Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0032285 (pneumonia)
 54,520 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have studied the pathogenesis of murine cytomegalovirus (MCMV) pneumonitis in immunocompetent ICR mice and in mice treated with cyclophosphamide (CP). Intranasal infection of immunocompetent mice with MCMV resulted in transient and self-limited pulmonary lesions. When mice were given 200 mg/kg of CP one day before virus infection, transient splenic atrophy and subsequent splenic hypertrophy were induced, and the lesions in the lung were markedly augmented in their number and size although there was no significant enhancement of the virus growth. The augmentation coincided with the period of splenic hypertrophy. A marked increase in the number of pulmonary lesions was also induced in mice given 100 mg/kg of CP every 4 days following the initial dose of 200 mg/kg. In these mice, however, continuous splenic atrophy and augmented replication of MCMV in the lung were observed. When the activity of xanthine oxidase (XO) in lung tissue homogenates was measured, the activity was found to significantly increase after intranasal infection with MCMV irrespective of CP administration and there was a good correlation between the elevation of XO activity and the degree of pathological changes in the lung. In addition, we found that the administration of allopurinol, a specific inhibitor of XO and superoxide dismutase, a superoxide radical scavenger, reduced the number of the pulmonary lesions. These results suggest that superoxide radicals are involved in the pathogenesis of MCMV-associated pneumonitis in ICR mice.
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PMID:Pathogenesis of cytomegalovirus-associated pneumonitis in ICR mice: possible involvement of superoxide radicals. 133 50

The authors describe the status of lipid peroxidation (diene conjugates and malonic dialdehyde) and the endogenous antioxidant enzyme superoxide dismutase in the course of the treatment of patients with acute focal pneumonia by means of the use of transthoracic intrapulmonary injections of unithiol and autologous ultraviolet blood radiation (AUVBR). Three groups of patients were entered into the study. The first group included 64 patients who were given transthoracic intrapulmonary injections of unithiol, the second group 58 patients who received 5-7 sessions of AUVBR, in the third group, 52 patients were given transthoracic intrapulmonary injections of unithiol coupled with 3-5 sessions of AUVBR. The control group was made up of 40 patients given intravenous unithiol injections in routine therapeutic doses. The results of the treatment evidence that combined correction of lipid peroxidation carried out in the third group patients was most effective. As regards the times, the positive dynamics of lipid peroxidation and superoxide dismutase activity correlated with the clinical, biochemical and x-ray improvement. Therefore the method of correction in question is a pathogenetically based approach, permitting one to enhance the clinical efficacy of the treatment of patients suffering from acute focal pneumonias and to reduce the times of their stay in the hospital by 5-7 days, on the average.
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PMID:[The clinical efficacy of treating patients with acute pneumonias by using drug and quantum correction of the lipid peroxidation-antioxidant system]. 144 Feb 70

Eosinophils (EOs) participate in a variety of inflammatory states characterized by endothelial cell damage, such as vasculitis, pneumonitis, and endocarditis. We find that 100 U/ml TNF-alpha/cachectin (TNF), a concentration attainable in the blood of humans with parasitic infestations, stimulates highly purified populations of EOs to damage human umbilical vein endothelial cells (HUVEC), a model of human endothelium. This TNF-dependent EO cytotoxicity is strongly inhibited by heparin and methyprednisolone but unaffected by the platelet-activating factor antagonist BN52012 or scavengers of superoxide anion and H2O2, superoxide dismutase and catalase. However, addition of a physiologically relevant concentration of Br- (100 microM) enhances EO/TNF damage to HUVEC, implicating the possible participation of EO peroxidase (EPO) in the killing mechanism. EOs adherent to FCS-coated plastic wells more than double their production of superoxide anion and the cytotoxic EPO-derived oxidant HOBr when exposed to TNF, showing that TNF activates the respiratory burst of EOs attached to a "physiologic" surface. Unlike PMNs, EOs were not irreversibly activated to kill unopsonized endothelium by previous exposure to TNF, and did not degranulate or upregulate CR3 expression as detected by Mo1 in the presence of 100 U/ml TNF. HUVEC exposed 18 h to TNF were considerably more susceptible to lysis by PMA-activated EOs and reagent H2O2, demonstrating a direct effect of TNF upon endothelium, perhaps through inhibition of antioxidant defenses. These findings suggest that abnormally elevated serum levels of TNF may provoke EOs to damage endothelial cells and thereby play a role in the pathogenesis of tissue damage in hypereosinophilic states.
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PMID:Tumor necrosis factor alpha/cachectin stimulates eosinophil oxidant production and toxicity towards human endothelium. 197 79

To investigate the involvement of oxygen free radicals and their scavenger systems in the defenses of compromised hosts against pulmonary infections, we determined superoxide anion (SOA) and superoxide dismutase (SOD; EC 1.15.1.1) concentrations in the blood of compromised hosts and noncompromised hosts, with or without pneumonia. In the compromised hosts without pneumonia (compromised controls), SOD concentrations were lower than in noncompromised hosts (healthy controls). However SOA values in compromised controls did not differ statistically from that in healthy controls. Similar changes were observed in noncompromised hosts with pneumonia. In compromised hosts with pneumonia, SOD concentrations were further decreased by pulmonary infections. By contrast, SOA values were increased in pneumonia. There were, however, no differences in the values for ceruloplasmin among all the groups. The values for alpha 2-macroglobulin and alpha1-antitrypsin were within normal limits in compromised controls but were greater in compromised hosts with pneumonia. These results suggest that a decreased activity concentration of SOD in compromised controls may be partly responsible for the depression of the host's immune defenses.
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PMID:Concentrations of superoxide dismutase and superoxide anion in blood of patients with respiratory infections and compromised immune systems. 244 6

Amiodarone (ADR), a new antiarrhythmic drug for life-threatening cardiac arrhythmias, causes pneumonitis or lung fibrosis in a sizeable minority of patients. The cause of lung damage is not known. We have shown that infusion of 10 mg amiodarone into the inflow circuit of ventilated and perfused rabbit lungs causes immediate increase in pulmonary artery pressure (mean +/- SEM) (from 13.6 +/- 1.2 to 40.6 +/- 9.5 mm Hg, p less than 0.01) and pulmonary edema with marked increase in the pulmonary generation of thromboxane and leukotrienes C4 and/or D4. Albumin (2 g%) in the perfusate prevents any increase in lung perfusion pressure or edema formation. When lung perfusion pressure increase is blocked with the combined cyclooxygenase and lipoxygenase inhibitor enolicam sodium (CG5391B, 35 microM in perfusate), significant lung edema still occurs after amiodarone, indicating that amiodarone causes increased alveolar-capillary membrane permeability. Addition of catalase (100 U/ml) or superoxide dismutase and catalase (100 U/ml each) to perfusate fails to protect from amiodarone lung injury. Immediate infusion of amiodarone (10 mg) into lungs ventilated with room air (ADR + RA) causes an increase in lung weight gain from baseline (delta W) of 5.7 +/- 1.5 g/min. Compared with ADR + RA, ventilation of lungs with 4% O2 (delta W = 0.7 +/- 0.3 g/min, p less than 0.05), pretreatment of rabbits for 3 days with butylated hydroxyanisole (BHA, 100 mg/kg/day i.p., delta W = 0.05 +/- 0.02 g/min, p less than 0.01), pretreatment of rabbits for 3 days with vitamin E (Vit E, 300 U/day orally, delta W = 0.6 +/- 0.2 g/min, p less than 0.05), or addition of N-acetylcysteine to the lung perfusate (NAC, 5 mM, delta W = 0.1 +/- 0.08 g/min, p less than 0.01) all protect from lung edema formation after amiodarone. Amiodarone (100 mg) also caused a marked increase in luminol-enhanced lung chemiluminescence, lung production of superoxide anion (O2-), and tissue levels of lung glutathione disulfide. These results suggest that amiodarone causes lung injury by an oxidant mechanism.
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PMID:Amiodarone causes acute oxidant lung injury in ventilated and perfused rabbit lungs. 245 31

The potential protective effects of ICRF 187, Didox, Amidox and VF 165 were investigated in models of bleomycin, or bleomycin and hyperoxia induced lung injury. ICRF 187, a bispiperazinedione compound, is a strong chelating agent which blocks a number of free radical mediated processes. The polyhydroxyphenyl derivatives, Didox, Amidox and VF 165, demonstrate degrees of Fe chelating activities and free radical scavenging abilities. Hamsters treated with 5.0 U/kg bleomycin followed by treatment with ICRF 187 or Didox exhibited similar mortality to the bleomycin alone treated group. In a second study, a low dose of bleomycin (1.2 U/kg) was used followed by exposure to 70% oxygen. Treatment with ICRF 187, Didox, Amidox, or VF 165 failed to protect against lung injury; with the ICRF 187 and Amidox groups exhibiting significantly increased rates of mortality over that seen in animals treated only with bleomycin and hyperoxia. No animals treated with the agents alone died. Histopathology documented that all bleomycin-treated hamsters died of severe pneumonitis. Additionally, in the agent-treated groups there was a prominent proliferation of type II pneumocytes, which demonstrated marked anaplasia, a feature not typical of early bleomycin and hyperoxia lung injury. In conclusion, ICRF 187 and the polyhydroxyphenyl derivative, Amidox, paradoxically increase bleomycin- and hyperoxia-induced lung injury. The possible mechanisms of this interaction include: (1) increased availability of Fe to bleomycin; (2) interference with the healing process; or (3) inhibition of endogenous protective effects of SOD.
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PMID:ICRF 187 and polyhydroxyphenyl derivatives fail to protect against bleomycin induced lung injury. 247 96

Eglin C is an inhibitor of polymorphonuclear leukocyte elastase and cathepsin G. Recently, it was suggested that Eglin C may inhibit bacterial clearance in an experimental animal model of pneumonia. Since the phagocytic-bactericidal activity of polymorphonuclear leukocytes is most important in the promotion of bacterial clearance, we determined the effect of Eglin C on a variety of functions of isolated human polymorphonuclear leukocytes such as phagocytic-bactericidal activity, superoxide production, degranulation and chemotaxis. Apart from a partial inhibition of superoxide production, which was shown to be due to a superoxide dismutase-like effect of Eglin C, there was no inhibition of polymorphonuclear leukocyte functions measured. Eglin C can therefore be considered as a protease inhibitor, which does not interfere with the phagocytic-bactericidal activity of human polymorphonuclear leukocytes.
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PMID:The effect of Eglin C on the function of human neutrophils in vitro. 285 14

The effectiveness of bovine superoxide dismutase (SOD) in the prevention of bronchopulmonary dysplasia was evaluated in a prospective double-blind controlled study in 45 neonates (mean gestational age 28.7 weeks, mean weight 1154 gm) with severe respiratory distress syndrome. All were ventilator dependent with FiO2 greater than or equal to 0.7 at 24 hours of age. Either bovine SOD (0.25 mg/kg) or saline solution was administered subcutaneously every 12 hours according to random selection until patients could be maintained in room air without ventilatory or continuous positive airway pressure (CPAP) support. SOD levels were detected in all patients given treatment. Mean peak values at 4 hours after dose ranged from 0.15 micrograms/ml (dose 1) to 0.45 micrograms/ml (dose 10). The drug was well tolerated, and no side effects were detected. Among the 31 survivors (SOD 14, placebo 17) radiologic evidence of BPD was significantly less in patients given SOD (3/14 vs 12/17, P = 0.008). Clinical signs of bronchopulmonary dysplasia (wheezing, pneumonia) were less in patients given SOD (3/14 vs 11/17, P = 0.019). Patients given SOD required fewer days of CPAP (P less than 0.003). There were no differences in days of O2 therapy, intermittent positive pressure breathing, or incidence and severity of patent ductus arteriosus or intraventricular hemorrhage. This preliminary study suggests that SOD may be helpful in reducing the severity of bronchopulmonary dysplasia in infants with respiratory distress syndrome.
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PMID:Prevention of bronchopulmonary dysplasia by administration of bovine superoxide dismutase in preterm infants with respiratory distress syndrome. 650 11

The preventive and therapeutic effect of the traditional Chinese compound medicine Feixiankang (FXK) on the mice pulmonary fibrosis formation have been studied with the mice model. The level of LPO and the activity of SOD in the mice lung showed that LPO increased remarkably (P < 0.01), while the activity of SOD decreased significantly (P < 0.01) during the alveolar pneumonia period, although the LPO content had no significant change (P < 0.01) during experimental pulmonary fibrosis formation. In addition, the effect of FXK on the reducing of LPO was much stronger than that of the antioxidative agent Vitamin E. Also, FXK could improve the activity of SOD.
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PMID:[Effect of promoting blood circulation to remove stasis and supplementing qi and nourishing yin on the lipid peroxide and superoxide dismutase during experimental pulmonary fibrosis]. 753 99

The involvement of free radical metabolism in the pathogenesis of interstitial pneumonitis was investigated in an animal model. Male Wistar rats were irradiated at the thoracic region by gamma-rays from a 60Co source. Histopathological examination confirmed that 50% of the rats developed pneumonitis between 2 and 8 weeks following a single dose of 14 Gy. Parallel biochemical studies in the lung of these rats showed that mitochondria and microsomes had higher levels of lipid peroxidation. In the cytoplasmic fraction of the lung the activities of superoxide dismutase and catalase were markedly reduced in the pneumonitic rat. In lung mitochondria, however, the levels of these two enzymes were not significantly altered. On the contrary, lipid peroxidation and superoxide dismutase, as well as catalase activities in lung tissue in the non-pneumonitic group of the irradiated rat were comparable with that of control animals. The results indicate that free radical-induced oxidative stress following thoracic irradiation may be one of the causative factors in the development of interstitial pneumonitis.
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PMID:Oxidative stress in radiation-induced interstitial pneumonitis in the rat. 759 65


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