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:2.6.1.1 (aspartate aminotransferase)
21,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To examine the effects of acute exposure to fumonisin-containing culture material (FCCM), 15 crossbred wether lambs were dosed intraruminally with FCCM containing 0 (CONTROL, n = 3), 11.1 (LOW, n = 4), 22.2 (MED, n = 4), or 45.5 (HIGH, n = 4) mg of total fumonisins (B1, B2, and B3)/kg BW daily for 4 d. Blood samples were collected daily, and on d 11 lambs were killed and necropsied. Changes in serum constituents in fumonisin-treated lambs indicative of liver damage, included increased (P < .05) activities of alkaline phosphatase, gamma-glutamyl transferase, aspartate aminotransferase, and lactate dehydrogenase. Serum concentrations of cholesterol, triglycerides, urea nitrogen, and creatinine were also increased (P < .05) in lambs dosed with FCCM. Hemoglobin tended to increase (P = .07) and white blood cell count tended to decrease (P = .08) in HIGH lambs and activated partial thromboplastin time tended to decrease (P < .10) in lambs dosed with LOW and MED treatments. Mitogen-induced lymphocyte blastogenesis was not different (P = .14) among treatments. Feed intake markedly decreased (P < .01) following the first dosing of FCCM and continued to decline throughout the study. Ruminal VFA concentrations and pH tended to decrease (P < .10) at d 11 in treated lambs. Relative liver and kidney weights (g/100 g of BW) increased (P < .05) in fumonisin-treated lambs. Histiolgical examination revealved tubular nephrosis and mild hepatopathy in dosed lambs. Lambs receiving the HIGH treatment died on d 3, 4, 5, and 7 of the study and on d 9 one lamb on the MED treatment died.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Acute hepatic and renal toxicity in lambs dosed with fumonisin-containing culture material. 760 85

Infection of naive North American horses with 10(4) cell culture infectious doses (CCID50) of virulence variants of African horsesickness virus (AHSV), designated AHSV/4SP, AHSV/9PI, and AHSV/4PI, reproduced three classical forms of African horsesickness: acute (pulmonary), subacute (cardiac), and febrile, respectively. Distinct clinicopathologic and hemostatic abnormalities were associated with each form of disease. Hemostatic abnormalities included increased concentration of fibrin degradation products and prolongation of prothrombin, activated partial thromboplastin, and thrombin clotting times. Hemostatic findings indicated activation of the coagulation and fibrinolytic systems with clotting factor consumption in acute and subacute cases of African horsesickness. Hematologic abnormalities in acute and subacute cases of African horsesickness included leukopenia, decreased platelet counts, elevated hematocrit, and increased erythrocyte counts and hemoglobin concentration. Leukopenia was characterized by lymphopenia, neutropenia, and a left shift. Increased levels of serum creatine kinase, lactate dehydrogenase, aspartate aminotransferase, and alkaline phosphatase, hypocalcemia, hypoalbuminemia, hypoproteinemia, and elevated creatinine, phosphorus, and total bilirubin levels were present in some but not all horses. Metabolic acidosis, indicated by decreased total bicarbonate and increased lactate and anion gap, was present in horses with the acute form of disease. Mild thrombocytopenia and leukopenia were occasionally associated with the febrile form of disease. These results suggest a role for intravascular coagulation in the pathogenesis of African horsesickness.
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PMID:Clinical pathology and hemostatic abnormalities in experimental African horsesickness. 777 Oct 50

In Italy, although a national decree (DPCM of 10/2/84) established that quality control programs involving clinical laboratories should be carried out on a regional basis, external quality assessment schemes (EQAS) are actually run only in some regions. Among these is Lombardy, where an EQAS in clinical chemistry concerning 20 analytes was set up in 1986, and where at present EQA programs (for clinical chemistry, haematology and coagulation) compulsory for both private and public laboratories, are under way. This was made possible by both regional laws and the constant care shown by the regional Committee on pathology department system (Comitato Regionale per l'Ordinamento dei Servizi di Patologia, CROSP). The participation in the schemes (including control material supply) is free of charge. The identity of participants is known only to officers in charge of quality control and analytical results are therefore managed anonymously. Consequently EQAS carried out in Lombardy are not exacting or punitive. In the EQAS for clinical chemistry the following analytes are considered: glucose, urea, proteins, albumin, chloride, sodium, potassium, total calcium, inorganic phosphate, iron, urate, creatinine, cholesterol, triglycerides, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, creatine phosphokinase, gamma glutamyl transferase and alkaline phosphatase. In the EQAS for haematology and coagulation the tests are: a) leukocytes, erythrocytes, haemoglobin, haematocrit, mean cell (erythrocyte) volume, platelets; b) prothrombin time, activated partial thromboplastin time, fibrinogen and antithrombin III. The general organization of the schemes, the statistical procedures adopted for the analysis of data, and some of the results obtained in the three EQA programs are reported in detail in the present article.
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PMID:External quality assessment programs in Lombardy, Italy. 854 65

Ten scientific organizations formed a joint international committee to provide expert recommendations for clinical pathology testing of laboratory animal species used in regulated toxicity and safety studies. For repeated-dose studies in rodent species, clinical pathology testing is necessary at study termination. Interim study testing may not be necessary in long-duration studies provided that it has been done in short-duration studies using dose levels not substantially lower than those used in the long-duration studies. For repeated-dose studies in nonrodent species, clinical pathology testing is recommended at study termination and at least once at an earlier interval. For studies of 2 to 6 weeks in duration in nonrodent species, testing is also recommended within 7 days of initiation of dosing, unless it compromises the health of the animals. If a study contains recovery groups, clinical pathology testing at study termination is recommended. The core hematology tests recommended are total leukocyte (white blood cell) count, absolute differential leukocyte count, erythrocyte (red blood cell) count, evaluation of red blood cell morphology, platelet (thrombocyte) count, hemoglobin concentration, hematocrit (or packed cell volume), mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration. In the absence of automated reticulocyte counting capabilities, blood smears from each animal should be prepared for reticulocyte counts. Bone marrow cytology slides should be prepared from each animal at termination. Prothrombin time and activated partial thromboplastin time (or appropriate alternatives) and platelet count are the minimum recommended laboratory tests of hemostasis. The core clinical chemistry tests recommended are glucose, urea nitrogen, creatinine, total protein, albumin, calculated globulin, calcium, sodium, potassium, total cholesterol, and appropriate hepatocellular and hepatobiliary tests. For hepatocellular evaluation, measurement of a minimum of two scientifically appropriate blood tests is recommended, e.g., alanine aminotransferase, aspartate aminotransferase, sorbitol dehydrogenase, glutamate dehydrogenase, or total bile acids. For hepatobiliary evaluation, measurement of a minimum of two scientifically appropriate blood tests is recommended, e.g., alkaline phosphatase, gamma glutamyltransferase, 5' -nucleotidase, total bilirubin, or total bile acids. Urinalysis should be conducted at least once during a study. For routine urinalysis, an overnight collection (approximately 16 hr) is recommended. It is recommended that the core tests should include an assessment of urine appearance (color and turbidity), volume, specific gravity or osmolality, pH, and either the quantitative or semiquantitative determination of total protein and glucose. For carcinogenicity studies, only blood smears should be made from unscheduled sacrifices (decedents) and at study termination to aid in the identification and differentiation of hematopoietic neoplasia.
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PMID:Harmonization of animal clinical pathology testing in toxicity and safety studies. The Joint Scientific Committee for International Harmonization of Clinical Pathology Testing. 874 16

Tepoxalin [5- (4-chlorophenyl)-N-hydroxy-1-(4-methoxyphenyl)-N-methyl-1H-pyrazole -3-propanamide] is an orally active anti-inflammatory agent, which inhibits both cyclooxygenase and 5-lipoxygenase activities. The oral toxicity of tepoxalin was evaluated in 1- and 6-month rat (up to 50 mg/kg/day) and dog (up to 150 mg/kg bid) studies. In rats, increased liver weight, centrilobular hypertrophy, and hepatic necrosis were observed at dosages >/=20 mg/kg/day. Renal changes indicative of analgesic nephropathy syndrome (i.e., papillary edema or necrosis, cortical tubular dilatation) were seen at >/=15 mg/kg. In rats treated for 1 month, these hepatic and renal effects were largely reversible after a 1-month recovery period. Gastrointestinal erosions and ulcers were seen in female rats given 40 mg/kg/day for 6 months. Changes in clinical pathology parameters included decreases in red blood cell count, hemoglobin, and hematocrit mean values; elevation in platelet counts; and an increase in prothrombin and activated partial thromboplastin times. Mild increases in alanine aminotransferase, aspartate aminotransferase, and cholesterol were also noted in rats. Decreased erythrocyte parameters, increased leukocyte counts, and decreased total protein, albumin, and/or calcium were noted in some dogs in the 300 mg/kg/day group following 6 months of dosing. Small pyloric ulcerations were seen at 100 and 300 mg/kg/day dosages for up to 6 months. In both rats and dogs, no accumulation of tepoxalin or its carboxylic acid metabolite was detected in plasma following multiple dosing over a range of 5 to 50 mg/kg/day for rats and 20 to 300 mg/kg/day for dogs. Plasma concentrations of the carboxylic acid metabolite were severalfold higher than those of the parent compound. The no-effect dosages in rats (5 mg/kg/day) and dogs (20 mg/kg/day) were approximately one and six times the ED50 (3.5 mg/kg), respectively, for inhibition of inflammatory effects in the adjuvant arthritic rat without gastric mucosal damage. In terms of severity, the relative lack of gastrointestinal side effects, within the estimated therapeutic dose range, distinguishes tepoxalin from most marketed anti-inflammatory drugs.
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PMID:Preclinical toxicity evaluation of tepoxalin, a dual inhibitor of cyclooxygenase and 5-lipoxygenase, in Sprague-Dawley rats and beagle dogs. 881 16

In long-term survivors of liver transplantation, hepatic function is obviously of vital importance. Therefore, we prospectively performed conventional and quantitative liver function tests in patients who had survived a first transplantation for at least 4 years. Compared to 6 months after transplantation, serum bilirubin concentration and gamma GT activity were significantly lower after 3, 4, and 5 years (bilirubin 1.2 +/- 0.2 mg/dl at 6 months vs 1.0 +/- 0.1, 1.0 +/- 0.2, and 0.8 +/- 0.1 mg/dl respectively; gamma GT 106 +/- 0 33 U/l at 6 months vs 56 +/- 17, 67 +/- 35, 39 +/- 10 U/l respectively). At these points in time, blood levels of cyclosporin A were also significantly lower. Other parameters of liver cell function and liver cell integrity (AP, AST, ALT, GLDH, total protein, thromboplastin time, partial thromboplastin time) were unchanged over time. Serial quantitative liver function tests (indocyanine green half-life, galactose elimination capacity, lidocaine half-life, and MEGX formation) also remained stable. Thus, we conclude that hepatic function remains stable in long-term survivors of liver transplantation for at least several years.
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PMID:Conventional and quantitative liver function tests after hepatic transplantation: a prospective long-term follow-up. 916 62

In a first experiment, 28 specific pathogen-free chickens aged 3 weeks showed clinical signs 1 to 5 days after intramuscular inoculation with Erysipelothrix rhusiopathiae. Twelve of 28 birds died 2 to 4 days after inoculation. Macroscopically, the liver, spleen and kidneys were seen to be enlarged and congested. Histologically, fibrinous thrombus formation, seen in the hepatic sinusoids, renal glomerular capillaries and small pulmonary blood vessels, was a characteristic feature. In addition, the liver showed marked congestion, increase of mononuclear cells and heterophils in the sinusoids, hyperplasia of sinusoidal lining cells, and vacuolar changes in hepatic cells. The spleen showed fibrinous exudation of the lymphoid follicles and ellipsoids with lymphocytic depletion, and hyperplasia of ellipsoidal reticular cells. There was oedema, congestion and cellular infiltration in the interstitium of the kidney. The bursa of Fabricius and thymus showed marked lymphocytic depletion. In a second experiment, the blood chemical values (uric acid, glutamic-oxalacetic transaminase, lactate dehydrogenase and gamma-glutamyl transpeptidase) of birds inoculated intramuscularly with E. rhusiopathiae were significantly higher than those of uninfected controls. The blood prothrombin times and activated partial thromboplastin times of the inoculated group were significantly greater than those of the control group. The pathological and haematological findings demonstrated that E. rhusiopathiae induced disseminated intravascular coagulation in the chickens.
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PMID:Disseminated intravascular coagulation in chickens inoculated with Erysipelothrix rhusiopathiae. 935 39

Prior studies have suggested that changes in liver function tests may vary with the postoperative time interval and may be related to the extent of hepatic resection. This study describes characteristic profiles in parenchymal liver enzymes and other serum liver function tests over a 4-week course comparing anatomic to nonanatomic hepatic resections. The records of 48 patients undergoing successful major hepatic resection during a 3-year period were retrospectively reviewed. Of these 48 patients, 28 underwent formal anatomic resection (hepatic lobectomy), and 20 underwent nonanatomic resections (wedge resection). Routine postoperative management in lobectomy patients included drawing liver function tests and enzymes daily for the first week, then at approximately 2 and 4 weeks postoperatively. These tests included: prothrombin time (PT), partial thromboplastin time, total serum bilirubin, total protein (TP), aspartate transaminase, lactate dehydrogenase (LDH), alkaline phosphatase, albumin (A), and glucose. Patients undergoing wedge resections had these values checked less frequently, approximately 3 to 5 days, 2 weeks, and 4 weeks postoperatively. Profiles of these values were plotted over the 4-week postoperative time course for each group of patients. Patients undergoing hepatic lobectomy showed a characteristic laboratory value profile. PT elevated within 48 hours to a mean high of 16.0 seconds, then returned to normal by postoperative day 4. Partial thromboplastin time levels remained normal throughout the entire perioperative course. Total bilirubin rose slightly, to a mean high of 2.6 mg/100 cc, then returned to normal by postoperative day (POD) 14. Parenchymal liver enzymes aspartate transaminase and LDH rose abruptly to very high levels, then returned abruptly to normal (by POD 5). TP and A both fell to approximately 50 per cent of normal, gradually rising to normal by POD 14. Glucose rose to a mean high of 199 mg/100 cc within the first 5 days, then returned to normal by POD 7. Alkaline phosphatase remained normal initially, then showed a progressive rise to a high of 288 mg/100 cc on POD 14. Patients undergoing wedge resections did not show the same changes in total serum bilirubin, but showed similar trends in all other tests, although the magnitude of these changes was smaller. TP and A levels fell acutely after resection, then began a slow rise toward normal by POD 21. TP and A profiles were similar for both lobectomy patients and those undergoing wedge resection. The only tests that may have altered clinical management were the PT and total bilirubin. Patients undergoing major hepatic resection have characteristic postoperative profiles of liver enzymes and liver function tests. These laboratory profiles differ with the extent of hepatic resection. The profiles reflect changes in volume status, parenchymal liver destruction, transient hepatic insufficiency, and postoperative hepatic regeneration. However, except possibly for PT and bilirubin, the routine use of these tests is not recommended, given that the results do not alter clinical management.
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PMID:Comparison of liver function tests after hepatic lobectomy and hepatic wedge resection. 958 73

In a phase I clinical trial the effect of the highly sulfated polyanion "Aprosulate" was studied in healthy volunteers using different coagulation and platelet function parameters. Eighteen healthy volunteers aged 21 to 30 years received two single subcutaneous doses of aprosulate (0.5 mg/kg body weight; 1.0 mg/kg body weight), or unfractionated heparin (Calciparin 7,500 IU). The washout period between the different drugs/doses was at least 7 days. Coagulation and platelet function parameters (activated partial thromboplastin time, Heptest, fibrinogen, von Willebrand factor, ristocetin cofactor, platelet adhesion to siliconized glass, and platelet-induced thrombin generation time [a new method for measuring thrombin generation in platelet-rich plasma in the presence of platelets]) were assessed during 24 hours after each injection. Aprosulate led to a significant and dose-dependent prolongation of activated partial thromboplastin time and Heptest. This effect lasted for 4 hours (activated partial thromboplastin time) to 8 hours (Heptest). Activated partial thromboplastin time was not prolonged after the injection of unfractionated heparin (7,500 IU). Fibrinogen, von Willebrand factor, and ristocetin cofactor remained unchanged with both drugs. Platelet induced thrombin generation time was slightly prolonged and platelet adhesion was slightly diminished up to 2 hours using 0.5 mg/kg aprosulate, and up to 4 hours using 1.0 mg/kg aprosulate while the platelet induced thrombin generation time system was not influenced by the subcutaneous injection (7,500 IU) of unfractionated heparin. Both drugs and doses were well tolerated. Plasma transaminase concentrations alanin aminotransferase and aspartate aminotransferase serum values were slightly increased in some volunteers but returned to normal during or after the study (< 4 weeks). Further clinical trials will have to establish whether aprosulate is an effective drug for the prophylaxis of deep venous thrombosis.
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PMID:Effects of aprosulate, a novel synthetic glycosaminoglycan, on coagulation and platelet function parameters: a prospective, randomized phase I study. 1072 9

We report factors associated with severe manifestations of histoplasmosis (such as shock, respiratory failure, and death) in patients with AIDS during an outbreak. Severe disease was present in 28 of 155 patients (17.9%). The following factors were associated with severe disease: black race (odds ratio [OR], 2.8; 95% confidence interval [CI], 1.2-6.2); hemoglobin level <9.5 g/dL (OR, 2.7; 95% CI, 1.2-6.4), partial thromboplastin time >45 s (OR, 3.1; 95% CI, 1.1-9.3); alkaline phosphatase level >2.5 times normal (OR, 3.4; 95% CI, 1.3-8.7); aspartate aminotransferase level >2.5 times normal (OR, 4.2; 95% CI, 1.7-10.0); bilirubin level concentration >1.5 mg/dL (OR, 9.2; 95% CI, 2.5-34.3); creatinine concentration >2.1 mg/dL (OR, 8.3; 95% CI, 2.2-31.9); and albumin concentration <3.5 g/dL (OR, 4.6; 95% CI, 1.3-16.4). Zidovudine use was associated with decreased risk of severe disease (OR, 0.3; 95% CI, 0.1-0.7). Multivariate analysis showed that a creatinine value >2.1 mg/dL (OR, 9.5; 95% CI, 1.7-52) and an albumin value <3.5 g/dL (OR, 4.8; 95% CI, 1.0-22) were associated with an increased risk of severe disease, and zidovudine therapy remained associated with a decreased risk (OR, 0.2; 95% CI, 0.1-0.6). Findings associated with severe histoplasmosis should be recognized early and the cases managed aggressively.
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PMID:Factors associated with severe manifestations of histoplasmosis in AIDS. 1085 63


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