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)

Six horses were immunized with the venoms of Bothrops asper, Crotalus durissus durissus and Lachesis muta stenophrys for the production of polyvalent (Crotalinae) antivenom. During the immunization, clinical and laboratory alterations were evaluated in these animals, and the development of humoral immune response was followed. Only moderate local tissue changes (edema, abscesses, fistules and fibrosis) were observed in these animals, whereas no systemic alterations occurred. Regarding laboratory tests, there was a drop in hemoglobin concentration and hematocrit, together with an increment in total serum protein. Horses developed a moderate leukocytosis, with increments in polymorphonuclear leukocytes and lymphocytes. No significant changes were observed in prothrombin time or platelet count. There were no alterations in serum lactic dehydrogenase and gamma glutamyl transferase activities, whereas minor increments in creatine kinase and alanine aminotransferase activities were observed, together with a decrease in aspartate aminotransferase. All these changes occurred after the injection of 9 mg venom, when sodium alginate was first used as adjuvant. Creatinine levels had a small increment, although no changes were observed in urea levels or in the urea/creatinine ratio. An important individual variability was observed in the humoral immune response, as judged not only by enzyme-linked immunosorbent assay, but also by assessing the neutralization of the indirect hemolytic activity of venoms.
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PMID:Clinical and laboratory alterations in horses during immunization with snake venoms for the production of polyvalent (Crotalinae) antivenom. 902 11

Case records of 27 dogs with medically managed congenital portosystemic shunts were reviewed. Fourteen were followed up by telephone questionnaires to the owners. Age, breed, sex, clinical signs and blood results were similar to previous studies. Weight and quality of life were stable or improved on treatment in all cases. Total serum protein concentration and alanine aminotransferase and alkaline phosphatase activities fell significantly during treatment. Fourteen dogs were euthanased, four were lost to follow-up and nine remained alive. Mean survival time for the dogs euthanased was 9.9 months. Mean follow-up period for the dogs still alive was 56.9 months and all had survived more than 36 months from diagnosis. Surviving dogs with intrahepatic shunts had a significantly shorter follow-up period than dogs with extrahepatic shunts. Two prognostic indicators were identified, age at initial signs and blood urea concentration on presentation, both correlating with survival time. It was demonstrated that a significant proportion of dogs with portosystemic shunts managed medically have a good prognosis.
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PMID:Medical management of congenital portosystemic shunts in 27 dogs--a retrospective study. 951 85

Preliminary short-term toxicity studies of sucrose acetate isobutyrate (SAIB) in the dog demonstrated that addition of this additive to the diet was associated with an increase in liver size and elevated serum alkaline phosphatase activity with no evidence of pathological change by light microscopy. To determine the basis for these changes, a 12-week oral toxicity study of SAIB was conducted in the dog and a similar study was performed in the rat. SAIB was fed in the diet to groups of six beagle dogs of each sex at 0, 0.5, 1.0, 2.0 and 4.0%. SAIB was also fed to groups of 40 Sprague-Dawley rats of each sex at levels of 0, 2.5, 5.0 and 10.0%. In the rat study, in addition to routine toxicology parameters, hepatic microsomal enzyme induction was determined using a zoxazolamine hypnotic test, urinary ascorbic acid excretion and determination of hepatic carboxylesterase activity. Sodium phenobarbital was fed to groups of 20 rats of each sex at a dose of 100 mg/kg body weight/day by gavage as a positive control for hepatic microsomal enzyme induction. In the dog study, routine toxicological tests were supplemented by tests for bromsulfophthalein (BSP) retention, histochemical staining of liver sections for glycogen, phosphorylase, succinate dehydrogenase, and acid and alkaline phosphatases. Levels of liver lipid, protein, glycogen and carboxylesterase activity were also determined. Electron microscopic examinations were made on liver sections from the dog study at the end of the 12-week SAIB feeding period and after a 2-week withdrawal period. Administration of SAIB to rats did not reveal evidence of any effect on hepatobiliary function, and there was no indication of microsomal enzyme induction. Body weight gain of male rats fed SAIB was decreased, probably as the result of decreased palatability of the diet; SAIB did not affect body weight gain in females. The changes observed in the dogs fed SAIB included increased serum alkaline phosphatase activity with no change in serum alanine aminotransferase, aspartate aminotransferase or lactic dehydrogenase activity and no change in serum electrolyte, serum protein, glucose or bilirubin levels. No haematological changes were observed. BSP retention was observed at all SAIB dose levels. There were no SAIB-related pathological changes in any organ when examined by light microscopy. Examination by electron microscope revealed dilatation of bile canaliculi and an increase in smooth endoplasmic reticulum compared with controls. Histochemical studies also indicated increased enzyme activity of the bile canaliculi. The electron-microscope-revealed changes were completely reversed during a 2-week treatment withdrawal period. The dog study did not establish a no-effect level for changes in hepatobiliary function induced by feeding SAIB.
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PMID:Subchronic toxicity studies of sucrose acetate isobutyrate (SAIB) in the rat and dog. 951 48

A retrospective case note review was undertaken to assess the clinical significance of hepatic dysfunction with jaundice in typhoid fever. Of the 57 patients, 21 (36.8%) had jaundice, while 36 (63.2%) did not have jaundice. Significantly higher proportions of jaundiced patients were females (P = 0.04). Confusion (P = 0.01), upper abdominal pain (P = 0.02), right upper quadrant tenderness (P = 0.0001), and low prothrombin index (P = 0.04) were statistically significant occurrences in jaundiced patients on admission. Admission mean values of serum bilirubin (P = 0.0001), gamma-glutamyltranspeptidase (GGT; P = 0.009), and alanine aminotransferase (ALT; P = 0.0005) were significantly higher in icteric patients while mean values of total serum protein (P = 0.0009) and albumin (P = 0.0001) were significantly higher in anicteric patients. There were no deaths. Glomerulonephritis occurred significantly (P = 0.001) more frequently in icteric patients. It is concluded that hepatic dysfunction with jaundice in typhoid fever indicates more severe hepatic injury, which may precipitate the development of clinically detectable glomerulonephritis.
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PMID:Clinical significance of hepatic dysfunction with jaundice in typhoid fever. 1008 Jan 55

Reperfusion after liver transplantation results in the induction of tumor necrosis factor-alpha (TNFalpha) as well as activation of the stress-associated signaling proteins, c-Jun N-terminal kinase (JNK), activating protein-1 (AP-1), and nuclear factor-kappaB (NF-kappaB). To test the hypothesis that Kupffer cells are involved in the activation of signal transduction cascades during rat liver transplantation, Kupffer cells were depleted from donor liver using gadolinium chloride (GdCl3), and then the activation of JNK, AP-1, and NF-kappaB were assessed after transplantation. The results showed that GdCl3 treatment did not inhibit the activation of these stress signals, although transplanted livers were depleted of Kupffer cells and partially protected from reperfusion injury. Interleukin-6 (IL-6) and IL-10 messenger RNAs (mRNAs) were induced by transplantation, and the induction was suppressed by Kupffer cell depletion. The induction of TNFalpha mRNA and serum protein during liver transplantation was unaffected by GdCl3. These results show that Kupffer cells are not a major source of TNFalpha production after liver transplantation and that stress-signaling protein activation occurs independently of Kupffer cells. Transplantation strongly activates the transcription factor NF-kappaB, which blocks TNFalpha-mediated apoptosis in hepatocytes in vitro. To assess the role of NF-kappaB activation during liver transplantation, the IkappaBalpha superrepressor was expressed in donor livers using adenoviral-mediated gene transfer. Inhibition of NF-kappaB resulted in increased serum alanine aminotransferase levels after 3 hours of transplantation. In addition, the blockade of NF-kappaB resulted in increased histological tissue injury and increased hepatic terminal deoxyribonucleotide transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) staining, indicating apoptosis. These results show that NF-kappaB activation has a protective role in the transplanted liver.
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PMID:Activation of nuclear factor-kappaB during orthotopic liver transplantation in rats is protective and does not require Kupffer cells. 1038 1

The serum protein designated 90K/Mac-2BP has been found at elevated concentrations in the sera of patients with various types of cancer and viral infections. The importance of the 90K/Mac-2BP serum concentrations in predicting the response towards interferon-alpha treatment for hepatitis C virus (HCV) infection prompted us to utilize a new ELISA for soluble human 90K/Mac-2BP to monitor the serum concentrations of this protein in our HCV-positive patients. Seventy HCV-PCR and anti-HCV antibody positive patients were analyzed for their serum levels of aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase, cholinesterase, HCV-viral load, viral subtypes, and 90K/Mac-2BP. On correlation of age and 90K/Mac-2BP levels, we found an apparent correlation that was proved rather to be a strong dependence of 90K/Mac-2BP concentrations on disease severity/duration, which increases with age. Multiple correlation analysis demonstrated the independent nature of 90K/Mac-2BP concentrations, underscoring the potential high utility of this new marker. Our data corroborate the potential of the scavenger receptor family protein 90K/Mac-2BP as an independent predictor of disease severity during HCV infection.
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PMID:Serum protein 90K/Mac-2BP is an independent predictor of disease severity during hepatitis C virus infection. 1090 55

The course of Trypanosoma congolense infections in African grey duiker (Sylvicapra grimmia) and sheep and goats were studied. Several parameters suggested that the grey duiker was much more resistant to trypanosomosis than sheep and goats. They showed increases in weight during infection, had a much longer pre-patent period, and their peak parasitaemia levels were about 100-fold lower than those of sheep and goats. Parasites were no longer detected in grey duiker blood 35 days after infection. Anaemia, measured as drops in packed cell volume (PCV), haemoglobin (Hb) concentration and erythrocyte (RBC) counts were not observed in the grey duiker. In contrast, sheep and goats suffered severe weight losses and had continuously high parasitaemia levels. Sheep and goats developed progressively severe normocytic normochromic anaemia and leucopenia from day 14 post-infection onwards. Serum levels of total protein, globulin and albumin of grey duiker did not change significantly throughout the course of infection, while the levels of total serum protein, globulin and gamma-globulin exhibited significant increases from day 21 post-infection onwards in sheep and goats, with peak values recorded on 28 and 35 days post-infection in sheep and goats, respectively. There were inconsistent variations in albumin levels in sheep and goats throughout the course of infection. There were no significant changes in erythrocyte activities of AST and ALT, while there were transient but significant elevations of ALP level on day 35, and GGT levels between 14 and 35 days post-infection in grey duiker. Conversely, the levels of all the enzymes were progressively depressed, especially from 14 to 49 days post-infection. In vitro erythrocyte peroxidation remained relatively unchanged throughout the period of the experiment in the grey duiker, except for slight but significant increase on day 42 post-infection. However, in vitro erythrocyte peroxidation increased significantly by between 100 and 300% of pre-infection levels from 14th to 42nd day p.i. both in sheep and goats, before returning to pre-infection levels after 14 days of treatment. Haematological values, serum and erythrocyte indices studied returned to near pre-infection levels 14 days after treatment with Berenil((R)). It is concluded that the grey duiker is inherently trypanotolerant. This is shown by its ability to control parasitaemia, suffer less severe anaemia, and to a relative degree resist pathobiochemical derangements of some serum and erythrocyte metabolites and enzymes, as well as reduction of infection-induced erythrocyte lipid peroxidase damage than sheep and goats.
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PMID:Pathobiochemical mechanisms involved in the control of the disease caused by Trypanosoma congolense in African grey duiker (Sylvicapra grimmia). 1118 35

In male albino mice, the petroleum ether extract of the leaves of Mentha arvensis L., at the doses 10 and 20 mg/mouse per day for 20, 40 and 60 days, when administered orally, showed a dose and duration dependent reduction in the number of offspring of the treated male mated with normal females. Negative fertility was observed in both dose regimens after 60 days of treatment. The body weight and libido of the treated ammals remain unaffected. However, a significant decrease in the weight of the testis, epididymis, cauda epididymal sperm count, motility, viability and normal morphology of the spermatozoa was observed. The levels of serum protein, bilirubin, GOT, GPT and acid phosphatase, blood urea and haematological indices were unaltered throughout the course of investigation. All the altered parameters were reversible following withdrawal of treatment. The results suggest that the petroleum ether extract of the leaves of M. arvensis possess reversible antifertility property without adverse toxicity in male mice.
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PMID:Antifertility investigation and toxicological screening of the petroleum ether extract of the leaves of Mentha arvensis L. in male albino mice. 1128 36

AIM:To investigate the interference of methionine-free parenteral nutrition plus 5-Fu (-MetTPN+5-Fu) in gastric cancer cell kinetics and the side effects of the regimen.METHODS:Fifteen patients with advanced gastric cancer were randomly divided intotwo groups, 7 patients were given preoperatively a seven-day course of standard parenteral nutrition in combination with a five-day course of chemotherapy (sTPN+5-Fu), while the other 8 patients were given methionine-deprived parenteral nutrition and 5-Fu (-MetTPN+5-Fu). Cell cycles of gastric cancer and normal mucosa were studied by flow cytometry (FCM). Blood samples were taken to measure the serum protein, methionine (Met) and cysteine (Cys) levels, and liver and kidney functions.RESULTS:As compared with the results obtained before the treatment, the percentage of G(0)/G(1) tumor cells increased and that of S phase decreased in the -MetTPN+5-Fu group, while the contrary was observed in the sTPN+5-Fu group. Except that the ALT, AST and AKP levels were slightly increased in a few cases receiving -MetTPN+5-Fu, all the other biochemical parameters were within normal limits. Serum Cys level decreased slightly after the treatment in both groups. Serum Met level of patients receiving sTPN+5-Fu was somewhat higher after treatment than that before treatment; however, no significant change occurred in the -MetTPN+5-Fu group, nor operative complications in both groups.CONCLUSION:-MetTPN+5-Fu exerted a suppressive effect on cancer cell proliferation, probably through a double mechanism of creating a state of "Met starvation" adverse to the tumor cell cycle, and by allowing 5-Fu to kill specifically cells in S phase. Preoperative shortterm administration of -MetTPN+5-Fu had little undesirable effect on host metabolism.
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PMID:A study of preoperative methionine-depleting parenteral nutrition plus chemotherapy in gastric cancer patients. 1181 69

Cyclododecatriene (CDDT, CAS No. 4904-61-4) was administered daily by oral gavage to groups of Crl:CD (SD)IGS BR rats at dose levels of 0 (control), 30, 100, or 300 mg/kg/day. Female rats were dosed for four weeks premating, through mating, gestation, and lactation (a total of 55 to 63 days of treatment). Male rats were treated for 55 days (four weeks premating and through mating). Premating, body weights, food consumption, and clinical signs were recorded. Hematology, clinical chemistry, and urine analyses were conducted at the end of the premating period. A neurobehavioral test battery was conducted prior to and after four weeks of treatment. After the premating period, females were paired with males from the same groups for 1-2 weeks. Litters were delivered, pups were evaluated for structural integrity, and pup body weights were recorded on days 0 and 4 postpartum. Lactating females and their offspring were sacrificed on postpartum day 4. Selected organs were weighed and the tissues were examined microscopically from the lactating females. Offspring were examined for clinical abnormalities. A test substance-related reduction in body weight gain occurred in male rats administered 300 mg/kg/day. Decreased body weight gain in the 300 mg/kg/day males was accompanied by increased food consumption and decreased food efficiency. Females administered 100 or 300 mg/kg/day had test substance-related, significantly decreased body weight and body weight gain during gestation, that was accompanied by a significant increase in food consumption (300 mg/kg/day group only), and significantly decreased food efficiency. There were no test-substance related effects on clinical observations in males or females during the premating phase, or in females during gestation or lactation. Neurobehavioral parameters and motor activity were unaffected by CDDT-treatment. During this study, statistically significant treatment-related changes were observed in several clinical pathology parameters. The decreases in red cell mass (RBC, HGB, HCT) were minimal and, due to the magnitude, were not expected to result in biological effects. Similarly, minimally increased potassium and mildly decreased triglycerides were not of a magnitude to be biologically significant. Finally, changes in serum enzymes (AST, ALT, ALP), urea nitrogen, and serum protein occurred in directions that are not associated with toxicity. The changes in urine volume, urine concentration, and urea nitrogen may be the result of elevated glomerular filtration rate and altered tubular fluid flow, in the absence of any histopathological change. No effects on reproduction in parental males or females were produced by CDDT. Body weights of pups in the 300 mg/kg group were significantly decreased on postpartum days 0 and 4. There were no test-substance related effects on clinical observations, number of pups born, and the number of pups born alive, or the number of pups surviving through lactation day 4. The no-observed-adverse-effect level (NOAEL) for CDDT was 30 mg/kg/day based on decreased body weight and body weight gain, increased food consumption, and decreased food efficiency in females administered 100 or 300 mg/kg/day. The NOEL in pups was 100 mg/kg/day, based on decreased body weights of pups in the 300 mg/kg/day group during lactation.
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PMID:Reproductive and repeated dose toxicity of cyclododecatriene (CDDT) in rats following oral (gavage) treatment. 1202


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