Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0034069 (
pulmonary fibrosis
)
7,050
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Bleomycin produces a dose- and time-dependent interstitial
pulmonary fibrosis
in humans, and is widely used to produce an animal model for the study of interstitial
pulmonary fibrosis
. The mechanism(s) for bleomycin-induced
pulmonary fibrosis
is (are) unknown, but the production of
oxygen
radicals by a ferrous ion-molecular
oxygen
pathway might be related to the fibrosis. Therefore, we studied the effect of iron deficiency on the biochemical, inflammatory, and morphologic parameters of bleomycin-induced
pulmonary fibrosis
in the hamster. Mild iron deficiency was induced in hamsters by bleeding via the retro-orbital sinus and maintenance on an iron-deplete diet. After intratracheal administration of bleomycin (1 U), there was no accumulation of lung collagen in the iron-deficient bleomycin-treated animals. In comparison, iron-replete animals treated with bleomycin exhibited a significant (p less than 0.01) increase in lung collagen. In addition, bleomycin-treated iron-replete animals had increased lung lipid peroxidation (p less than 0.05), whereas bleomycin-treated iron-deficient animals did not (p greater than 0.05). Lung DNA and morphometric estimates of the lesion severity were significantly increased in both iron-replete and iron-deficient bleomycin-treated animals. These data indicate that iron deficiency is associated with a reduction in the severity of bleomycin-induced
pulmonary fibrosis
, possibly by the prevention of iron-catalyzed
oxygen
-radical formation and lipid peroxidation.
...
PMID:Effect of iron deficiency on bleomycin-induced lung fibrosis in the hamster. 244 14
Bleomycin is an antineoplastic compound which produces a time- and dose-dependent
pulmonary fibrosis
. The mechanisms which cause this fibrosis are not known. The ability of bleomycin to produce
oxygen
radicals in the presence of iron and molecular
oxygen
appears to be related to the fibrosis. Previous studies, which have examined single time points utilizing the ferric ion chelator deferoxamine and iron-deficient diets, suggest that iron plays a central role in bleomycin-induced
pulmonary fibrosis
. Therefore, the present study was designed to determine the effects of deferoxamine on the development of bleomycin-induced
pulmonary fibrosis
. Deferoxamine pretreatment and daily injections resulted in a significant reduction in lung collagen content and lung lipid peroxidation 21 days after intratracheal bleomycin compared with bleomycin treatment alone. In addition deferoxamine treatment significantly inhibited lung DNA increases at 4, 7, and 14 days after bleomycin treatment compared with bleomycin treatment alone. These data indicate that deferoxamine treatment reduces the development of bleomycin-induced
pulmonary fibrosis
in the later phase. The mechanism might be by the prevention of iron-catalyzed, free-radical formation and modulation of some cellular functions.
...
PMID:Modulation of the development of bleomycin-induced fibrosis by deferoxamine. 245 18
In 10 patients with precapillary pulmonary hypertension due to
pulmonary fibrosis
, the arterial blood pressure, right heart hemodynamics, cardiac output, and arterial
oxygen
partial pressure were measured to evaluate the benefits of acute sublingual (5 mg) nitrendipine. Additionally, the effect of
oxygen
enriched air was compared to control. At rest, nitrendipine significantly diminished arterial blood pressure [102 +/- 3 to 93 +/- 3 mm Hg (mean +/- SEM)], right atrial pressure (5.7 +/- 0.9 to 3.4 +/- 0.8 mm Hg), mean pulmonary artery pressure (33.4 +/- 3.5 to 29.8 +/- 3.3 mm Hg), and pulmonary artery wedge pressure (13.0 +/- 2.0 to 6.8 +/- 0.8 mm Hg). During exercise, nitrendipine reduced mean pulmonary artery pressure (54.5 +/- 4.8 to 49.3 +/- 4.7 mm Hg) and right atrial pressure (9.3 +/- 1.3 to 6.8 +/- 1.4 mm Hg). A diminuation of arterial partial
oxygen
pressure did not occur at rest (63.2 +/- 3.8 mm Hg) or during exercise (50.9 +/- 5.1 mm Hg). Thus, nitrendipine causes a slight but significant improvement of right heart hemodynamics. The occurrence of arteriovenous intrapulmonary shunting due to vasodilatating effects of nitrendipine can be excluded. Also, nitrendipine can safely be used in combined arterial hypertension and
pulmonary fibrosis
.
...
PMID:Effects of 5 mg sublingual nitrendipine in patients with precapillary pulmonary hypertension due to pulmonary fibrosis. 246 66
Bleomycin, an important cause of
pulmonary fibrosis
, is known to produce DNA damage. The mechanism for this damage in vitro is related to free radical production by a bleomycin and iron complex. To determine whether bleomycin causes damage to DNA in vivo by a similar mechanism, we used a viral minichromosome that is replicated in cultured cells. Bleomycin causes dose-dependent damage to intracellular DNA, and this damage is augmented by Fe2+ but not Fe3+. The augmentation of the bleomycin-induced DNA damage caused by Fe2+ is also dose dependent in that increasing DNA damage occurs with increasing amounts of Fe2+. These studies demonstrate that bleomycin causes damage to DNA in vivo and suggest that bleomycin must rely on Fe2+ to donate an electron for
oxygen
radical-induced DNA strand scission.
...
PMID:Augmentation of bleomycin-induced DNA damage in intact cells. 248 Jul 14
Twenty-three patients with pulmonary hypertension underwent right cardiac catheterization and measurement of their response to a short-term infusion of prostacyclin. Pulmonary vasodilation with a greater than 20 percent fall in PVR occurred in all five patients with primary pulmonary hypertension where the predominant lesions were plexogenic; in three out of five patients where the predominant lesions were thrombotic; in three out of five patients with pulmonary hypertension and obstruction of proximal vessels; in three out of five patients with COPD; in both patients with
pulmonary fibrosis
due to sarcoidosis; and in the one patient with pulmonary veno-occlusive disease, where the pulmonary vasodilation was offset by a fall in arterial
oxygen
content. Prostacyclin is a safe and effective drug to use for testing the response of the pulmonary circulation to a vasodilator in pulmonary hypertension due to different causes. Short-term testing for a vasodilator response, with a view to instituting long-term therapy, should not be restricted to those patients with primary pulmonary hypertension due to plexogenic pulmonary arteriopathy.
...
PMID:Pulmonary vasodilation with prostacyclin in primary and secondary pulmonary hypertension. 250 32
Bleomycin is a commonly used antineoplastic compound that can produce a dose- and time-dependent pneumonitis and fibrosis in humans. The mechanism of bleomycin-induced fibrosis is not known. However, current data suggest that the production of
oxygen
radicals by way of a ferrous ion-molecular
oxygen
mechanism might be related to the
pulmonary fibrosis
. Therefore, we evaluated the possibility that parenterally administered deferoxamine, an iron chelating compound, could modulate the morphologic and biochemical estimates of bleomycin-induced lung fibrosis in hamsters. Deferoxamine pretreatment and daily injection for 21 days after intratracheally administered bleomycin resulted in a 33% reduction in lung collagen accumulation compared with that after bleomycin treatment alone. However, fibrosis was still present in the bleomycin-deferoxamine group; the animals showed a 142 and 150% increase in lung collagen compared with that in saline- and deferoxamine-treated control animals, respectively. Morphologic estimates of the severity of fibrosis in the bleomycin-deferoxamine treatment group were reduced when compared with the bleomycin treatment group alone, but was increased compared with saline- and saline-deferoxamine-treated control animals. These data indicate that deferoxamine treatment reduces the severity of bleomycin-induced
pulmonary fibrosis
in hamsters. The mechanism might be by the prevention of iron-catalyzed, free-radical formation.
...
PMID:The effect of deferoxamine on bleomycin-induced lung fibrosis in the hamster. 258 89
A 61-year-old man was admitted to our hospital because of persisting cough, sputum and shortness of breath for four months. Brushing specimens and BALF bronchoscopically obtained revealed acid-fast bacilli and TBLB showed pathological findings consistent with interstitial pneumonia. Based on these results, clinical symptoms, chest roentgenograms on admission and identification of M. kansasii, a diagnosis of M. kansasii lung infection occurred in idiopathic pulmonary fibrosis was made. The patient's symptoms consistent with M. kansasii lung infection and his sputum became negative 6 weeks after antituberculosis chemotherapy with INH, SM and RFP. Because of an increasing dyspnea due to
pulmonary fibrosis
, however, the patient received
oxygen
therapy. This case suggested an increasing tendency of compromised hosts associated with M. kansasii lung infection.
...
PMID:[M. kansasii lung infection occurring in a compromised host with idiopathic pulmonary fibrosis]. 258 49
Three patients underwent single left lung transplantation for end-stage
pulmonary fibrosis
between June and November 1987. Preoperatively all were housebound, receiving continuous, supplemental
oxygen
, and their pulmonary function had deteriorated despite corticosteroid and cyclophosphamide therapy. Pulmonary preservation was by means of pulmonary arterial perfusion with modified Euro-Collins solution, 60 ml/kg, at 4 degrees C with adjunctive iloprost (synthetic prostacyclin) infusion. The heart from each donor was used successfully for transplantation. Good early graft function enabled extubation 11, 46, and 96 hours after transplantation. An omental wrap was used around the bronchial anastomosis, and bronchial healing was satisfactory in all. All patients had episodes of pulmonary rejection diagnosed by a combination of symptoms, chest x-ray infiltrates, the exclusion of pneumonitis by bronchoalveolar lavage, and prompt response to "pulse" steroid therapy. Two of the three patients had three episodes of opportunistic pulmonary infections: Herpes simplex pneumonitis, Pneumocystis carinii infection, and Aspergillus pneumonitis. The three patients were discharged from the hospital after 5, 6, and 7 1/2 weeks, respectively. The first and third patients remain alive and well, living essentially normal lives 24 and 19 months after transplantation with no evidence of arterial desaturation on exercise testing while breathing room air. The second patient had symptoms of deteriorating lung function with a progressive decline in forced expiratory volume in 1 second, vital capacity, and diffusion capacity despite repeated "pulse" therapy with combinations of methylprednisolone, antithymocyte globulin, and OKT3 (Ortho Diagnostic Systems Inc., Raritan, N.J.). An open lung biopsy specimen showed obliterative bronchiolitis, and this patient underwent orthotopic lung retransplantation, on the right side. Despite excellent early graft function and early extubation, he died of uncontrolled rejection and general debility after 3 weeks. This early experience in our center with two of three patients surviving 19 to 24 months, respectively, confirms the restoration of good pulmonary function and near normal life-style in patients with end-stage
pulmonary fibrosis
after single lung transplantation, as first reported by the Toronto Lung Transplant Group. We have used an alternative method of lung preservation (cold crystalloid pulmonary perfusion as opposed to topical cooling, used by the Toronto group), which provided excellent pulmonary preservation up to and beyond 4 hours' storage.(ABSTRACT TRUNCATED AT 400 WORDS)
...
PMID:Early results of single lung transplantation in patients with end-stage pulmonary fibrosis. 267 9
Reactive
oxygen
species (ROS) have been closely associated with a number of pathological disorders, including interstitial
pulmonary fibrosis
. While models of ROS-induced fibrosis offer advantages over chemically-induced fibrosis, the biochemical and morphological features of ROS-induced fibrosis have yet to be extensively documented. In this study, we evaluated the effect of initial ROS dose on lung injury and repair. Male hamsters received a single dose of glucose, glucose oxidase and lactoperoxidase via the intratracheal route. From 3 to 14 days post-treatment, a significant dose-related body weight loss was observed. There was a trend towards greater mortality with increasing dose. After 2 weeks, we noted significant, dose-related increases in lung levels of collagen, lipid peroxidation products, nucleic acids, and protein. Similarly, total lung catalase, lactic dehydrogenase and glutathione reductase activities were also elevated significantly above control values in a dose-related fashion. A concurrent, dose-dependent thickening of alveolar septa in ROS-treated lungs was composed of epithelial hyperplasia, hyperemia, edema and accumulations of interstitial fibers and macrophages. Interstitial and alveolar macrophages in ROS-induced lesions were enlarged and contained numerous primary and secondary lysosomes. These results demonstrate that, in the hamster lung, injury induced by enzyme-generated ROS can initiate dose-dependent fibroproliferative changes which eventuate into interstitial fibrosis.
...
PMID:Dose-related effects of enzyme-generated oxidants on the biochemistry and morphology of the hamster lung. 267 4
We investigated the prognosis of chronic respiratory diseases in children by questionnaires to the pediatric departments of 4 universities and 14 national or public hospitals in Fukuoka Prefecture. The total number of patients was 155, consisting of 77 males and 78 females. These diseases included bronchiectasis, which had the highest incidence (37, 23.9%), prolonged respiratory disorders in the newborn, pulmonary hypoplasia, pulmonary cysts and
pulmonary fibrosis
, etc. These 5 diseases comprised 65.8% of all cases. The number of cases on
oxygen
therapy was 9 (5.8%) and 5 of these 9 cases were on home
oxygen
therapy. A total of 18 cases (11.6%) were surgically treated. Of 155 cases, 91 cases were cured or improved, while 31 cases were unchanged, 6 cases deteriorated and 6 cases died. The prognosis of 21 cases was unknown. The number of cases whose daily activities were limited was 25 (16.1%).
...
PMID:[Prognosis of chronic respiratory diseases in children]. 269 83
<< Previous
1
2
3
4
5
6
7
8
9
10
Next >>