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

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Query: EC:2.6.1.2 (alanine aminotransferase)
26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Prospective studies have shown that the annual incidence of non-A, non-B (NANB) hepatitis may be high in haemodialysis patients. To assess whether hepatitis C virus (HCV), the major causative agent of post-transfusion and community-acquired NANB hepatitis, has a role in the pathogenesis of liver disease in dialysed patients, we have studied the prevalence and significance of antibodies to HCV in a cohort of patients with end-stage renal disease on chronic haemodialysis treatment. Seventy-four (30%) had circulating antibodies to HCV. Statistically significant associations with the anti-HCV carrier status were duration of haemodialysis treatment, blood transfusions, and the finding of abnormally elevated ALT on retrospective analysis. In contrast, only one of 103 dialysis staff members showed transient positivity for anti-HCV, suggesting a low risk of professional exposure to HCV. These findings suggests that HCV infection is relatively frequent in haemodialysis patients and may be responsible for a significant proportion of liver disease in this clinical setting.
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PMID:Abnormal alanine aminotransferase activity reflects exposure to hepatitis C virus in haemodialysis patients. 171 92

The most common toxicities of nonsteroidal anti-inflammatory drugs (NSAIDs) are gastropathy, renal dysfunction, and liver function abnormalities. We outline an approach to monitoring patients on long-term NSAID therapy, focusing on the early detection of complications. Gastropathy caused by NSAID use is more common in elderly patients or those with a history of dyspepsia, peptic ulcer disease, or alcohol abuse. Fecal occult blood testing and hemograms are less accurate in detecting gastropathy than direct visualization but are convenient and relatively inexpensive. We recommend the periodic use of these tests to detect NSAID-induced acute or chronic blood loss. Renal toxicity is seen in patients with preexisting renal disease or functional volume depletion and in the elderly. Complications include renal insufficiency, hyponatremia, hyperkalemia, and protein-uria. Renal function should be monitored during the first few weeks of NSAID therapy, especially in high-risk patients, with periodic testing thereafter. Hepatic toxicity is less common but warrants occasional determinations of alanine aminotransferase levels. Elderly patients and those with renal insufficiency or alcohol abuse have a higher risk of complications. Nonsteroidal anti-inflammatory drugs should be used cautiously in those patients at high risk for complications. Strategies can be used to limit toxicity. Patients taking these drugs long term should be monitored periodically for signs of blood loss, renal dysfunction, and hepatic dysfunction.
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PMID:Nonsteroidal anti-inflammatory drugs. Proposed guidelines for monitoring toxicity. 187 28

To study the potential of multivariate classification methods in order to obtain more insight into abnormal laboratory data from patients with sickle cell disease, we investigated standard haematological and clinical chemical variables of 18 controls and 37 apparently healthy persons with heterozygous sickle cell disease (Hb AS), all women, using both univariate and multivariate classification methods. In the univariate method, those with Hb AS showed decreased serum log aspartate aminotransferase (log AST) activity, mean corpuscular volume and mean corpuscular haemoglobin (MCH) and increased sodium concentration. The multivariate method identified sodium, potassium, urea, uric acid, log AST, alanine aminotransferase and MCH as the variables that produced maximal separation between persons with Hb As and controls. It increased the 'non-error rate' for classification of persons with Hb AS by 16.4% compared with classification based on the variable, MCH, that produced maximal separation by the univariate method. The frequency distribution of percentage Hb S in the Hb AS group proved bimodal with maximal separation at 37.0% Hb S. The subgroup with 37.0% or less (n = 16) was considered to have concomitant heterozygous alpha-thalassaemia-2. In the univariate method the subgroup characterized by greater than 37.0% Hb S (n = 21) had increased serum sodium and uric acid concentrations, perhaps related to sickle cell nephropathy, whereas the subgroup with less than or equal to 37% Hb S did not. The multivariate method added information to the univariate method by additionally identifying abnormalities in serum potassium and urea concentrations in the former subgroup.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Potential of descriptive linear discriminant analysis for studying clinical chemical and haematological data from persons with heterozygous sickle cell disease. 189 49

Male and female Sprague-Dawley rats were administered the sodium salt of monochloroacetic acid (SMCA) by oral gavage for a period of 90 consecutive days. Dosage levels of 15, 30, 60 or 120 mg/kg per day were employed. SMCA clearly induced toxicity in both females and males, with the greatest severity in the male animals. Both the liver and kidneys were identified as target organs. At 120 mg/kg per day, 30% of females and 80% of the males died, most within the first 2 days of treatment. Hemorrhagic and congested lungs (possibly a postmortem change) were seen in the early deaths (1-3 days) whereas liver lesions were observed in later deaths. In addition, there was nephrotoxicity as evidenced by elevated creatinine, blood calcium (BCAL), and blood urea nitrogen (BUN) levels. Hepatotoxicity was indicated by increases in the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Both organs showed increased organ-to-body weight ratios. Microscopic examination revealed a significant (P less than or equal to 0.001) increase in chronic renal nephropathy and increased splenic pigmentation at 60 mg/kg per day in the males. Based on the observation of toxicity at all treatment levels in males, a lowest observed adverse effect level (LOAEL) of 15 mg/kg per day is proposed for a 90-day exposure to SMCA by oral gavage to the Sprague--Dawley rat.
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PMID:Ninety-day toxicity study of sodium monochloroacetate in Sprague-Dawley rats. 203 Dec 51

The therapeutic effect of corticosteroid in hepatitis B virus (HBV) related membranous nephropathy was investigated in a 29-year-old chronic HBV carrier. Prednisolone (60 mg/day) was given for eight weeks and gradually reduced over the subsequent four months. In the renal biopsies taken before and after corticosteroid therapy, light microscopy revealed progression of sclerosis. Immunofluorescent staining showed glomerular capillary deposition of hepatitis B core antigen (HBcAg) by polyclonal antisera and hepatitis B e antigen (HBeAg) by monoclonal antibodies. Electron microscopy revealed 40-50 nm diameter virus-like particles in the glomeruli only from the biopsy performed after corticosteroid therapy. The serum concentrations of alanine aminotransferase, HBeAg, and HBV DNA increased with corticosteroid therapy suggesting active viral replication despite the absence of overt clinical hepatitis. Renal function did not improve and corticosteroid therapy was apparently not helpful in this patient. Our results conflict with the earlier notion that short-term corticosteroid does not interfere with a favorable outcome of the infection of the related renal disease.
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PMID:Replication of hepatitis B virus with corticosteroid therapy in hepatitis B virus related membranous nephropathy. 249 7

Blood lithium (Li) levels, renal functional parameters and urine excretion of enzymatic activities having different intracellular sites were investigated on rats submitted to acute and subacute Li chloride administration. In acute experiments increased levels of all detected enzymes were assayed following Li single doses of 5 and 10 mEq/kg b.w. In subacute poisoning, urine output of lactate dehydrogenase, aspartate transaminase and alanine transaminase was significantly over the basal ranges following 15 days in concomitance with marked elevation of plasma Li levels and exhibited progressive increase until 30 days; on the 10th day following Li withdrawal, elevated excretion of enzymatic activities was still assayed. The results are in agreement with data about the localization of the histologic lesions involving different sites of the nephron in acute Li poisoning and the distal tubular tract in subacute toxicity. In subacute administration the output of cytoplasmic and mitochondrial activities can be assumed as an index of damage of the nephron cells which can persist following Li withdrawal. Our findings indicate that the urine enzyme assay is a valuable tool to detect renal damage in experimental Li nephropathy.
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PMID:Urinary enzyme excretion in acute and subacute experimental lithium administration. 287 33

We found in two previous studies (Down syndrome patients and end-stage kidney patients receiving renal dialysis) that total serum iron is higher on average in carriers of the hepatitis B virus than in those who are not. The elevation of the serum iron is independent of elevations of serum L-alanine:2-oxoglutarate aminotransferase, EC 2.6.1.2) (SGPT), an indicator of liver cell damage. We have followed for 10 yr a large number of patients with end-stage renal disease receiving renal dialysis. In this paper we describe studies of serum iron and SGPT levels in patients (i) 1 mo before infection, (ii) after infection but within the month of infection, and (iii) 6-12 mo after infection. Comparisons of serum iron levels were made between those infected who retained the virus (carriers) and those who rejected the infection (transients). There were no differences between these groups before infection. Serum iron remained high in the carrier group and dropped in the transients. However, not all of the carriers retained high levels, although this was the case in general. Individual changes in the pre- and postconversion period were then considered. All carriers who had a preconversion decline in iron had an increase after infection, whereas this occurred in only some of the transients. Those carriers who had a decline after infection had raised levels before infection, and the decline was generally less than the increase. Consideration of the SGPT and the iron levels together led to the same conclusion as the previous studies, that elevation of iron may be independent of rise in SGPT. Several hypotheses were derived from these findings. Individuals who are carriers in general have higher iron levels and, therefore, are more likely to become infected with bacteria; this may contribute to increased morbidity and mortality. From experimental evidence, iron is required for the growth of tumor cells. Carriers with elevated iron levels may be more likely to develop detectable cancer of the liver than those who do not.
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PMID:Changes in serum iron levels due to infection with hepatitis B virus. 694 27

Serum creatine kinase (CK), aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), and lactic dehydrogenase (LDH) levels were studied at initial peritoneal dialysis in two groups of patients with renal failure. In Group I the patients underwent no intracorporeal interventions other than the implantation of a permanent catheter for peritoneal dialysis. In Group II the patients received injections or infusions in addition to the insertion of the catheter. CK was found to be significantly raised in Group II as a result of the injections or infusions. ASAT and ALAT were within normal range for both groups. LDH was significantly raised in Group II, probably to be explained by the degree of severity of the renal disease. It is concluded that the implantation of a permanent catheter for peritoneal dialysis and the institution of peritoneal dialysis do not per se lead to a rise in the serum concentrations of the enzymes CK, ASAT, ALAT, and LDH.
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PMID:Serum enzyme levels during initial peritoneal dialysis. 705 67

Reference intervals for prothrombin time (PT) and activated partial thromboplastin time (APPT) of undiluted and serial dilutions of citrated platelet-poor plasma were determined for 30 healthy dogs. The PT and APTT were similarly determined for 32 dogs with naturally occurring hepatic disease. Hepatic disease was confirmed by histopathologic examination of hepatic biopsy materials and comprised degeneration (13 dogs), inflammation (11 dogs), cirrhosis (4 dogs), and neoplasia (4 dogs). Coagulation test values were compared with serum alanine aminotransferase, alkaline phosphatase, and gamma-glutamyl transpeptidase activities and Bromsulphalein retention for sensitivity in detecting hepatic disease in the dog. Coagulation test results were at variance with reference values in 66% of the 32 dogs with hepatic disease; serum alanine aminotransferase, alkaline phosphatase, and gamma-glutamyl transpeptidase were increased in 59%, 72%, and 75%, respectively and Bromsulphalein retention was increased in 22% of the 32 dogs. Thus, the PT and APTT were sensitive indicators of hepatic disease. However, the PT and APTT lacked specificity for any given hepatic disease. The sensitivity of the coagulation tests for detecting hepatic disease was enhanced by using dilutions of citrated platelet-poor plasma. Only 15% of dogs with hepatic disease showed variances from reference values in the coagulation tests done with undiluted plasma, but 66% showed variances in the tests with dilutions of plasma. Coagulation tests were also done in 13 dogs with normal hepatic function amd morphology, but with various extrahepatic diseases: chronic renal disease (5 dogs), dirofilariasis (4 dogs), encephalitis (1 dog), cutaneous disease (2 dogs), and femoral fracture (1 dog). Twelve of the 13 dogs had coagulation test values within the reference intervals.
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PMID:Alterations of prothrombin time and activated partial thromboplastin time in dogs with hepatic disease. 734 May 74

Nitrotoluenes are high-production-volume chemicals used in the synthesis of agricultural chemicals and in various dyes. Because of differences in the metabolism of the three isomers and their capabilities to bind to DNA, comparative toxicity studies of o-, m-, and p-nitrotoluene were conducted in F344 rats and B6C3F1 mice. o-, m-, or p-Nitrotoluene was administered in the feed to male and female rats and mice at doses ranging from 625 to 10,000 ppm for 13 weeks. These doses delivered approximately 40 to 700 mg/kg body wt/day for rats and 100 to 1700 mg/kg/day for mice. There were no treatment-related effects on survival in any of the studies. Decreased body weights relative to controls occurred in dosed rats and mice in all studies at the higher dose levels and were most pronounced in rats receiving o-nitrotoluene. Mesotheliomas of the tunica vaginalis were observed in 3 of 10 male rats receiving o-nitrotoluene at 5000 ppm, and mesothelial cell hyperplasia was observed in 2 of 10 male rats receiving o-nitrotoluene at 10,000 ppm. Kidney toxicity was observed in male rats receiving o-, m-, or p-nitrotoluene and included hyaline droplet nephropathy and an associated increase in the renal concentration of alpha 2U-globulin. Evidence of liver toxicity in the male rats receiving o-nitrotoluene included hepatocyte vacuolization, oval cell hyperplasia, and increased serum bile acids, sorbitol dehydrogenase, and alanine aminotransferase. Although there was no histopathologic evidence of hepatic toxicity in male or female rats given the m- or p-isomers or in female rats given the o-isomer, treatment-related hepatic effects were detected in these groups, as measured by an increase in the relative liver weights and by elevations in serum bile acids and liver-specific enzymes. The spleens of treated male and female rats had a mild increase in hematopoiesis, hemosiderin deposition, and/or congestion. These splenic changes were slightly more prominent in rats administered the o- and p-isomers. Administration of o-, m-, or p-nitrotoluene impaired testicular function in the rat, as shown by testicular degeneration and reduction in the density, motility, and number of sperm cells. Administration of each isomer to rats caused increases in the length of the estrus cycle. The only histopathologic evidence for treatment-related toxicity in mice in the 13-week studies occurred in animals receiving the o-nitrotoluene isomer where the chemical caused degeneration and metaplasia of the olfactory epithelium.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Comparative toxicities of o-, m-, and p-nitrotoluene in 13-week feed studies in F344 rats and B6C3F1 mice. 751 72


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