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)

The influence of hepatitis B (HBV) and hepatitis C virus (HCV) infection on blood hemoglobin (Hb) and serum erythropoietin (Epo) and interleukin-6 (IL-6) concentrations was studied in 48 anemic patients on regular hemodialysis. They were grouped as follows: (I) 19 patients whose Hb values improved after infection (Hb > 85 g/L), (II) 10 patients with persisting anemia after infection (Hb < 75 g/L), and, without hepatitis virus markers (III) 8 patients with Hb > 85 g/L and (IV) 11 patients with Hb < 75 g/L. Serum immunoreactive Epo levels were significantly higher in group I (34.4+/-47.1 U/L) than in the other groups (II, 10.8+/-6.0; III, 7.9+/-3.2; IV, 8.4+/-4.3). Serum IL-6 was higher in group I than group III (7.7+/-7.8 pg/ml vs. 3.6+/-2.4; p = 0.05) but similar to the other groups. Hb levels in group I were maximal at the time of serum alanine aminotransferase normalization. Red cell production increases as a result of elevated circulating Epo during hepatic regeneration after HBV or HCV infection.
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PMID:Serum erythropoietin and interleukin-6 levels in hemodialysis patients with hepatitis virus infection. 1033 88

Docetaxel has been reported to show promising anti-tumour activity in pancreatic ductal cancer (PC). This study was conducted to evaluate the activity and toxicity of moderate-dose (60 mg m(-2)) docetaxel in Japanese chemo-naive patients with measurable metastatic PC. The patients had a performance status of 0-2. They received docetaxel intravenously over a 1- to 2-h period without any premedication for hypersensitivity reactions. This treatment was repeated every 3-4 weeks with dose adjustments based on the toxic effects observed. Twenty-one patients were eligible and treated with docetaxel. The median number of courses was 2 (range, 1-4). None of the patients achieved an objective response; seven showed no change and 13 showed progressive disease. In one patient, the response was not assessable because of early death. The median survival time for all patients was 118 days. The main grade 3-4 toxicities by patient were leucocytopenia (67%) and neutropenia (86%). Other grade 3-4 toxicities included anaemia (10%), thrombocytopenia (5%), nausea/vomiting (29%), anorexia (29%), GOT/GPT increase (10%), alkaline phosphatase increase (14%), malaise/fatigue (33%) and alopecia (24%). In conclusion, docetaxel, administered on this schedule, did not show significant anti-tumour activity in patients with metastatic PC.
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PMID:Phase II study of docetaxel in patients with metastatic pancreatic cancer: a Japanese cooperative study. Cooperative Group of Docetaxel for Pancreatic Cancer in Japan. 1040 50

The aim of the paper is to present a case of self-poisoning with paracetamol, overdosed just before a delivery. A 21-year-old woman was admitted to Obstetric and Gynecology Ward of local hospital in the second stage of physiological delivery, more than 6 hours after she had ingested 19 g of acetaminophen for self-poisoning. She delivered a normal infant weighing 3520 g who had Apgar scores of 10, and then both infant and mother were sent in an emergency ambulance to the nearest poison centre. Blood samples for toxicological examination were taken on admission to toxicological intensive care unit i.e. 11 hours post maternal ingestion. Acetaminophen levels of both patients were above the acetaminophen overdose nomogram line and the antidote treatment, i.v. N-acetylcysteine was administered according to the protocol: the mother within 11 hours post-ingestion and approximately 4 hours after a delivery; the neonate within 11 hours post maternal ingestion and 4 hours of life. Higher paracetamol concentration in the blood of infant compared to the mother's was noted in the first and then control toxicological examination performed within 35 hours post maternal ingestion. Peak maternal aspartate aminotransferase (AST) activity was 326 U/L within 35 hours and alanine aminotransferase (ALT) activity was 262 U/L within 56 hours post-ingestion. The highest neonatal enzyme activity was noted within 11 hours post maternal ingestion of paracetamol, and the elevation was not high. Except moderate anaemia in the mother, no clinical or biochemical symptoms of renal, cardiovascular or CNS injury were stated in the mother or infant. Normalisation in the maternal enzymes activity was stated within 226 hours, while in the neonatal within 58 hours post maternal ingestion. The woman recovered without sequelae and was discharged from hospital on the 11th day following paracetamol overdosing. No evidence of the liver injury was found in the infant either.
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PMID:Suicidal paracetamol poisoning of a pregnant woman just before a delivery. 1046 99

A toxicity study was made on Lepidium sativum L. seeds used in Saudi traditional medicine for the treatment of various ailments. Lepidium sativum L. seed fed to Wistar albino rats at 2% (w/w) was non-toxic, Ten percent (w/w) was toxic but not fatal and 50% (w/w) of the diet for 6 weeks was lethal and caused depression in growth rate and entero-hepato-nephrotoxicity. Organ lesions accompanied by anemia and leukopenia were correlated with alterations in serum AST and ALT activities and concentrations of total protein, cholesterol, urea, and other serum constituents.
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PMID:Effects of various levels of dietary Lepidium sativum L. seeds in rats. 1059 49

Some haematological and biochemical parameters were studied in guinea-pigs infected intraperitoneally with Salmonella dublin 493 at 1 x 10(6) viable cells per animal. The infected animals showed a rise in temperature within 24 h, followed by depression and loss of body weight. On the 15th day post infection, haematological studies revealed a significant increase in the total leukocyte count due to both lymphocytosis and neutrophilia, and a decrease in the total erythrocyte count and haemoglobin concentration. There was also a significantly higher mean corpuscular volume and lower mean corpuscular haemoglobin concentration, indicating a macrocytic hypochromic anaemia. The infection caused a significant increase in alanine aminotransferase activity and creatinine, blood urea nitrogen and globulin concentrations, and a decrease in albumin and triiodothyronine. There was no significant effect on serum total protein or on thyroxine, or in the activity of aspartate aminotransferase in the serum.
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PMID:Experimental salmonellosis in guinea-pigs: haematological and biochemical studies. 1059 73

This study was constructed to investigate the relationship between renal anaemia and erythropoietin (EPO) concentrations in chronic renal failure (CRF) patients and to evaluate the possible role of the liver. Serum EPO levels were measured in blood samples from 20 CRF patients on hemodialysis (HD), 20 liver cirrhosis (LC) patients, 20 patients having both CRF and LC and undergoing HD, and 20 normal control subjects. Blood cell counts, iron indices (iron, total iron-binding capacity (TIBC) and ferritin), renal function (blood urea nitrogen (BUN) and creatinine), hepatic function (ALT, AST, ALP and bilirubin) investigations were carried out for all the subjects enrolled in this study. CRF patients without LC had serum EPO concentration of 6.21 +/- 0.53 mU/ml (mean +/- SE), which was significantly higher than that in patients having both CRF and LC (4.32 +/- 0.52) (p < 0.01). Both groups showed significantly lower values than the controls (12.75 +/- 0.70) (p < 0.001). LC patients with intact kidneys had significantly higher EPO level (22.70 +/- 1.70) (p < 0.001). No correlation was found between EPO level and any of the hematologic or iron indices.
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PMID:Assessment of erythropoietin levels and some iron indices in chronic renal failure and liver cirrhosis patients. 1068 46

Blood transfusion or blood products are a important route for transmission of hepatitis C virus(HCV) infection. Routes of infection other than blood transfusion are medical treatments including hemodialysis, exposure of hospital employees to needles contaminated with blood, drug abusers, acupuncture, tattooing, certain types of sexual behavior and mother-to-infant infection. The prevalence of anti-HCV antibodies in blood donors in Kumamoto Prefecture was 1.30%(1,704 of 131,376) between February and October 1992 and 0.46%(622 of 132,847) between April 1998 and May 1999, respectively. Also, the prevalence of anti-HCV was 22.9%(126 of 550) in the highly endemic area. The prevalence of HCV infection was evaluated in 548 patients undergoing hemodialysis, and 216 members of the hospital dialysis staff. Of 548 hemodialysis patients, 166(30.3%) were positive and significantly higher than those for either hospital staff members(2.3%; p < 0.01) or healthy blood donors(1.3%; p < 0.01). Patients with a history of blood transfusion tended to have a higher positivity rate for anti-HCV than did the non-transfused group. Positivity for anti-HCV was related to the duration fo hemodialysis. Although hemodialysis patients remain a high-risk group for HCV infection, the prevalence of anti-HCV antibodies has decreased recently thanks to the use of erythropoietin for renal anemia, the universal screening of blood donors for anti-HCV antibodies, and improvements in infection control measures for this virus. To evaluate the effect of interferon(IFN) therapy on the incidence of hepatocellular carcinoma(HCC) or decompensated liver cirrhosis, 490 patients with chronic hepatitis or liver cirrhosis type C who had undergone liver biopsy since 1987, were followed periodically. Of these patients, 411 received IFN and 79 were untreated. The degree of liver fibrosis was assessed from stage F0(no fibrosis) to stage F4(cirrhosis). Response to IFN was determined virologically and biochemically. HCC developed in IFN-treated patients and in 17 untreated patients with stage F3 or F4 fibrosis. In multivariate analysis, IFN therapy was associated with a reduced risk of HCC, especially among patients with sustained virological response(CR), among those with persistently normal serum ALT levels, and among those with ALT levels less than two times the upper limit of normal(PR). Also, the cumulative incidence of decompensated liver cirrhosis and cumulative survival in treated and untreated patients differed significantly. None of the patients with CR or PR progressed to the decompensated state and all patients with CR or PR have survived to date. In conclusion, IFN therapy significantly reduces the risk for HCC or decompensated cirrhotic stage, especially among virological or biochemical responders.
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PMID:[Hepatitis C: epidemiology and therapy--with special reference to long-term prognosis after IFN therapy]. 1075 68

The demonstrated utility of the nucleoside analog ribavirin in the treatment of certain viral diseases can be ascribed to its multiple distinct properties. These properties may vary in relative importance in differing viral disease conditions and include the direct inhibition of viral replication, the promotion of T-cell-mediated immune responses via an enhanced type 1 cytokine response, and a reduction of circulating alanine aminotransferase (ALT) levels associated with hepatic injury. Ribavirin also has certain known toxicities, including the induction of anemia upon chronic administration. To determine if all these properties are linked, we compared the D-nucleoside ribavirin to its L-enantiomer (ICN 17261) with regard to these properties. Strong similarities were seen for these two compounds with respect to induction of type 1 cytokine bias in vitro, enhancement of type 1 cytokine responses in vivo, and the reduction of serum ALT levels in a murine hepatitis model. In contrast, ICN 17261 had no in vitro antiviral activity against a panel of RNA and DNA viruses, while ribavirin exhibited its characteristic activity profile. Importantly, the preliminary in vivo toxicology profile of ICN 17261 is significantly more favorable than that of ribavirin. Administration of 180 mg of ICN 17261 per kg of body weight to rats by oral gavage for 4 weeks generated substantial serum levels of drug but no observable clinical pathology, whereas equivalent doses of ribavirin induced a significant anemia and leukopenia. Thus, structural modification of ribavirin can dissociate its immunomodulatory properties from its antiviral and toxicologic properties, resulting in a compound (ICN 17261) with interesting therapeutic potential.
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PMID:The ribavirin analog ICN 17261 demonstrates reduced toxicity and antiviral effects with retention of both immunomodulatory activity and reduction of hepatitis-induced serum alanine aminotransferase levels. 1077 Jul 62

We report a case of hepatitis C virus-associated glomerulonephropathy presenting with MPO-ANCA-positive, rapidly progressive glomerulonephritis(RPGN). A 60-year-old woman was admitted to our hospital for evaluation of RPGN. Laboratory evaluation revealed microhematuria, proteinuria(800 mg/day), anemia, renal failure(blood urea nitrogen 27 mg/dl, serum creatinine 2.2 mg/dl), cryoglobulinemia, hypocomplementemia, positive MPO-ANCA(232 EU), and hepatitis C virus infection(GOT 58 IU/l, GPT 38IU/l, HCV-RNA(PCR) 1,200 kcopy/ml, serotype 1). After admission, the patient's renal function and anemia deteriorated rapidly, then prednisolone(30 mg/day) was started. After treatment her renal function gradually improved, then a renal and liver biopsy was performed. The renal biopsy revealed six sclerosing fibrous crescentic glomeruli in twelve glomeruli. Immunofluorescent examination revealed granular deposits of IgG, C3, and fibrinogen along the glomerular basement membrane and mesangial matrix. The pathogenesis of RPGN in this case may relate to the deposition of immune complexes in the glomeruli because immunofluorescent examination was revealed to be the immune-complex type, but not pauci immune type nephritis. Liver histology revealed chronic active hepatitis with mild piecemeal necrosis and did not reveal vasculitis. Although her renal function was improved after treatment with prednisolone, she suffered from pulmonary manifestations(dry cough etc.) on the 120th hospital day. Suddenly she died because of pulmonary hemorrhage on the 180th hospital day. These findings suggest that various HCV-induced immunological abnormalities, such as positive MPO-ANCA, cryoglobulinemia and hypocomplementemia, play an important role in the pathogenesis of this RPGN, although we could not demonstrate deposition within glomeruli of immune complexes containing HCV. The effect of interferon therapy on such immunological abnormalities remains to be documented. Since interferon is known to have immunomodulatory effects, we selected corticosteroid therapy. Future studies need to focus on the optimal treatment strategy for hepatitis C virus-associated glomerulonephritis.
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PMID:[A case of hepatitis C virus-associated glomerulonephropathy presenting with MPO-ANCA-positive rapidly progressive glomerulonephritis]. 1089 95

The toxicity of diet containing 10% of Citrullus colocynthis fruits or 10% of Nerium oleander leaves or their 1:1 mixture (5%+5%) for rats treated for 6 weeks was determined. Dullness, ruffled hair, decreased body weight gains and feed efficiency, and enterohepatonephropathy characterised treatment with C. colocynthis and N. oleander given alone. Diarrhoea was a prominent sign of C. colocynthis poisoning. Organ lesions were accompanied by leucopenia, anaemia and alterations in serum AST, ALT and ALP activities and concentrations of total protein, albumin, urea, bilirubin and other serum constituents. Feeding the mixture of C. colocynthis and N. oleander caused more marked effects and death of rats.
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PMID:Preliminary toxicity study on the individual and combined effects of Citrullus colocynthis and Nerium oleander in rats. 1092 8


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