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)

Nephropathy due to radiocontrast media presents with a wide spectrum of changes from reversible renal dysfunction to oliguria requiring dialysis. Nineteen patients (mean age 4.5 +/- 3.7 years) were included. Mean +/- SD values of the variables obtained before and 48 hours after angiography were the following: plasma creatinine: 0.6 +/- 0.10 and 0.6 +/- 0.16 mg/dl; endogenous creatinine clearance: 76.1 +/- 17.0 and 80.9 +/- 19.3 ml/min/1.73 m2; plasma osmolality: 279 +/- 23 and 298 +/- 39 mOsm/kg H2O; urine osmolality: 429 +/- 225 and 459 +/- 196 mOsm/kg H2O; fractional sodium excretion: 2.1 +/- 1.3% and 2.4 +/- 1.3%; plasma uric acid: 3.9 +/- 1.3 and 3.4 +/- 1.0 mg/dl; urinary AST/creatinine: 5.2 +/- 4.8 and 4.2 +/- 2.6 mU/mg; ALT/creatinine: 16.8 +/- 12.4 and 15.3 +/- 12.6 mU/mg; LDH/creatinine: 52.0 +/- 39.6 and 42.3 +/- 31.5 mU/mg; NAG/creatinine: 20.1 +/- 2.8 and 16.8 +/- 2.3 mU/mg, respectively. The changes in renal function parameters and urinary enzyme levels were insignificant statistically (p > 0.05). In conclusion, iopromid injection at maximum doses of 5 ml/kg does not result in injury to the tubular epithelium leading to increased urinary enzyme levels.
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PMID:Urinary enzyme changes in children undergoing cineangiographic evaluation using iopromid. 759 67

Groups of 10 male and 10 female Sprague-Dawley rats were administered 1,1-dichloro-2-propanone in corn oil by gavage at 0, 10, 20, 40, or 80 mg/kg/day for 90 consecutive days. Food and water consumption, body and organ weights, organ-to-body weight ratios, hematology, and clinical chemistry parameters were determined. Gross and microscopic pathology examinations also were conducted. No treatment-related mortality was observed during the study; however, liver, forestomach, and kidney toxicity was evident. Liver changes consisted of cytoplasmic alteration, cytomegaly, karyomegaly, and bile duct hyperplasia. These occurred with significance of p < or = 0.05 at or above 10 mg/kg/day in both sexes. The forestomach lesions included hyperkeratosis and epithelial hyperplasia in both sexes at 40 and 80 mg/kg/day, and ulcerations at 80 mg/kg/day. Also, an increased incidence and severity of spontaneously occurring chronic progressive nephropathy was most apparent in high dose males. Increases in organ-to-body weight ratios were noted for the liver and kidneys in females at the highest dose level and in males at the two highest dose levels. Serum enzymes (ALT, AST, and LDH) were increased in females and decreased in males. Based on liver lesions and biochemical changes, it was concluded that there was no experimentally definable NOAEL.
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PMID:Subchronic toxicity study of 1,1-dichloro-2-propanone in Sprague-Dawley rats. 840 48

The toxicity of cadmium (Cd) chloride was studied in ovariectomized (OX) female rats and non-OX female rats after intravenous administration of the compound at doses of 2.0 and 3.0 mg/kg for 14 days. Mild hypochromic microcytic anemia developed in all rats treated with Cd, but growth retardation in the OX rats was more prominent than that in the non-OX rats. There was an increase of AST and ALT and a decrease of total cholesterol and the A/G ratio in both OX and non-OX rats treated with Cd. The hepatic and renal Cd concentrations increased in a dose-dependent manner, and the concentrations in both organs on Day 14 were comparable in the 3.0 mg/kg OX group (liver, 270.0 +/- 39.6 micrograms/g; kidney, 121.3 +/- 10.1 micrograms/g) and non-OX group (liver, 277.0 +/- 29.9 micrograms/g; kidney, 100.8 +/- 1.3 micrograms/g). Hepatocyte necrosis developed only in OX rats treated with Cd, and the nephrotoxicity of Cd was also notably enhanced by ovariectomy, since Cd nephropathy affected the proximal convoluted epithelium more severely and more frequently in OX rats than in non-OX rats. BrdU-labeled cells in the renal cortex were increased by approximately 2.7-fold in OX rat (7.4 cells/mm2) over those in the renal cortex in non-OX rat (2.7 cells/mm2). In conclusion, the present study demonstrated that ovariectomy enhanced Cd-induced nephrotoxicity and hepatotoxicity in rats.
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PMID:Ovariectomy enhances cadmium-induced nephrotoxicity and hepatotoxicity in rats. 848 Mar 35

Hepatitis C virus (HCV) is the predominant cause of posttransplant non-A, non-B hepatitis among renal allograft recipients. Prior studies evaluating the impact of HCV in kidney transplantation have been retrospective in design and based largely on changes in serum transaminases. We studied a group of HCV-infected end-stage renal disease patients prospectively with pretransplant liver biopsies and close virologic and biochemical follow-up posttransplant. Fourteen patients have been followed a mean of 11.6 +/- 5.6 months posttransplant (range, 5-21 months). Six had changes of chronic hepatitis on pretransplant liver biopsy while 8 showed only mild histologic abnormalities. Circulating viral titers increased several-fold over baseline levels during posttransplant follow-up. Viral replication was particularly enhanced immediately following a course of antilymphocyte therapy. Although all patients showed a 2-3 fold increase in alanine aminotransferase (ALT) following transplantation, there were no association noted between pretransplant liver histology, the use of FK506 and/or cyclosporine-based immunosuppression, and the magnitude of ALT change posttransplant. The only clinical outcome found to differ significantly was a higher incidence of cytomegalovirus infection among patients with chronic hepatitis. All patients are alive with functioning grafts. There have been no episodes of fulmiinant or subfulminant liver failure. We conclude that HCV-infected patients can be safely transplanted with excellent short-term follow-up. Continued monitoring with sequential liver biopsies will be needed to define the long-term course of HCV infection in an immuno-suppressed population.
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PMID:A prospective study of hepatitis C virus infection in renal allograft recipients. 862 54

The U.S. Air Force is converting from JP-4 jet fuel to the less volatile JP-8 jet fuel, which is similar to commercial Jet Fuel A. Our previous 90-day inhalation study with JP-8 vapor, using F-344 rats and C57BL/6 mice, resulted in no treatment-related adverse effects other than alpha 2-microglobulin nephropathy in male rats (Mattie et al., 1991). In the present study, male rats were dosed with neat JP-8 (0, 750, 1500, 3000 mg/kg) daily by gavage for 90 days in an effort to characterize the kidney lesion and assess further any additional adverse effects associated with prolonged oral exposure to this fuel. Results of this study revealed a significant dose-dependent decrease in body weights of rats exposed to JP-8. Male rat-specific alpha 2-microglobulin nephropathy was observed by histopathologic examination. A number of significant changes were also seen in blood and urine that were not dose-dependent. Additional treatment-related effects were a gastritis and a perianal dermatitis. Although there were no histopathological or weight changes in the livers of exposed rats, there was an increase in the liver enzymes AST and ALT. The elevated enzymes did not increase with increasing dose of JP-8.
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PMID:The effects of JP-8 jet fuel on male Sprague-Dawley rats after a 90-day exposure by oral gavage. 874 23

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

Toxicity studies were performed by exposing F344/N rats and B6C3F1 mice to 2- and 4-chloronitrobenzene (CNB) by whole-body inhalation 6 hr/day, 5 days/week, for 13 weeks. Animals were evaluated for clinical chemistry (rats), hematology (rats), histopathology, and body/organ weights. Exposure concentrations were 0, 1.1, 2.3, 4.5, 9, and 18 ppm for 2-CNB and 0, 1.5, 3, 6, 12, and 24 ppm for 4-CNB. All rats in the 2-CNB study survived until the end of the study. Two male mice in the 18-ppm group in the 2-CNB study, however, died during Week 12; no deaths attributable to 4-CNB exposure occurred in rats or mice. In both studies, the mean body weight gains of exposed animals were similar to those of the respective controls. In rats, inhalation exposure to 2- or 4-CNB resulted in methemoglobinemia leading to a regenerative anemia and a variety of tissue changes secondary to the oxidative erythrocyte injury. In the 2-CNB study, methemoglobinemia resulted in a normocytic, normochromic, responsive anemia, whereas with 4-CNB, the methemoglobinemia was more severe and resulted in a macrocytic, hyperchromic, responsive anemia. Alterations of erythrocyte morphology were observed in both studies; changes included Heinz bodies, poikilocytes, and polychromasia. In rats, both isomers caused increases in serum activities of alanine aminotransferase and sorbitol dehydrogenase and increased bile acid concentrations. Microscopic liver changes included hemosiderin deposition in Kupffer cells (rats and mice exposed to 4-CNB), hepatocytomegaly (mice), and cytoplasmic basophilia (rats). Hepatocellular necrosis and chronic inflammation observed in mice were rather specific to the 2-CNB isomer, as only slight evidence of focal necrosis in the liver was observed in mice exposed to 4-CNB. Splenic lesions included hemosiderin accumulation capsular fibrosis, and increased hematopoietic cell proliferation. Increased bone marrow hemosiderin and hematopoietic cell proliferation and kidney tubule hemosiderin deposition were also observed. Other findings, attributed to chemical exposure but not to the hematotoxicity, were described. Lesions included hyaline droplet nephropathy and degeneration of the testis in male rats exposed to 4-CNB, inflammation of the harderian gland in rats exposed to 4-CNB, hyperplasia of the nasal cavity epithelium in rats exposed to 2-CNB, and hyperplasia of the forestomach epithelium in mice exposed to 4-CNB; these lesions have not been described previously in studies with these chemicals. Based on the exposure concentrations evaluated, A no-observed-adverse-effect level (NOAEL) for histopathological injury in mice was 4.5 ppm for 2-chloronitrobenzene and 6 ppm for 4-chloronitrobenzene; a NOAEL was not determined for rats.
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PMID:Thirteen-week inhalation toxicity of 2- and 4-chloronitrobenzene in F344/N rats and B6C3F1 mice. 881 32

The etiology of liver disease remains unknown in about 4 to 23% of dialysis patients and 10 to 16% of renal transplant recipients. A search for other causative agents of liver disease led to the discovery of the GB group of viruses. We studied the association between the presence of GB virus C (GBV-C) infection, known risk factors for parenterally-transmitted infections and history or laboratory evidence of liver disease among end-stage renal disease (ESRD) patients referred for renal transplantation to the New England Organ Bank, MA. Stored sera from patients on the renal transplantation waiting list between November 1986 and June 1990 were tested for antibody to hepatitis C virus (HCV). Sera were available in 1544 of 3243 (48%) patients, and anti-HCV was detected by ELISA3 in 287 (19%). All 287 anti-HCV positive patients formed the anti-HCV positive cohort and 286 randomly selected anti-HCV negative patients formed the anti-HCV negative cohort (573 patients overall). Additional sera were available for GBV-C RNA testing in 465 of 573 (81%) patients, and GBV-C RNA was detected by RT-PCR in 146. The overall extrapolated prevalence of serum GBV-C RNA was 29%. The prevalence of serum GBV-C RNa among anti-HCV positive patients (35%) was not significantly different from that among anti-HCV negative patients (29%; P = 0.22). In a univariate analysis, compared to patients without GBV-C RNA, patients with serum GBV-C RNA were younger [odds ratio (OR) 0.98 per year of age, P = 0.01], had a lower proportion of males (OR 0.64, P = 0.03), lower proportion of patients with diabetes mellitus (OR 0.44, P = 0.01), higher proportion of patients with a previous transplantation (OR 1.53, P = 0.04), longer duration of dialysis at the time of enrollment (OR 1.004 per month on dialysis, P = 0.03), and a higher proportion of patients with history of transfusions (OR 4.58, P = 0.01). Serum GBV-C RNA was not associated with a significantly increased OR for history of liver disease or non-A, non-B hepatitis, or elevated serum alanine aminotransferase levels. In a step-wise multivariate regression analysis, a younger age (OR 0.98 per year of age, P = 0.03), and history of blood transfusions (OR 3.89, P = 0.03) were associated with an increased OR for serum GBV-C RNA, while diabetes mellitus was associated with a decreased OR for GBV-C RNA (OR 0.47, P = 0.01). Anti-HCV was not a predictor of serum GBV-C RNA (OR 1.07, P = 0.77). The results of this study support the fact that GBV-C is a parenterally transmitted virus and shed light on the modes of transmission of GBV-C among ESRD patients. However, the association with liver disease remains to be established.
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PMID:Predictors of GBV-C infection among patients referred for renal transplantation. 960 18

The biological dynamics of hepatitis C virus (HCV) viremia in uremic patients with chronic infection have not been fully characterized. We prospectively studied fluctuations of HCV-RNA in sera from 52 patients with end-stage renal disease who were undergoing maintenance hemodialysis (HD) and had chronic HCV infection. We measured HCV viremia monthly over the course of 13 months with the branched-chain DNA (bDNA) signal amplification assay and prospectively analyzed liver function, expressed by monthly serum aspartate (AST) and alanine aminotransferase (ALT) determinations. We observed three different patterns of HCV viremia: (1) patients persistently positive by bDNA assay (persistent viremia; 23 of 52 patients; 44%), (2) individuals with alternatively positive and negative results (intermittent viremia; 17 of 52 patients; 33%), and (3) patients persistently negative by bDNA assay (12 of 52 patients; 23%). The HCV viral load over the follow-up was greater among patients with persistent compared with intermittent viremia (persistent, 31.7 x 10(5) Eq/mL; range, 6.3 x 10(5) to 16.03 x 10(6) Eq/mL versus intermittent, 10.4 x 10(5) Eq/mL; range, 1.1 x 10(5) to 9.4 x 10(6) Eq/mL; P = 0.0001). In addition, patients with persistent viremia had over time greater AST and/or ALT activities than the intermittent group (AST: persistent, 26.5 IU/L; range, 9.6 to 73.7 IU/L versus intermittent, 21.3 IU/L; range, 8 to 56.8 IU/L; P = 0.001 and ALT: persistent, 14.7 IU/L; range, 3.7 to 57.9 IU/L versus intermittent, 10.9 IU/L; range, 2.3 to 52.1 IU/L; P = 0.001). In the group with persistent viremia, the mean difference between maximum and minimum values of HCV-RNA observed in each individual patient was 2.09 +/- 0.7 natural logarithm (Log(n)) and in intermittent viremic patients, 1.55 +/- 1 Log(n) (P = 0.045). The HCV load at study entry (19.4 x 10(5) Eq/mL) was rather low and did not change versus the end of follow-up in all patients (P = not significant [NS]). In the entire group, the fluctuations in HCV-RNA levels over time between and within individuals were not significant (P = NS). No difference in variability of HCV-RNA values over time between patients infected with different HCV genotypes was seen. In conclusion, three different patterns of HCV viremia in HD over time were assessed; one third of viremic patients had intermittent viremia, and those patients had less HCV-RNA, enzyme-linked immunosorbent assay, and aminotransferase activity than did patients with persistent HCV load. Larger fluctuations in HCV RNA levels occurred in patients with persistent than with intermittent HCV viremia. However, the viremic HCV load was low and relatively stable over a 13-month follow-up in our population. Studies with longer observation periods are warranted to understand fully the natural history of HCV in these immunosuppressed individuals.
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PMID:Biological dynamics of viral load in hemodialysis patients with hepatitis C virus. 1062 May 53

Patients with end-stage renal disease (ESRD) appear to be at high risk for GBV-C/HGV infection. This information has been obtained with virological techniques (RT-PCR) but few serological data exist. A prototype enzyme immunoassay has now been developed to detect antibodies against the putative envelope protein (E2) located on the surface of the GBV-C/HGV virion particle. We studied the prevalence of GBV-C/HGV infection, as detected by RT-PCR and anti-E2 GBV-C/HGV antibody, in a cohort of chronic dialysis patients (n=157) and renal transplant (RT) recipients (n=77); as a control group, 136 healthy blood donors were tested. The total prevalence of GBV-C/HGV in ESRD was 23% (54/234). The frequency of GBV-C/HGV viremia was 7.7% (18/234) in ESRD and 4.4% (3/68) among healthy blood donors; the prevalence of anti-E2 GBV-C/HGV was 15% (36/234) and 8.8% (12/136) in ESRD and controls, respectively. No relationship was seen between anti-E2 GBV-C/HGV antibody (or GBV-C/HGV viremia) and age, sex, time on renal replacement therapy, anti-HCV, HBsAg and transfusion requirement. No statistical association was observed between GBV-C/HGV and AST/ALT activity. Two of 54 GBV-C/HGV positive patients (3.7%) had raised ALT but were negative for HBV/HCV. In the majority of patients (35/36, 97%) the presence of anti-E2 GBV-C/HGV antibody was linked with the loss of GBV-C/HGV viremia from serum. In conclusion, GBV-C/HGV infection, as detected by RT-PCR and anti-E2 antibody, was common in ESRD, and the rate of infection was higher than in controls. No association was seen between GBV-C/HGV and various demographic or clinical factors. A small group of GBV-G/HGV positive patients tested negative for HBV/HCV and had raised ALT. In many patients exposed to GBV-C/HGV infection the virus was cleared. The clinical significance of GBV-C/HGV in ESRD remains controversial. Prospective studies with additional serological assays are in progress.
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PMID:GBV-C/HGV infection in end-stage renal disease: a serological and virological survey. 1072 Feb 18


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