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)

Cyclic nucleotides play an important role in the regulation of fibroblast proliferation and collagen metabolism. In the present study, the antifibrotic potential of dibutyrylcAMP (Bt2cAMP) was evaluated in the bleomycin (BLM)-hamster model of pulmonary fibrosis. Bt2cAMP (10 mg kg-1, s.c.) or saline (SA, s.c.) was given daily two days prior to the first intratracheal (i.t.) dose of BLM or SA and thereafter throughout the study. BLM or SA was instilled i.t. in three consecutive doses (2.5, 2.0 and 1.5 U 5ml-1 kg-1) at weekly intervals. Hamsters were killed at 7, 14 and 20 days after the third i.t. instillation. Bt2cAMP significantly reduced the contents of lung hydroxyproline and lung thiobarbituric acid reactive substance equivalents in BLM-treated animals at 7 and 14 days. Bt2cAMP significantly elevated lung superoxide dismutase activity in BLM-treated animals at 7 days. Lung prolyl hydroxylase activity was significantly elevated at 14 and 20 days in SABLM- and Bt2cAMPBLM-treated animals. The ratio of cAMP/cGMP was significantly reduced at all time points in SABLM-treated animals but only at 7 and 14 days in Bt2cAMPBLM-treated animals. Bt2cAMP caused no significant changes in lung calcium and calmodulin levels and protein content of the bronchoalveolar lavage. BLM significantly increased various inflammatory cell counts in the lavage at all three time points. The cell counts in the Bt2cAMPBLM groups were generally lower at 7 days and higher at 20 days than those of the SABLM groups. Histological evaluation showed that the lungs of Bt2cAMPBLM-treated hamsters progressed from an inflammatory cell lesion to a fibrotic lesion at a slower rate than the SABLM groups. It was concluded that Bt2cAMP attenuated BLM-induced pulmonary fibrosis in hamsters in part by delaying the acute phase of the inflammatory reaction.
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PMID:Effects of dibutyrylcyclic adenosine monophosphate on bleomycin-induced lung toxicity in hamsters. 137 23

The development of bleomycin-induced pulmonary fibrosis in rats was studied over a period of 30 days after an intratracheal instillation of bleomycin. Fibronectin was visualized in histological sections and quantified in bronchoalveolar lavage fluid (BALF) and related to simultaneous measurements of hyaluronan, collagen and albumin in BALF and/or lung tissue extracts. An increase in BALF fibronectin levels was noted after 3 days and the peak value a sixty fold increase was noted at day 7. Thereafter, the fibronectin levels declined and reached control values on day 21. A pronounced, patchily distributed staining for fibronectin appeared in the injured alveolar tissue parallel to the increased lavage fluid fibronectin levels on days 3-7. A fainter, streakily distributed fibronectin staining remained within the alveolar walls in areas with proliferating fibroblasts on days 14-30. Albumin in BALF increased to a peak level, 20 times control values, after 3 days and then rapidly declined. Thus, the ratio of fibronectin to albumin increased to a peak value of 43 times control values on day 7, indicating that plasma leakage cannot be the only source of the observed increase in lavage fibronectin. Lung tissue hydroxyproline increased between days 7 and 30, whereas extractable hyaluronan in lung tissue and bronchoalveolar lavage fluid peaked on days 3-7 and then gradually declined towards normal values on days 21-30. These data demonstrate that fibronectin accumulates in the alveolar tissue during the early inflammatory phase of the bleomycin-induced lung injury, parallelling hyaluronan accumulation and preceding the development of pulmonary fibrosis.
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PMID:Alveolar accumulation of fibronectin and hyaluronan precedes bleomycin-induced pulmonary fibrosis in the rat. 137 89

Pulmonary changes induced in a murine model by intraperitoneal injections of bleomycin were morphologically studied by light and electron microscopy. The number of pulmonary macrophages and the distribution of fibronectin in these cells were evaluated by acid phosphatase and affinity staining using anti-fibronectin horseradish peroxidase conjugates. The onset of acute inflammation occurred 4 days after intraperitoneal injection of bleomycin and reached its peak on the 14th day post-injection. The inflammatory reaction then gradually decreased. Areas of subpleural fibrosis was observed on day 42. On day 14, the ratio of the macrophage in bleomycin-treated mice to that in control mice was 5:1. Many activated and foamy macrophages were observed at that time. These findings indicate that macrophage turnover activity is remarkably increased during the acute inflammatory phase. Fibronectin was detected in the cytoplasm of macrophages on day 14, 21, and 28. It was also detected in both alveolar capillary and epithelial basal lamina as well as in interstitial collagen fibers. On day 42, fibronectin staining was strongly positive in areas of subpleural fibrosis. These results suggest that fibronectin released from pulmonary macrophages plays a role in the process of pulmonary fibrosis.
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PMID:[A morphological study of pulmonary macrophages in bleomycin-injected murine models]. 137 83

The bleomycin (BL)-hamster model of interstitial pulmonary fibrosis (IPF) is generally associated with increased lung lipid peroxidation, measured as malondialdehyde equivalent (MDAE), calcium and collagen content; and superoxide dismutase (SOD), prolyl hydroxylase (PH) and poly(ADP-ribose) polymerase activities. We found that combined treatment with taurine in drinking water (1%) and niacin IP (250 mg/kg) daily, significantly decreased the BL-induced increases in lung MDAE and calcium content, and SOD, PH and poly(ADP-ribose) polymerase activities. This treatment almost completely ameliorated the BL-induced increases in the lung collagen accumulation as well. Findings of a similar nature were also demonstrated when taurine (2.5%) and niacin (2.5%) were supplemented in the diet of hamsters used in the same BL model of IPF. The diet supplemented with taurine (2.5%), niacin (2.5%), or taurine (2.5%) + niacin (2.5%) also reduced AD-induced increases in lung collagen accumulation, phospholipids, MDAE and SOD activity. It was concluded that diet supplemented with taurine and/or niacin would completely or partially ameliorate chemically-induced pulmonary fibrosis.
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PMID:Taurine and niacin offer a novel therapeutic modality in prevention of chemically-induced pulmonary fibrosis in hamsters. 138 Jul 62

With the purpose of evaluating the therapeutic effect of colchicine on lung fibrosis in rats, bleomycin A5 (BLM-A5) was injected intratracheally to produce a lung fibrosis model. The animals were then treated with colchicine, 50 micrograms/d i.m. One month later, collagen fiber deposition scores (stained by Masson trichrome) were significantly lower in the treated group than in the untreated group (P less than 0.01). This result was proved further by assaying total lung hydroxyproline content (P less than 0.05). Histopathologic findings showed that the proliferation of fibroblasts dropped slightly in the treated group as compared with the untreated group. From this study, we conclude that colchicine has certain antifibrotic effects and may be used in the treatment of pulmonary fibrosis.
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PMID:The protective effect of colchicine on bleomycin-induced pulmonary fibrosis in rats. 138 84

Sixteen beagles were allocated into 4 groups, each group consisting of 2 males and 2 females, which were injected sc with 1,3,5 or 7 mg paraquat/kg. The beagles were observed for 2 w after the administration. At the end of the observation period all the dying and surviving dogs were studied pathologically. The LD50 was calculated as 1.8 (1.0-6.1) in males and 3.5 (2.4-10.1) mg/kg in females. Clinical laboratory tests showed increases in segmented neutrophils and monocytes, decreases in lymphocytes, slight decreases in chloride, moderate increases in BUN, GOT, GPT and phospholipids, slight increases in uric acid, total protein, creatine, total cholesterol and total bilirubin, and prolonged prothrombin times. Marked edema, congestion and hemorrhage of lungs, as well as slight congestion in various organs, were observed grossly. In histopathological examination, marked pulmonary hemorrhage and congestion, fibroblast-like cells in alveolar septa, breakdown of alveolar walls, thickening of alveolar walls and pleura, mild congestion and degeneration of the liver, and mild degeneration of renal tubules were observed. The cause of death was respiratory distress and renal failure. The surviving animals had mild atelectasis of the lungs. Electromicroscopic examination on the surviving animals revealed the appearance of spindle-shaped cells, proliferation of type II alveolar cells and fibroblasts, mitosis of fibroblasts, and abundant collagen fiber in the lung, calcium deposition, stratification and thickening of basement membranes, and localized necrotic epithelial cells in the proximal tubules of kidneys, and stratification of intramitochondrial cristae of the liver. Pulmonary fibrosis in the switchover stage was present with participation from type II alveolar cells, fibroblasts and myofibroblasts.
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PMID:Acute toxicological studies on paraquat: pathological findings in beagle dogs following single subcutaneous injections. 150 67

Pulmonary fibrosis is a feared sequelae of paracoccidioidomycosis. We sought to determine if mice exposed to Paracoccidioides brasiliensis conidia would develop pulmonary fibrosis. BALB/c mice were infected intranasally with P. brasiliensis conidia and sacrificed at regular intervals. One lung was sectioned for histopathology and sections were stained with haematoxylin and eosin, trichromic and argentic stains; the other lung was homogenized and cultured to determine the viability of the fungus. One week post-challenge, only small peribronchial foci were apparent. After 4 weeks, reticular fibres appeared disorganized and disrupted. Six to 8 weeks later peribronchial infiltrates were larger and appeared surrounded by reticular fibres; thick collagen I fibres were noticed in the infiltrated areas at this time. On weeks 10-12, infiltrates were confluent and reticular fibres were concentrated around the inflammatory foci; collagenization was apparent. Observations up to 16 weeks revealed diffuse involvement of the lung parenchyma with extensive collagenization. Lung cultures were always positive. We suggest that inhalation of P. brasiliensis conidia induces adverse lung responses leading to changes in the proportion of collagen fibres I and III.
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PMID:Development of pulmonary fibrosis in mice during infection with Paracoccidioides brasiliensis conidia. 151 56

Rats were exposed to saline or cadmium chloride (CdCl2) at 25, 100, or 400 micrograms/kg body weight by intratracheal instillation. At 3, 7, 14, and 28 days after exposure five animals/treatment were euthanized, the lungs were lavaged, and bronchoalveolar lavage fluid (BALF) was analyzed for lactate dehydrogenase (LDH), total protein, N-acetylglucosamindase (NAG), and cell number, type, and viability. Lung hydroxyproline concentration was characterized as a marker of lung collagen. Alveolar macrophages (AM) obtained in BALF were cultured and the release of fibronectin and TNF was determined. Lung tissue was examined microscopically at 28 and 90 days after exposure. Exposure to CdCl2 resulted in lung injury and inflammation demonstrated by increases in BALF LDH, total protein, NAG, and inflammatory cells. AM TNF release was not significantly changed by CdCl2 treatment. All doses of CdCl2 stimulated AM fibronectin secretion, a response which persisted throughout the 28-day postexposure period examined. Pulmonary fibrosis was demonstrated biochemically and/or histologically (trichrome staining tissue) at all CdCl2 dose levels. The association of CdCl2-induced AM fibronectin release with lung fibrosis confirms and extends previous observations relating AM-derived fibronectin to the development of interstitial lung disease and provides further evidence that the persistent increase in AM fibronectin release represents an early indicator of fibrosis.
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PMID:Stimulation of rat alveolar macrophage fibronectin release in a cadmium chloride model of lung injury and fibrosis. 152 50

Bronchopulmonary dysplasia (BPD) is a common pulmonary complication in preterm infants that leads to fibrosis of the bronchoalveolar walls and often to severe clinical consequences. Type III collagen is deposited early in progressive fibrosis. Because the N-terminal propeptide of type III collagen (PIIINP), a by-product of type III collagen synthesis, reflects the degree of pulmonary fibrosis in adults, we hypothesized that PIIINP in tracheal aspirates and/or serum may be a useful early marker of developing BPD in neonates. We serially measured PIIINP in tracheal fluid and serum samples during the first weeks of life in 41 consecutive respirator-treated preterm infants (mean birth weight 1067 g, mean gestational age 28.3 wk). Eight of the infants died and 22 infants fulfilled the criteria for BPD at age 28 d. The mean level of PIIINP decreased with advancing postnatal age in tracheal fluid but not in serum. The mean tracheal fluid PIIINP during d 1 and 2 of life, respectively, was 175 and 200 ng/mg protein in infants who were still in a respirator at age 28 d (n = 13), 122 and 97 ng/mg protein in those who were weaned earlier (n = 20), and 50 and 30 ng/mg protein in those who died before age 28 d (n = 8). These differences are not statistically significant, and the variability of the values was large. The PIIINP concentrations in tracheal aspirates of infants subsequently developing BPD did not differ from those without BPD. Neither did the levels correlate with the degree of BPD or radiologically defined fibrosis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:N-terminal propeptide of type III collagen in tracheal fluid and serum in preterm infants at risk for bronchopulmonary dysplasia. 157 Feb

The in vivo role of interferons in the development of fibrosis is not fully understood but it is known that interferons can suppress fibroblast proliferation and collagen synthesis in vitro. We have recently demonstrated that in a group of patients with sarcoidosis having predominant pulmonary involvement, patients with the highest levels of circulating interferon-gamma (IFN-gamma) more frequently resolved on corticosteroids, suggesting that they had a less 'fibrotic' component to their disease. We now report that in two other diseases, where the tendency to develop pulmonary fibrosis is greater than in sarcoidosis, namely cryptogenic fibrosing alveolitis (CFA) and fibrosing alveolitis associated with the systemic connective tissue disease progressive systemic sclerosis (FA + PSS), very few patients have elevations in IFN-gamma in their serum. However, as in sarcoidosis, those with the highest levels responded to corticosteroids (P less than 0.05). Attempts to measure IFN-gamma levels in the lungs, using cell-free bronchoalveolar lavage (BAL) fluid supernatants, were negative in all the study groups, suggesting that these samples may be inadequate for such studies. To investigate whether there might be an intrinsic defect in T lymphocyte function associated with predisposition to fibrosing lung diseases, we then investigated the in vitro production of IFN-gamma by lymphocytes separated from the blood of 18 untreated patients (six with CFA, six with FA + PSS and six with sarcoidosis). IFN-gamma production was impaired in 10 (56%) (two with CFA, four with FA + PSS and four with sarcoidosis). A higher proportion of the fibrosing alveolitis patients (CFA or FA + PSS) with impaired IFN-gamma production have subsequently shown spontaneous lung functional deterioration. These findings suggest that impaired IFN-gamma release might be a potentiating factor in the pathogenesis of these fibrosing lung diseases.
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PMID:In vivo levels and in vitro production of interferon-gamma in fibrosing interstitial lung diseases. 157 93


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