benzofurans and Pneumonia

Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Dose-Response Relationship, Drug; Drug Interactions; Half-Life; Humans; Pneumonia

Of the side effects that complicate amiodarone therapy, pulmonary fibrosis is potentially the most serious. Therefore, the development of techniques to predict the onset of this troublesome reaction would be of great practical value. Reports of 39 patients who developed pulmonary toxicity with amiodarone were evaluated for clues to precipitating factors and information on the response to corticosteroid treatment. The majority of patients were being given maintenance doses greater than 400 mg/day. Patients appeared to improve after withdrawal of amiodarone, both with and without corticosteroid treatment. In addition, a case report is presented of a patient who developed pulmonary changes that disappeared when amiodarone was withdrawn and did not recur when amiodarone was reinstituted. Data from sequential pulmonary function tests and cumulative amiodarone dosage in 35 patients were also examined to determine their value in predicting pulmonary complications. Pulmonary function tests did not appear to be useful in predicting the likelihood of an individual patient's developing pulmonary complications. Although none of the available information identifies the mechanism mediating amiodarone pulmonary toxicity, the frequency of the complication probably can be reduced by timely reductions in maintenance dosage.

Topics: Adrenal Cortex Hormones; Adult; Aged; Amiodarone; Benzofurans; Dose-Response Relationship, Drug; Female; Humans; Inclusion Bodies; Lung Diseases; Male; Middle Aged; Pneumonia; Pulmonary Fibrosis; Respiratory Function Tests; Risk; Structure-Activity Relationship

Pulmonary fibrosis (PF) is an interstitial lung disease characterized by interstitial inflammation and fibrosis. Salvianolic acid B (SAB) and sodium tanshinone IIA sulfonate (STS) are representative components in Salvia miltiorrhiza, which have been reported using in the treatment of PF. The aim of the study was to explain the role of inflammation in the process of PF and to investigate the effect of SAB and STS on inflammation and fibrosis in vitro. The results clearly indicated that lipopolysaccharide (LPS)-stimulated inflammatory response could induce fibroblast proliferation and fibroblast to myofibroblast transformation (FMT). Both SAB and STS significantly inhibited LPS-induced inflammation in vitro, including down-regulated the protein expression levels of IL-1β and TNF-α and the mRNA expression levels of IL1B and TNFA. Furthermore, both SAB and STS inhibited TGF-β1-induced the proliferation in MRC-5 cells and the overexpression of α-SMA and COL1α1, both the protein and mRNA levels. In conclusion, these results indicate that the inflammatory response is necessary for the development of PF, and the therapeutic effect of SAB and STS on PF may be related to anti-inflammatory and anti-fibrotic effects.

Topics: Actins; Anti-Inflammatory Agents; Benzofurans; Cell Proliferation; Coculture Techniques; Collagen Type I; Collagen Type I, alpha 1 Chain; Cytokines; Fibroblasts; Humans; Inflammation Mediators; Lung; Macrophages; Phenanthrenes; Pneumonia; Pulmonary Fibrosis; THP-1 Cells

Benzofuran derivatives have wide range of biological activities as anti-oxidant, anti-inflammatory and anticonvulsant agent. In this study, we investigated whether the novel benzofuran derivative, DK-1014 has the anti-inflammatory effects on macrophage and lung epithelial cells and anti-asthmatic effects on ovalbumin-treated mice. A series of 2-arylbenzofuran analogues were synthesized and evaluated for NO and interleukin-6 (IL-6) inhibition in LPS-stimulated Raw264.7 cells. Of these analogues, compounds 8, 22a, 22d, and 22 f (DK-1014) exhibited notable inhibitory activity with respect to IL-6 and NO production. In particular, compound DK-1014 strongly reduced IL-6, IL-8, and MMP-9 mRNA expression and IL-6, IL-8, and MCP-1 production in phorbol myristate acetate stimulated A549 cells, reduced MAPKs phosphorylation and c-fos translocation, and attenuated AKT, p70S6K and GSK phosphorylation. In vivo experiments were also performed on ovalbumin-sensitized and challenged BALB/c mice. DK-1014 reduced the airway hyperresponsiveness, inflammatory cell counts and cytokine levels (IL-4, 5, 13) in bronchial alveolar lavage fluid (BALF) and immunoglobulin E in serum, and attenuated inflammatory cell infiltration and mucus hypersecretion in lung tissue. These findings indicate that DK-1014 can protect against allergic airway inflammation through the AP-1 and AKT/mTOR pathways and could be useful source for the development of a therapeutic agent for asthma.

Topics: Animals; Anti-Inflammatory Agents; Asthma; Benzofurans; Cells, Cultured; Cytokines; Disease Models, Animal; Humans; Macrophages; Mice; Mice, Inbred BALB C; Nitric Oxide; Pneumonia; Proto-Oncogene Proteins c-akt; Respiratory Mucosa; Signal Transduction; TOR Serine-Threonine Kinases; Transcription Factor AP-1

Endothelial cell injury and subsequent inflammation play pivotal roles in the pathogenesis of pulmonary fibrosis, a progressive and fatal disorder. We found previously that salvianolic acid B (SAB) attenuated experimental pulmonary fibrosis. Pulmonary fibrosis is driven by inflammation, but the anti-inflammatory role and mechanism of SAB on the treatment of pulmonary fibrosis is still unknown. Here, our in vivo studies showed that SAB had a strong anti-inflammatory effect on bleomycin-instilled mice by inhibiting inflammatory cell infiltration and inflammatory cytokine production. Moreover, SAB protected endothelial cells against oxidative stress injury and inhibited endothelial cell apoptosis in bleomycin-treated mice. The in vitro studies also showed that SAB decreased the H

Topics: Animals; Benzofurans; Cell Line; Cytokines; Cytoprotection; Disease Models, Animal; Endothelial Cells; Humans; Hydrogen Peroxide; MAP Kinase Signaling System; Mice; Mice, Inbred C57BL; NF-kappa B; Oxidative Stress; Permeability; Pneumonia; Signal Transduction; Tight Junctions

Salvianolic acid B (Sal B), a bioactive compound isolated from the Chinese herb Radix Salviae Miltiorrhizae, has been reported to exhibit anti-inflammatory and anti-oxidantive effects. The aim of this study was to investigate the protective effects of Sal B on cigarette smoke (CS)-induced acute lung inflammation. Sal B was given intraperitoneally (i.p.) to mice 1h before CS exposure daily for four consecutive days. Bronchoalveolar lavage fluid (BALF) was collected to assess the levels of inflammatory cytokines and cell counts. Lung tissues were used to analysis pathological changes, total glutathione (GSH), nuclear factor erythroid-2 related factor 2 (Nrf-2), and nuclear factor-kappa B (NF-κB) expression. The results showed that Sal B inhibited CS-induced lung pathological changes, the infiltration of inflammatory cells, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), and monocyte chemoattractant protein 1 (MCP-1) productions. Sal B also up-regulated CS-induced total glutathione (GSH) production. Furthermore, Sal B was found to up-regulate Nrf-2, hemeoxygenase1 (HO1) expression and suppress CS-induced NF-κB activation. In conclusion, the current study demonstrated that Sal B exhibited a protective effect on CS-induced lung injury and the possible mechanism was involved in activating Nrf-2 and inhibiting NF-κB activation.

Topics: Animals; Anti-Inflammatory Agents; Benzofurans; Bronchoalveolar Lavage Fluid; Cytokines; Cytoprotection; Disease Models, Animal; Glutathione; Heme Oxygenase-1; Lung; Male; Membrane Proteins; Mice, Inbred C57BL; NF-E2-Related Factor 2; NF-kappa B; Pneumonia; Smoke; Tobacco Smoke Pollution

Radiotherapy is the most significant non-surgical cure for the elimination of tumor, however it is restricted by two major problems: radioresistance and normal tissue damage. Efficiency improvement on radiotherapy is demanded to achieve cancer treatment. We focused on radiation-induced normal cell damage, and are concerned about inflammation reported to act as a main limiting factor in the radiotherapy. Psoralidin, a coumestan derivative isolated from the seed of Psoralea corylifolia, has been studied for anti-cancer and anti-bacterial properties. However, little is known regarding its effects on IR-induced pulmonary inflammation. The aim of this study is to investigate mechanisms of IR-induced inflammation and to examine therapeutic mechanisms of psoralidin in human normal lung fibroblasts and mice. Here, we demonstrated that IR-induced ROS activated cyclooxygenases-2 (COX-2) and 5-lipoxygenase (5-LOX) pathway in HFL-1 and MRC-5 cells. Psoralidin inhibited the IR-induced COX-2 expression and PGE(2) production through regulation of PI3K/Akt and NF-κB pathway. Also, psoralidin blocked IR-induced LTB(4) production, and it was due to direct interaction of psoralidin and 5-lipoxygenase activating protein (FLAP) in 5-LOX pathway. IR-induced fibroblast migration was notably attenuated in the presence of psoralidin. Moreover, in vivo results from mouse lung indicate that psoralidin suppresses IR-induced expression of pro-inflammatory cytokines (TNF-α, TGF-β, IL-6 and IL-1 α/β) and ICAM-1. Taken together, our findings reveal a regulatory mechanism of IR-induced pulmonary inflammation in human normal lung fibroblast and mice, and suggest that psoralidin may be useful as a potential lead compound for development of a better radiopreventive agent against radiation-induced normal tissue injury.

Topics: 5-Lipoxygenase-Activating Proteins; Animals; Arachidonate 5-Lipoxygenase; Benzofurans; Cells, Cultured; Coumarins; Cyclooxygenase 2 Inhibitors; Humans; Lipoxygenase Inhibitors; Lung; Male; Mice; Mice, Inbred BALB C; NF-kappa B; Phosphatidylinositol 3-Kinases; Pneumonia; Proto-Oncogene Proteins c-akt; Radiation-Protective Agents

Sulfuretin is one of the main flavonoids produced by Rhus verniciflua, which is reported to inhibit the inflammatory response by suppressing the NF-κB pathway. Because NF-κB activation plays a pivotal role in the pathogenesis of allergic airway inflammation, we here examined the effect of sulfuretin on an ovalbumin-induced airway inflammation model in mice. We isolated sulfuretin from R. verniciflua. Sulfuretin was delivered intraperitoneally after the last ovalbumin challenge. Airway hyper-responsiveness, cytokines, mucin, and eosinophilic infiltration were analyzed in bronchoalveolar lavage fluid and lung tissue. A single administration of sulfuretin reduced airway inflammatory cell recruitment and peribronchiolar inflammation and suppressed the production of various cytokines in bronchoalveolar fluid. In addition, sulfuretin suppressed mucin production and prevented the development of airway hyper-responsiveness. The protective effect of sulfuretin was mediated by the inhibition of the NF-κB signaling pathway. Our results suggest that sulfuretin may have therapeutic potential for the treatment of allergic airway inflammation.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Benzofurans; Bronchoalveolar Lavage Fluid; Chemotaxis; Cytokines; Eosinophilia; Flavonoids; Male; Mice; Mice, Inbred BALB C; Mucins; NF-kappa B; Pneumonia; Respiratory Hypersensitivity

Matrix metalloprotease 12 plays a significant role in airway inflammation and remodeling. Increased expression and production of MMP-12 have been found in the lung of human COPD patients. MMP408 (14), a potent and selective MMP-12 inhibitor, was derived from a potent matrix metalloprotease 2 and 13 inhibitor via lead optimization and has good physical properties and bioavailability. The compound blocks rhMMP-12-induced lung inflammation in a mouse model and was advanced for further development for the treatment of COPD.

Topics: Animals; Benzofurans; Biological Availability; Haplorhini; Humans; In Vitro Techniques; Matrix Metalloproteinase Inhibitors; Mice; Mice, Inbred C57BL; Models, Molecular; Pneumonia; Pulmonary Disease, Chronic Obstructive; Rats; Recombinant Proteins; Sheep; Species Specificity; Stereoisomerism; Structure-Activity Relationship; Sulfonamides

Topics: Amiodarone; Benzofurans; Humans; Pneumonia

Topics: Aged; Amiodarone; Benzofurans; Humans; Immunoglobulins; Male; Middle Aged; Pneumonia; Therapeutic Irrigation

Topics: Amiodarone; Benzofurans; Gallium Radioisotopes; Humans; Pneumonia; Radionuclide Imaging

Topics: Amiodarone; Benzofurans; Humans; Hyperglycemia; Leukocyte Count; Pneumonia; Therapeutic Irrigation

Topics: Amiodarone; Benzofurans; Humans; Lung Diseases; Pneumonia; Pulmonary Fibrosis

A case of pneumonitis and pulmonary fibrosis occurring during long term treatment with amiodarone hydrochloride is described. The patient, a 68 year old woman, presented with severe dyspnoea and weakness 13 months after the institution of amiodarone therapy, 200 mg. bid 6 days/week. Chest x-ray showed patchy infiltrates involving the parahilar and medullary areas of both upper lobes. The clinical symptoms and the pulmonary signs improved only after amiodarone discontinuation and steroid treatment. Radiographic abnormalities gradually cleared over 45 days except for residual lines of fibrosis in the zones of previous alveolar consolidation still present 4 months later.

Topics: Aged; Amiodarone; Benzofurans; Coronary Disease; Female; Humans; Pneumonia; Pulmonary Fibrosis; Radiography

A 69 year-old woman with no previous history of lung disease was treated with 500 mg of Amiodarone per week. After 21 months of treatment, she developed a clinical picture of alveolitis with fibrosis, which was confirmed by histological examination. No other drug known for its fibrotic properties had been administered. Treatment with Nifedipine and Isosorbide dinitrate had been prescribed prior to the Amiodarone. Simply stopping the Amiodarone led to a regression or disappearance of the clinical, radiological and functional signs. Immunological investigations revealed the presence of antinuclear antibodies and a positive lymphoblastic transformation test for the drug, which are the abnormalities that one finds in other types of drug-induced fibrosis (nitrofuradantin). A new finding was the presence of cutaneous immunofluorescence of granular deposits of IgG, IgM and complement at the dermo-epidermal junction. So far, there have been 13 cases of lung disease related to the administration of Amiodarone reported in the literature.

Topics: Aged; Amiodarone; Benzofurans; Drug Hypersensitivity; Female; Follow-Up Studies; Humans; Pneumonia; Pulmonary Fibrosis

Topics: Aged; Amiodarone; Benzofurans; Humans; Male; Pneumonia; Recurrence

Topics: Adult; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Dose-Response Relationship, Drug; Humans; Male; Pneumonia

Topics: Aged; Amiodarone; Benzofurans; Humans; Male; Pneumonia; Pulmonary Alveoli; Radiography; Tachycardia

Topics: Amiodarone; Benzofurans; Humans; Lung; Pneumonia

Amiodarone (Cordarone) is an antiarrhythmic cardiac drug that is currently being evaluated in the United States. Pulmonary infiltrates developed in six of 34 patients who were receiving amiodarone in daily doses of 200-800 mg over a period of 1.5 to 12 months. Two patients died, one returned to normal after amiodarone had been discontinued for six months, and three have residual radiographic abnormalities (two continue to receive amiodarone with steroids). Radiologists should be aware of the history of amiodarone therapy and this possible serious side effect so that they can detect the earliest changes in the lung.

Topics: Aged; Amiodarone; Benzofurans; Female; Humans; Lung; Male; Middle Aged; Pneumonia; Radiography

Three further patients are presented who developed evidence of a parenchymal pulmonary disturbance in the course of treatment with amiodarone. In one case the progress of the condition was rapid and ended fatally. Histological examination of the lungs showed evidence of diffuse alveolar damage. The concentration of amiodarone was from four to seven times higher in the lungs than in other organs studied. The concentration of the metabolite desethylamiodarone in the lungs was even higher in relation to other organs studied. The remaining two patients showed a more insidious onset and improvement after withdrawal of amiodarone and treatment with corticosteroids. Gallium 67 scintigraphy appeared to be a sensitive indicator of this adverse effect. Review of published reports revealed 35 cases of amiodarone pneumonitis, including the cases reported in this study. In 11 instances the dose of amiodarone was 400 mg or less. The onset was either insidious or rapidly progressive. Exertional dyspnoea was always present and a nonproductive cough, hypoxaemia, a raised erythrocyte sedimentation rate and diminished carbon monoxide diffusing capacity (transfer factor) were usually noted. Chest radiographs showed either a reticular pattern or diffuse patchy alveolar infiltrates. Discontinuation of amiodarone and an institution of corticosteroid treatment was usually followed by improvement or resolution.

Topics: Adult; Aged; Amiodarone; Benzofurans; Female; Gallium Radioisotopes; Humans; Lung; Male; Middle Aged; Pneumonia; Prednisolone; Radionuclide Imaging

Amiodarone is a new and powerful antiarrhythmic agent currently under investigation in North America. In the past two years, there have been increasing reports of serious side effects associated with its use, including 14 cases of pneumonitis or pulmonary fibrosis. This report describes a case of acute necrotizing pneumonitis, a complication that has not been observed previously with amiodarone therapy. Amiodarone also appeared to alter carbohydrate metabolism in this patient. Metabolic changes induced by this drug may be mediated by superoxide radicals. A high index of suspicion for pulmonary complications should be maintained in patients taking amiodarone, and nonspecific respiratory complaints should be investigated carefully.

Topics: Acute Disease; Aged; Amiodarone; Benzofurans; Humans; Hyperglycemia; Lung; Male; Necrosis; Pneumonia; Radiography; Tachycardia

Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Humans; Pneumonia

Topics: Amiodarone; Benzofurans; Female; Humans; Middle Aged; Pneumonia; Prednisone

In a case of severe alveolitis and polyarthropathy occurring within two to five months of starting amiodarone treatment high plasma concentrations of immune complexes were found, suggesting a drug mediated hypersensitivity reaction. Initial symptomatic response followed high dosage corticosteroid and immunosuppressant treatment, but reduction in the dosage of corticosteroids was achieved only by successive plasma exchange with concomitant reduction in plasma concentrations of both amiodarone and immune complexes.

Topics: Amiodarone; Benzofurans; Female; Humans; Joint Diseases; Middle Aged; Plasma Exchange; Pneumonia; Prednisolone; Pulmonary Fibrosis

A patient with types A and B of Wolff-Parkinson-White syndrome developed subacute pneumonitis during long-term treatment with amiodarone. The pneumopathy occurred only when the maintenance dose was increased to 800 mg/day. Lung specimens obtained by transbronchial biopsy showed chronic pneumonitis with C3 deposition by immunofluorescence. Pulmonary signs spontaneously disappeared two months after the drug was discontinued.

Topics: Amiodarone; Benzofurans; Female; Humans; Lung; Middle Aged; Pneumonia; Wolff-Parkinson-White Syndrome

Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Humans; Male; Middle Aged; Pneumonia; Prednisone; Pulmonary Fibrosis

Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Humans; Male; Middle Aged; Pneumonia; Tachycardia

Topics: Aged; Amiodarone; Benzofurans; Humans; Lung; Male; Pneumonia; Pulmonary Alveoli; Radiography

Six patients are presented who developed pulmonary infiltrates of undetermined origin while being treated for severe ventricular arrhythmias with amiodarone hydrochloride. Biopsy material was available in four patients and revealed interstitial or alveolar fibrosis and pneumonitis. Four patients recovered and two died of severe cardiopulmonary decompensation; all of the patients who recovered received corticosteroid therapy. Pulmonary fibrosis is a previously unreported complication of amiodarone therapy.

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Coronary Disease; Female; Heart Failure; Humans; Lung; Male; Middle Aged; Myocardial Infarction; Pneumonia; Pulmonary Fibrosis

Topics: Amiodarone; Benzofurans; Humans; Male; Middle Aged; Pneumonia