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Query: UMLS:C0034069 (pulmonary fibrosis)
 7,050 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Serum copper (Cu) concentration was evaluated as an index of lung injury in two rat models of pneumotoxicity: hemithoracic irradiation and monocrotaline ingestion. In both models there was a dose- and time-dependent increase in serum Cu concentration. This hypercupremia paralleled the development of pulmonary endothelial dysfunction (decreased lung plasminogen activator activity and increased prostacyclin production) and pulmonary fibrosis (hydroxyproline accumulation). In the radiation model, lung injury and hypercupremia persisted for at least 6 months, and were spared similarly when the total dose was delivered in multiple daily fractions as compared to single doses. In irradiated rats, the elevated serum Cu concentration was accompanied by increases in plasma ceruloplasmin, lung Cu concentration, and lung Cu/Zn superoxide dismutase (SOD) activity. In monocrotaline-treated rats, lung damage and hypercupremia also were accompanied by a reduction in liver Cu concentration, and by a direct correlation between the concentrations of Cu and SGOT in the serum. In both models, some but not all modifiers of lung damage (penicillamine, angiotensin converting enzyme inhibitors, pentoxifylline) also partially prevented the insult-induced hypercupremia. In contrast, serum iron concentration was largely independent of treatment in all experiments. These data suggest that elevated serum copper concentration is an accurate and minimally invasive index of lung injury in irradiated and monocrotaline-treated rats.
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PMID:Serum copper concentration as an index of experimental lung injury. 251 9

The purpose of this study was to characterize paraquat toxicity in monkeys and to determine the feasibility of using the monkey as an animal model for the study of paraquat-induced pulmonary fibrosis in humans. Sixteen Japanese monkeys (Macaca fuscata), more than 3.5 years of age, with bodyweight ranging from 3.2 kg to 10.2 kg, were randomly divided into two groups. They were administered paraquat dichloride (PQ) by injection (s.c.) at a dose of 2.0 mg/kg bodyweight (12 monkeys) or s.c. saline, at a dose of 0.2 ml/kg bodyweight (control group, 4 monkeys), every two days for a period of four to five times. Eight monkeys (66.7%) from the PQ treatment groups expired due to subchronic PQ toxicity from days 11 to 35. Four monkeys (33.3%) from the PQ treatment group and all four monkeys from the control group survived the observation period of 66 days. On day 66, all of the surviving monkeys were sacrificed and examined for possible histopathological changes and the lung hydroxyproline content was determined. Our results indicate that the concentration of free hydroxyproline and plasma fibronectin did not vary significantly. The serum ceruloplasmin for the monkeys of the PQ treatment groups was significantly increased from day 14 to 21, compared to the control group. Also the total lung collagen of both the expired and surviving monkeys in the PQ treatment groups was elevated significantly, compared to the control group. The monkeys can provide extensive opportunities for research on the mechanism and the treatment of PQ poisoning in man.
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PMID:Effect of paraquat on plasma fibronectin, serum free hydroxyproline, serum ceruloplasmin and lung collagen content in monkeys. 369 21

A cross-sectional study, with 1,237 employees solely exposed to hard alloy dust and 502 controls in four hard metal works and two tool and grinder manufacturers in China, was conducted. Results showed prevalence of symptoms of respiratory system, and abnormalities in lung function and serum level of ceruloplasmin and urine cobalt content in exposed group were significantly higher than those in controls. Eight cases of pneumoconiosis were detected by chest X-ray films with a prevalence of 0.65% and an average length of employment in dust environment of 25.2 years. It suggested hard alloy dust could cause pulmonary fibrosis and pneumoconiosis in exposed workers.
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PMID:[An epidemiologic study on pulmonary fibrosis caused by hard alloy dust]. 779 83

Tetrathiomolybdate (TM), a drug developed for the treatment of Wilson's disease, produces an antiangiogenic effect by reducing systemic copper levels. Several angiogenic cytokines appear to depend on normal levels of copper for activity. In both animal tumor models and in cancer patients, TM therapy has proved effective in inhibiting the growth of tumors. We have hypothesized that the activities of fibrotic and inflammatory cytokines are also subject to modulation by the availability of copper in a manner similar to angiogenic cytokines. As a first step in evaluating whether TM plays a therapeutic role in diseases of inflammation and fibrosis, we studied the effects of TM on a murine model of bleomycin-induced pulmonary fibrosis. Oral TM therapy resulted in dose-dependent reduction in serum ceruloplasmin, a surrogate marker of systemic copper levels. Significant decreases in systemic copper levels were associated with marked reduction in lung fibrosis as determined on the basis of histopathologic findings and a biochemical measure of fibrosis. The protection afforded by TM was also reflected in significantly reduced bleomycin-induced body-weight loss. In the next phase of this work, we will seek to determine the mechanisms by which TM brings about this therapeutic benefit.
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PMID:Tetrathiomolybdate therapy protects against bleomycin-induced pulmonary fibrosis in mice. 1262 2