Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.2 (alanine aminotransferase)
 26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Amiodarone is a potent and efficacious antiarrhythmic agent, yet associated with its use are life-threatening pulmonary fibrosis and hepatotoxicity. We have investigated the susceptibility of the male Sprague-Dawley rat to pulmonary and hepatic toxicity after repeated exposure to amiodarone and the effects of such exposure on hepatic and extrahepatic drug metabolizing enzymes. Animals received amiodarone (200 mg.kg-1.day-1 i.p., 5 days/week) for 1 week followed by 150 mg.kg-1.day-1 (5 days/week) for 3 additional weeks. No signs of pulmonary fibrosis or hepatotoxicity were observed, based on histological examination, lung hydroxyproline content, and plasma alanine aminotransferase activity. Analysis of tissues revealed extensive accumulation of amiodarone and desethylamiodarone in lung and liver, but concentrations were significantly lower in animals treated for 4 weeks than for 1 week. In a separate experiment, rats received amiodarone 150 mg.kg-1.day-1 i.p. (5 days/week) for 1 or 4 weeks. No differences in tissue concentrations of amiodarone and desethylamiodarone were detected between animals treated for 1 or 4 weeks. This regimen did not affect hepatic or extrahepatic monooxygenase activities. These results indicate that, in the male Sprague-Dawley rat, there is no observable pulmonary or hepatic toxicity following short-term amiodarone exposure, and there is enhanced elimination of amiodarone and desethylamiodarone when the daily dose of amiodarone is decreased after 1 week from 200 to 150 mg/kg.
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PMID:Repeated amiodarone exposure in the rat: toxicity and effects on hepatic and extrahepatic monooxygenase activities. 227 89

We evaluated the therapeutic efficacy of ceftibuten (CETB, 7432-S), a new cephem antibiotic for oral use, in chronic respiratory tract infections. A daily dose of 400 mg (b.i.d.: 15 cases) or 600 mg (t.i.d.: 5 cases) of CETB was given orally for 3-14 days (mean: 10.6 days) to 20 patients: 9 with infected bronchiectasis, 3 with infection supervened on pulmonary emphysema, 3 with acute pneumonia (supervened on bronchiectasis in 2 of 3 cases), 2 with infected bronchial asthma, 1 each with infection supervened on old pulmonary tuberculosis, chronic bronchitis and pulmonary fibrosis. The clinical effects were excellent in 3, good in 11, fair in 3 and poor in 3. Eighteen strains were identified as causative organisms. Eight of 15 strains for which bacteriological responses were evaluable were eradicated by the use of CETB. Eosinophilia in 2 patients and an elevation of S-GPT value was observed in 1 patient. These adverse reactions disappeared after the completion of the therapy. From the above results, we conclude that CETB is one of the most useful antibiotics for oral use as a first choice in chronic respiratory tract infections.
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PMID:[Therapeutic efficacy of ceftibuten in chronic respiratory tract infections]. 239 48

As variable functions of cytokines have been proved in recent years, cytokine levels in biological fluids such as serum, plasma, and synovial fluid of patients with every kind of disease have been enthusiastically measured. As a result, many studies have shown an increase or decrease in the production of cytokines or abnormal cytokine levels in biological fluids. However, the relationship between the abnormal levels of cytokines and the intensity of the clinical symptoms or the prognosis remains unclear. The significance for the measurement of cytokines depends on whether it should be valid for detecting a preclinical status such as AST or ALT used for health checks or for disease screening such as some tumor markers. The purpose of this study is to know whether or not some cytokine levels in serum could be biomarkers for preventive purposes. Serum cytokine levels (IL-4, 6, 8, 12, and IFN-gamma) were measured in three different types of cohorts (nursery school infants, manufacturing workers and middle and old aged women) with chemiluminescence ELISA. The results showed no differences with atopic status in infants, pulmonary fibrosis in workers or with the decrease in bone stiffness, these results are mainly due to a great inter-individual variability of serum cytokine levels. This study concludes that serum cytokine levels are inappropriate as biomarkers for preventive purposes. However, a further detailed evaluation in healthy people with high serum cytokine levels may be necessary.
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PMID:[The public health significance of the measurement of cytokines in serum]. 1071 50

This study examined effects of S-allyl cysteine (SAC) on carbon tetrachloride (CCl4)-induced interstitial pulmonary fibrosis in Wistar rats. CCl4 (0.5 ml/kg) was intraperitoneally injected into rats twice a week for 8 weeks, and SAC (50, 100, or 200 mg/kg), N-acetyl cysteine (NAC, 200 or 600 mg/kg), or L-cysteine (CYS, 600 mg/kg) were orally administrated to rats everyday for 8 weeks. SAC significantly reduced the increases of transforming growth factor beta, lipid peroxides, AST, and ALT in plasma, induced by CCl4. Although CCl4 is mainly metabolized by hepatic cytochrome P450, CCl4 induced systemic inflammation and some organ fibrosis. SAC dose-dependently and significantly attenuated CCl4-induced systemic inflammation and fibrosis of lung. SAC also inhibited the decrease of thiol levels, the increase of inducible nitric oxide synthase expression, the infiltration of leukocytes, and the generation of reactive oxygen species in lungs. Although NAC and CYS attenuated CCl4-induced pulmonary inflammation and fibrosis, the order of preventive potency was SAC > NAC > CYS according to their applied doses. These results indicate that SAC is more effective than other cysteine compounds in reducing CCl4-induced lung injury, and might be useful in prevention of interstitial pulmonary fibrosis.
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PMID:S-allyl cysteine attenuated CCl4-induced oxidative stress and pulmonary fibrosis in rats. 1661 85

Pulmonary fibrosis is characterized by excessive deposition of extracellular matrix components in the alveolar space, which hampers normal respiration process. Pathophysiological enzymes, glycoprotein moieties and matrix degrading lysosomal hydrolases are key markers and play a crucial role in the progression of fibrosis. Bleomycin is an anti-neoplastic drug, used for the treatment of various types of cancers and induces pulmonary fibrosis due its deleterious side effect. Tea catechin epigallocatechin-3-gallate (EGCG) is known for its wide array of beneficial effects. The present study was intended to evaluate the beneficial efficacy of EGCG against bleomycin-induced glycoconjugates, lysosomal hydrolases and ultrastructural changes in the lungs of Wistar rats. Intratracheal instillation of bleomycin (6.5 U/kg body weight) to rats increased the activities of pathophysiological enzymes such as aspartate transaminase, alanine transaminase, lactate dehydrogenase and alkaline phosphatase, which were attenuated upon EGCG treatment. The increased level of hydroxyproline and histopathological parameters in bleomycin-induced rats were decreased upon EGCG treatment. Bleomycin-induced increase in the level of glycoconjugates was restored closer to normal levels on EGCG treatment. Furthermore, the increased activities of matrix degrading lysosomal enzymes in bleomycin-induced rats were reduced upon EGCG supplementation. Treatment with EGCG also attenuated bleomycin-induced ultrastructural changes as observed from transmission electron microscopy studies. The results of the present study put-forward EGCG as a potential anti-fibrotic agent due to its attenuating effect on potential fibrotic markers.
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PMID:Epigallocatechin-3-gallate exhibits anti-fibrotic effect by attenuating bleomycin-induced glycoconjugates, lysosomal hydrolases and ultrastructural changes in rat model pulmonary fibrosis. 1949 26

Objective: To investigate the risk factors for pulmonary fibrosis in patients with paraquat (PQ) poisoning. Methods: A total of 120 patients with PQ poisoning who were admitted from January 2012 to December 2014 were enrolled. According to the presence or absence of pulmonary fibrosis, the patients were divided into non-pulmonary fibrosis group (67 patients) and pulmonary fibrosis group (53 patients) . The Acute Physiology and Chronic Health Evaluation II (APACHE II) score was obtained on days 1 and 3 of poisoning. Routine blood test results, blood biochemical parameters, and radiological parameters were recorded, and the patients with PQ poisoning were followed up for survival and pulmonary fibrosis. Results: A total of 39 patients with PQ poisoning died, resulting in a mortality rate of 32.5%. There were 53 patients who developed pulmonary interstitial fibrosis, yielding an incidence rate of 44.2%. Compared with the non-pulmonary fibrosis group, the pulmonary fibrosis group had a significantly higher age, a significantly higher dose of PQ, and significantly higher APACHE II scores on days 1 and 3 of poisoning (P<0.01) , as well as significantly higher white blood cell (WBC) count and neutrophil count on day 1, significantly higher levels of urea nitrogen, creatinine, and blood glucose on days 1 and 3, and significantly higher activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) (P<0.01) . The logistic regression analysis showed that the dose of PQ, WBC count and neutrophil count on day 1, APACHE II scores on days 1 and 3 of poisoning, levels of urea nitrogen, creatinine, and blood glucose, and activities of AST and ALT were associated with the development of pulmonary fibrosis in patients with PQ poisoning. Conclusion: Oral dose of PQ, APACHE II scores on days 1 and 3 of poisoning, levels of urea nitrogen, creatinine, and blood glucose, activities of AST and ALT, and WBC count and neutrophil count on day 1 are risk factors for pulmonary fibrosis in patients with paraquat poisoning.
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PMID:[Risk factors for pulmonary fibrosis in patients with paraquat poisoning]. 2768 88

Objective: To investigate the clinical effect of compound monoammonium glycyrrhizinate combined with dandelion in the treatment of acute paraquat poisoning. Methods: A total of 80 patients with acute paraquat poisoning who were admitted to our hospital were enrolled as study subjects and randomly divided into routine treatment group (38 patients) and traditional Chinese medicine (TCM) group (42 patients) . The patients in the TCM group were given compound monoammonium glycyrrhizinate and dandelion in addition to the treatment in the control group. Serum alanine aminotransferase (ALT) , total bilirubin (TBil) , blood urea nitrogen (BUN) , creatinine (Cr) , and arterial blood lactate (Lac) and partial pressure of oxygen (PaO2) during different time periods on day 3, 7, and 9 of treatment were observed in both groups, and ulceration of oral mucosa, pulmonary fibrosis, multiple organ dysfunction syndrome (MODS) , and mortality were compared between the two groups. Results: On days 3, 7, and 9 of treatment, the routine treatment group had significantly higher serum ALT, TBil, BUN, Cr, and arterial blood Lac than the TCM group. The routine treatment group had significantly lower arterial blood PaO2 than the TCM group, while the TCM group had significantly lower incidence rates of ulceration of oral mucosa, pulmonary fibrosis, and MODS and a significantly lower mortality rate than the routine treatment group (P<0.05) . Conclusion: In the treatment of patients with acute paraquat poisoning, compound monoammonium glycyrrhizinate combined with dandelion can effectively improve organ function, reduce the incidence of pulmonary fibrosis and MODS, improve the healing rate of oral ulcer, improve prognosis, and reduce mortality rate.
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PMID:[Clinical effect of compound monoammonium glycyrrhizinate combined with dandelion in treatment of acute paraquat poisoning]. 2768 93

PM014 (HL301) is a standardized herbal mixture derived from a traditional Korean medicine, Chung-Sang-Bo-Ha-Tang. Previously, we reported that PM014 treatment significantly suppressed pulmonary fibrosis, one of the frequent adverse effects of anticancer therapy in lung cancer. Before the clinical application of PM014 in anticancer therapy, the safety and efficacy of PM014 in combination with conventional anticancer drugs should be addressed to determine whether PM014 can be used in lung cancer. Lewis lung cancer-bearing mice were injected with 10 mg/kg of cisplatin or paclitaxel on day 5. Starting on day 7, the mice were administered 200 mg/kg PM014 every 2 days. On day 15, all mice were assessed by biochemical and histological analyses. PM014 did not block the antitumor activity of cisplatin and paclitaxel. Coadministration of PM014 and antitumor agents did not elevate the aspartate transaminase/alanine transaminase ratio or the blood urea nitrogen/creatinine ratio. Histopathological analysis also showed that PM014 did not induce hepatic or renal injury. Moreover, PM014 had no apparent inhibitory effects on drug metabolizing enzymes, indicating that PM014 did not alter the pharmacokinetics of chemotherapeutic drugs. Overall, these data show the safety and compatibility of combination therapy of PM014 and chemotherapies for the treatment of lung cancer.
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PMID:Evaluation of the Efficacy and Safety of the Herbal Formula PM014 in a Cisplatin- and Paclitaxel-Treated Tumor-Bearing Mouse Model. 3259 Sep 12