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)

D-Penicillamine is used against a variety of diseases. For many years it has been successful in treating Wilson's disease, cystinuria and heavy-metal poisonings. It also proved to be effective against rheumatoid arthritis, scleroderma, chronic active hepatitis, pulmonary fibrosis and multiple sclerosis. However, the use of D-penicillamine is still limited owing to the frequent occurrence of considerable, though generally reversible, side effects. This article deals with the history of D-penicillamine as well as the methods of its synthesis, its pharmacokinetics, effects and side effects. In addition, the significance of the stereo isomeric L-penicillamine is discussed.
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PMID:[D-Penacillamine. From constituent of penicillins to significant drug]. 50 43

The purpose of this study was to determine whether Captopril (an angiotensin converting enzyme inhibitor) or D-penicillamine (an inhibitor of collagen crosslinking) can ameliorate pulmonary fibrosis induced by the plant alkaloid monocrotaline. Rats were randomly assigned to one of six treatment groups: (1) control; (2) Captopril, 60 mg/kg/day, p.o.; (3) D-penicillamine, 30 mg/kg/day, p.o.; (4) monocrotaline, 2.4 mg/kg/day, p.o.; (5) monocrotaline plus Captopril, as above; (6) monocrotaline plus penicillamine, as above; and were killed after 6 weeks of continuous drug administration. Monocrotaline-treated rats exhibited several anatomic correlates of pulmonary hypertension, including cardiomegaly, right heart enlargement, and muscularization of the pulmonary arteries and arterioles. These monocrotaline reactions were accompanied by decreased lung activities of angiotensin converting enzyme (ACE) and plasminogen activator (PLA), indicative of endothelial dysfunction; and by increased lung hydroxyproline concentration, indicative of interstitial fibrosis. The presence of interstitial fibrosis was confirmed by electron microscopy. When given concomitantly with monocrotaline, both Captopril and penicillamine partially prevented the cardiomegaly, right heart enlargement, and vascular muscularization. Both agents also diminished the decreased lung PLA activity and increased hydroxyproline concentration observed in monocrotaline-treated animals. Neither modifying agent influenced the monocrotaline-induced decrease in lung ACE activity. Compared with control rats, the rats receiving Captopril alone exhibited decreased heart weight and increased serum ACE activity, and animals receiving penicillamine alone did not differ significantly from control animals for any of the endpoints studied. These data demonstrate that Captopril and penicillamine ameliorate monocrotaline-induced pulmonary fibrosis in rats. Penicillamine, known to inhibit radiation-induced lung injury, thus is shown to be effective in a second model of pulmonary fibrosis. Perhaps more importantly, the hydroxyproline data demonstrate that the ACE inhibitor Captropril exhibits antifibrotic activity in monocrotaline-treated rat lung.
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PMID:Monocrotaline-induced pulmonary fibrosis in rats: amelioration by captopril and penicillamine. 299 75

We studied 12 patients with pulmonary fibrosis treated with D-Penicillamine in an attempt to regulate the collagen metabolism that is seriously affected in this group of patients. After six years follow-up we found a 33% survival rate compared to a 5% survival rate in patients treated with corticosteroids (p less than 0.01). Functional respiratory tests as well as quality of life were improved in all patients. No side effects attributable to D-Penicillamine were detected probably due to the fact that we used smaller doses than those reported in the treatment of other diseases of the connective tissue. We conclude that D-Penicillamine can be a useful alternative drug in the therapy of patients with pulmonary fibrosis.
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PMID:D-penicillamine in the therapy of fibrotic lung diseases. 395 84

The angiotensin converting enzyme (ACE) inhibitor captopril, a free-thiol compound used widely as an antihypertensive agent, also inhibits radiation-induced pulmonary fibrosis in rats (Ward et al., Int J Radiat Oncol Biol Phys 19:1405, 1990). In an attempt to clarify the antifibrotic mechanism of captopril in vivo, the present study examined the effect of the drug on proliferation of human lung fibroblasts in culture. Captopril produced a drug dose-dependent reduction in fibroblast proliferation and 3H-thymidine incorporation during a 24-72-hr incubation. This cytostatic action of captopril was not the result of cytotoxicity as assessed by trypan blue exclusion, or by 51Cr or lactate dehydrogenase (LDH) release. Fibroblasts stimulated to proliferate by basic FGF were more sensitive to the antimitotic effect of captopril than were unstimulated cells. The ability of captopril to inhibit 3H-thymidine incorporation was not reversed by exogenous angiotensin 2, and was not mimicked by the nonthiol ACE inhibitor lisinopril. These data indicate that the cytostatic effect of captopril was not attributable to ACE inhibition. Penicillamine, a thiol compound with virtually no ACE inhibitory activity, also reduced fibroblast 3H-thymidine incorporation, indicating that the antimitotic action of captopril may represent a nonspecific sulfhydryl effect. This study suggests that the antifibrotic activity of captopril in irradiated lung may result in part from a direct inhibition of fibroblast proliferation, particularly in fibroblasts responding to mitogenic stimuli.
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PMID:Captopril inhibits proliferation of human lung fibroblasts in culture: a potential antifibrotic mechanism. 811 54

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