mocetinostat and Diabetes-Mellitus

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) affects small blood vessels and causes severe systemic organ injury commonly affecting the lungs and kidney. However, gastrointestinal, especially pancreatic, lesions are rare. We report the case of a 67-year-old Japanese man diagnosed with myeloperoxidase (MPO) AAV who developed pancreatic lesions and diabetes mellitus. The patient was admitted to our hospital due to fever, cough, and weight loss. He developed progressive glomerulonephritis, lung nodules, and pancreatic swelling and mass. Additionally, laboratory examination revealed positive MPO-ANCA and elevated glycated hemoglobin A1c, which were suggestive of diabetes mellitus. Renal biopsy revealed necrotizing crescentic glomerulonephritis and vasculitis in the small arteries. Endoscopic ultrasound-guided fine needle aspiration of the pancreas was performed, and histological findings suggested the possibility of pancreatic vasculitis and parenchymal injury. The patient was diagnosed with AAV, which was managed with glucocorticoids. This improved the renal function and pancreatic lesions. Furthermore, blood glucose levels improved despite treatment with glucocorticoids. These findings suggest that AAV-related pancreatic lesions worsened glycemic control. However, glucocorticoid therapy improved vasculitis and pancreatic lesions, which resulted in improved glycemic control.

Topics: Aged; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Antineutrophil Cytoplasmic; Diabetes Mellitus; Glomerulonephritis; Humans; Male; Pancreas; Pancreatic Neoplasms; Peroxidase

Protein folding is a natural phenomenon through which a linear polypeptide possessing necessary information attains three-dimension functionally active conformation. This is a complex and multistep process and therefore, the presence of several intermediary structures could be speculated as a result of protein folding. In in vivo, this folding process is governed by the assistance of other proteins called molecular chaperones and heat shock proteins. Due to the mechanism of protein folding, these intermediary structures remain major challenge for modern biology. Mutation in gene encoding amino acid can cause adverse environmental conditions which may result in misfolding of the linear polypeptide followed by the formation of aggregates and amyloidosis. Aggregation contributes to the pathophysiology of several maladies including diabetes mellitus, Huntington's and Alzheimer's disease. The propensity of native structure to form aggregated and fibrillar assemblies is a hallmark of amyloidosis. During aggregation of a protein, transition from α helix to β sheet is observed, and mainly β sheeted structure is visualised in a mature fibril. Heme proteins are very crucial for major life activities like transport of oxygen and carbon dioxide, synthesis of ATP, role in electron transport chain, and detoxification of free radicals formed during biochemical reactions. Any structural variation in the heme proteins may lead to a fatal response. Hence characterization of the folding intermediates becomes crucial. The characterization has been deciphered with the help of strong denaturants like acetonitrile and TFE. Moreover, possible role of elimination of these aggregates and prevention of protein denaturation is also discussed. Current review deals with the basic process and mechanism of the protein folding in general and the ultimate outcomes of the protein misfolding. Since Native conformation of heme proteins is essential for some vital activities as listed above, we have discussed possible prevention of denaturation and aggregation of heme proteins such as Hb, cyt c, catalase & peroxidase.

Topics: Alzheimer Disease; Amyloid; Amyloidosis; Catalase; Cytochromes c; Diabetes Mellitus; Gene Expression; Heat-Shock Proteins; Hemoglobins; Humans; Huntington Disease; Molecular Chaperones; Peroxidase; Protein Aggregates; Protein Conformation; Protein Folding

In response to physiologic stimuli, endothelial cells dynamically regulate arterial vascular tone by producing vasodilators and vasoconstrictors. Risk factors for atherosclerosis, such as diabetes, smoking, hypercholesterolemia, and hypertension, interfere with this response, promoting endothelial dysfunction and atherosclerosis. This review explores whether oxidative stress might be a common feature of both endothelial dysfunction and atherosclerosis. Using biomarkers to assess endothelial function might provide insights into the pathways for oxidative stress in vascular disease. However, currently available markers of oxidative stress and endothelial function are unsuitable for routine clinical use because they are too expensive and inadequately validated. Thus, there is a need to develop and validate new markers that could be used to both measure oxidative stress and monitor therapies that specifically interrupt oxidative pathways in vascular tissue. Such markers might eventually help to identify susceptible individuals at a stage when cardiovascular complications could be prevented.

Topics: Atherosclerosis; Biomarkers; Diabetes Mellitus; Diabetic Angiopathies; Electron Transport; Endothelium, Vascular; Humans; Lipoproteins, LDL; Mitochondria; Oxidative Stress; Peroxidase; Vascular Diseases

Topics: Diabetes Mellitus; Disease Susceptibility; Humans; Neutrophils; Peroxidase

Multi-nanozymes are widely applied in disease treatment, biosensing, and other fields. However, most current multi-nanozyme systems exhibit only moderate activity since reaction microenvironments of different nanozyme are often distinct or even incompatible. Conventional assemble strategies are inapplicable for designing multi-nanozymes consisting of incompatible nanozymes. Herein, a versatile fiber-based compartmentalization strategy is developed to construct multi-nanozyme system capable of simultaneously performing incompatible reactions. In this system, the incompatible nanozymes are spatially distributed in distinct compartmentalized fibers, where different microenvironments can be tailored by controlling the doping reagent, endowing each nanozymes with the preferential microenvironments to exhibit their highest activity. As a proof of concept, pH-incompatible peroxidase-like and catalase-like catalytic reactions are tested to verify the feasibility of this strategy. By doping with benzoic acid in the desired location, the two pH-incompatible nanozymes can work simultaneously without interference. Further, it is demonstrated that the oxygen supply and antimicrobial power of the integrated platform can be applied for accelerating diabetic wound healing. It is hoped that this work provides a way to integrate incompatible nanozyme and broadens the application potential of multi-nanozymes.

Topics: Catalysis; Coloring Agents; Diabetes Mellitus; Peroxidase; Peroxidases; Wound Healing

Topics: Antioxidants; Blood Glucose; Diabetes Mellitus; Glucose Oxidase; Gold; Humans; Hydrogels; Metal Nanoparticles; Peroxidase; Superoxide Dismutase; Wound Healing

Diabetic complications present a serious health problem. Functional damage to proteins due to post-translational modifications by glycoxidation reactions is a known factor contributing to pathology. Extracellular proteins are especially vulnerable to diabetic damage because robust antioxidant defenses are lacking outside the cell. We investigated glucose-induced inactivation of peroxidasin (PXDN), a heme protein catalyzing sulfilimine crosslinking of collagen IV that reinforce the basement membranes (BM). Experiments using physiological diabetic glucose levels were carried out to exclude several potential mechanisms of PXDN inactivation i.e., direct adduction of glucose, reactive carbonyl damage, steric hindrance, and osmotic stress. Further experiments established that PXDN activity was inhibited via heme degradation by reactive oxygen species. Activity of another extracellular heme protein, myeloperoxidase, was unaffected by glucose because its heme was resistant to glucose-induced oxidative degradation. Our findings point to specific mechanisms which may compromise BM structure and stability in diabetes and suggest potential modes of protection.

Topics: Diabetes Mellitus; Extracellular Matrix Proteins; Glucose; Heme; Hemeproteins; Humans; Hyperglycemia; Peroxidase; Peroxidasin; Reactive Oxygen Species

Accumulating evidence indicates the association between changes in circulating sex steroid hormone levels and the development of diabetic nephropathy. However, the renal synthesis of steroid hormones during diabetes is essentially unknown. Male Wistar rats were injected with streptozotocin (STZ) or vehicle. After one week, no changes in functional or structural parameters related to kidney damage were observed in STZ group; however, a higher renal expression of proinflammatory cytokines and HSP70 was found. Expression of Steroidogenic Acute Regulatory protein (StAR) and P450scc (CYP11A1) was decreased in STZ kidneys. Incubation of isolated mitochondria with 22R-hydroxycholesterol revealed a marked inhibition in CYP11A1 function at the medullary level in STZ group. The inhibition of these first steps of renal steroidogenesis in early STZ-induced diabetes led to a decreased local synthesis of pregnenolone and progesterone. These findings stimulate investigation of the probable role of nephrosteroids in kidney damage associated with diabetes.

Topics: Animals; Blood Glucose; Carrier Proteins; Cholesterol Side-Chain Cleavage Enzyme; Cytokines; Diabetes Mellitus; Diabetes Mellitus, Experimental; Gene Expression Regulation; HSP70 Heat-Shock Proteins; Inflammation; Inflammation Mediators; Kidney; Lipid Metabolism; Male; Peroxidase; Phosphoproteins; Pregnenolone; Progesterone; Rats, Wistar; Receptors, GABA-A; RNA, Messenger; Steroids; Streptozocin; Testosterone

The majority of fatalities thus far in the COVID-19 pandemic have been attributed to pneumonia. As expected, the fatality rate reported in China is higher in people with chronic pulmonary disease (6.3%) and those who have cancer (5.6%). According to the American College of Cardiology Clinical Bulletin "COVID-19 Clinical Guidance for the CV Care Team", there is a significantly higher fatality rate in people who are elderly (8.0% 70-79 years; 14.8% ≥80 years), diabetic (7.3%), hypertensive (6.0%), or have known cardiovascular disease (CVD) (10.5%). We propose a biological reason for the higher mortality risk in these populations that is apparent. We further present a set of pathophysiological reasons for the heightened danger that could lead to therapies for enhanced management and prevention.

Topics: Adult; Aging; Cardiovascular Diseases; Child; COVID-19; Diabetes Mellitus; Disease Susceptibility; Humans; Hydrogen Peroxide; Hypertension; Hypochlorous Acid; Immunity, Innate; Lung; Microcirculation; Microvessels; Neutrophils; Pandemics; Peroxidase; Risk Factors; United States

Topics: Biomarkers; Cardiovascular Diseases; Diabetes Mellitus; Glycated Hemoglobin; Humans; Inflammation; Lipoproteins, LDL; Peroxidase; Physicians; Prediabetic State; Risk Factors; Risk Reduction Behavior

Cobalt oxyhydroxide (CoOOH) nanoflakes, an emerging type of two-dimensional nanomaterial, show great potential for use in molecular detection. Previous assays utilizing such materials have largely been based on their outstanding fluorescence quenching ability and oxidizing power. Herein, we report the intrinsic peroxidase-like activity of cobalt oxyhydroxide (CoOOH) nanoflakes, and we show how this activity can be employed for glucose detection. We found that, in the presence of hydrogen peroxide (H

Topics: Benzidines; Biosensing Techniques; Blood Glucose; Catalysis; Cobalt; Colorimetry; Diabetes Mellitus; Glucose Oxidase; Humans; Hydrogen Peroxide; Limit of Detection; Nanostructures; Oxides; Peroxidase; Point-of-Care Testing

Diabetes mellitus leads to many systemic complications, including changes in the morphology, function of the salivary glands, and the composition of saliva.. The study comprised a randomly selected 156 adults, of both genders, aged from 21 to 79, out of which patients with diabetes type 1 and 2, and healthy subjects forming two control age- and gender matched to the ill subjects. In unstimulated mixed saliva, total protein, peroxidase, myeloperoxidase and immunoglobulin A were measured as well as salivary flow rate. The periodontal condition was assessed with the use of GI, mSBI and PSR index. The obtained data were analysed with the use of U Mann-Whitney's test, Spearman's rang correlation and Chi-square test at a significant level of p < 0.05 with use of Statistica 9.0 software.. Type 1 diabetics in comparison to healthy age and gender matched control group had a lower salivary flow rate (p < 0.01), a higher content of total protein (p < 0.01), myeloperoxidase (p < 0.001) and immunoglobulin A (p < 0.001). Similarly, type 2 diabetics in comparison to control subjects had a higher level of total protein concentration (p < 0.01), myeloperoxidase (p < 0.05) and immunoglobulin A (p < 0.001). We also found worse periodontal condition.. Within the limitation of the study it may be stated that diabetes type 1 and 2 can cause abnormalities in salivary glands function resulting in the diminishing of salivary flow rate and the increase in total protein content. Higher levels of myeloperoxidase and IgA in the saliva can be linked to worse periodontal condition in the diabetic patients.

Topics: Adult; Aged; Case-Control Studies; Diabetes Mellitus; Female; Humans; Immunoglobulin A; Male; Middle Aged; Periodontal Index; Peroxidase; Saliva; Salivary Proteins and Peptides; Salivation

While inflammation has been proposed to contribute to the adverse cardiovascular outcome in diabetic patients, the specific pathways involved have not been elucidated. The leukocyte derived product, myeloperoxidase (MPO), has been implicated in all stages of atherosclerosis. The relationship between MPO and accelerated disease progression observed in diabetic patients has not been studied.. We investigated the relationship between MPO and disease progression in diabetic patients. 881 patients with angiographic coronary artery disease underwent serial evaluation of atherosclerotic burden with intravascular ultrasound. Disease progression in diabetic (n = 199) and non-diabetic (n = 682) patients, stratified by baseline MPO levels was investigated.. MPO levels were similar in patients with and without diabetes (1362 vs. 1255 pmol/L, p = 0.43). No relationship was observed between increasing quartiles of MPO and either baseline (p = 0.81) or serial changes (p = 0.43) in levels of percent atheroma volume (PAV) in non-diabetic patients. In contrast, increasing MPO quartiles were associated with accelerated PAV progression in diabetic patients (p = 0.03). While optimal control of lipid and the use of high-dose statin were associated with less disease progression, a greater benefit was observed in diabetic patients with lower compared with higher MPO levels at baseline.. Increasing MPO levels are associated with greater progression of atherosclerosis in diabetic patients. This finding indicates the potential importance of MPO pathways in diabetic cardiovascular disease.

Topics: Aged; Cholesterol, LDL; Coronary Angiography; Coronary Artery Disease; Diabetes Complications; Diabetes Mellitus; Disease Progression; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Inflammation; Male; Middle Aged; Peroxidase; Plaque, Atherosclerotic; Ultrasonography, Interventional

Molybdenum disulfide (MoS2) has attracted increasing research interest recently due to its unique physical, optical and electrical properties, correlated with its 2D ultrathin atomic-layered structure. Until now, however, great efforts have focused on its applications such as lithium ion batteries, transistors, and hydrogen evolution reactions. Herein, for the first time, MoS2 nanosheets are discovered to possess an intrinsic peroxidase-like activity and can catalytically oxidize 3,3',5,5'-tetramethylbenzidine (TMB) by H2O2 to produce a color reaction. The catalytic activity follows the typical Michaelis-Menten kinetics and is dependent on temperature, pH, H2O2 concentration, and reaction time. Based on this finding, a highly sensitive and selective colorimetric method for H2O2 and glucose detection is developed and applied to detect glucose in serum samples. Moreover, a simple, inexpensive, instrument-free and portable test kit for the visual detection of glucose in normal and diabetic serum samples is constructed by utilizing agarose hydrogel as a visual detection platform.

Topics: Benzidines; Blood Glucose; Colorimetry; Diabetes Mellitus; Disulfides; Dose-Response Relationship, Drug; Humans; Hydrogels; Hydrogen Peroxide; Hydrogen-Ion Concentration; Kinetics; Microscopy, Electron, Transmission; Molybdenum; Nanostructures; Nanotechnology; Peroxidase; Sepharose; Temperature

Haptoglobin (Hp) protein is responsible for hemoglobin clearance after intra-plaque hemorrhage. Hp gene exists as Hp-1 and Hp-2 alleles and the phenotypes show important molecular heterogeneity. We tested the hypothesis that hemoglobin clearance may be deficient in diabetic atheroma from patients with Hp2-2, triggering increased oxidative, inflammatory, and angiogenic patterns compared with controls.. Forty patients with diabetes mellitus were genotyped and their peripheral plaques compared after atherectomy. Plaque hemorrhage, iron content, hemoglobin-binding protein CD163, and heme-oxygenase-1 were quantified. Oxidative, inflammatory, and angiogenic patterns were evaluated by measuring myeloperoxidase, interleukin-10, macrophages, vascular cell adhesion molecule-1, smooth muscle actin, and plaque neovascularization (CD34/CD31). Plaques with Hp2-2 (n=7) had increased hemorrhage (P<0.005), iron content (P<0.001), and reduced CD163 expression (P<0.002) compared with controls (n=14). Hp2-2 plaques had increased heme-oxygenase-1 protein (P<0.02), myeloperoxidase gene (P<0.05), and protein (P<0.0001). Anti-inflammatory interleukin-10 gene (P<0.04), and protein expressions (P<0.0001) were decreased in Hp2-2. Finally, macrophage (P<0.0001), vascular cell adhesion molecule-1 (P=0.001), smooth muscle actin (P=0.002) scores, and neovessels density (P<0.0001) were increased in Hp2-2.. Genotype-dependent impairment of hemoglobin clearance after intra-plaque hemorrhage is associated with increased oxidative, inflammatory, and angiogenic response in human diabetic atherosclerosis.

Topics: Actins; Aged; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Atherosclerosis; Biomarkers; Case-Control Studies; Diabetes Mellitus; Diabetic Angiopathies; Female; Genotype; Haptoglobins; Heme Oxygenase-1; Hemoglobins; Humans; Inflammation; Interleukin-10; Iron; Male; Middle Aged; Neovascularization, Pathologic; Oxidative Stress; Peroxidase; Phenotype; Prospective Studies; Receptors, Cell Surface; Vascular Cell Adhesion Molecule-1

Measurement of hemoglobin A(1c) (HbA(1c)) is a key diagnostic criterion and a key parameter for the follow-up of the treatment of diabetes mellitus. Typically, immunochemical assays of HbA(1c) are performed in clinical chemistry analyzers. In this study, we applied the HbA(1c) assay on a microplate reader at room temperature.. HbA(1c) samples were measured using the Direct Enzymatic HbA(1c) Assay from Diazyme Laboratories (Poway, CA, USA) using a Plate Chameleon Microplate Reader (Hidex Co., Turku, Finland) according to the manufacturer's protocol and a modification of the method to room temperature. The Tosoh G7 HPLC method for HbA(1c) (Tosoh Co., Tokyo, Japan) was used as a comparative method.. There was good correlation of HbA(1c) results when the assay was performed at room temperature (+22°C) compared with that at +37°C (r=0.987). The modified method was linear over the HbA(1c) range 4%-14%. Analysis of HbA(1c) results from 50 blood samples by the modified method showed good agreement with the HPLC method (r=0.990).. The modified Diazyme Direct Enzymatic HbA(1c) Assay™ appears to work as good at +22°C as that performed according to manufacturer's protocol at +37°C.

Topics: Blood Chemical Analysis; Diabetes Mellitus; Enzyme Assays; Glycated Hemoglobin; Humans; Immunoassay; Peroxidase; Temperature

Prostacyclin synthase (PGIS) is tyrosine nitrated in diseased animals. Whether PGIS nitration occurs in human diabetic atherosclerotic arteries has not been reported. The present study was designed to determine PGIS nitration and its association with the inflammatory response in atherosclerotic carotid arteries from patients with or without type 2 diabetes, and carotid plaques were obtained from patients who underwent carotid endarterectomy. PGIS nitration, nitric oxide synthases, adhesion molecules, myeloperoxidase, osteopontin, and matrix metalloproteinase (MMP) were measured by using immunohistochemistry and Western blotting. In low stenosis areas, diabetes enhanced reactive nitrogen species production, as evidenced by increases in 3-nitrotyrosine and PGIS nitration. In parallel, diabetes dramatically increased inflammatory markers including intracellular adhesion molecule-1, vascular adhesion molecule-1, and osteopontin. In both diabetic and nondiabetic patients, MMP-2 and MMP-9 protein levels were significantly increased in the arteries with high stenosis as compared with those with low stenosis. Moreover, diabetes enhanced inducible nitric oxide synthase expression in the plaques from low stenosis areas and up-regulated myeloperoxidase expression in the plaques from both high and low stenosis areas. These data demonstrate that diabetes preferentially increases PGIS nitration that is associated with excessive vascular inflammation in atherosclerotic carotid arteries from patients with type 2 diabetes, suggesting a possible role of tyrosine nitration of PGIS in the development of atherosclerosis in patients with diabetes.

Topics: Aged; Atherosclerosis; Carotid Arteries; Cytochrome P-450 Enzyme System; Diabetes Mellitus; Diabetes Mellitus, Type 2; Female; Gene Expression Regulation, Enzymologic; Humans; Inflammation; Intramolecular Oxidoreductases; Male; Middle Aged; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; Oxidative Stress; Peroxidase; Tyrosine

Increased fructose concentration in diabetes mellitus causes fructation of several proteins. Here we have studied fructose-induced modifications of hemoglobin. We have demonstrated structural changes in fructose-modified hemoglobin (Fr-Hb) by enhanced fluorescence emission with excitation at 285 nm, more surface accessible tryptophan residues by using acrylamide, changes in secondary and tertiary structures by CD spectroscopy, and increased thermolability by using differential scanning calorimetry in comparison with those of normal hemoglobin, HbA(0). Release of iron from hemoglobin is directly related with the extent of fructation. H2O2-induced iron release from Fr-Hb is significantly higher than that from HbA(0). In the presence of H2O2, Fr-Hb degrades arachidonic acid, deoxyribose and plasmid DNA more efficiently than HbA(0), and these processes are significantly inhibited by desferrioxamine or mannitol. Thus increased iron release from Fr-Hb may cause enhanced formation of free radicals and oxidative stress in diabetes. Compared to HbA(0), Fr-Hb exhibits increased carbonyl formation, an index of oxidative modification. Functional modification in Fr-Hb has also been demonstrated by its decreased peroxidase activity and increased esterase activity in comparison with respective HbA(0) activities. Molecular modeling study reveals Lys 7alpha, Lys 127alpha and Lys 66beta to be the probable potential targets for fructation in HbA(0).

Topics: Adult; Arachidonic Acid; Calorimetry, Differential Scanning; Catalysis; Circular Dichroism; Deoxyribose; Diabetes Mellitus; DNA; Esterases; Fructose; Glycated Hemoglobin; Hemoglobin A; Hemoglobins; Humans; Hydrogen Peroxide; Iron; Lipid Peroxidation; Models, Molecular; Oxidative Stress; Peroxidase; Protein Carbonylation; Protein Denaturation; Spectrometry, Fluorescence; Spectrophotometry; Transition Temperature

Previous methods to measure glycohemoglobin (GHb) have been time-consuming or imprecise; we therefore developed a new enzymatic assay for GHb.. Blood cells were first hemolyzed, and hemoglobin was digested with protease to yield fructosyl amino acid. Fructosyl amino acid oxidase acts on the fructosyl amino acid and generates hydrogen peroxide, which reacts with chromogens in the presence of peroxidase. Total hemoglobin was measured spectrometrically in the same reaction tube. The results were reported as the ratio of the concentrations of GHb and hemoglobin.. The measured values were comparable to those determined with a HPLC method and with an immunoassay in blood samples from 2854 patients with diabetes. Regression analysis for the enzymatic assay (y) vs the HPLC method (x) produced the following: r = 0.979; slope, 0.994 [95% confidence interval (CI), 0.986-1.001]; y-intercept, 0.04% (95% CI, -0.09% to 0.01%); n = 2854. For the enzymatic assay (y) vs the immunoassay (x), the regression statistics were as follows: r = 0.982; slope, 1.002 (95% CI, 0.995-1.009); y-intercept, 0% (95% CI, -0.05% to 0.05%); n = 2854.. The values measured by the new enzymatic assay are sufficiently correlated with those of the conventional HPLC method and immunoassay, but the proposed assay for GHb is rapid and has high precision.

Topics: Amino Acid Oxidoreductases; Chromatography, High Pressure Liquid; Diabetes Mellitus; Glycated Hemoglobin; Humans; Hydrogen Peroxide; Immunoassay; Indicators and Reagents; Metalloendopeptidases; Peroxidase; Reference Values

The infiltration of neutrophils into injured tissue is known to protect wounds from invading pathogens. However, more recent studies suggest that neutrophils might inhibit the wound repair process. To investigate the role of neutrophils in wounds, mice were neutrophil-depleted by injection with rabbit anti-mouse neutrophil serum. Remarkably, epidermal healing, measured by wound closure, proceeded significantly faster in neutropenic than control mice (77.7+14.2% vs. 41.2+0.9%, P<0.02 at day 2). Dermal healing was not affected by neutrophil depletion, as neither collagen deposition nor wound-breaking strength was significantly different between neutropenic and control mice. As the delayed repair of diabetic individuals exhibits robust inflammation, the effect of neutrophil depletion on diabetic wound healing was investigated. Similar to the observations in wild-type mice, wound closure was accelerated by nearly 50% in neutropenic, diabetic mice. The results suggest that although neutrophils may provide protection against infection, they may retard wound closure.

Topics: Animals; Collagen; Diabetes Mellitus; Epithelial Cells; Female; Flow Cytometry; Macrophages; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Neutropenia; Neutrophils; Peroxidase; Rabbits; Skin; Wound Healing; Wounds and Injuries

We measured infarct size after coronary occlusion (30 min) and reperfusion (24 h) in genetic non-insulin-dependent Zucker diabetic fatty (ZDF) rats with and without 4-wk cholesterol feeding. Infarct size was similar in ZDF rats and lean control rats but was significantly larger in cholesterol-fed diabetic rats than in cholesterol-fed lean rats (P < 0.05). Plasma levels of glucose, insulin, and triglycerides were significantly higher in diabetic rats and were not influenced by cholesterol feeding. The increase in total plasma cholesterol induced by cholesterol feeding was significantly greater in diabetic rats than in lean rats (P < 0.05). A significant positive correlation was found between total plasma cholesterol and infarct size (P < 0.05). Myeloperoxidase activity, as an index of neutrophil accumulation, was significantly higher and expression of P-selectin was more marked in the ischemic myocardium of cholesterol-fed diabetic rats than of cholesterol-fed lean rats. Acetylcholine-induced endothelium-dependent relaxation (EDR) of aortic rings was markedly impaired in cholesterol-fed diabetic rats. Thus cholesterol feeding significantly exacerbated myocardial injury produced by coronary occlusion-reperfusion in non-insulin-dependent diabetic rats, possibly because of enhanced expression of P-selectin and impairment of EDR in the coronary bed.

Topics: Acetylcholine; Animals; Aorta; Cell Adhesion Molecules; Cholesterol, Dietary; Diabetes Mellitus; Diabetes Mellitus, Type 2; Endothelium, Vascular; Hemodynamics; In Vitro Techniques; Male; Myocardial Infarction; Myocardium; Neutrophils; Obesity; Peroxidase; Rats; Rats, Zucker; Vasodilation; Vasodilator Agents

To further understand the mechanisms behind defective neutrophil function in diabetes mellitus, the ability of insulin to affect the production and metabolism of reactive oxygen metabolites in normal human neutrophils was studied.. Neutrophil granulocytes from healthy adults were studied for their N-formyl-methionyl-leucyl-phenylalanine (fMet-Leu-Phe)-stimulated production of reactive oxygen metabolites and release of myeloperoxidase or elastase following treatment with insulin.. Preincubation of the neutrophils for 30 min with insulin (40-320 microU/ml), before activation with 1 microM fMet-Leu-Phe, revealed that the hormone at 80 and 160 microU/ml reduced the luminol-enhanced chemiluminescence without affecting the superoxide secretion. The insulin-induced reduction of the chemiluminescence response was reversed by the addition of exogenous peroxidase and was also paralleled by a reduced myeloperoxidase activity, with no effect on the elastase activity, in cell-free supernatants from fMet-Leu-Phe-stimulated neutrophils. Superoxide dismutase removed the inhibitory effect of insulin on myeloperoxidase activity.. These results suggest that elevated levels of insulin do not affect the NADPH-oxidase activity but, together with superoxide anions, interfere with myeloperoxidase availability and a subsequent myeloperoxidase-dependent generation of reactive oxygen metabolites in fMet-Leu-Phe-stimulated normal human neutrophils.

Topics: Adult; Diabetes Mellitus; Humans; Insulin; Leukocyte Elastase; Luminescent Measurements; N-Formylmethionine Leucyl-Phenylalanine; NADPH Oxidases; Neutrophils; Peroxidase; Reactive Oxygen Species

Data on the function of neutrophils in diabetes mellitus not infrequently accompanied by inflammatory complications are scarce. The aim of this work is to investigate the state of some components of neutrophil granules (cationic proteins, activity of myeloperoxidase, alkaline phosphatase) that play a major role in the mechanisms of destruction of microorganisms in phagocytosis.

Topics: Adult; Alkaline Phosphatase; Blood Proteins; Cations; Diabetes Mellitus; Humans; Middle Aged; Neutrophils; Peroxidase

Reduced bacterial killing by polymorphonuclear leucocytes has been reported in patients with diabetes mellitus. Whether this is due to reduced content of bactericidal granular proteins has not been determined. We therefore immunochemically measured the content of myeloperoxidase, lactoferrin, lysozyme, cathepsin G and elastase in polymorphonuclear leucocytes from 50 insulin-treated diabetic patients. The peroxidase activity was also measured. Normal contents of myeloperoxidase and lactoferrin as well as normal peroxidase activity were found. The average contents of cathepsin G, elastase and lysozyme were 2.5, 3.2 and 2.6 micrograms/10(6) polymorphonuclear leucocytes, respectively, and thus 14, 45 and 18% higher than the contents of normal polymorphonuclear leucocytes. The results indicate that reduced intracellular killing of bacteria demonstrated in previous studies in diabetic patients does not appear to be related to a reduction in the content of bactericidal proteins.

Topics: Age Factors; Blood Bactericidal Activity; Cathepsin G; Cathepsins; Diabetes Mellitus; Humans; Lactoferrin; Muramidase; Neutrophils; Pancreatic Elastase; Peroxidase; Serine Endopeptidases; Time Factors

Cytochemical indices of leukocytes were determined in 16 patients with diabetes mellitus in the period of unbalancing and balancing. The following tests were made: content of glycogen and lipids, acid phosphatase (AP), alkaline phosphatase (AIP), myeloperoxidase (MPO) and nonspecific alpha-naphtol acetate esterase (NANAE) activity. In unbalanced diabetics an evident decrease in the activity of AP and MPO could be noted as well as a decrease of glycogen content and an increase of lipid content. An insignificant decrease could be observed in the activity of ALP and NANAE in granulocytes. A slight increase in the activity of NANAE in monocytes would be found. Balancing this disease induced the increase of all parameters in granulocytes except MPO activity. It is interesting to note that balancing diabetes mellitus deepened the observed changes in the decrease or increase of tested parameters. The presented findings clearly indicate the role of metabolic disorders in diabetes mellitus on the activity of some neutrophilic enzymes and the glycogen and the content of lipids in neutrophils.

Topics: Acid Phosphatase; Adult; Alkaline Phosphatase; Diabetes Mellitus; Female; Glycogen; Humans; Leukocytes; Lipids; Male; Middle Aged; Naphthol AS D Esterase; Peroxidase

Topics: Blood Glucose; Capillaries; Colorimetry; Diabetes Mellitus; Glucose Oxidase; Humans; Indicators and Reagents; Isoenzymes; Paper; Peroxidase; Peroxidases

Topics: alpha-Macroglobulins; Diabetes Mellitus; Disulfides; Enzyme Activation; Fibroblasts; Glutathione; Humans; Hydrogen Peroxide; Microbial Collagenase; Neutrophils; Peroxidase; Skin; Synovial Fluid

Using an automated cytochemical analyzer used for routine differential counts, we have been able to demonstrate acquired myeloperoxidase deficiency in 102 patients at our institution. Clinical and laboratory data on these patients showed a high incidence of diabetes mellitus (25.5%) and thrombotic diseases (24.5%), as well as a strikingly constant hyperfibrinogenemia (mean = 635 mg/100 ml; range = 360-1015 mg/100 ml). In 4 additional acute leukemia patients in complete remission, a close time correlation was noted between acquired MPO deficiency, diffuse intravascular coagulation and relapse. These findings indicate the importance of the relationships between neutrophil granulocytes and blood coagulation, and suggest that similar changes in neutrophil MPO activity may represent an early morphological indicator of subclinical activation of blood coagulation.

Topics: Adolescent; Adult; Aged; Blood Coagulation; Child; Child, Preschool; Diabetes Mellitus; Disseminated Intravascular Coagulation; Female; Fibrinogen; Humans; Infant; Infant, Newborn; Leukemia, Myeloid, Acute; Male; Middle Aged; Neutrophils; Peroxidase; Peroxidases; Thrombosis

Topics: Blood Glucose; Diabetes Mellitus; Evaluation Studies as Topic; Glucose Oxidase; Humans; Peroxidase; Peroxidases; Reagent Strips; Reproducibility of Results

Neutrophil myeloperoxidase (MPO) activity was analyzed by a semi-quantitative cytochemical method in 268 subjects divided into several groups. 17 subjects with significantly reduced MPO activity were found: 11 of 23 in the preleukemia group, 2/14 AMLs, 1/20 myeloproliferative syndrome, 1/7 carcinoma with bone marrow metastases, 1/33 diabetes mellitus and 1/50 normals. Only in the preleukemia group, was MPO significantly reduced in comparison to the normal group (p less than 0.005). The high frequency of acquired MPO deficiency in preleukemia represents a useful criterium for this diagnosis. Furthermore, in these patients, as well as in the other subjects studied, no apparent correlation between MPO level and infection could be demonstrated.

Topics: Candidiasis, Chronic Mucocutaneous; Clinical Enzyme Tests; Diabetes Mellitus; Diagnosis, Differential; Humans; Infections; Leukemia, Myeloid, Acute; Lymphoproliferative Disorders; Myeloproliferative Disorders; Neoplasms; Peroxidase; Peroxidases; Preleukemia

Topics: Acetylglucosaminidase; Acid Phosphatase; Adult; Aged; Alkaline Phosphatase; Diabetes Mellitus; Female; Glucuronidase; Glycogen; Histocytochemistry; Humans; Lipids; Male; Middle Aged; Neutrophils; Peroxidase

Topics: Bacteriolysis; Chediak-Higashi Syndrome; Chemotaxis; Complement System Proteins; Diabetes Mellitus; Glucosephosphate Dehydrogenase Deficiency; Humans; Leukocytes; Opsonin Proteins; Peroxidase; Phagocytosis