 3-chlorotyrosine, a specific biomarker of the neutrophil oxidant, hypochlorous acid, in tracheal aspirate proteins (144 samples) from 69 infants with birth weight <1500 g. 3-Chlorotyrosine levels were higher in these infants than in larger infants without respiratory distress (median 83 compared with 13 micromol/mol tyrosine). They correlated strongly with myeloperoxidase activity (correlation coefficient 0.75, p < 0.0001) and to a lesser extent with protein carbonyls. 3-Chlorotyrosine levels (at 1 wk after birth) correlated negatively with birth weight or gestational age. They were significantly higher in infants who developed chronic lung disease (oxygen requirement at 36 wk postmenstrual age) than in those who did not (median 88 and 49 micromol/mol tyrosine, respectively) and correlated with days of supplemental oxygen. 3-Chlorotyrosine was also significantly higher in infants who had lung infection or were Ureaplasma urealyticum positive. Our results are the first evidence that chlorinated proteins are produced in the lungs of premature infants and that they are higher in infection. The higher 3-chlorotyrosine levels in infants who develop chronic lung disease suggest that neutrophil oxidants contribute to the pathology of this disease.

Topics: Biomarkers; Chronic Disease; Gestational Age; Humans; Infant, Newborn; Infant, Premature; Infant, Very Low Birth Weight; Neutrophils; Oxidative Stress; Peroxidase; Respiratory Distress Syndrome, Newborn; Trachea; Tyrosine; Ureaplasma Infections; Ureaplasma urealyticum

Mucosal tissue damage in chronic inflammatory bowel disease (IBD) is partly caused by an enduring exposure to excessive amounts of reactive oxygen metabolites (ROM). To protect themselves from the toxic effects of ROM, most intestinal cell types constitutively express the highly specific, key ROM-neutralizing cytosolic enzyme Cu/Zn-superoxide dismutase (SOD). Under inflammatory conditions, however, its protein and activity levels have consistently been reported as being decreased. To elucidate a direct functional relationship between intracellular Cu/Zn-SOD expression and intestinal inflammation, we investigated the effects of transgenic human Cu/Zn-SOD overexpression in acute and chronic murine dextran sodium sulfate (DSS)-induced colitis. When subjected to a mild form of acute colitis, the Cu/Zn-SOD overexpressing mice showed a significantly lower colonic activity of neutrophilic myeloperoxidase (MPO) than their nontransgenic littermates. This difference was particularly evident in the male animals. In contrast, a severe acute colitis did not lead to any differences in MPO activity between both groups. Yet, when the animals were subsequently allowed to recover, MPO levels were again significantly lower in the transgenes, suggesting an involvement of Cu/Zn-SOD in, particularly, the clearance of neutrophils. Specific, immunohistochemical identification of neutrophils confirmed the validity of the MPO activity measurements. In addition, transgenic animals showed a remarkable survival benefit from severe DSS colitis over their nontransgenic littermates, particularly during or shortly after the acute inflammatory phase. During the chronic inflammatory phase, which was not characterized by massive neutrophil infiltration, no effects of Cu/Zn-SOD overexpression were noted. Paradoxically, overexpression of Cu/Zn-SOD did not obviously improve the colitis-related (oxidative) injury or symptoms at any stage of the experiment. Surprisingly, however, we did observe a pronounced male gender preference for DSS susceptibility that was reflected by increased male colitis mortality. Our findings provide direct in vivo evidence for a protective, neutrophil-related role for Cu/Zn-SOD in intestinal inflammation. As such, they support the concept of SOD-based (adjunct) antioxidant treatment strategies for inflammatory bowel disease.

Topics: Acute Disease; Animals; Antioxidants; Catalase; Chronic Disease; Colitis; Colon; Dextran Sulfate; DNA Primers; Female; Glutathione Peroxidase; Humans; Indicators and Reagents; Inflammation; Male; Metabolic Clearance Rate; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neutrophils; Oxidation-Reduction; Oxidative Stress; Peroxidase; Polymerase Chain Reaction; Superoxide Dismutase; Survival Rate

Pancreatic stellate cells have some similarities to hepatic stellate cells and an intrinsic renin-angiotensin system is present in the pancreas and is enhanced in acute pancreatitis and chronic pancreatic hypoxia. We assessed the effects of lisinopril, an angiotensin-converting enzyme (ACE) inhibitor, on spontaneously occurring chronic pancreatitis.. Lisinopril in drinking water (20, 50, or 200 mg/L) was administered to 10-week-old male Wistar Bonn/Kobori (WBN/Kob) rats for 10 weeks and then the inflammatory parameters, fibrosis, serum and pancreatic ACE activity, and expression of transforming growth factor-beta1 (TGF-beta1) messenger RNA (mRNA) as well as positive immunostaining for alpha-smooth muscle actin (alpha-SMA) were assessed.. Lisinopril attenuated gross alterations in the pancreas. This protective effect was confirmed quantitatively by significant increases in pancreatic weights and decreases in pancreatic myeloperoxidase (MPO) activity (an index of granulocyte infiltration), pancreatic hydroxyproline content (an index of collagen deposition), ratio of fibrous tissue, and histologic scores. Lisinopril significantly reduced serum ACE activity but it did not affect pancreatic activity. High doses of lisinopril suppressed the overexpression of TGF-beta1 mRNA measured by reverse-transcription polymerase chain reaction (RT-PCR) and decreased the number of alpha-SMA-positive cells (activated pancreatic stellate cells) in the pancreas.. Lisinopril alleviated chronic pancreatitis and fibrosis in male WBN/Kob rats. It suppressed the expression of TGF-beta1 mRNA, resulting in the prevention of pancreatic stellate cell activation, which may be involved in the observed protection. We propose that an ACE inhibitor may be useful for treating chronic pancreatitis.

Topics: Actins; Angiotensin-Converting Enzyme Inhibitors; Animals; Body Weight; Chronic Disease; Fibrosis; Gene Expression; Hydroxyproline; Immunohistochemistry; Lisinopril; Male; Organ Size; Pancreas; Pancreatitis; Peptidyl-Dipeptidase A; Peroxidase; Rats; Rats, Wistar; Transforming Growth Factor beta; Transforming Growth Factor beta1

The new prostatitis classification proposes the inclusion of seminal leukocytes in the diagnosis of inflammatory chronic pelvic pain syndrome (CPPS). The present study has been performed to clarify the role of seminal leukocytes and inflammatory seminal plasma parameters in order to contribute to the differential diagnosis between inflammatory (category IIIA) and non-inflammatory (category IIIB) CPPS. A total of 112 consecutive symptomatic patients (mean age 37.3 years; range 21-64) attending our prostatitis outpatient clinic were investigated. Men with evidence for bacterial infection were excluded by prior standardized lower urinary tract localization studies. Men were categorized into inflammatory and non-inflammatory CPPS according to the leukocyte analysis in expressed prostatic secretions (EPS) and urine after prostatic massage (VB 3). Ejaculate analysis was performed after lower urinary tract localization studies. Inflammatory markers included peroxidase positive leukocytes (PPL) and PMN-elastase. Receiver operating characteristic curves were constructed to analyze cutpoints provided that the differences were significant. Increased leukocyte counts in EPS/VB 3 were found in 64 men, while in 48 this was not the case. No differences could be detected in relation to patients' age ( P>0.05). In men with category IIIA prostatitis, PPL and elastase in the seminal fluid were significantly increased ( P<0.001). For PPL and elastase, a cutpoint of 0.113 x 10(6)/ml and 280 ng/ml, respectively, were suggested. Increased PPL (>0.113 x 10(6)/ml) and elastase (>280 ng/ml) in the seminal fluid indicate inflammatory disease provided that the ejaculate analysis is performed on the same day after lower urinary tract localization studies.

Topics: Adult; Biomarkers; Chronic Disease; Humans; Inflammation; Leukocyte Elastase; Leukocytes; Male; Middle Aged; Pelvic Pain; Peroxidase; Prostate; Prostatitis; Semen

Topics: Biopsy, Needle; Chronic Disease; Fatigue; Humans; Hypothyroidism; Peroxidase; Sensitivity and Specificity; Thyroglobulin; Thyroid Gland; Thyroiditis, Autoimmune; Thyrotropin

The involvement of enteropathogenic microorganisms in the pathogenesis of inflammatory bowel disease (IBD) and their importance in the different phases of inflammation are still unknown.. To quantify the aerobic bacterial load in models of acute and chronic 'reactivated' colitis, and correlate this with damage.. Acute colitis was induced in rats by administration of trinitrobenzene sulfonic acid (TNBS) or dextran sulfate sodium (DSS). Colitis was 'reactivated' 6 weeks later by intravenous administration of TNBS. The distal colon was removed and scored macroscopically before inoculating samples.. Bacterial load in rats with acute colitis (72 h) and chronic 'reactivated' colitis or their controls was significantly higher than untreated (p < 0.05); however, there were significantly more bacteria in acute colitis than in chronic 'reactivated' or their controls (p < 0.05). Both acute and chronic 'reactivated' colitis had significantly higher damage scores than untreated animals (p < 0.05). Bacterial load and damage score were significantly correlated only with acute colitis.. The role of enteric microflora in the pathogenesis of IBD is greater during the acute phase of colitis. The correlation between bacterial load and tissue damage suggests that damage contributes to bacterial multiplication and exacerbation of colitis. Normal colonic flora may contribute to the relapse of the disease.

Topics: Acute Disease; Animals; Bacteria; Chronic Disease; Colitis; Colony Count, Microbial; Dextran Sulfate; Indicators and Reagents; Male; Models, Animal; Peroxidase; Rats; Rats, Sprague-Dawley; Recurrence; Trinitrobenzenesulfonic Acid

In human, digestive disorders are often associated with visceral pain. In these pathologies, visceral pain threshold is decreased indicating a visceral hypersensitivity. Pregabalin [CI-1008; S-(+)-3-isobutylgaba] presents antihyperalgesic actions in inflammatory somatic pain models. This study was designed to evaluate 1) the effect of injection of TNBS into the colon on visceral pain threshold, and 2) the antihyperalgesic effect of pregabalin on TNBS-induced chronic colonic allodynia. A significant decrease in the colonic pain threshold was observed in trinitrobenzene sulfonic acid (TNBS)-treated animals (17.8 +/- 1.27 versus 43.4 +/- 1.98 mm Hg). Pregabalin (30-200 mg/kg s.c.) and morphine (0.1-1 mg/kg s.c.) showed a dose-related inhibition of TNBS-induced colonic allodynia. Pregabalin did not inhibit the colonic inflammatory effect of TNBS. In normal conditions (control animals), morphine (0.3 mg/kg s.c.) significantly increased the colonic pain threshold, whereas pregabalin (200 mg/kg s.c.) did not modify the colonic pain threshold. Pregabalin suppressed the TNBS-induced colonic allodynia but did not modify the colonic threshold in normal conditions. The ability of pregabalin to block the chronic colonic allodynia indicates that it is effective in abnormal colonic hypersensitivity, suggesting a possible effect in chronic pain in irritable bowel syndrome.

Topics: Analgesics, Opioid; Animals; Chronic Disease; Colon; Colonic Diseases; gamma-Aminobutyric Acid; Hyperemia; Male; Morphine; Organ Size; Pain; Peroxidase; Pregabalin; Rats; Rats, Sprague-Dawley; Time Factors; Trinitrobenzenesulfonic Acid

In the present trial, the hypothesis was examined that the local PMN responses in untreated and treated chronic periodontitis can be differentiated by gingival crevicular fluid lysosomal enzyme activities and elastase-alpha-1-proteinase inhibitor complex.. In nine subjects (average age 49.2 +/- 7.1 years) with chronic periodontitis, clinical parameters and markers of the PMN-derived inflammatory tissue response in gingival crevicular fluid (GCF) were assessed before and 6 months after surgical periodontal therapy. Myeloperoxidase (MPO), beta-N-acetyl-hexosaminidase (beta-NAH) and cathepsin D (CD) were analyzed as indicators of the PMN-associated host tissue destruction, and elastase-alpha-1-proteinase inhibitor complex (alpha-1-EPI) as the major serum protein inactivating PMN elastase. The total activities of the lysosomal enzymes MPO and beta-NAH were evaluated spectrophotometrically, the CD levels by liquid scintillation counting with [14C] hemoglobin as substrate, and the total alpha-1-proteinase inhibitor complex using a sandwich-immunoassay.. The clinical parameters revealed a statistical significant decrease at the 6-month reexamination. PD levels dropped from 5.40 to 2.88 mm (change 2.52 +/- 1.04 mm), the CAL scores from 6.67 to 4.43 mm (change 2.24 +/- 0.77 mm). The 30 s GCF volumes dropped from 129.8 to 68.6, displaying a change of 61.1 +/- 18.6, p

Topics: Adult; alpha 1-Antitrypsin; beta-N-Acetylhexosaminidases; Carbon Radioisotopes; Cathepsin D; Chronic Disease; Down-Regulation; Female; Follow-Up Studies; Gingival Crevicular Fluid; Humans; Leukocyte Elastase; Lysosomes; Male; Middle Aged; Neutrophil Activation; Neutrophils; Periodontal Attachment Loss; Periodontal Pocket; Periodontitis; Peroxidase; Radiopharmaceuticals; Spectrophotometry; Statistics, Nonparametric; Wound Healing

Exaggerated neutrophil responses are a critical component in the pathogenesis of periodontal disease. We investigated whether leukocyte activity in aggressive periodontitis (AP) is increased compared with that in chronic periodontitis (CP) by gingival crevicular fluid (GCF) analysis of myeloperoxidase (MPO), beta-N-acetyl-hexosaminidase (beta-NAH), cathepsin D (CD), and elastase-alpha-1-proteinase inhibitor complex (alpha-1-EPI) before and 6 months after therapy. Initial AP neutrophil responses were significantly amplified compared with those in CP (MPO, 3.2-fold; beta-NAH, 37.5-fold; CD, 2.2-fold; alpha-1-EPI, 1.4-fold; p < 0.05). Surgical therapy resulted in a significant reduction of GCF markers compared with non-surgical treatment. However, the changes in clinical parameters were not different between AP and CP (P > 0.05). Analysis of the results suggests that the local inflammatory response in AP is characterized by increased release of inflammatory mediators of neutrophil origin into the GCF. Analysis of the data further suggests that surgical therapy is a more predictable method for removal of the pro-inflammatory etiology.

Topics: Adult; alpha 1-Antitrypsin; beta-N-Acetylhexosaminidases; Cathepsin D; Chronic Disease; Dental Plaque Index; Dental Scaling; Follow-Up Studies; Gingival Crevicular Fluid; Humans; Inflammation Mediators; Leukocyte Elastase; Middle Aged; Neutrophils; Periodontal Attachment Loss; Periodontal Index; Periodontal Pocket; Periodontitis; Peroxidase; Root Planing; Serine Proteinase Inhibitors; Statistics, Nonparametric

The role of CXCR during allergic airway and asthmatic diseases is yet to be fully characterized. Therefore, the present study addressed the role of CXCR2 during Aspergillus fumigatus-induced asthma. Mice deficient in CXCR2 (CXCR2-/-) and wild-type counterparts (CXCR2+/+) were sensitized to A. fumigatus Ags and challenged with A. fumigatus conidia, and the resulting allergic airway disease was monitored for up to 37 days. At days 3 and 7 after conidia, CXCR2-/- mice exhibited significantly greater methacholine-induced airway hyperreactivity than did CXCR2+/+ mice. In contrast, CXCR2-deficient mice exhibited significantly less airway hyperresponsiveness than the wild-type control groups at days 14 and 37 after conidia. At all times after conidia, whole lung levels of IL-4, IL-5, and eotaxin/CC chemokine ligand 11 were significantly lower in CXCR2-/- mice than in the wild-type controls. Eosinophil and T cell, but not neutrophil, recruitment into the airways of A. fumigatus-sensitized CXCR2-/- mice was significantly impaired compared with wild-type controls at all times after the conidia challenge. Whole lung levels of IFN-gamma, inflammatory protein-10/CXC ligand (CXCL) 10, and monokine induced by IFN-gamma (MIG)/CXCL9 were significantly increased in CXCR2-/- mice compared with CXCR2+/+ mice at various times after conidia. Interestingly, at day 3 after conidia, neutrophil recruitment and airway hyperresponsiveness in CXCR2-/- mice was mediated by inflammatory protein-10/CXCL10 and, to a lesser degree, MIG/CXCL9. Taken together, these data suggest that CXCR2 contributes to the persistence of asthmatic disease due to A. fumigatus.

Topics: Animals; Aspergillus fumigatus; Asthma; Bronchial Hyperreactivity; Bronchoalveolar Lavage Fluid; Cell Movement; Chemokine CCL11; Chemokine CCL4; Chemokine CCL5; Chemokine CXCL10; Chemokines, CC; Chemokines, CXC; Chronic Disease; Disease Models, Animal; Eosinophils; Female; Immunity, Innate; Immunoglobulin E; Interferon-gamma; Interleukin-12; Interleukin-4; Interleukin-5; Lung; Macrophage Inflammatory Proteins; Methacholine Chloride; Mice; Mice, Knockout; Neutrophils; Peroxidase; Receptors, Interleukin-8B; Spores, Fungal; T-Lymphocytes

Prolonged cough is a common problem in patients seen in general practice. Using a simple method of sputum induction and processing of sputum samples, we determined whether eosinophilic airway inflammation could be a cause of undiagnosed prolonged cough. Eighty-two patients who had had cough for more than 1 month were enrolled into the study, in six primary healthcare centres. Patients with known pulmonary disease, including asthma or chronic obstructive pulmonary disease (COPD), or who were known to have another cause of cough, or to have recently suffered from a respiratory infection, were excluded. Fifty-three healthy individuals served as controls. Sputum was induced by inhalation of 3% saline. Inflammatory cells in smears were studied semi-quantitatively. Concentrations of eosinophil cationic protein (ECP), eosinophil peroxidase (EPO), myeloperoxidase (MPO) and human neutrophilic lipocalin (HNL) were determined. Sputum induction proved safe and adequate samples were obtained from 91%. Sputum eosinophilia (eosinophils accounting for more than 5% of all cells in smears) was present in 14 patients with prolonged cough (19%) but in no healthy individual (P=0.001). Five of the 14 individuals (36%) who exhibited sputum eosinophilia appeared to have asthma, while nine of the 14 (64%) did not. Concentrations of ECP and EPO were higher in patients with prolonged cough than in healthy individuals (P=0.02 for ECP; 0.005 for EPO). We conclude that eosinophilic airway inflammation is a fairly common cause of prolonged cough, even in patients not suffering from asthma or COPD, or in whom no other cause of cough is known to be present. Induced sputum samples obtained in health centres can be studied in a central laboratory. Detection of eosinophilic airway inflammation could aid the decision regarding treatment.

Topics: Acute-Phase Proteins; Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Blood Proteins; Carrier Proteins; Case-Control Studies; Chronic Disease; Cough; Eosinophil Granule Proteins; Eosinophil Peroxidase; Eosinophilia; Eosinophils; Female; Humans; Inflammation; Leukocyte Count; Lipocalin-2; Lipocalins; Male; Middle Aged; Oncogene Proteins; Peroxidase; Peroxidases; Proto-Oncogene Proteins; Respiratory Tract Diseases; Ribonucleases; Sputum

To identify the relationship of neutrophil activity to allergy as reflected by the level of myeloperoxidase (MPO) in ears of atopic patients with chronic otitis media with effusion (OME) by objective testing.. Evidence of neutrophils was measured in the effusion of atopic patients with chronic OME. Atopy was determined by intradermal and/or in vitro testing of allergic reaction to 10 inhalants, 2 molds, and 5 foods.. Effusion MPO was measured prospectively in 138 ears from 106 consecutive patients with chronic OME.. A total of 86 (81%) of 106 patients with OME tested atopic by in vitro or in vivo testing. Excluding 36 ears with purulence, the mean MPO level was 3132 microg/L in 84 atopic vs 142 microg/L in 18 nonatopic ears (P<.001). A total of 78 (90%) of 87 patients with OME were atopic.. The surprising finding of marked elevation of effusion MPO in atopic patients but very low levels in nonatopic patients (P < .001) suggests that atopy may contribute to elevated levels of neutrophil activity in OME. An atopic patient may respond differently from a nonatopic one to the microbial or viral products of acute inflammation owing to the presence of primed inflammatory cells. This study provides confirmation on a cellular level that neutrophils are an integral part of the inflammatory process in OME to a disproportionate degree among atopic patients.

Topics: Adult; Biomarkers; Case-Control Studies; Child; Child, Preschool; Chronic Disease; Humans; Hypersensitivity, Immediate; In Vitro Techniques; Infant; Models, Immunological; Neutrophils; Otitis Media with Effusion; Peroxidase; Prospective Studies; Statistics, Nonparametric

Teprenone, an anti-ulcer drug, has been reported to promote the healing of acetic acid-induced chronic gastric ulcers in rats by stimulating gastric mucus synthesis and secretion. Recently, it has been implicated that neutrophil infiltration and lipid peroxidation in ulcerated gastric tissues have an inhibitory effect on the healing of acetic acid-induced chronic gastric ulcers in rats. Therefore, we attempted to clarify whether teprenone exerts a healing-promoting effect on acetic acid-induced chronic gastric ulcers through its inhibitory effect on neutrophil infiltration and lipid peroxidation in ulcerated gastric tissues. In rats with chronic gastric ulcers made by applying acetic acid to the stomach, gastric ulcer healing started later than 3 days after the acetic acid application. Gastric mucosal myeloperoxidase (MPO) activity, an index of tissue neutrophil infiltration, and lipid peroxide content were higher in the ulcerated region than in the intact region on the 8th, 15th, and 22nd day after the acetic acid application. Gastric mucosal non-protein SH content was lower in the ulcerated region than in the intact region on the 8th, 15th, and 22nd day after the acetic acid application, and gastric mucosal adherent mucus content was lower in the ulcerated region than in the intact region on the 8th and 15th day. Daily oral administration of teprenone (100 mg kg(-1)x 2) for 7 or 14 days, starting on the 8th day after the application of acetic acid to the stomach, enhanced the reduction of the ulcer area with attenuation of all these biochemical changes found in the ulcerated region. The teprenone administration caused a decrease in MPO activity and an increase in adherent mucus content in the gastric mucosa of the intact region. These results suggest that the healing-promoting effect of teprenone on acetic acid-induced chronic gastric ulcers in rats could be due not only to stimulation of gastric mucus secretion but also to inhibition of neutrophil infiltration and enhanced lipid peroxidation in the ulcerated gastric tissue.

Topics: Acetic Acid; Administration, Oral; Animals; Anti-Ulcer Agents; Chronic Disease; Diterpenes; Gastric Mucosa; Lipid Peroxidation; Lipid Peroxides; Male; Mucus; Neutrophil Infiltration; Peptic Ulcer; Peroxidase; Rats; Rats, Wistar; Sulfhydryl Compounds

To determine the effect of intranasal treatment with IRS-19, an immunomodulating agent, on the number of polymorphonuclear leukocytes (PMNL), H2O2 concentration and myeloperoxidase (MPO) activity in nasal washings.. 28 adult patients of both sexes with chronic bronchitis participated in an open study of intranasal treatment with IRS-19.. The number of PMNL recovered from nasal spaces increased from 4460 +/- 3960 to 10,490 +/- 10,950 cells/ml (p < 0.02) after two month administration of IRS-19. It was accompanied by 2.6- and 1.4-fold increase (p < 0.001) in MPO activity and H2O2 concentration, respectively. However, no correlation was found between increments in these three variables.. Since PMNL and MPO--H2O2--Cl- system are involved in the first line of defense against invading pathogens it is suggested that the above mentioned changes may represent one among mechanisms leading to enhancement of antibacterial defence in the airways in response to treatment with IRS-19.

Topics: Adjuvants, Immunologic; Adult; Bacteria; Bronchitis; Chronic Disease; Female; Humans; Hydrogen Peroxide; Leukocyte Count; Male; Middle Aged; Neutrophils; Peroxidase; Spectrometry, Fluorescence

The effect of chronic granulomatous inflammation of the intestine was studied on the prejunctional modulation of cholinergic nerve activity in the mouse ileum. Contractions to carbachol (0.01 - 0.3 microM) and to electrical field stimulation (EFS, 0.25 - 8 Hz) of enteric neurons were higher in inflamed ileum as compared to control ileum. However, when the neurally-mediated contractions to EFS were expressed as percentage of the direct smooth muscle contraction to carbachol, the responses to EFS were similar in control and inflamed ileum. Atropine (1 microM) abolished all contractions to EFS and carbachol in control and inflamed ileum. DMPP (3 - 30 microM), a nicotinic receptor agonist, induced concentration-dependent contractions that were more pronounced in inflamed ileum as compared to control ileum. Hexamethonium (100 microM), a nicotinic receptor blocker, significantly inhibited the contractions to EFS in inflamed ileum but not in control ileum. In control ileum, histamine (10 - 100 microM) and the histamine H(1) receptor agonist HTMT (3 - 10 microM) inhibited the contractions to EFS concentration-dependently without affecting the contractions to carbachol. The inhibitory effect of histamine and HTMT was prevented by the histamine H(1) antagonist mepyramine (5 - 10 microM) but not by the H(2)- and H(3)-receptor antagonists cimetidine and thioperamide (both 10 microM). In chronically inflamed ileum however, histamine (10 - 100 microM) and HTMT (3 - 10 microM) failed to inhibit the contractions to EFS. The histamine H(2) and H(3) receptor agonists dimaprit and R(-)-alpha-methylhistamine did not affect the contractions to EFS in control and inflamed ileum. The alpha(2)-receptor agonist UK 14.304 (0.01 - 0.1 microM) inhibited the contractions to EFS in control and inflamed ileum without affecting the contractions to carbachol. The effect of UK 14.304 was reversed by the alpha(2)-receptor antagonist yohimbine (1 microM). The inhibitory effect of UK 14.304 on contractions to EFS was of similar potency in control and inflamed ileum. Our results suggest that the prejunctional modulation of cholinergic nerve activity by nicotinic and histaminic H(1) receptors is disturbed during chronic intestinal inflammation whereas the modulation by alpha(2)-receptors is preserved. Such a disturbance of cholinergic nerve activity may contribute to the motility disturbances that are often observed during chronic intestinal diseases in humans.

Topics: Adrenergic Agonists; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-2 Receptor Antagonists; Adrenergic Antagonists; Animals; Brimonidine Tartrate; Carbachol; Cholinergic Agents; Cholinergic Agonists; Cholinergic Antagonists; Chronic Disease; Dimethylphenylpiperazinium Iodide; Dose-Response Relationship, Drug; Electric Stimulation; Granuloma; Hexamethonium; Histamine; Histamine Agonists; Histamine Antagonists; Ileum; In Vitro Techniques; Male; Mice; Muscle Contraction; Neuromuscular Junction; Peroxidase; Quinoxalines; Receptors, Histamine; Schistosoma mansoni; Schistosomiasis mansoni; Synaptic Transmission; Tetrodotoxin

Matrix metalloproteinases (MMPs) represent a group of enzymes that regulate cell-matrix composition playing a major role in the inflammatory response. In the present study we evaluated the ability of the MMP inhibitor Batimastat (BB-94) to modify the course of experimental colitis induced in the rat by trinitrobenzensulfonic acid (TNB).. Colitis was induced in 40 rats by intracolonic administration of TNB. Animals were divided into four groups of ten rats each: group 1 received only intracolonic TNB, group 2 received TNB+5 mg/kg intraperitoneal BB-94, group 3 TNB+10 mg/kg BB-94 and group 4 TNB+20 mg/kg BB-94. The MMP inhibitor was administered 30 min before induction of colitis and twice daily until death. Ten rats receiving only intracolonic 0.9% saline served as controls. Animals were killed after seven days; segments of colon were removed and used for histological score of inflammation and myeloperoxidase (MPO) activity.. Rats receiving only intracolonic 0.9% saline showed no evidence of colitis. The inflammation score was 0.9, MPO activity 0.235 U/mg. Group 1 (TNB-treated rats) exhibited a high inflammation score (12.4) and MPO activity (0.715 U/mg). Conversely, BB-94-treated rats showed, compared to the TNB group, a significantly lower inflammation score and MPO activity in a dose-dependent fashion. Group 2: inflammatory score 10.1, MPO activity 0.474 (p < 0.05 vs. TNB); group 3: inflammatory score 8.3, MPO activity 0.287 (p < 0.01 vs. TNB); group 4: inflammatory score 5.0, MPO activity 0.256 (p < 0.01 vs. TNB).. Treatment with BB-94 has dose-dependent beneficial effects on the inflammatory alterations in rat experimental colitis. Thus, the inhibition of MMPs may represent a novel therapeutic approach for treatment of intestinal inflammation.

Topics: Animals; Chronic Disease; Colitis, Ulcerative; Disease Models, Animal; Hematoxylin; Intestinal Mucosa; Male; Matrix Metalloproteinase Inhibitors; Matrix Metalloproteinases; Peroxidase; Phenylalanine; Protease Inhibitors; Rats; Rats, Sprague-Dawley; Severity of Illness Index; Thiophenes; Trinitrobenzenesulfonic Acid

To study mechanisms of biocenosis action of neutrophils in alcoholics with chronic pyelonephritis (CP).. Functional potential of oxidase neutrophil system was studied in 37 males with chronic alcoholism stage II. 17 of them had CP. They were compared to 18 CP non-alcohol abusers (controls).. CP alcoholics had lower potential of oxidase neutrophil system than controls and healthy subjects.. Dysfunction of axygen-dependent mechanisms of biocidic action of neutrophils in chronic alcoholics weakens the ability of the organism to eliminate infection and can entail defects in immune response.

Topics: Adult; Alcoholism; Animals; Cells, Cultured; Chi-Square Distribution; Chronic Disease; Humans; Male; Mice; Mice, Inbred CBA; Neutrophil Activation; Neutrophils; Oxidoreductases; Peroxidase; Pyelonephritis; Time Factors

Leucocyte recruitment to sites of intestinal inflammation is a crucial, multi-step process that leads ultimately to the accumulation of cells in the inflamed tissue. We established a new in vivo model system of experimental colitis to quantify leucocyte-endothelial cell interaction and leucocyte extravasation in the inflamed mucosa of the colon. Furthermore, we investigated the pathophysiological role of ICAM-1 in the intestinal microcirculation in vivo. Using the model of dextran sodium sulphate (DSS)-induced acute and chronic colitis in mice, in vivo microscopy was performed in the colonic submucosal postcapillary venules and the submucosal collecting venules in normal or inflamed murine colonic segments. ICAM-1 expression was blocked by an anti-ICAM-1 monoclonal antibody or by suppressing NF-kappaB activation by gliotoxin. Significant increases in leucocyte adhesiveness (51-fold in postcapillary venules, 30-fold in collecting venules, P < 0.01) and extravasation (6.5-fold) could be demonstrated as early as day 2 of DSS-application in acute colitis (P < 0.01). This was paralleled by increases in both the histological damage scores and myeloperoxidase activities. In chronic dextran sodium sulphate-induced colitis significant increases in leucocyte-endothelium interactions and leucocyte extravasation were observed. Blocking ICAM-1 expression with a monoclonal antibody or gliotoxin, leucocyte sticking and extravasation were significantly down-regulated in vivo compared to controls (> 70%; P < 0.01). This new model system offers the possibility to specifically assess the role of adhesion molecules in the colonic mucosa in vivo as well as to investigate and quantify the effectiveness of experimental therapeutic approaches in acute or chronic intestinal inflammation.

Topics: Acute Disease; Animals; Cell Adhesion; Cell Communication; Cell Movement; Chronic Disease; Colitis; Dextran Sulfate; Endothelium, Vascular; Female; Immunohistochemistry; Intercellular Adhesion Molecule-1; Intestinal Mucosa; Leukocytes; Mice; Mice, Inbred BALB C; Microscopy, Electron; Microscopy, Fluorescence; Peroxidase

The fact that tumour necrosis factor-alpha (TNF-alpha) is clearly involved in the pathogenesis of intestinal bowel disease, especially Crohn's disease, suggests that TNF-alpha synthesis inhibitors could be beneficial for treatment. The present study assessed the effect of chronic oral gavage of two in vitro TNF-alpha synthesis inhibitors, JM 34 maleate or [N-(4,6-dimethylpyridin-2-yl)-furane-2-carboxamide)] maleate and XC 21 or (N-betapicolyl-tetrafluorophtalimide), on colonic inflammation in trinitrobenzene sulphonic acid-induced colitis in rats. Rats received JM 34 maleate (100 mg/kg) and XC 21 (50 mg/kg) 1 h before colitis induction and then daily for 8 days by oral gavage. The colon was removed on day 8 and processed for clinical score, myeloperoxidase activity, and soluble TNF-alpha release. Treatment with XC 21, as well as dexamethasone and sulphasalazine, reduced colonic damage and decreased (except with dexamethasone) the incidence of diarrhoea. JM 34 maleate failed to improve the clinical signs of chronic colitis. After trinitrobenzene sulphonic acid-induced colitis, myeloperoxidase activity and TNF-alpha colonic mucosal production were substantially increased compared to the control (saline instillation). Both of these inflammatory indicators were then significantly decreased (P< or =0.05) after the four chronic treatments (JM 34 maleate, XC 21, sulphasalazine, and dexamethasone). XC 21 appeared to be as efficient as sulphasalazine in improving colonic inflammation.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Benzamides; Chronic Disease; Colitis; Colon; Disease Models, Animal; Enzyme Inhibitors; Peroxidase; Rats; Rats, Wistar; Sulfasalazine; Trinitrobenzenesulfonic Acid; Tumor Necrosis Factor-alpha

It is supposed that an inflammatory reaction is one of the major factors responsible for the chronic venous insufficiency (CVI) of lower limbs which cause leg ulcers.. The main objective of the present study was to determine the differences in the levels of typical inflammatory mediators and markers produced by neutrophils of patients with CVI and normal control subjects.. 26 patients with CVI and 39 clinically healthy subjects were included in the study. In peripheral neutrophils of both groups the production of superoxide, total reactive oxygen intermediates and activities of lysosomal enzymes were measured together with the expression of 8 adhesion molecules.. Increased formation of superoxide by patient neutrophils and activities of elastase in both neutrophils and serum of patients were demonstrated. On the contrary, activities of myeloperoxidase and beta-D-glucuronidase were decreased in patient neutrophils. Comparing to control group adhesion molecules CD11b, CD18, CD31, CD49d, CD54 and CD62L were increased on the surface of patient neutrophils whereas no differences were observed in the expression of CD11a abd CD15.. The neutrophils of patients with CVI are primed and/or activated because they are able to release higher amount of superoxide, lysosomal enzymes and express elevated number of adhesion molecules. It may serve as one of the important evidences of an inflammatory mechanism involved in the pathogenesis of chronic venous insufficiency. (Tab. 3, Ref. 27.)

Topics: Adult; Aged; Cell Adhesion Molecules; Chronic Disease; Female; Glucuronidase; Humans; Inflammation Mediators; Leg; Male; Middle Aged; Muramidase; Neutrophils; Pancreatic Elastase; Peroxidase; Superoxides; Venous Insufficiency

Morin, a bioflavonoid with antioxidant properties, shows intestinal anti-inflammatory activity in the acute phase of the trinitrobenzenesulphonic acid model of rat colitis.. To assess the anti-inflammatory activity of morin in the chronic stages of trinitrobenzenesulphonic acid-induced rat colitis.. Rats were rendered colitic by a single colonic instillation of 30 mg of the hapten trinitrobenzenesulphonic acid dissolved in 0.25 mL of 50% ethanol. A group of colitic animals was given morin orally at doses of 25 mg/kg daily. Animals were sacrificed every week for 4 weeks. Colonic damage was evaluated macroscopically and microscopically. Different biochemical markers of colonic inflammation were also assayed, including myeloperoxidase activity, leukotriene B4 and interleukin-1beta synthesis, glutathione and malonyldialdehyde levels and nitric oxide synthase activity.. The administration of morin facilitated tissue recovery during the 4 weeks following colonic insult with trinitrobenzenesulphonic acid, as demonstrated macroscopically and microscopically, as well as biochemically by a reduction in myeloperoxidase activity. The intestinal anti-inflammatory effect of morin was accompanied by a significant reduction in colonic leukotriene B4 and interleukin-1beta levels, improvement in colonic oxidative stress and inhibition of colonic nitric oxide synthase activity.. Morin exerts a beneficial anti-inflammatory effect in the chronic phase of trinitrobenzenesulphonic acid-induced rat colitis through the down-regulation of some of the mediators involved in the intestinal inflammatory response, including free radicals, cytokines, leukotriene B4 and nitric oxide.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Chronic Disease; Colitis; Disease Models, Animal; Female; Flavonoids; Interleukin-1; Intestinal Mucosa; Leukotriene B4; Nitric Oxide; Nitric Oxide Synthase; Peroxidase; Rats; Rats, Wistar; Trinitrobenzenesulfonic Acid

Investigation of functional-metabolic activity of leukocytes by assessment of basic components of the microbicidal system in the course of chronic brucellosis with reference to the stage, severity, complications and concomitant diseases.. Time course of changes in myeloperoxidase, acid and alkaline phosphatase activity, levels of cation protein, glycogen and lipids in leukocytes were studied in seventy-one 16-70-year-old patients with exacerbation of chronic brucellosis. The diagnosis of primary-chronic, secondary-chronic brucellosis, subcompensation was made in 13, 58 and 69 patients, respectively. 14 patients had chronic infectious inflammatory diseases, 13 patients had chronic non-inflammatory diseases.. Patients with chronic brucellosis at the height of the exacerbation had suppressed activity of myeloperoxidase and lowered level of cationic protein with high activity of acid and alkaline phosphatases, elevated glycogen and lipids in leukocytes. General condition of the patients improved in parallel with multidirectional shifts in the levels of microbicidal system components with normalization at the stage of persistent remission.. Changes in the level of intracellular components of leukocytes depended on brucellosis stage, severity, complications, concomitant diseases, completeness of recovery. This is of clinico-diagnostic significance.

Topics: Acid Phosphatase; Adolescent; Adult; Aged; Alkaline Phosphatase; Blood Bactericidal Activity; Brucellosis; Chronic Disease; Female; Glycogen; Humans; Leukocytes; Lipids; Male; Middle Aged; Peroxidase

To evaluate the role of intercellular adhesion molecule 1 (ICAM-1) in cutaneous leukocyte trapping in venous disease, we used our rodent model of venous hypertension (VH).. VH was created in adult rats by ligation of the inferior vena cava, bilateral common iliac veins, and bilateral common femoral veins. In the Phase I experimental (exptl) group, anti-ICAM-1 monoclonal antibody (1A29) was given intravenously prior to venous ligations. Acute venous pressures were measured in the exptl and control (ctrl) (ligation only) groups. Bilateral forelimb and hindlimb skin specimens were harvested for myeloperoxidase (MPO) assay. In Phase II, VH was created in a chronic group; in a sham-operated group, ties were placed around the same vessels without ligations. Two weeks later, venous pressures were measured and radiolabeled ((125)I and (131)I) monoclonal antibody (mAb) to ICAM-1 was injected and allowed to circulate for 5 min before the level of radiolabeled antibody within forelimb and hindlimb specimens was measured.. In the acute study with 1A29, hindlimb pressures were significantly elevated in both the ctrl (n = 4) and exptl (n = 4) hindlimbs (15.4 +/- 0.239 and 13.8 +/- 1.89 mm Hg, respectively) compared with ctrl and exptl forelimbs (1.38 +/- 0.554 and 1.50 +/- 0.612 mm Hg, respectively). However, MPO activity was significantly elevated in the hindlimbs of the ctrl group compared with the hindlimbs of the exptl animals (19.8 +/- 1.54 U vs 6.71 +/- 2.46 U). In the chronic VH rats (n = 5) given radiolabeled anti-ICAM-1 mAb, the hindlimb pressures (10.1 +/- 4.52 mm Hg) were significantly elevated (P < 0.05) compared with forelimb pressures (1 +/- 0.447 mm Hg) and compared with the forelimb and hindlimb pressures in the sham-operated animals (n = 4) (1.63 +/- 0.813 and 4.25 +/- 2.13 mm Hg, respectively). However, there was not a significant difference in the quantity of ICAM-1-hindlimb versus forelimb or chronic VH versus sham.. Anti-ICAM-1 mAb decreased MPO activity in hypertensive hindlimb skin, supporting the instrumental role of ICAM-1 in cutaneous leukocyte trapping. However, the constituent endothelial ICAM-1 is not elevated by VH.

Topics: Animals; Chronic Disease; Endothelium, Vascular; Intercellular Adhesion Molecule-1; Male; Peroxidase; Rats; Rats, Wistar; Venous Insufficiency; Venous Pressure

There is increasing evidence that the intestinal microflora plays an important role in the pathogenesis of inflammatory bowel disease. In the present study, we examined the role of the resident intestinal flora in our model of dextran sulfate sodium (DSS)-induced acute and chronic colitis in mice.. Acute colitis was induced in BALB/c mice with 5% DSS in their drinking water for 7 days. Chronic colitis was established after four cycles of feeding 5% DSS for 7 days and water for 10 days. For eliminating intestinal bacteria, mice were injected intraperitoneally with metronidazole and ciprofloxacin. We analysed four parameters: (1) body weight, (2) length of the colon, (3) histological score, and (4) myeloperoxidase activity.. In acute DSS colitis treatment with antibiotics led to an improvement of the histological parameters (epithelial damage, P< 0.05; inflammatory infiltrate, P< 0.05) and colon length (P < 0.0028). A significant reduction in granulocyte infiltration was indicated by a 52.6% reduced myeloperoxidase activity in colonic biopsies. By contrast, in chronic colitis, treatment of mice with antibiotics failed to show significant effects.. In acute DSS-induced colitis bacteria and/or bacterial products play a major role in initiation of inflammation but not in chronic DSS colitis.

Topics: Acute Disease; Animals; Anti-Bacterial Agents; Biopsy; Body Weight; Chronic Disease; Ciprofloxacin; Colon; Dextran Sulfate; Disease Models, Animal; Female; Inflammatory Bowel Diseases; Interleukins; Metronidazole; Mice; Peroxidase

Trimetazidine (TMZ), an anti-ischemic agent with proposed antioxidant properties, was used in a chronic colitis model in order to evaluate its effectiveness as a therapeutic agent in chronic colitis. Treatment of male Swiss Albino rats with ethanol (50%) and trinitrobenzenesulfonic acid (TNBS) (30 mg/kg) produced colitis as evidenced by histopathologic damage and inflammatory alterations, lipid peroxidation [increased malondialdehyde (MDA) levels], and enhanced neutrophil infiltration [increased myeloperoxidase (MPO) activity] without marked change in glutathione status. Administration of TMZ (5 mg/kg) to TNBS-treated rats failed to affect the TNBS-induced changes in histopathology and MPO activities. Unexpectedly, intrarectal (i.r.) administration of TMZ significantly elevated colonic MDA levels to a greater extent than TNBS alone. Intraperitoneal (i.p.) TMZ treatment seemed to increase total glutathione (tGSH), GSH, and GSH/GSSG values. In conclusion, our results demonstrated that (a) i.r. administration of ethanol and TNBS is an effective way of inducing a chronic colitis model, (b) inflammation and lipid peroxidation augment tissue damage in the chronic colitis model, (c) i.p. TMZ treatment significantly inhibits MDA production in the chronic colitis model, (d) TMZ treatment is more effective via the i.p. compared to i.r. route, and (e) TMZ seems to show its antioxidant effect via preserving the tissue's GSH/GSSG ratios.

Topics: Administration, Rectal; Animals; Chronic Disease; Colitis; Ethanol; Glutathione; Injections, Intraperitoneal; Lipid Peroxidation; Male; Malondialdehyde; Peroxidase; Rats; Rats, Sprague-Dawley; Solvents; Trimetazidine; Trinitrobenzenesulfonic Acid; Vasodilator Agents

Mice deficient in both inducible nitric oxide synthase (iNOS) and interleukin (IL)-10 (iNOS(-/-)/IL-10(-/-)) were created to examine the role of iNOS in spontaneously developing intestinal inflammation. IL-10(-/-)/iNOS(-/-) mice were compared with IL-10(-/-) (iNOS(+/+)) littermates over 6 mo. RT-PCR, Western blot analysis, and immunohistochemistry were performed to measure iNOS message and protein levels. Plasma nitrate/nitrite (NO(x)) levels were assessed by HPLC. Damage scores (macroscopic and microscopic) and granulocyte infiltration were assessed. At 3-4 wk, IL-10(-/-) and IL-10(-/-)/iNOS(-/-) mice had no signs of colonic inflammation or granulocyte infiltration. Plasma NO(x) levels were not different from controls. By 3-4 mo, IL-10(-/-) mice had increased damage scores and granulocyte infiltration concurrent with increased mRNA and protein synthesis (restricted to the epithelium) for iNOS in intestinal tissues but not other tissues. Plasma NO(x) levels increased fivefold. Interestingly, in the absence of iNOS induction or increased plasma NO(x), iNOS(-/-)/IL-10(-/-) mice had damage and granulocyte infiltration equivalent to those observed in IL-10(-/-) littermates. These data suggest that iNOS does not impact on the development or severity of spontaneous chronic inflammation in IL-10-deficient mice.

Topics: Age Factors; Animals; Blotting, Western; Chronic Disease; Colitis; Colon; Female; Fluorescent Antibody Technique; Gene Expression Regulation, Enzymologic; Interleukin-10; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Nitrites; Peroxidase; RNA, Messenger

The involvement of pancreatic acinar cell apoptosis and its relation to glucocorticoid exposure were investigated in spontaneously occurring chronic pancreatitis in male Wistar Bonn/Kobori (WBN/Kob) rats. Although most lobules were not inflamed in 10-week-old WBN/Kob, increased apoptosis of pancreatic acinar cells, confirmed by TUNEL staining was focally observed (0.10 +/- 0.10 vs. 0.05 +/- 0.10/field in 10-week Wistar rats). Localized hemorrhagic lesions and brown foci in the splenic lobes were apparent, with significant decrease in pancreas weight in 20-week WBN/Kob rats along with marked apoptosis (1.95 +/- 0.31 vs. 0.07 +/- 0.04/field in 20-week Wistar rats). Electron microscopy revealed apoptotic bodies to be present in acinar cells. Pancreatic myeloperoxidase activities, indirect indices of granulocyte infiltration, as well as histologic scores were significantly increased at 15 and 20 weeks, and endogenous corticosterone levels were significantly decreased at 10, 15, and 20 weeks as compared with values for age-matched Wistar rats. Prednisolone in the drinking water (0.01 mg/mL; calculated dose, 1.03 0.03 mg/kg/d) for 10 weeks significantly attenuated increases in numbers of apoptotic acinar cells and pancreatic myeloperoxidase activities and tended to reduce the histologic scores in 20-week WBN/Kob rats as compared with the vehicle group. In summary, (a) apoptosis of pancreatic acinar cells is involved in chronic pancreatitis, (b) endogenous corticosterone is decreased, and (c) prednisolone treatment attenuates both apoptosis of pancreatic acinar cells and chronic pancreatitis in male WBN/Kob rats. We conclude that apoptosis of acinar cells related to decreased corticosterone may be a trigger of chronic pancreatitis in this model.

Topics: Adrenocorticotropic Hormone; Animals; Apoptosis; Blood Glucose; Body Weight; Cell Nucleus; Chronic Disease; Coloring Agents; Corticosterone; Glucocorticoids; In Situ Nick-End Labeling; Insulin; Male; Microscopy, Electron; Organ Size; Pancreas; Pancreatitis; Peroxidase; Prednisolone; Rats; Rats, Wistar

A group of 100 totally or subtotally myeloperoxidase (MPO)-deficient individuals was compared to a reference population of 118 probands selected at random. Data for a protective effect of the deficiency against cardiovascular damage are presented. On the other hand, a significantly higher occurrence of severe infections and chronic inflammatory processes was noted among the deficient patients. An increased incidence of cancer among the MPO-deficient individuals was not demonstrated.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Arthritis; Cardiovascular Diseases; Case-Control Studies; Chi-Square Distribution; Child; Child, Preschool; Chronic Disease; Female; Humans; Infections; Male; Middle Aged; Myocardial Infarction; Neoplasms; Peroxidase; Risk Factors

The pathophysiologic mechanism for tissue damage in chronic venous insufficiency (CVI) is venous hypertension (VH), the primary mediator behind leukocyte trapping in tissues. We developed a new rodent model of chronic hindlimb VH to allow testing of the microvascular dysfunction that occurs in clinical CVI.. Hindlimb VH was created in adult rats ( approximately 350 g, male, Wistar) by ligation of the inferior vena cava, bilateral common iliac veins, and bilateral common femoral veins. In a sham group, a loose tie was placed around the same vessels. One week later, pressure catheters were placed in the right common carotid artery, right internal jugular vein (forelimb), and right superficial epigastric vein (hindlimb). Measurements were taken 15 min later, to allow for stabilization. Bilateral forelimb and hindlimb skin specimens were harvested. The myeloperoxidase (MPO) assay, an indicator of tissue leukocyte trapping, was performed using a well-described, standard technique.. In the chronic rats (n = 8), the hindlimb pressures (12.6 +/- 3.2 mm Hg) were significantly elevated (P < 0.05) when compared to forelimb pressures (1.75 +/- 0.71) and to chronic sham rat (n = 6) hindlimb (3.3 +/- 1.2) pressures. There was a significant (P < 0.05) elevation of MPO activity in hindlimbs of the chronic group (32.9 +/- 13.9 units) when compared to forelimbs (17 +/- 11.3) and sham hindlimbs (18 +/- 10.2).. In our chronic model, as in clinical studies and previous acute investigations, we have demonstrated, using an MPO assay, an increase in the amount of cutaneous leukocytes in the hindlimbs with chronic VH but not in experimental forelimbs or sham hindlimbs or forelimbs.

Topics: Animals; Chronic Disease; Disease Models, Animal; Femoral Vein; Hindlimb; Hypertension; Iliac Vein; Leukocyte Count; Ligation; Male; Peroxidase; Rats; Rats, Wistar; Vena Cava, Inferior; Venous Insufficiency; Venous Pressure

Eryngium foetidum L. (Apiaceae) is a Caribbean endemic plant, used in folk medicine for the treatment of several antiinflammatory disorders. A preliminary phytochemical study showed that the hexane extract is rich in terpenic compounds. Chromatographic fractionation of this extract yielded: alpha-cholesterol, brassicasterol, campesterol, stigmasterol (as the main component, 95%) clerosterol, beta-sitosterol, delta 5-avenasterol, delta (5)24-stigmastadienol and delta 7-avenasterol. The topical antiinflammatory activity of the hexane extract and of stigmasterol was evaluated by auricular oedema, induced by 12-0-tetradecanoylphorbol acetate (TPA), in the mouse, using single and multiple applications of the phlogistic agent. Both reduced the oedema in a similar proportion in the two model assays (acute and chronic). Meloperoxidase activity was strongly reduced by both the extract and the compound, in the acute but not the chronic model. These results indicate that the leaves of Eryngium foetidum L may be effective against topical inflammation processes. Stigmasterol also exerts a significant topical antiinflammatory activity although it cannot be considered to be a major antiinflammatory agent, therefore other bioactive components are probably involved in the activity of the hexane extract.

Topics: Acute Disease; Administration, Topical; Animals; Anti-Inflammatory Agents; Caribbean Region; Chronic Disease; Edema; Female; Inflammation; Mice; Peroxidase; Phytosterols; Plants, Medicinal; Tetradecanoylphorbol Acetate

The trefoil peptides are major secretory products of mucus cells of the gastrointestinal tract and show increased expression after inflammatory or ulcerative damage. Recombinant human TFF2 (spasmolytic polypeptide) has been shown to be cytoprotective, and enhances repair in models of gastric injury.. To test the healing effects of recombinant human (h)TFF2 in a rat model of chronic colitis.. Colitis was induced by intracolonic administration of dinitrobenzene sulphonic acid in ethanol. Mucosal repair was quantified macroscopically, microscopically by image analysis of tissue histology, and by measuring myeloperoxidase activity.. Initial validation studies showed that maximal injury and inflammation occurred at the end of the first week after colitis induction (active phase), and that spontaneous healing was complete by eight weeks. Once daily intrarectal application of hTFF2 (2.5 mg/kg; approximately 0.5 mg/rat) for five days after maximal damage had been sustained, reduced both microscopic and macroscopic injury by 80% and inflammatory index by 50% compared with vehicle controls. In addition, endogenous concentrations of rat TFF2 and TFF3 (intestinal trefoil factor) were increased in the active phase of colitis and were reduced to basal levels by hTFF2 treatment.. This study has shown that hTFF2 enhances the rate of colonic epithelial repair, and reduces local inflammation in a rat model of colitis, and suggests that luminal application of trefoil peptides may have therapeutic potential in the treatment of inflammatory bowel disease.

Topics: Administration, Rectal; Animals; Benzenesulfonates; Chronic Disease; Colitis; Disease Models, Animal; Ethanol; Growth Substances; Humans; Male; Mucins; Muscle Proteins; Neuropeptides; Peptides; Peroxidase; Rats; Rats, Wistar; Recombinant Proteins; Trefoil Factor-2; Trefoil Factor-3

Content of antibodies to neutrophil cytoplasma--myeloperoxidase (MPO)--and proteinase-3 (PR-3) was measured in the sera of 65 patients with SLE and 20 donors. Antibodies to MPO (a-MPO) and proteinase-3 (a-PR-3) significantly outnumbered those of the control. The number of a-MPO appeared elevated in 13, lowered in 7, moderate in 6 cases and directly correlated with anemia, pulmonary lesions, a-PR-3 level, inversely correlated with cerebrovasculitis and polyneuritis. The number of a-PR-3 was elevated in 14 cases (10 low titers and 4 moderate titers). High levels of both a-PR-3 and a-MPO were recorded in 8 sera. The content of a-PR-3 correlated directly with age of SLE onset but inversely with leukocyte count. Neither course of the disease nor inflammation activity were related to level of neutrophil antibodies. Factor analysis has identified groups of elements influencing the value of a-MPO and a-PR-3.

Topics: Acute Disease; Adult; Antibodies; Chronic Disease; Endopeptidases; Enzyme-Linked Immunosorbent Assay; Female; Humans; Lupus Erythematosus, Systemic; Male; Peroxidase

We present here a case of MPO-ANCA positive rapidly progressive glomerulonephritis (RPGN) after 34 months of D-penicillamine (D-PC) therapy for rheumatoid arthritis (RA). A 27-year-old Japanese woman was diagnosed as having RA in June 1994 at our out-patient clinic. Oral D-PC administration was initiated at a dose of 100 mg per day in January 1995. In August 1997, proteinuria, hematuria, renal insufficiency, and anemia developed. D-PC was withdrawn promptly, and prednisolone 5 mg per day was started. The patient was admitted to our hospital in September. On admission, anti-neutrophil cytoplasmic antibody against mycloperoxidase (MPO-ANCA) was strongly positive in the serum. Renal biopsy showed glomerulonephritis with cellular crescent formation in 60% of the glomeruli observed. Immunofluorescence examinations revealed deposits of granular IgG, IgA, C 1 q, and C 3 in the mesangium. The patient was treated with steroid pulse therapy along with administration of anti-coagulation and anti-platelet agents under the diagnosis of MPO-ANCA positive D-PC-induced RPGN. The renal function was gradually recovered and MPO-ANCA disappeared. Since RPGN is potentially a fatal disease, frequent monitoring of renal function and discontinuation of D-PC are required. In case MPO-ANCA becomes positive, prompt and correct diagnosis of the renal disorder could lead to a good prognosis as in this case. The present case may provide some important immunological insights into medical procedures to treat D-PC-induced RPGN and MPO-ANCA related glomerulonephritis.

Topics: Adult; Antibodies, Antineutrophil Cytoplasmic; Antirheumatic Agents; Arthritis, Rheumatoid; Chronic Disease; Female; Glomerulonephritis; Humans; Penicillamine; Peroxidase

We have produced a chloroform extract from Achillea which includes stigmasterol and sitosterol. By comparing it with the pure compounds an anti-inflammatory effect (with mouse ears) is assumed. The topical anti-inflammatory effect of the chloroform extract from Achillea ageratum (Asteraceae) and of stigmasterol and beta-sitosterol, isolated of this extract has been evaluated, against to 12-0-tetradecanoylphorbol acetate (TPA)-induced mouse ear edema, using simple (acute model) and multiple applications (chronic model) of the phlogistic agent. Myeloperoxydase activity also was studied in the inflamed ears. In the acute model the extract exerted a dose-dependent effect. All the doses assayed (1, 3 and 5 mg/ear) significantly reduced the edema (50%, 66% and 82%, respectively). The isolated sterols stigmasterol and beta-sitosterol (with doses of 0.5 mg/ear) had similar effect as the extract with doses of 1 and 3 mg (59% and 65% respectively). In the chronic model the anti-inflammatory effect generally was a more moderate one. The highest dose of the extract decreased the edema reduction to 26% with the highest dose of the extract applied. With the compounds the effect decreased to 36% with stigmasterol, and 40.6% with beta-sitosterol. Myeloperoxydase activity (MPO) was reduced by the extract and the compounds in the acute model, however, in the chronic edema, the enzyme inhibition was very weak with all treatments even with the standard substance. These results indicate that the chloroform extract of Achillea ageratum and some of the its components stigmasterol and beta-sitosterol are more effective as topical anti-inflammatory agents in acute than in the chronic process and their action is markedly influenced by the inhibition of neutrophil migration into inflamed tissue.

Topics: Acute Disease; Animals; Anti-Inflammatory Agents; Chloroform; Chronic Disease; Dexamethasone; Disease Models, Animal; Ear; Edema; Indomethacin; Mice; Peroxidase; Plant Extracts; Plants, Medicinal; Sitosterols; Stigmasterol; Tetradecanoylphorbol Acetate

We reported two cases of chronic bronchiectasis and rapidly progressive necrotizing glomerulonephritis/severe renal failure which were also positive for anti-myeloperoxidase antibody, and followed their treatment and outcome. Immunosuppressive therapy was complicated by superimposed chest infection in both cases. Nonetheless, cautious use of immunosuppressive and antibiotic therapy reversed dialysis-dependent renal failure in one of the two cases.

Topics: Antibodies, Antineutrophil Cytoplasmic; Bronchiectasis; Chronic Disease; Enzyme-Linked Immunosorbent Assay; Female; Glomerulonephritis; Humans; Immunosuppressive Agents; Male; Middle Aged; Peroxidase; Treatment Outcome

This study was performed to demonstrate the pathogenetic role of mucoid-alginate produced by Pseudomonas aeruginosa in relation to immuno-interaction in host cells. The obtained results are as follows. 1. Clinical Observation The concentration of MPO, TNF alpha, and IFN gamma in peripheral blood of 37 cases of chronic airway infection were observed. The cases were divided into the groups with mucoid strain positive (21 cases) and negative (16 cases), and each group was also divided into subgroups with active clinical symptom and without. High concentration of serum IFN gamma was shown in the group of mucoid strain positive cases (0.10 +/- 0.08 IU/ml in healthy volunteers group, 0.54 +/- 0.56 IU/ml in mucoid group with symptom: p < 0.01, 0.09 +/- 0.15 IU/ml in mucoid group without symptom, 0.13 +/- 0.13 IU/ml in non-mucoid group with symptom, 0.09 +/- 0.13 IU/ml in non-mucoid group without symptom). But plasma concentrations of MPO and serum concentrations of TNF alpha were not increased in all groups, except MPO in non-mucoid group with symptom. It indicates that IFN gamma has a characteristic role in chronic airway infection with mucoid Pseudomonas aeruginosa (P. aeruginosa). 2. Experimental Observation One hundred twenty-two of alginate-immunized mice were made by 5 times of intraabdominal injection with purified alginate extracted from mucoid P. aeruginosa PT-1252. 4 x 10(6) CFU/body of mucoid P. aeruginosa PT-1252 or 20 micrograms/body of purified alginate was intubated per trachea into the immunized mice, and changes in mean fluorescence intensity (MFI) of MPO and TNF alpha on neutrophils and IFN gamma on CD3 positive lymphocytes in BALF were observed. MFI of MPO (99.7 +/- 16.5-->177.0 +/- 23.1: p < 0.001) and TNF alpha (59.2 +/- 13.3-->197.0 +/- 62.0: p < 0.001) were increased on day 2 and they were kept up till on day 30 in P. aeruginosa group. But in alginate group they were temporally decreased on day 2, and they were gradually increased (MPO: 99.7 +/- 16.5-->212.6 +/- 12.1: p < 0.001, TNF alpha: 59.2 +/- 13.3-->162.4 +/- 30.9: p < 0.01). The temporally decrease of MPO and TNF alpha on day 2 in alginate group may suggest that a large amount of alginate inhibits neutrophils chemotaxis. MFI of IFN gamma in P. aeruginosa was also increased (110.0 +/- 32.9-->198.3 +/- 23.0: p < 0.01) on day 2 and it was gradually decreased on day 30 (156.0 +/- 13.8). In alginate group, MFI of IFN gamma in BALF was increased on day 5 (110.0 +/- 32.9-->201.0 +/- 49.3:

Topics: Alginates; Animals; Chronic Disease; Female; Glucuronic Acid; Hexuronic Acids; Humans; Interferon-gamma; Mice; Mice, Inbred ICR; Peroxidase; Pseudomonas Infections; Respiratory Tract Infections; Tumor Necrosis Factor-alpha

Earlier studies have shown the antiinflammatory effects of histamine and nitric oxide (NO) in a model of colitis induced by DSS. However, the defense system against free radicals in this model remained unclear. The aim of this study was to evaluate the effects of rebamipide, which inhibits the production of free radicals, in this model using male Sprague-Dawley rats. Colitis induced by 1% DSS is characterized by slow, weak inflammation and is regarded as a chronic inflammation model. In contrast, colitis induced by 4% DSS is characterized by fast, strong inflammation and is regarded as the acute inflammation model. Endoscopic examinations, peripheral white blood cell (WBC) counts, and assays of myeloperoxidase activity (MPO) in homogenates of colon mucosa were performed after one week (4% DSS model) and eight weeks (1% DSS model). Inflammation of colon mucosa was milder in the rats given rebamipide compared with controls in both the 4% and 1% DSS model. Furthermore, peripheral WBC counts correlated with colonic MPO activity. These findings indicate that rebamipide works as an antiinflammatory agent in both acute and chronic inflammation.

Topics: Acute Disease; Alanine; Animals; Anti-Inflammatory Agents; Anti-Ulcer Agents; Anticoagulants; Chronic Disease; Colitis; Colonoscopy; Dextran Sulfate; Drug Administration Schedule; Leukocyte Count; Male; Peroxidase; Quinolones; Rats; Rats, Sprague-Dawley

We have recently phenotyped inflammation in non-infectious allergic and non-allergic chronic maxillary sinusitis using sinus biopsies and lavage fluids. In this first paper, we have concentrated our work on the eosinophil, T cell, mast cell and macrophage infiltrates. However, many unresolved questions remain and particularly the role of neutrophils needed to be addressed. In the present study, we focused on the neutrophilic inflammation: myeloperoxidase (MPO) and interleukin-8 (IL-8) were measured by immunoassays and neutrophils were enumerated by conventional staining in the sinus lavage fluids of 16 patients with chronic sinusitis and six control subjects. Both MPO and IL-8 levels were significantly higher in patients than in controls (P < 0.01 and 0.005, respectively). There was a significant correlation between MPO levels and neutrophil numbers, and between MPO and IL-8 levels in the sinus lavage fluid (P < 0.0001, Spearman rank correlation). The presence of high levels of IL-8 in the lavage fluids of patients suffering from chronic sinusitis, levels which correlate with those of MPO, suggests that this cytokine may activate neutrophils in this chronic disease.

Topics: Adolescent; Adult; Aged; Chronic Disease; Female; Humans; Interleukin-8; Male; Middle Aged; Nasal Lavage Fluid; Peroxidase; Phenotype; Sinusitis

A 55-year-old man was admitted to our hospital with of hemoptysis, progression of anemia and renal failure in February, 1996. Idiopathic interstitial pneumonia had been diagnosed and he had been followed at a regional hospital since 1988. On the third day after admission, he suffered from sudden and massive hemoptysis. Goodpasture's syndrome was diagnosed because anti-GBM antibody was detected in serum. A high titer of MPO-ANCA was also recognized simultaneously. Steroid pulse therapy, immunosuppressive therapy, and plasmapheresis were begun, but he died on the 28th hospital day because of severe hypoxemia and multi-organ failure. Histological examination after autopsy revealed crescentic glomerulonephritis with linear deposition of IgG in the glomerular capillary wall, and interstitial pneumonia accompanied by massive alveolar hemorrhage. It was suggested that in this patient, not only anti-GBM antibody but also circulating MPO-ANCA might have participated in the progression of the crescentic glomerulonephritis and alveolar hemorrhage observed in Goodpasture's syndrome.

Topics: Anti-Glomerular Basement Membrane Disease; Antibodies; Antibodies, Antineutrophil Cytoplasmic; Antibody Specificity; Autoantibodies; Chronic Disease; Humans; Lung Diseases, Interstitial; Male; Middle Aged; Peroxidase

Allergy may play a role in the middle ear inflammation that leads to otitis media with effusion. The purpose of this study was to determine whether an elevated mediator correlated with the patient's disease and thus could be used to differentiate allergy vs. infection as the cause of the middle ear inflammation.. WE evaluated 57 individuals with otitis media with effusion, 32 with persistent effusion but no recent acute infection, 14 with recent infection and purulent otitis media with effusion, and II healthy subjects. The mediator activity of eosinophils and neutrophils in effusion was studied in patients characterized as having allergy by positive intradermal skin test results and positive radioallergosorbent test results. Eosinophils were characterized by measurement of eosinophil cationic protein in the effusion. Neutrophils were characterized by measurement of myeloperoxidase in the effusion. The levels of eosinophil cationic protein and myeloperoxidase in patients with and without allergy were correlated to patient history.. Significantly elevated levels of both eosinophil cationic protein and myeloperoxidase indicated that inflammation in the ear of patients with otitis media with effusion was characterized by a pronounced involvement of both eosinophils and neutrophils. Eighty-nine percent of all patients with disease had allergy. A higher ratio of myeloperoxidase to eosinophil cationic protein in patients with purulent otitis media with effusion indicated that in patients with a superimposed acute infection, neutrophil activity was increased even further. The level of eosinophil cationic protein was elevated only during the effusion of patients with allergies as compared with controls (p < 0.01). Among 29 cases of nonpurulent otitis media with effusion, 96.5% had allergic immune-mediated disease proved by skin testing, which was related clinically to their ear disease. Eighty-nine percent (89.6%) of these patients had eosinophil cationic protein levels greater than 10 microgram/L.. Middle ear eosinophil cationic protein may be used as a marker of related allergy.

Topics: Adolescent; Adult; Aged; Biomarkers; Blood Proteins; Child; Child, Preschool; Chronic Disease; Diagnosis, Differential; Eosinophil Granule Proteins; Eosinophils; Humans; Hypersensitivity, Immediate; Immunoglobulin E; Inflammation Mediators; Middle Aged; Neutrophils; Otitis Media; Otitis Media with Effusion; Otitis Media, Suppurative; Peroxidase; Radioallergosorbent Test; Ribonucleases; Sensitivity and Specificity; Skin Tests

Spontaneous bacterial infections and septicaemia result in morbidity and mortality in patients with portal hypertension and obstructive jaundice.. The aim of this study in rats was to investigate the incidence of bacterial translocation in portal hypertension and obstructive jaundice, and to evaluate the effects of allopurinol and glutamine.. Rats were subjected to sham laparotomy (SL), portal hypertension (PH) by calibrated stenosis of the portal vein, and common bile duct ligation (CBDL). Animals of each group were either treated with allopurinol (50 mg/kg twice a week), glutamine (1 g/kg/d), and allopurinol and glutamine.. After four weeks, significant bacterial translocation in the untreated PH and CBDL rats occurred. Intestinal mucosal malondialdehyde concentrations (MDA), as an indicator for lipid peroxidation, and myeloperoxidase activity (MPO) released from activated neutrophils were also significantly increased (p < 0.01). Allopurinol and glutamine in PH and CBDL rats improved bacterial translocation, and decreased MDA and MPO values (p < 0.01).. In PH and CBDL rats significant bacterial translocation, ileal mucosal lipid peroxidation, and neutrophil derived MPO activity occurred. Allopurinol and glutamine significantly reduced bacterial translocation, as well as ileal mucosal MDA and MPO activities.

Topics: Allopurinol; Analysis of Variance; Animals; Bacterial Translocation; Cholestasis, Extrahepatic; Chronic Disease; Common Bile Duct; Enzyme Inhibitors; Glutamine; Hypertension, Portal; Ileum; Laparotomy; Ligation; Male; Malondialdehyde; Peroxidase; Random Allocation; Rats; Rats, Sprague-Dawley

Thyroid dysfunction developed in 35 patients among a series of 300 (190 men and 110 women) treated with alpha-interferon (35/300 = 12%. No relationship was observed between the type of alpha-interferon, the dose, or hepatic response, but there were more women (24/35). Antithyroid antibody levels were frequently elevated before treatment (8/35, 23%). Hypothyroidism developed in 27 patients, 7 with clinical hypothyroidism, 10 with moderate hypothyroidism and 5 with elevated TSH only. Patients with severe symptoms and highly elevated thyroid antibodies were more prone to develop sustained or irreversible hypothyroidism (10 patients). Twelve patients recovered a normal thyroid function within a few months, but antibody levels fell more slowly. Primary hyperthyroidism of variable severity appeared in 13 patients. In 8 patients, normal thyroid function was recovered within a few weeks but thyroid antibodies remained high for at least one year. In 5 others spontaneous hypothyroidism occurred within a few weeks ("biphasic" hypothyroidism). Direct toxicity appears to be less probable than an autoimmune mechanism; elevated antithyroid antibodies were observed in only 20 patients (57%). In clinical practice, TSH levels should be regularly monitored during and after alpha-interferon therapy.

Topics: Adult; Aged; Antibodies; Antiviral Agents; Chronic Disease; Female; Hepatitis C; Humans; Hyperthyroidism; Hypothyroidism; Interferon Type I; Interferon-alpha; Male; Middle Aged; Peroxidase; Recombinant Proteins; Thyroglobulin

Autoimmune diseases, such as rheumatoid arthritis and inflammatory bowel disease are characterized by chronic inflammatory responses resulting in tissue damage. These diseases have a number of common denominators including: abnormal cytokine expression, aberrant antigen-antibody complexes, T cell anomalies, and increased numbers of neutrophils and macrophages. We propose that the interaction between neutrophils and macrophages induces a state of chronic inflammation which contributes to the disease state. One of the central players in this scenario is myeloperoxidase (MyPo). This enzyme functions in the 'cytotoxic triad' and is involved in cell killing. Studies done by the present investigators have known that MyPo, which is released from neutrophils, induces macrophages to secrete interleukin-1, interferon alpha beta and tumor necrosis factor alpha. Furthermore, our studies have suggested a major immunoregulatory role of this enzyme. We propose that the release of MyPo from neutrophils and subsequent binding to macrophages initiates a cascade of events which enhance the production of reactive oxygen intermediates and cytokine expression resulting in the chronic inflammatory state associated with autoimmune diseases.

Topics: Animals; Arthritis, Rheumatoid; Autoimmune Diseases; Chronic Disease; Cytokines; Humans; Inflammation; Inflammatory Bowel Diseases; Macrophages; Neutrophil Activation; Neutrophils; Peroxidase; Reactive Oxygen Species

Bronchial inflammation in chronic bronchitis has not been characterised as well as in asthma. The present study was undertaken to assess whether a characteristic pattern of bronchial inflammatory markers could be found in patients with chronic bronchitis.. Bronchoscopy with bronchial lavage was performed in 42 patients with chronic bronchitis and in 13 healthy controls. Twenty three of the patients had non-obstructive chronic bronchitis and 19 had chronic bronchitis and chronic obstructive pulmonary disease (COPD). Eighteen of the patients with bronchitis had recurrent infective exacerbations and 24 did not. Intrabronchial bacterial cultures were taken with a protected specimen brush.. Increased activity of neutrophils, fibroblasts, and eosinophils was found in the patients with chronic bronchitis as assessed by the levels of myeloperoxidase (MPO) and interleukin-8 (IL-8), hyaluronan, and eosinophil cationic protein (ECP), respectively. The levels of tryptase did not differ from the controls. High correlations were found between the levels of MPO and IL-8, as well as ECP and IL-8. No differences were found between the patients with COPD and those with non-obstructive chronic bronchitis.. Recruitment and activation of both neutrophils and eosinophils seem to be a characteristic of chronic bronchitis. This activation is associated with IL-8. The patients with intrabronchial cultures of Streptococcus pneumoniae had the highest individual levels of MPO, ECP, and IL-8 of all subjects in the study, indicating that colonisation with S pneumoniae could promote bronchial inflammation.

Topics: Adult; Aged; Biomarkers; Blood Proteins; Bronchitis; Bronchoalveolar Lavage Fluid; Chronic Disease; Eosinophil Granule Proteins; Eosinophils; Fibroblasts; Humans; Hyaluronic Acid; Interleukin-8; Lung Diseases, Obstructive; Middle Aged; Neutrophils; Peroxidase; Ribonucleases; Streptococcus pneumoniae

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Bromodeoxyuridine; Cell Division; Chronic Disease; Edema; Humans; Isoxazoles; Leflunomide; Leukotriene B4; Male; Mice; Mice, Inbred Strains; Neutral Red; Peroxidase; Phorbol Esters; Skin Diseases

The objective of this study was to assess the role that nitric oxide (NO) may play in mediating the colonic inflammation observed in a model of chronic granulomatous colitis using two pharmacologically different inhibitors of nitric oxide synthase (NOS). The NOS inhibitors NG-nitro-L-arginine methyl ester (L-NAME; 15 mumol/kg/day) and aminoguanidine (AG; 15 mumol/kg/day) were administered to rats in their drinking water, beginning 3 days before the induction of colitis and continuing for the entire 3-week period. We found that chronic NOS inhibition by L-NAME or AG significantly attenuated the peptidoglycan/polysacchride (PG/PS)-induced increases in macroscopic colonic inflammation scores and colonic MPO activity. Only AG, and not L-NAME, attenuated the PG/PS-induced increases in colon dry weight. Both L-NAME and AG significantly attenuated the PG/PS-induced increases in spleen inflammation, whereas neither drug significantly attenuated the PG/PS-induced liver inflammation. Although both L-NAME and AG inhibited NO production in vivo, as measured by decreases in plasma nitrite and nitrate levels, only AG was found to attenuate these values significantly (38 +/- 3 vs. 83 +/- 8 microM, respectively; P < .05). Finally, administration of L-NAME, but not of AG, significantly increased mean arterial pressure from 83 mm Hg in colitic animals to 105 mm Hg in the PG/PS+L-NAME-treated animals (P < .05). We conclude that NO may play an important role in mediating some of the pathophysiology associated with this model of chronic granulomatous colitis.

Topics: Amino Acid Oxidoreductases; Animals; Arginine; Blood Pressure; Chronic Disease; Crohn Disease; Female; Guanidines; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Synthase; Peroxidase; Rats; Rats, Inbred Lew

The proinflammatory cytokines tumor necrosis factor (TNF) and interleukin-1 (IL-1) are produced within the lung during sepsis, and may induce neutrophil sequestration resulting in neutrophil-mediated lung injury. We hypothesized that, if there is a cause and effect between TNF alpha or IL-1 production and lung neutrophil sequestration during chronic sepsis, TNF alpha mRNA and IL-1 mRNA levels in the lung after cecal ligation and puncture should correlate with the number of sequestered neutrophils as measured by the myeloperoxidase (MPO) content of the lung. To test this hypothesis, Swiss Webster mice were subjected to varying degrees of infectious challenge by single and double-puncture cecal ligation and puncture, or simultaneous antibiotic treatment, and their lungs and blood were harvested at 24 h. Lung TNF alpha and IL-1 beta mRNAs were measured by the reverse-transcription differential polymerase chain reaction, and MPO was measured by colorimetric assay. TNF alpha serum levels showed no correlation with the MPO content of the lung, whereas IL-1 levels were undetectable. Lung TNF alpha mRNA correlated weakly, and IL-1 beta mRNA exhibited a strong correlation with lung MPO (r = .9, p < .01), but administration of anti-TNF alpha- or anti-IL-1-neutralizing antibodies did not prevent a rise in lung MPO. IL-1 beta mRNA in bronchoalveolar macrophages correlated well with whole lung tissue IL-1 beta mRNA levels (r = .91, p < .01).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Antibodies, Monoclonal; Bronchoalveolar Lavage Fluid; Cecum; Chronic Disease; Endotoxins; Gene Expression; Immunization, Passive; Interleukin-1; Lung; Male; Mice; Neutrophils; Peroxidase; Polymerase Chain Reaction; RNA, Messenger; Sepsis; Tumor Necrosis Factor-alpha

Nitric oxide synthesis appears to be elevated in inflammatory bowel disease, but little is known about the contribution of nitric oxide to the pathophysiological process. To address this issue, we included the nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME) in the drinking water (10 or 100 micrograms/ml) of guinea pigs immediately after induction of ileitis by intraluminal trinitrobenzenesulfonic acid (TNBS 30 mg/kg in 50% ethanol). Guinea pigs were sacrificed after 7 days of this ad libitum treatment. Control groups received either intraluminal TNBS, saline or ethanol (TNBS vehicle) without L-NAME or TNBS + D-NAME (100 micrograms/ml), the inactive enantiomer. Immediately before sacrifice, guinea pigs were anesthetized and saline was administered intraluminally at the site of TNBS or saline administration and then withdrawn after 30 min. Change in lavage volume and lavage protein and nitrite levels were measured, as well as tissue myeloperoxidase and bowel wall thickness (weight/length). TNBS administration resulted in an increase in tissue thickness, myeloperoxidase and lavage protein and nitrite levels over sham controls. Oral L-NAME prevented these responses. D-NAME was ineffective with the exception of tissue thickness. The change in intestinal lavage fluid volume indicated that reabsorptive processes dominated in the sham and TNBS + L-NAME groups, and secretory responses predominated in TNBS and TNBS + D-NAME animals. In contrast to TNBS-induced ileitis, L-NAME (100 micrograms/ml, p.o., 7 days) administration to intact animals resulted in a local inflammatory response (i.e., increased myeloperoxidase activity and a fluid secretory response).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Amino Acid Oxidoreductases; Animals; Arginine; Chronic Disease; Disease Models, Animal; Guinea Pigs; Ileitis; Ileum; Intestinal Mucosa; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Synthase; Organ Size; Peroxidase; Therapeutic Irrigation; Trinitrobenzenesulfonic Acid

The objective of this study was to characterize the acute and chronic inflammation induced by the intramural injection of peptidoglycan-polysaccharide (PG-PS) into the distal colon of genetically susceptible rats.. Blood-to-lumen clearance of 51Cr-ethylenediaminetetraacetic acid, colonic myeloperoxidase activity, colon weight, and plasma nitrite and nitrate levels were determined to quantitate colonic mucosal injury, inflammation, and nitric oxide (NO) production, respectively.. Intramural injection of PG-PS into the distal colon produced a local biphasic inflammatory response composed of an acute episode 3 days after injection; this was followed by a spontaneous reactivation of chronic granulomatous colitis manifested by colonic thickening, adhesions, and infiltration of the submucosa and muscularis propria with macrophages, neutrophils, and lymphocytes at 3-4 weeks. Mucosal ulcers were evident only at 3 weeks, but hepatic nodules, splenic necrosis, and arthritis were evident at both 3 and 4 weeks after PG-PS injection. PG-PS produced significant increases in colonic mucosal permeability, myeloperoxidase activity, and plasma nitrite and nitrate levels at 3 weeks postinjection compared with controls. PG-PS stimulated the production of nitrite by elicited peritoneal macrophages and neutrophils in vitro.. PG-PS produces a chronic granulomatous colitis in rats; this colitis is characterized by enhanced NO production.

Topics: Amino Acid Oxidoreductases; Animals; Chronic Disease; Colitis; Crohn Disease; Disease Models, Animal; Enzyme Induction; Female; Granuloma; Intestinal Mucosa; Nitric Oxide Synthase; Peptidoglycan; Peroxidase; Rats; Rats, Inbred Lew; Streptococcus pyogenes

The objective of this study was to characterize the mechanisms of acute and chronic intestinal mucosal injury and inflammation induced by subcutaneously injected indomethacin (Indo). One injection of Indo (7.5 mg/kg) produced acute injury and inflammation in the distal jejunum and proximal ileum that were maximal at three days and completely resolved within one week. Two daily subcutaneous injections of Indo produced a more extensive and chronic inflammation that lasted in an active form in more than 75% of the rats for at least two weeks. Epithelial injury, as measured by enhanced mucosal permeability, was significantly elevated only at one day in the acute model (one injection) but was persistently elevated in the chronic model (two injections). Bile duct ligation completely attenuated increased mucosal permeability in the acute model, however, depletion of circulating neutrophils had no effect. Neither Indo (0-0.1 mg/ml) nor normal bile was cytotoxic to cultured rat intestinal epithelial cells; however, they synergistically promoted significant cytotoxicity. Bile collected from rats treated with Indo was cytotoxic towards the epithelial cells in a dose-dependent manner. Sulfasalazine and metronidazole (100 mg/kg/day, both) attenuated enhanced mucosal permeability in the chronic model. Massive bacterial translocation into the mesenteric lymph nodes, liver, and spleen following two injections of Indo was significantly attenuated by metronidazole. We conclude that: (1) a single injection of Indo produces acute intestinal mucosal injury and inflammation that resolve completely within three to seven days, whereas two daily injections of Indo produce both acute and chronic injury and inflammation, (2) enterohepatic circulation of Indo is important in promoting the acute phases of injury and inflammation, (3) circulating neutrophils do not play a role in the pathogenesis of this model, and (4) endogenous bacteria play an important role in exacerbating and/or perpetuating the chronic phases of injury and inflammation.

Topics: Acute Disease; Animals; Bacteria; Bile; Chronic Disease; Disease Models, Animal; Enteritis; Indomethacin; Injections, Subcutaneous; Intestinal Mucosa; Intestines; Male; Metronidazole; Neutrophils; Permeability; Peroxidase; Rats; Rats, Sprague-Dawley; Sulfasalazine

To assess the manifestation and location of airway inflammation in smokers with chronic bronchitis (CB) or chronic obstructive pulmonary disease (COPD), we lavaged the airways of 12 smokers with CB and 11 smokers with COPD and coexisting CB (OCB). For comparison, the airways of 5 asymptomatic smokers (AS) and 10 healthy nonsmokers (HNS) were lavaged. In all cases, the first lavage aliquot, labeled "bronchial lavage" (BL), was processed separately from the four subsequent aliquots, which were combined and labeled "bronchoalveolar lavage" (BAL). The composition of BL and BAL fluids indicate an ongoing inflammatory process in the airways of all three groups of smokers. CB patients with obstruction had significantly lower concentrations of inflammatory cells in the BL and BAL fluids compared with subjects with nonobstructed CB. Furthermore, airway obstruction, indicated by a reduced FEV1, was significantly correlated with the concentrations of glutathione (p < 0.001), myeloperoxidase (MPO; p < 0.01), and eosinophil cationic protein (ECP; p < 0.01) in BAL fluids. Taken together, these findings suggest that the manifestations of inflammation present in the airways of smokers with CB are different in those who have developed obstruction compared with those who have not.

Topics: Adult; Albumins; Blood Proteins; Bronchi; Bronchitis; Bronchoalveolar Lavage Fluid; Cell Count; Chronic Disease; Eosinophil Granule Proteins; Female; Forced Expiratory Volume; Glutathione; Humans; Inflammation; Lung Diseases, Obstructive; Male; Middle Aged; Peroxidase; Ribonucleases; Smoking

Plasma myeloperoxidase levels in patients with cirrhosis were compared with those in patients with chronic hepatitis and healthy controls by means of a specific radioimmunoassay for myeloperoxidase. The mean concentration of plasma myeloperoxidase in cirrhotic patients (309.1 +/- 17.2 ng/ml, n = 41) was markedly higher than that in chronic hepatitis patients (222.6 +/- 17.2 ng/ml, n = 21) (p < 0.01) and normal controls (219.5 +/- 5.7 ng/ml, n = 50) (p < 0.01). Plasma myeloperoxidase showed good negative correlations with neutrocyte count (r = -0.32, p < 0.01), thrombocyte count (r = -0.40, p < 0.01), red blood cell count (r = -0.32, p < 0.01), serum albumin (r = -0.35, p < 0.01), and cholinesterase (r = -0.32, p < 0.02) and positive correlations with serum alkaline phosphatase (r = 0.49; p < 0.01) and lactate dehydrogenase (r = 0.31, p < 0.01) in patients with cirrhosis or chronic hepatitis. Among lactate dehydrogenase isozymes, a good positive correlation was seen between plasma myeloperoxidase and lactate dehydrogenase-2 (r = 0.40, p < 0.01) and lactate dehydrogenase-1 (r = 0.03, p < 0.02). Plasma myeloperoxidase was significantly higher in the cirrhotic and chronic hepatitis patients with splenomegaly (341.1 +/- 19.4 ng/ml, n = 31) than in those without splenomegaly (217.4 +/- 12.2 ng/ml, n = 29) (p < 0.01). We also examined the difference between plasma levels of myeloperoxidase in the portal and peripheral blood.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Biomarkers; Chronic Disease; Clinical Enzyme Tests; Hepatitis; Humans; Hypersplenism; Liver; Liver Cirrhosis; Middle Aged; Pancytopenia; Peroxidase; Portal Vein; Radioimmunoassay; Splenomegaly

Eosinophils but not neutrophils may play a role in the airway inflammation of asthma. In chronic bronchitis (CB) and chronic obstructive pulmonary disease (COPD), neutrophils are present in the airways. To differentiate among the pathology of asthma, CB, and COPD eosinophils and neutrophils were studied in peripheral blood, bronchial biopsy specimens, and bronchoalveolar lavage fluid (BALF).. We studied nine nonsmoking healthy subjects, 20 nonsmoking patients with asthma, 10 nonatopic smoking patients with CB (forced expiratory volume in 1 second: 98.4% +/- 11.3%) and 17 patients with COPD (forced expiratory volume in 1 second: 51.2% +/- 14.3%). Eosinophils were characterized by their enumeration in biopsy specimens (EG2 monoclonal antibody), peripheral blood, and BALF and by measurement of eosinophil cationic protein in BALF. Neutrophils were characterized by their enumeration in biopsy specimens (anti-elastase monoclonal antibody) and BALF and by measurement of neutrophil-specific myeloperoxidase in BALF.. In patients with asthma we found degranulated eosinophils in biopsy specimens and significantly increased eosinophil cationic protein levels in BALF. In patients with CB or COPD, eosinophil numbers in biopsy specimens were not significantly different from those of patients with asthma, but cells were not degranulated and eosinophil cationic protein levels in BALF were similar to those of normal subjects. In patients with CB or COPD neutrophils were not increased in the mucosa, but neutrophil numbers and myeloperoxidase levels in BALF were significantly increased.. The percentages of neutrophils in BALF were greater in patients with COPD than in those with CB, suggesting a role in the chronic airflow limitation.

Topics: Adult; Aged; Asthma; Blood Proteins; Bronchitis; Bronchoalveolar Lavage Fluid; Chronic Disease; Eosinophil Granule Proteins; Eosinophils; Humans; Leukocyte Count; Lung Diseases, Obstructive; Middle Aged; Neutrophils; Peroxidase; Respiratory Function Tests; Ribonucleases

Topics: Acute Disease; Antigens, CD; Bone Marrow Examination; Chronic Disease; Gene Rearrangement; Hematologic Tests; Humans; Immunoglobulin Heavy Chains; Karyotyping; Leukemia; Peroxidase; Receptors, Antigen, T-Cell

Acute and chronic sialoadenitis were induced in ovalbumin-immunized guinea pigs by a single or repeated (once a day for 5 days) instillation of antigen into the parotid gland via the parotid duct. The acute sialoadenitis was characterized by infiltration of inflammatory polymorphonuclear leukocytes and the chronic one, by extensive tissue destruction together with infiltration of mononuclear leukocytes. In acute sialoadenitis, myeloperoxidase activity in the parotid gland, which was a marker of accumulation of neutrophils, was elevated, but in the chronic stage, it returned nearly to the control level. This observation is in accord with the histological findings that infiltrating cells in acute and chronic sialoadenitis were mainly polymorphonuclear and mononuclear leukocytes, respectively. Although cyclophosphamide suppressed the inflammation, both in acute and chronic sialoadenitis, indomethacin exerted its anti-inflammatory effect only in the acute stage. Our experimental models of acute and chronic sialoadenitis were easy to prepare, and had a high incidence. As the typical features of inflammatory development from acute to chronic phases were observed in these models, these models may be useful for studying the mechanism of the chronic course in immunologically induced inflammation and the effects of drugs on each phase and the chronic course of inflammation.

Topics: Acute Disease; Animals; Chronic Disease; Cyclophosphamide; Disease Models, Animal; Guinea Pigs; Hypersensitivity; Indomethacin; Male; Parotid Gland; Peroxidase; Sialadenitis

Spontaneous colitis in CTT's presents cytological characteristics similar to chronic ulcerative colitis in humans, e.g. inflammatory cell infiltrate and crypt abscesses. To better characterize CTT colitis as a potential model for human inflammatory bowel disease (IBD), inflammatory mediators identified in colonic tissue of human IBD patients and/or experimental colitis models were assayed. Inflammatory mediator changes in plasma and colon from tamarins with acute (n = 10) and chronic (n = 10) colitis (by mucosal biopsy) were assayed by RIAs. Similar inflammatory mediators were found in the CTT's with acute colitis. In the plasma, PAF and PGE2 levels were lower in acute colitis CTT's, no LTB4 was detected, and histamine levels were not different from chronic colitic animals. In the colon, myeloperoxidase and interleukin-1 beta were significantly higher in acute colitis, PGE2 and LTB4 were higher but not significantly, and PAF was not different from chronic CTT's. These data suggest that a combination of events are occurring in the pathogenesis of tamarin colitis that involves some of the same mediators that are found in the human disease and in other experimental models. The importance of these findings to human IBD remains for further investigation; however, the spontaneous primate model offers an exciting approximation of the disease development and merits further investigation for understanding the pathogenesis of human IBD as well as to aid in development of targeted therapeutics.

Topics: Acute Disease; Animals; Chronic Disease; Colitis; Dinoprostone; Disease Models, Animal; Histamine; Interleukin-1; Leukotriene B4; Peroxidase; Platelet Activating Factor; Saguinus

The assessment of lymphocytic functional activity and immunological reactivity in 114 cases of acute pneumonia provided additional information on the disease severity, potential complications, effectiveness of the treatment conducted, completeness of recovery. The study of immunological reactivity in acute pneumonia is beneficial in poor clinico-roentgenological manifestations. Combined treatment with levamisole promoted improvement of immunological reactivity and reduced the duration of disability.

Topics: Acute Disease; Adolescent; Adult; Alkaline Phosphatase; Bronchitis; Chronic Disease; Clinical Enzyme Tests; Female; Glycogen; Humans; Lymphocyte Activation; Male; Middle Aged; Peroxidase; Phytohemagglutinins; Pneumonia

The role of leukotrienes in the pathogenesis of chronic colitis was investigated using a rat model. Ulceration and inflammation of the distal colon was initiated by the intracolonic administration of the hapten trinitrobenzene sulfonic acid in 50% ethanol. Leukotriene B4 synthesis increased significantly within 4 h after induction of damage, with the greatest increase observed 24-72 h after administration of the hapten. The increase in leukotriene B4 synthesis correlated well (r = 0.88) with an increase in colonic myeloperoxidase activity, a biochemical marker of neutrophil infiltration. Daily intracolonic treatment with a specific 5-lipoxygenase inhibitor, L651,392, during the first 4 days after initiation of colitis, resulted in significant reductions of colonic leukotriene B4 synthesis, colonic damage score, and colon wet weight. When examined 2 wk after initiation of colitis, the group treated with L651,392 (for the first 4 days) showed significantly less colonic damage (assessed macroscopically and histologically) and colonic inflammation (assessed histologically and by measurement of myeloperoxidase activity). The healing produced by treatment with L651,392 was comparable to that observed after treatment with 5-aminosalicylic acid in a similar manner. Although a reduction of colonic damage could be produced in this model by intracolonic pretreatment with a prostaglandin E1 analogue (rioprostil), the mechanism of action of L651,392 did not appear to be through prevention of the initial injury induced by the hapten and ethanol solution. These results demonstrate that inhibition of leukotriene synthesis results in a marked acceleration of the healing of colonic ulcers and resolution of colonic inflammation in this animal model of chronic colitis. The results are therefore consistent with the hypothesis that leukotrienes play an important role in the pathogenesis of intestinal inflammation.

Topics: 6-Ketoprostaglandin F1 alpha; Aminosalicylic Acids; Animals; Chronic Disease; Colitis; Colon; Leukotriene B4; Lipoxygenase Inhibitors; Male; Mesalamine; Peroxidase; Phenothiazines; Prostaglandins E; Rats; Rats, Inbred Strains; Rioprostil

Previous experiments with rats have suggested that pyelonephritic scarring after acute ascending Escherichia coli pyelonephritis partly results from excessive polymorphonuclear leukocyte (PMN) infiltration and activation in the kidney parenchyma. We have studied the role of PMN oxidative metabolism in generating tissue injury during acute pyelonephritis. Rats with acute pyelonephritis were treated with dapsone (25 mg/kg twice daily for 3 days), a compound known to prevent PMN oxidant damage. In vitro, levels of dapsone easily achieved in vivo inhibited myeloperoxidase (MPO)-mediated reactions involving the oxidation of halides to reactive cytotoxic hypohalites (such as MPO-mediated iodination and luminol-enhanced chemiluminescence). In contrast, dapsone had no effect on superoxide production, lysosomal enzyme release, or bacterial killing by activated PMN. In vivo, dapsone treatment had no significant effect on acute pyelonephritis with respect to (i) bacterial counts, (ii) inflammatory swelling, and (iii) PMN infiltration. However, dapsone-treated animals sacrificed 2 months after acute pyelonephritis had a 65% reduction of renal scars when compared with controls. Since dapsone had no antibacterial effect, this protection is compatible with the hypothesis that dapsone prevented oxidant-generated tissue injury due to the extracellular release of the MPO system by activated PMN during acute suppurative pyelonephritis.

Topics: Acute Disease; Animals; Chronic Disease; Cicatrix; Cytoplasmic Granules; Dapsone; Escherichia coli; Free Radicals; Growth Inhibitors; Male; Neutrophils; Oxygen; Peroxidase; Pyelonephritis; Rats; Rats, Inbred Strains; Superoxides

Alkaline phosphatase and myeloperoxidase was examined in patients with chronic ischemic heart disease and myocardial infarction. It was established that patients with myocardial infarction showed high values of alkaline phosphatase while the values of myeloperoxidase were low. Dynamic evaluation of alkaline phosphatase and myeloperoxidase of leucocytes allows to assess the course of myocardial infarction and efficacy of its treatment.

Topics: Aged; Alkaline Phosphatase; Chronic Disease; Clinical Enzyme Tests; Coronary Disease; Female; Granulocytes; Humans; Male; Middle Aged; Myocardial Infarction; Peroxidase; Prognosis; Recurrence; Time Factors

The mass fraction of certain elements was measured in isolated granulocytes and isolated granulocyte granule fractions from patients with active inflammatory arthritides (N = 6) and healthy controls (N = 6). The patients had significantly increased amounts of Ca in the granulocytes, in the specific and light azurophil granules, but normal Ca amounts in the dense azurophil granules. Sr was below the detection limit in the granulocytes and granule fraction from controls, but it appeared in high concentrations in the granulocytes and all granule fractions from the patients. The patients had considerably increased granulocyte amounts of Mn but only slightly increased Mn concentrations in the specific granules. Mn was not detectable in azurophil granules from patients and controls. A prominent accumulation of Fe was seen in the granulocytes from the patients, together with an Fe accumulation in the specific granules. Fe was below the detection limit in azurophil granules from patients and controls. The patients had reduced granulocyte Zn and reduced amounts of Zn in the dense and light azurophil granules but normal Zn amounts in the specific granules. The results obtained indicate that the granulocyte accumulation of Ca, Sr, and Fe observed during chronic inflammation is associated with corresponding granule accumulation of these metals; the considerable Mn accumulation in granulocytes during inflammation is not localized in their granules; and the granule subpopulations differ in their capacity to store certain metals.

Topics: Arthritis; Chronic Disease; Cytoplasmic Granules; Humans; Lactoferrin; Metals; Neutrophils; Peroxidase; Spectrometry, X-Ray Emission

Although the etiology of rheumatoid interstitial lung disease (RILD) remains unknown, bronchoalveolar lavage (BAL) has been useful in studying potentially pathogenic mechanisms in this disorder. Previous investigations in patients with rheumatoid arthritis (RA) and RILD revealed abnormal BAL T-lymphocyte subpopulations and a significant elevation in BAL neutrophils. Because neutrophils have been implicated as important effector cells in inflammatory disorders such as ARDS and idiopathic pulmonary fibrosis, we evaluated BAL fluid in patients with RA for neutrophil chemotactic and activating properties and for evidence of neutrophil activation. The BAL fluid from patients with RILD contained significant neutrophil chemotactic activity derived from both lipid and nonlipid components. Evidence for neutrophil stimulation in the lower respiratory tract of patients with RILD was suggested by elevations in both myeloperoxidase activity and immunologically determined levels of human neutrophil elastase in BAL fluid. Free uninhibited elastolytic activity, however, was not demonstrated, suggesting that adequate protease inhibitor levels were present to inhibit active elastase activity. In addition to elevated myeloperoxidase activity, a potential role for neutrophil-derived oxidant injury was indirectly suggested by the enhanced release of superoxide anion (O2-) from resting normal human blood neutrophils challenged with concentrated BAL fluid from patients with RA and interstitial lung disease. Significant correlations were found between physiologic parameters and the percentage of BAL neutrophils, as well as levels of neutrophil-derived mediators. For example, levels of human neutrophil elastase were strongly correlated with diminished diffusion capacity (r = -0.73, p less than 0.001) and reduced forced vital capacity (r = -0.63, p less than 0.006).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Arthritis, Rheumatoid; Bronchoalveolar Lavage Fluid; Chemotaxis, Leukocyte; Chronic Disease; Humans; Leukocyte Count; Neutrophils; Pancreatic Elastase; Peroxidase; Prospective Studies; Pulmonary Fibrosis; Respiratory System; Superoxides

Topics: Acid Phosphatase; Alkaline Phosphatase; Chronic Disease; Glycogen; Humans; Neutrophils; Pancreatitis; Peroxidase; Phagocytosis

Candidal peritonitis is a tenacious infection in patients undergoing chronic peritoneal dialysis. Since little is known about host defenses of the human peritoneal cavity against fungi, we investigated the interaction of peritoneal macrophages (PM phi) from uninfected dialysis patients with Candida albicans blastospores. Chemiluminescence (CL) techniques were used to assess the respiratory burst activity of these cells, and candidacidal activity was evaluated with a fluorochrome microassay. In sharp contrast to peripheral blood polymorphonuclear leukocytes (PMNs) from healthy donors, which gave a brisk luminol-enhanced CL response to opsonized blastospores and killed 35% of cell-associated organisms, PM phi produced barely detectable luminol-enhanced CL and killed only 13% of intracellular Candida. These findings appeared to be associated with a decreased level of myeloperoxidase in PM phi. The mechanism of intracellular survival of C albicans also appeared to be related to relatively poor triggering of superoxide production during phagocytosis of viable blastospores. The CL response of PMNs to C albicans was opsonin-dependent, and peritoneal dialysis effluent was devoid of opsonic activity. These studies suggest that local cellular and humoral mechanisms of defense are inadequate for protection of peritoneal dialysis patients against candidal peritonitis.

Topics: Acridine Orange; Candida albicans; Candidiasis; Chronic Disease; Gastrula; Humans; In Vitro Techniques; Intracellular Fluid; Leukocytes; Luminescent Measurements; Luminol; Macrophages; Opsonin Proteins; Peritoneal Cavity; Peritoneal Dialysis; Peroxidase; Time Factors

In 20 patients with chronic neutropenia, serum lactoferrin (S-LF) and serum myeloperoxidase (S-MPO) levels were assessed. By immunofluorescence, granulocyte-bound immunoglobulins were detected in 12 patients, whereas circulating immune complexes were found in the blood of 8 patients by the 125-I-C1q-binding test (C1q-BT). In both groups of patients, there was a relative increase of S-LF and a relative or sometimes absolute increase of S-MPO. In the latter group, results of the C1q-BT correlated positively with S-MPO but negatively with neutrophil counts. No correlations between S-LF or S-MPO and the results of the granulocyte immunofluorescence test were found. Our results suggest that S-LF and S-MPO levels may be helpful in the further study of patients with chronic neutropenia, to gain more insight into the pathogenetic mechanisms operative in this disease.

Topics: Agranulocytosis; Chronic Disease; Complement Activating Enzymes; Complement C1q; Fluorescent Antibody Technique; Granulocytes; Humans; Lactoferrin; Lactoglobulins; Leukocyte Count; Neutropenia; Peroxidase

Topics: Adult; Chronic Disease; Female; Foot Dermatoses; Humans; Male; Middle Aged; Neutrophils; Onychomycosis; Peroxidase; Tinea Pedis

Topics: Adolescent; Child; Chronic Disease; Health Resorts; Histocytochemistry; Humans; Mitochondria; Multienzyme Complexes; NADH, NADPH Oxidoreductases; Neurodermatitis; Neutrophils; Peroxidase; Russia

Topics: Acid Phosphatase; Adult; Anemia, Hypochromic; Catalase; Chronic Disease; Female; Glucuronidase; Histocytochemistry; Humans; Neutrophils; Peroxidase

Polymorphonuclear leukocyte function: chemotaxis, NBT and myeloperoxidases activity, was investigated in a group of asthmatic pediatric patients, 26 with intrinsic and 27 with extrinsic asthma, during intercrisis. There was no difference between the extrinsic asthma group and the control one while the group with intrinsic asthma showed an increase of chemotaxis activity (p less than 0.001) and NBT reduction (p less than 0.01); myeloperoxidases activity was similar to the control group. The comparative study of the two types of asthma shows a significant increase of NBT reduction (p less than 0.02) and chemotaxis activity (p less than 0.001) in the intrinsic group. These findings demonstrate that polymorphonuclear function is different in the two main types of asthma during the asymptomatic period.

Topics: Asthma; Caseins; Chemotactic Factors; Chemotaxis, Leukocyte; Child; Child, Preschool; Chronic Disease; Diagnosis, Differential; Humans; Neutrophils; Nitroblue Tetrazolium; Nucleotides, Cyclic; Peroxidase

Topics: Aged; Blood Proteins; Chemotaxis, Leukocyte; Chromatography, Gel; Chronic Disease; Cytoplasmic Granules; Eosinophil Granule Proteins; Female; Granulocytes; Humans; Lactoferrin; Leukocyte Count; Muramidase; Neutrophils; Peroxidase; Pruritus; Ribonucleases

Tissue proteolytic enzymes are currently believed to be critical to the pathogenesis of panacinar emphysema. Polymorphonuclear leukocytes (Polys) have several enzymes including elastase and cathepsin G in their azurophil granules. They have collagenase in their specific granules. We have found that this collagenase is doubly latent. It has the lysosomal type of latency that depends on the impermeability of the unit membrane that surrounds each specific granule. In addition it has a latency that is converted to activity by proteolytic enzymes. The cathepsin G of the azurophil granule is a potent activator of this latent collagenase once the collagenase is released from its membrane dependent latency. Thus latency of enzymes, the nature of the latency and accessibility of the latent enzymes to activating mechanisms must all be taken into account in any analysis of their contribution to pathogenesis of local lung disease. Equally important is that fact that polys are not a prominent cellular component of normal lung. Polys must be attracted to the lung by chemotactic peptides. These peptides must be released by the interaction of inflammatory stimuli, such as smoke particles, with complement components or they must be provided by other sources. The hypothesis that lung damage in panacinar emphysema is mediated by polys and their proteases is attractive and suggestive evidence supporting this is available. However, more evidence that takes into full account the cell biology of the proteases any poly turnover in the lung are needed to extend the hypothesis and to form a rational basis for therapeutic and prophylactic measures.

Topics: Cathepsin G; Cathepsins; Chemotaxis, Leukocyte; Chronic Disease; Connective Tissue; Cytoplasmic Granules; Enzyme Activation; Exocytosis; Humans; Microbial Collagenase; Neutrophils; Pancreatic Elastase; Peptide Hydrolases; Peroxidase; Phagocytosis; Pulmonary Emphysema; Serine Endopeptidases

Reported here is a case of hereditary myeloperoxidase deficinecy in a diabetic patient suffering from a Candida albicans liver abscess. Peroxidase activity is completely absent from the neutrophils and monocytes although it is present in the eosinophils. The different forms of myeloperoxidase deficiency are discussed.

Topics: Adult; Candidiasis; Chronic Disease; Diabetes Complications; Female; Histocytochemistry; Humans; Leukocytes; Liver Abscess; Peroxidase; Peroxidases

Topics: Acid Phosphatase; Adult; Aged; Alkaline Phosphatase; Carrier State; Chronic Disease; Enzyme Activation; Female; Humans; Male; Middle Aged; Neutrophils; Peroxidase; Typhoid Fever

Topics: Adult; Amylases; Chronic Disease; Electrophoresis; Female; Humans; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Lactoferrin; Lactoglobulins; Muramidase; Parotitis; Peroxidase; Recurrence; Saliva; Transferrin