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)

Bleomycin (BLM) induces lung inflammation and subsequent fibrosis in humans and animal models. We hypothesized that monocytes-macrophages represent target cells for BLM toxicity and participate in the initial stages of pulmonary inflammation. We developed an animal model of early lung lesions using systemic administration of BLM (2 U.100 g-1 body weight over 5 days) (BLM-rats). We observed a significant decrease in body weight and in serum angiotensin converting enzyme activity in BLM-rats as compared to matched controls rats, but no evidence of fibrosis was seen in optic microscopy of the lungs from BLM-rats. In contrast, electron microscopy revealed accumulation of intracapillary polymorphonuclear leucocytes and unusual presence of eosinophils. We then investigated the in vivo effects of BLM on the respiratory burst of monocytes-macrophages. As compared to control rats, production of superoxide (O2-) by alveolar macrophages from BLM-rats was increased upon stimulation with either phorbol myristate acetate (21.04 +/- 2.78 versus 11.45 +/- 2.26 nmol.10(6) cells.20 min-1, p less than 0.05) or opsonized zymosan (9.35 +/- 0.87 versus 7.03 +/- 0.66 nmol.10(6) cells.20 min-1, p less than 0.05). We also found in BLM-rats an increased number of circulating monocytes and an increased production of O2- by these cells. Monocytes-macrophages may represent a target cell in the early events of BLM toxicity in vivo and the increased production of O2- by these cells participates in tissue injury in pulmonary fibrosis.
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PMID:Bleomycin primes monocytes-macrophages for superoxide production. 170 65

A model of pulmonary fibrosis caused by a single intratracheal injection 0.1 mg pingyangmycinum in mice was reported. The effect of tetrandrine, a herbal powder, 50 mg/kg time, on the pathological development of pulmonary fibrosis, and the activity of superoxide dismutase (SOD), angiotensin converting enzyme (ACE), quantity of hydroxyproline (HYP) in this mice model were investigated. We also contrast tetrandrine with cortisol. The result showed that tetrandrine may inhibit the formation and development of pulmonary fibrosis. On the other hand, tetrandrine and cortisol may increase the activity of SOD of lung tissue, reduce the quantity of HYP of lung tissue and decrease the activity of serum ACE.
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PMID:[A study on the inhibition effect of tetrandrine on the pingyangmycinum induced pulmonary fibrosis]. 172 67

Male rats were exposed to single doses (0-30 Gy) of 60Co gamma rays to the right hemithorax. Half of each dose group consumed only control powdered chow after irradiation, and half consumed feed containing 0.10% (w/w) pentoxifylline (50 mg/kg/day). The severity of epilation and desquamation in the field of the radiation port was scored weekly. Two months after irradiation the animals were killed, and pulmonary endothelial function was monitored by the activity of lung angiotensin converting enzyme (ACE) and plasminogen activator (PLA), and by production of prostacyclin (PGI2) and thromboxane (TXA2). The amount of hydroxyproline (HP) in the lung served as an index of pulmonary fibrosis. Radiation produced a dose-dependent decrease in ACE and PLA activity in the right lung and an increase in the production of PGI2 and TXA2. This endothelial dysfunction was accompanied by an increase in wet weight and in protein and HP content in the irradiated lung. Pentoxifylline spared only the increase in lung wet weight and protein content, and actually elevated the radiation-induced hyperproduction of PGI2 and TXA2. The severity of the epilation and desquamation reactions increased with increasing radiation dose and time but was independent of diet. These data indicate that pentoxifylline, despite some promising pharmacological actions, has no beneficial effect on acute radiation reactions in rat lung and skin.
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PMID:Pentoxifylline does not spare acute radiation reactions in rat lung and skin. 172 51

The present study determined whether inhibitors of angiotensin converting enzyme (ACE) can ameliorate radiation-induced pulmonary endothelial dysfunction and pulmonary fibrosis in rats sacrificed 2 months after a range of single doses of 60Co gamma rays to the right hemithorax. Four indices of pulmonary endothelial function were monitored: right lung ACE and plasminogen activator (PLA) activity, and prostacyclin (PGI2) and thromboxane (TXA2) production. Hydroxyproline (HP) content served as an index of pulmonary fibrosis. Rats consumed either control powdered chow or feed containing one of five modifying agents continuously after irradiation. The modifiers included three ACE inhibitors: Captopril, CL242817, and CGS13945, respectively, a thiol, a thioacetate, and a nonthiol compound. All of the ACE inhibitors are analogues of proline. Two additional modifiers were tested: penicillamine, a thiol with no ACE inhibitory activity; and pentoxifylline, a vasodilator that is neither a thiol nor an ACE inhibitor. Radiation produced a dose-dependent decrease in lung ACE and PLA activity, and an increase in PGI2 and TXA2 production and in HP content. All ACE inhibitors attenuated the radiation-induced suppression in lung ACE and PLA activity. All thiol or thioacetate compounds ameliorated the radiation-induced increase in PGI2, TXA2, and HP. The two agents that were both thiols and ACE inhibitors (Captopril and CL242817) spared all of the radiation reactions, while the compound that was neither a thiol nor an ACE inhibitor (pentoxifylline) spared none of the reactions. These data suggest a novel application for ACE inhibitors in general, and for Captopril in particular, as modifiers of radiation pneumotoxicity.
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PMID:Radiation pneumotoxicity in rats: modification by inhibitors of angiotensin converting enzyme. 173 1

Substantial differences between mouse strains have been reported in the lesions present in the lung during the early phase of radiation injury. Some strains show only classical pneumonitis, while other strains develop substantial fibrosis and hyaline membranes which contribute appreciably to respiratory insufficiency, in addition to pneumonitis. Other strains are intermediate between these extremes. These differences correlate with intrinsic differences in activities of lung plasminogen activator and angiotensin converting enzyme. The genetic basis of these differences was assessed by examining histologically the early reaction in lungs of seven murine hybrids available commercially after whole-thorax irradiation. Crosses between fibrosing and nonfibrosing parents were uniformly nonfibrosing, and crosses between fibrosing and intermediate parents were uniformly intermediate. No evidence of sex linkage was seen. Thus the phenotype in which fibrosis is found is controlled by autosomal recessive determinants. Strains prone to radiation-induced pulmonary fibrosis and hyaline membranes exhibited intrinsically lower activities of lung plasminogen activator and angiotensin converting enzyme than either the nonfibrosing strains or the nonfibrosing hybrid crosses. The median time of death of the hybrids was genetically determined primarily by the longest-lived parent regardless of the types of lesions expressed.
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PMID:The genetic basis of strain-dependent differences in the early phase of radiation injury in mouse lung. 185 22

Procollagen III aminopeptide (P-III-P), a peptide released during the conversion of type III procollagen to type III collagen, is considered a potential marker of fibroblast activity in a variety of pulmonary and extrapulmonary diseases. The aim of the present article was to investigate the levels of P-III-P in serum samples (sP-III-P) from a large number of sarcoid patients, in particular looking at its relationship with other markers of disease activity and its presumed role as a marker of pulmonary fibrosis. sP-III-P has been radioimmunoassayed in an overall series of 57 patients and the levels were higher (19.18 +/- 9.17 ng/ml) than in 25 age- and sex-matched controls (11.32 +/- 2.15 ng/ml; p less than 0.001). The elevation was neither sex-related nor related to obvious liver sarcoid localization. Although sP-III-P levels were slightly higher in patients with stage II, there was no significant difference in patients with stage I or III. We found a positive relationship with serum angiotensin-converting enzyme (S-ACE) levels (p less than 0.04), but not with other markers of disease activity (67Ga uptake, bronchoalveolar lavage [BAL] lymphocyte percent, vital capacity, and lung diffusing capacity). The relationship with S-ACE was confirmed in a longitudinal follow-up study, where sP-III-P strictly paralleled the S-ACE behavior. Finally, the initial sP-III-P levels did not predict cases either with disease relapse or resistance to corticosteroid treatment. We conclude that, in our study, sP-III-P levels failed to characterize sarcoid patients with radiologic fibrotic pattern (stage III), and, in addition, were unable to predict which patients would have a poor prognosis. Rather, they reflect a metabolic activity of sarcoid granuloma cells. Thus, the usefulness of sP-III-P in the treatment of patients with sarcoid may be considered similar to that of S-ACE.
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PMID:Elevated serum procollagen III aminopeptide levels in sarcoidosis. 217 97

More than a century ago, Jonathan Hutchingson, a surgeon-dermatologist, identified the first case of sarcoidosis at King's College, London. The disease is now known as a commonplace multisystem disorder characterized by the formation of noncaseating granulomata. The diagnosis of sarcoidosis is established by recognizing clinicoradiologic findings and providing histologic evidence of non-caseating granuloma. Serum angiotensin converting enzyme levels are high in about two thirds of the patients and hypercalcemia is a feature in one of every ten victims of sarcoidosis. Immunologic abnormalities include depression of cutaneous delayed-type hypersensitivity, accumulation of T-cells at the site of activity, hyperactive B-cells, and the presence of circulating immune complexes. The course and prognosis of the disease usually correlate with the mode of onset. An acute onset with erythema nodosum indicates a good prognosis and spontaneous resolution; whereas, an insidious onset may be followed by relentless, progressive fibrosis. Mortality and morbidity are caused by pulmonary fibrosis, cardiac arrhythmias, renal failure, neurologic involvement, and blindness. Corticosteroids and chloroquine relieve symptoms and suppress inflammation and granuloma formation.
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PMID:Sarcoidosis. 220 9

Sarcoidosis can affect almost every organ. It has diverse clinical presentations and a variable natural history. Lungs and intrathoracic lymph nodes are the most commonly involved tissues. A major challenge to clinicians is the early identification of those patients with aggressive disease in whom therapy might arrest progression. Although lung uptake of 67Ga citrate, elevated serum angiotensin converting enzyme (ACE) levels and elevated T lymphocyte count in bronchoalveolar lavage fluid are all thought to reflect disease activity, they are by no means reliable markers. Because recent studies have shown that corticosteroid treatment does not avert pulmonary fibrosis and permanent impairment of pulmonary function, the use of these agents is restricted to the palliative treatment of disabling symptoms and physiological derangements. Corticosteroids are effective in reducing ocular inflammation, correcting hypercalcaemia, improving pulmonary function and alleviating symptoms related to hepatic, splenic, articular, myocardial, neural and cutaneous involvement. In the small proportion of patients who do not respond to moderate tolerable doses of steroids, alternative drug therapy such as immunosuppressives or immune modulators must be considered.
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PMID:Current concepts in the management of sarcoidosis. 222 14

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

C57BL mice exposed to 14 Gy of whole-thorax irradiation develop significant histologic lung fibrosis within 52 weeks, whereas CBA and C3H mice do not exhibit substantial fibrosis during this time. The purpose of the present study was to determine whether this strain-dependent difference in radiation histopathology is associated with genetic differences in pulmonary endothelial metabolic activity or in endothelial radioresponsiveness. C57BL/6J, C57BL/10J, CBA/J, and C3H/HeJ mice were sacrificed 12 weeks after exposure to 0 or 14 Gy of 300-kV X rays to the whole thorax. Lung angiotensin converting enzyme (ACE) activity and plasminogen activator (PLA) activity were measured as indices of pulmonary endothelial function; and lung hydroxyproline (HP) content served as an index of pulmonary fibrosis. Lung ACE and PLA activities in sham-irradiated C57BL/6J and CB57BL/10J mice were only half as high as those in sham-irradiated CBA/J and C3H/HeJ mice. Exposure to 14 Gy of X rays produced a slight but nonsignificant reduction in lung ACE and PLA activity in the C57BL strains, and a significant reduction in the CBA/J and C3H/HeJ mice. Even after 14 Gy, however, lung ACE and PLA activities in CBA/J and C3H/HeJ mice were higher than those in sham-irradiated C57BL/6J and C57BL/10J mice. Lung HP content in all four strains increased significantly after irradiation, but this increase was accompanied by an increase in lung wet weight. As a result, HP concentration (per milligram wet weight) remained constant or increased slightly in both C57BL strains and actually decreased in the CBA/J and C3H/HeJ mice. These data demonstrate significant genetic differences in both intrinsic pulmonary endothelial enzyme activity and endothelial radioresponsiveness among the four strains of mice. Specifically, strains prone to radiation-induced pulmonary fibrosis (C57BL/6J, C57BL/10J) exhibit only half as much lung ACE and PLA activity as do strains resistant to fibrosis (CBA and C3H).
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PMID:Radiation-induced pulmonary endothelial dysfunction and hydroxyproline accumulation in four strains of mice. 255 96


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