Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034069 (pulmonary fibrosis)
 7,050 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tetrandrine, an herbal drug, has been employed in China to treat pulmonary fibrosis. To date, the mechanisms governing the antifibrotic action of tetrandrine are unknown. The present study employs a fibroblast mitogenic assay to determine whether tetrandrine directly inhibits the ability of fibroblasts to respond to stimulation by growth factors. The data indicate that tetrandrine blocks proliferation and the incorporation of tritiated thymidine into DNA by fibroblasts stimulated with human serum, PDGF plus plasma, FGF plus plasma, or TNF plus plasma. Since tetrandrine inhibits the response to a variety of growth factors, its action does not appear to involve the blockade of a specific stimulatory receptor. Tetrandrine is effective in inhibiting thymidine incorporation when added up to 6 hr after stimulation of quiescent cells, suggesting either that tetrandrine does not block the attainment of competence by fibroblasts or that its activity is not limited to blocking the attainment of competence by these cells. Growth factor-induced mitogenesis is also inhibited by nitrendipine, a calcium channel blocker, and by cytochalasin B, a microfilament blocker. However, tetrandrine treatment of fibroblasts neither results in the changes of morphology seen with cytochalasin B nor is limited to the early events of stimulus-response coupling. Therefore, the mechanism of action for tetrandrine is not identical to that for either cytochalasin B or nitrendipine. In summary, these results suggest that the antifibrotic action of tetrandrine may be mediated in part by direct inhibition of fibroblast proliferation normally associated with the development and progression of silicosis.
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PMID:Inhibition of proliferative activity of pulmonary fibroblasts by tetrandrine. 810 60

Silica is a well-known occupational fibrogenic agent and its primary target cell is alveolar macrophage. Particle-stimulated macrophages are believed to release various mediator which can regulate the inflammation as well as pulmonary fibrosis. Even though oxygen radicals play the major role among these mediators, the mechanisms concerning the stimulation of alveolar macrophages are not clear yet. The present study was carried out to investigate the signal transduction pathway on oxygen radical generation in silica-stimulated alveolar macrophages. Silica induced oxygen radical generation in a dose-response pattern. Extracellular calcium depletion, calcium channel blockers, and calcium release blocker decreased the effect of silica on oxygen radical generation. Silica increased intracellular calcium through the influx of calcium through the calcium channel and the calcium release from the intracellular calcium store. To know the role of protein kinase C (PKC), phospholipase C (PLC), and protein tyrosine kinase (PTK) in silica-induced oxygen radical generation, we pretreated alveolar macrophages with inhibitors of these enzymes. Inhibitors of PKC (sphingosine and staurosporine), PLC (neomycin and U-73122), and PTK (genistein and erbstatin) suppressed the silica-induced oxygen radical generation. Silica increased the PLC activity at the concentration of 5 mg/ml. The inhibitors of PTK and PLC suppressed the action of silica on the PLC activity. From these results, we suggest that silica induces oxygen radical generation through PTK, PLC, and PKC in alveolar macrophages.
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PMID:Silica-induced oxygen radical generation in alveolar macrophage. 924 22

Systemic sclerosis is an extremely variable disease in its manifestations and consequently, treatment needs to be individualized depending on the specific problems that each patient has. Limited scleroderma patients have a prolonged duration of Raynaud's phenomenon and puffy fingers before they develop any skin thickening, digital ulcers or gastrointestinal symptoms. They are likely to present with all the classic manifestations of scleroderma. Diffuse scleroderma patients have a much more acute systemic onset with marked whole hand swelling and may initially have only subtle skin thickening. A good understanding of the differences between the natural history of limited and diffuse scleroderma will enable the physician to treat present problems and anticipate future ones more effectively. One should determine which major subset and organ systems are involved before deciding on the appropriate therapy. Advances in organ-specific therapy, particularly calcium channel antagonists in Raynaud's phenomenon, proton pump inhibitors in esophageal reflux, intravenous iloprost and endothelin receptor antagonists in pulmonary hypertension, and ACE inhibitors in renal crisis, have decreased morbidity and mortality in patients with scleroderma. Studies of aggressive therapies to prevent or improve pulmonary fibrosis are in progress. Further clinical experience in wound healing, gastrointestinal malabsorption and physical therapy for loss of motion has helped patients to have a more comfortable life. In recent years, a significant number of controlled clinical trials have been performed and there has been improved understanding of the best way to perform studies and of which patients are most likely to respond to therapy. Penicillamine, methotrexate, photopheresis, relaxin, interferons, and cyclosporine have all been studied in controlled trials with variable outcomes. Although an overall remittive therapy has not yet been determined, new, potentially useful agents are being investigated.
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PMID:Treatment of systemic sclerosis. 1172 50

Cardiac arrhythmias are a common problem in the perioperative period. The incidence found in the current literature varies depending on the population studied and the definition of arrhythmia used. Overall supraventricular arrhythmias, namely atrial fibrillation, are the most common form. Because of its broad spectrum amiodarone is often used to suppress supraventricular and ventricular arrhythmias. It is believed to be safe for treating patients with severe cardiac disease and it has less proarrhyhmogenic potential than many other antiarrhythmic drugs. However, the use of amiodarone is limited by its cardiac and non-cardiac adverse effects, such as life-threatening bradycardia, pulmonary fibrosis or thyrotoxicosis. According to the guidelines of the American Heart Association, amiodarone can be used to treat atrial fibrillation. Because spontaneous conversion rates in the perioperative setting are high and the advantage of a rhythm control strategy over rate control is questionable, a rate control strategy using less toxic drugs like beta blockers or calcium channel blockers should be preferred in hemodynamically stable patients. The current guidelines of the European Resuscitation Council (ERC) recommend amiodarone to treat hemodynamically stable ventricular tachycardia and in this setting ajmaline is also highly effective. Amiodarone should be administered to patients with cardiac arrest if ventricular tachycardia or ventricular fibrillation persists after three attempts at defibrillation. Dronedarone is a derivate of amiodarone with a similar mechanism of action but with less non-cardiac side effects and is currently being tested in clinical trials. The use of the atrial-specific potassium channel blockers AZD7009 and vernakalant are also being investigated. Furthermore, the role of statins, ACE inhibitors and angiotensin receptor blockers in the prevention of atrial fibrillation has to be evaluated.
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PMID:[Amiodaron for treatment of perioperative cardiac arrythmia: a broad spectrum antiarrythmetic agent?]. 1870 41

We performed a cross-sectional study of the demography, clinical and laboratory features of patients with systemic sclerosis patients followed up in our centre from 1984 to 2007. There were 23 cases with the majority of them (96%) being female. They have a mean age of 50.3 years and a mean disease duration of 6.02 (SD 5.82) years. Our patients comprised of multi-ethnic groups with predominantly Chinese (52%), Sarawak natives (35%) and Malays (13%). They have a mean lag time to diagnosis of 24.8 (SD 34.8) months. All the patients have sclerodermatous skin changes with 16(70%) having diffuse scleroderma and 7(30%) having limited scleroderma. The common clinical manifestations found in our patients were Raynaud's phenomenon (91%), sclerodactyly (65%), digital ulcers (52%) and pulmonary fibrosis (52%). There was low incidence of pulmonary hypertension (13%) and renal involvement (4%). The majority of our patients (67%) have positive ANA with 33% positive Scl-70. The majority received calcium channel blockers (87%), aspirin (48%) and low-dose prednisolone (48%). One patient developed adenocarcinoma of the lung on follow-up. This study demonstrated the rarity of systemic sclerosis in our centre with considerable lag time to diagnosis in our patients. Diffuse cutaneous systemic scleroderma is more common in our centre with rare pulmonary hypertension and renal involvement.
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PMID:Systemic sclerosis in Sarawak: a profile of patients treated in the Sarawak General Hospital. 1937 65

In patients with atrial fibrillation, a betablocker is generally used initially to prevent recurrence or to slow the heart rate. Amiodarone is a last resort, mainly because of its numerous adverse effects. Dronedarone, chemically similar to amiodarone,was recently authorised for this indication in the European Union. In a double-blind trial versus amiodarone in 504 patients, the failure rate was significantly higher with dronedarone (75.1% versus 58.8%). Two placebo-controlled trials in heart failure patients yielded conflicting results. Dronedarone was associated with a statistically significant increase in mortality in a trial in 627 symptomatic patients free of arrhythmias. However, there was no statistically significant difference in a trial including 4630 patients with atrial fibrillation and a lower risk of cardiovascular events. There are no comparative trials versus other antiarrhythmic drugs or heart-rate-lowering agents, including betablockers and calcium channel blockers. Like other antiarrhythmic drugs, dronedarone also has arrhythmogenic effects, including bradycardia and QT prolongation. Other adverse effects include diarrhoea, nausea and vomiting, and cutaneous disorders. Transient elevation of creatinine levels is also frequent, and cases of renal failure have been reported. In the trial versus amiodarone, dronedarone had a different pattern of short-term adverse effects, including more gastrointestinal disorders but less frequent thyroid disorders, neurological disorders, hypersensitivity reactions, hypertension, and QT prolongation. Little is known of potential long-term adverse effects, especially pulmonary fibrosis. In practice, dronedarone is better tolerated but less effective than amiodarone in the short term.When antiarrhythmic drug therapy is needed, it is better to continue to use a betablocker or, as a last resort, amiodarone, a drug with better-documented adverse effects, especially during long-term treatment.
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PMID:Dronedarone. atrial fibrillation: too many questions about long-term adverse effects. 2093 39