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)

Fischer 344 rats were treated with 0, 100, 500, 2500, or 12,500 ppm di(2-ethylhexyl)phthalate (DEHP) in the diet for up to 104 weeks. Blood and urine were analyzed at weeks 26, 52, 78, and 104 from 10 animals per sex per group. Survival was slightly but not statistically reduced for rats receiving 12,500 ppm DEHP. Body weights and food consumption were significantly reduced for rats receiving the highest dose level of DEHP and occasionally for the male 2500-ppm group. BUN and albumin were significantly higher and globulin lower at nearly every sampling interval for the 12,500-ppm group compared with the controls. There was an increase in the mean activities of AST and ALT at 104 weeks, but no statistically significant differences were seen. Erythrocyte count, hemoglobin, and hematocrit values for the 12,500-ppm group were significantly lower than controls at nearly every sampling interval. No other differences in hematology were seen. No toxicologically significant changes were observed in urinalysis. At termination, relative lung weights for the 2500- and 12,500-ppm male groups of rats were significantly higher than for the controls. Absolute and relative liver and kidney weights for the 2500- and 12,500-ppm male rats, and liver weights for 12,500-ppm female rats were higher compared with the controls. Absolute and relative testes weights for the 12, 500-ppm male rats were lower compared with the controls. All organs were examined for histopathology. The incidence of hepatocellular lesions has been reported separately and correlated with the induction of peroxisomal enzyme activity (David et al., 1999). A dose level of 500 ppm was the NOEL for peroxisome proliferation. Bilateral aspermatogenesis in the testes, castration cells in the pituitary gland, spongiosis hepatis, and pancreatic acinar cell adenoma were observed for 12,500-ppm male rats. Aspermatogenesis and spongiosis hepatis were observed for 2500-ppm male rats, and aspermatogenesis was seen at 500 ppm. DEHP exposure exacerbated age-, species- or strain-related lesions such as mineralization of the renal papilla and chronic progressive nephropathy in male rats. Kupffer cell pigmentation and renal tubule pigmentation were seen in male and female 12,500-ppm rats. The increased incidence of spongiosis hepatis correlated with increased palmitoyl CoA oxidase activity, but the incidence of pancreatic acinar cell adenoma was increased only at the highest dose level of 12,500 ppm. These lesions, although typical of those seen with other peroxisome proliferators, may respond differently depending on the potency of the peroxisome proliferator. A dose level of 500 ppm (28.9-36.1 mg/kg/day) was considered to be the NOAEL.
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PMID:Chronic toxicity of di(2-ethylhexyl)phthalate in rats. 1082 76

The aim of the study was to evaluate epidemiology and clinical course of HCV infection in children and adolescents with end-stage renal disease. The study involved 70 patients, aged 1-25 years, 31 M, 39 F: group of 40 dialysed (27 HD, 13 CAPD) and 30 patients suffering from different chronic renal disease as a control group. Anti-HCV antibodies were assayed by EIA 3rd gene (Abbott Diagnostic) and were sought by LIATEK HCV 3rd gene. HCv RNA was detected and measured by a standardised HCV RNA PCR assay (Amplicor Roche). HCV genotypes were identified by InnoLIPA (Innogenetics). HCV infection was diagnosed in 20 (50%) dialysed and in 3 (10%) non-dialysed patients. None of the HCV infected patients presented the clinical symptoms of hepatitis; the mild activity of ALT was observed in 8 cases only. HCV viremia was relatively low: 365 x 103 copies/mL in PD and 110,9 x 103 copies/mL in HD patients. 3 genotypes of HCV were identified: 1a, 1b and 4c/4d. In 3 cases liver biopsy was performed, no cirrhosis was diagnosed.
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PMID:[Epidemiology and clinical course of HCV infection in children and adolescents with chronic renal failure]. 1089 36

Gastrointestinal and hepatic disorders are commonly associated with end-stage renal disease, hemodialysis, and renal transplantation. Recent studies indicate that the prevalence of dyspepsia, ulcer disease, and Helicobacter pylori gastritis is not significantly different from the general population. Bleeding from angiodysplasia, however, is more common in chronic renal failure, as is gastroparesis. The prevalence of chronic hepatitis B has been dramatically reduced among hemodialysis patients since the advent of universal precautions. Response rates to hepatitis B vaccine in noninfected patients, however, are lower in these individuals. Chronic hepatitis C is found in 20% to 25% of HD patients worldwide and accounts for approximately 1% of all infected individuals. Levels of alanine aminotransferase and aspartase aminotransferase are often within normal limits but may be elevated compared with a patient's preinfection levels. Dialysis has been shown to reduce the level of hepatitis C virus viremia. Treatment is similar to non-renal failure patients, although interferon is generally not used in renal transplant recipients owing to concerns of graft failure.
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PMID:Gastrointestinal and hepatic disorders in end-stage renal disease and renal transplant recipients. 1092 10

The study is to evaluate the effect of levamisole on steroid-sensitive nephrotic syndrome (SSNS) children with multiple relapses, from October 1996 through December 1998, we prospectively recruited 27 SSNS children. Eight children had minimal change nephrotic syndrome and nine had mesangial nephropathy proven by renal biopsy. The other 10 children had normal renal function and no secondary cause of nephrotic syndrome (NS). Nine were frequent relapsers (FR), (> 4 attack per year), nine were steroid-dependent (SD), and another nine were both FR and SD. The dosage of levamisole given was 2 to 3 mg/kg daily or every other day, depending on the patients' response. All were followed regularly at outpatient department. Follow-up items included a routine urinalysis every month, complete blood count (CBC) every 3 months and BUN/Cr, AST/ALT every 6 months. After 6 to 24 (mean 12.2) months of follow-up, the frequency of relapse (FoR) decreased (5.74 +/- 3.24 vs 1.91 +/- 2.0/year p < 0.05). Seven (26%) had no relapse at all. Nine (33.3%) had less than 1/3 the FoR; four (14.8%) had 1/3 to 1/2 the FoR; and seven (26%) still had more than 1/2 FoR as before levamisole. The oral prednisolone dosage also decreased (0.62 +/- 0.42 vs 0.21 +/- 0.35 mg/kg/day, p < 0.05). The levamisole response was independent of the age of NS onset, the interval between NS onset and initiation of levamisole, previous number of relapse, the FoR, and previous use of cytotoxic drug. There were 7 episodes of leukopenia, which returned to normal after discontinuing levamisole for 1 to 2 weeks in 4 patients. Two (7.5%) had reversible leukopenia for more than 4 weeks. No abnormal BUN/Cr, or ALT/AST levels were noted during follow-up. Levamisole is an effective and safe drug for children who have SSNS with FR and/or SD. Two thirds of patients obtain satisfactory control. The dosage can be 2 to 3 mg/kg daily or every other day. The most common side effect is transient leukopenia.
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PMID:Levamisole in steroid-sensitive nephrotic syndrome children with steroid-dependency and/or frequent relapses. 1092 44

We report a patient, a 23-year-old man, who was a hepatitis B virus(HBV) carrier complicated with nephrotic syndrome. He was admitted to our hospital because of generalized edema and massive ascites. Laboratory data on admission were as follows: proteinuria 9,850 mg/day, Cr 2.7 mg/dl, BUN 73 mg/dl, albumin 1.9 g/dl, cholesterol 501 mg/dl, GOT 23 IU/l, GPT 19 IU/l, HBsAg(+), and HBeAg(222.7). Since his nephrotic symptoms were seriously complicated with renal failure, we selected steroid therapy for nephrosis preference. His renal function was improved and the urinary protein decreased immediately, but his liver function deteriorated. The renal biopsy revealed focal mesangial proliferative glomerulonephritis. Immunofluorescent examination revealed slight deposits of IgG, IgM, and C3 along the glomerular basement membrane and mesangial matrix. He was not compliant and often stopped taking the steroid therapy, thereby causing nephrosis to recur each time. After all, nephrotic symptoms have been well-controlled with cyclosporin and steroid. In spite of the seroconversion of HB virus by formation of HBe antibody, mutant HBV infection continued. The fact that liver biopsy revealed severe lymphoid infiltration at the portal area suggested chronic active hepatitis. His clinicopathologic course suggests that HBV-associated nephropathy does not always remit as there are some cases in whom hepatitis remains in an active state even after seroconversion, due to its mutant status. In these cases, the long-term prognosis of HBV nephropathy has not been defined. Further study is necessary to establish the optimal treatment for HB nephropathy in adults.
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PMID:[A case of hepatitis B virus carrier complicated with nephrotic syndrome]. 1099 20

Artemisia abyssinica leaves, a traditional medicine for the treatment of various disorders, were fed to male Wistar rats at 2% and 10% of the standard diet for 6 weeks. A 2% A. abyssinica leaf diet was not toxic to rats. Depression in growth, hepatopathy and nephropathy were observed in rats fed a diet containing 10% of A. abyssinica leaves. These findings were accompanied by leukopenia, anaemia and alterations of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma glutamyl transferase (GGT) activities with changes in concentrations of total protein, albumin, cholesterol and urea.
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PMID:Effects of various levels of dietary Artemisia abyssinica leaves on rats. 1103 26

Hepatitis C is the most common cause of liver disease in the dialysis patient. The prevalence of chronic hepatitis C determined by anti-HCV testing in this population ranges from 6% to 38%. Using second generation EIA assays, the prevalence of anti-HCV among patients participating in the 1997 National Surveillance of Dialysis Associated Diseases in the United States was 9.3%. Polymerase chain reaction testing for HCV RNA has shown that the prevalence of HCV infection can be as high as 20% to 30% of dialysis patients. The causes and source of infection in patients with chronic renal failure on hemodialysis are multiple. Before the introduction of routine screening of blood donors for anti-HCV, blood transfusions were an important risk factor for acquisition of hepatitis C. Other potential sources of infection include exposure to contaminated equipment and nosocomial routes such as patient-to-patient exposure. The risk of infection appears to correlate with the duration of hemodialysis and the number of transfusions. Interestingly, dialysate and buffers have been shown to be virus free even when used in hepatitis C infected patients. The natural history of chronic hepatitis C infection in patients with renal failure is not well characterized. Although persistent elevations in ALT levels occur in 12% to 50% of dialysis patients, the frequency of persistently normal ALT levels in HCV-infected dialysis patients appears to be higher than in HCV-infected patients without renal failure. Overt liver disease and liver failure rarely occur. The degree of inflammation in liver biopsies of renal failure patients is usually mild. Thus, progressive liver disease may be less common in patients with advanced renal disease but further studies are required to assess the true impact of hepatitis C infection in this high risk population. The impact of hepatitis C infection on morbidity and mortality of patients with end-stage renal disease remains poorly defined. Initial studies have failed to show a significant increase in mortality among HCV-infected hemodialysis or renal transplant patients within the first 5 years following transplantation. In contrast, recent studies with extended follow-up of renal transplant recipients suggest that hepatitis C infection may affect patient and graft survival during the second decade. Further studies are required to identify the mechanisms of infection of patients with end-stage renal disease and to define better treatment strategies for these patients before and after kidney transplantation.
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PMID:Hepatitis B and C and renal failure. 1157 Jan 46

Glucose and other reducing sugars react non-enzymatically with proteins leading to the formation of advanced glycosylation end products (AGEs) and AGE-derived protein cross-linking. Formation of AGEs is a normal physiological process, which is accelerated under the hyperglycaemic condition in diabetes. Under normal conditions, AGEs build up slowly and accumulate as one ages. Numerous studies have indicated that AGEs contribute to the pathological events leading to diabetic complications, such as age-related diseases, including nephropathy, retinopathy, vasculopathy and neuropathy. Potential therapeutic approaches to prevent these complications include pharmacological inhibition of AGE formation and disruption of pre-formed AGE-protein cross-links. Studies using animal models and preliminary clinical trials have shown the ability of the AGE-inhibitor, pimagedine and the cross-link breaker, ALT-711, to reduce the severity of pathologies of advanced glycosylation. These agents offer potential treatments for glucose-derived complications of diabetes and ageing.
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PMID:Therapeutic potential of AGE inhibitors and breakers of AGE protein cross-links. 1177 1

Streptozotocin (STZ) has drawn attention as a potential source of oxidative stress, which induces genotoxicity. We investigated the effects of STZ on DNA damage in the liver and kidney, as well as the protective effects of antioxidants, by using the alkaline single-cell gel electrophoresis assay, and by measuring the ratio of 8-hydroxy-2'-deoxyguanosine (8-OHdG) to dG. A single intraperitoneal injection of STZ (150 mg/kg) increased serum levels of glucose, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and blood urea nitrogen (BUN), and also caused DNA damage in the liver and kidney, which recovered slowly with time. Antioxidants,(ascorbic acid, trolox and probucol) prevented the STZ-induced elevation of DNA damage in the liver and kidney and inhibited the increase in serum levels of AST, ALT and BUN. Thus ascorbic acid, trolox, and probucol protected the mice against STZ-induced DNA damage that might contribute to the development of hepatic or renal disease.
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PMID:DNA damage and the effect of antioxidants in streptozotocin-treated mice. 1206 20

Leptospirosis is an infectious disease caused by pathogenic leptospires and is characterized by a broad spectrum of clinical manifestations, varying from inappearent infection to fulminant, fetal disease. Eighty-five to 90% of leptospirosis infections are self-limiting. However, 5-10% of infection by L. interrogans can cause renal tubular damage, microvascular injury, acute renal failure (ARF), and interstitial nephritis. We studied 36 patients with leptospirosis. Twenty-seven (65%) cases of 36 patients had ARF. Fourteen (51%) had nonoliguric ARF. In thirteen (48%) oliguria appeared on the third or fourth days of hospitalization. Serum BUN, creatinine, serum bilirubine, ALT, AST, potassium and thrombocytopenia levels were higher in oliguric than nonoliguric patients (p < 0.05). However, serum sodium, CPK levels were not different between oliguric and nonoliguric groups (p > 0.05). Thirteen patients (48%) needed in renal replacement therapy (RRT). 8 of them were treated by hemodialysis (HD) alone and 5 patients by HD in combination with hemoperfusion. Twenty-five patients (92%) recovered completely after 3-5 weeks. Two patients (7.4%) who had severe hepatorenal and hemorrhagic syndromes, died. We concluded that till now leptospirosis is actual problem for nephrologist in the developing countries because of very high percentage of renal disease, with good prognosis in patients without multiorgan failure and early treatment.
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PMID:Acute renal failure in leptospirosis in the black-sea region in Turkey. 1209 Mar 20


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