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)

An attempt was made to determine the effect of steroidal contraceptives on the utilization of Vitamins-B1 and B6. Subjects, aged 22-38 years, were not taking any external source of vitamins. A 24-hour urine sample was collected and a fasting blood sample drawn for the estimation of erythrocyte amino-transferases and transketolase. Then each subject was given 2 gm of L-tryptophan. Another 24-hour urine specimen was then collected. Xanthurenic acid values in urine specimens were compared. Ovral or norgestrel was then given for 3 cycles. After these 3 cycles, blood collections and tryptophan load tests were repeated. Erythrocyte alanine aminotransferase (EAIT) and aspartates aminotransferases (EAsT) were measured. Also, erythrocyte transketolase (ETK) was estimated and the "TPP" effect determined by adding 75 mcg of thiamine pyrophosphate. of 11 women taking Ovral, 7 showed an abnormal response to the tryptophan load as shown by the xanthurenic acid excretion. Responses of all 11 women on norgestrel to tryptophan loads were normal. EAIT and EAsT tests were normal with both drugs (p more than .05). Erythrocyte transketolase activity was not significantly changed by either preparation (p more than .05). The increased xanthurenic acid excretion with Ovral after tryptophan load is thought to indicate Vitamin-B6 deficiency. Basal levels of ETK decreased in 7 of 10 women on Ovral but increased in 5 of 8 women on norgestrel therapy. Also, in vitro stimulation with TPP was observed in 4 of these women. The relation of this finding to Vitamin-B1 is not clear. Urinary thiamine, blood pyruvic acid, and alpha-ketoglutaric acid and transketolase activity require study to assess the Vitamin-B1 status under contraceptive therapy.
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PMID:Short-term effect of ovral and norgestrel on the vitamin B6 and B1 status of women. 119 31

CLN2 neuronal ceroid lipofuscinosis is a hereditary lysosomal storage disease with primarily neurological signs that results from mutations in TPP1, which encodes the lysosomal enzyme tripeptidyl peptidase-1 (TPP1). Studies using a canine model for this disorder demonstrated that delivery of TPP1 enzyme to the cerebrospinal fluid (CSF) by intracerebroventricular administration of an AAV-TPP1 vector resulted in substantial delays in the onset and progression of neurological signs and prolongation of life span. We hypothesized that the treatment may not deliver therapeutic levels of this protein to tissues outside the central nervous system that also require TPP1 for normal lysosomal function. To test this hypothesis, dogs treated with CSF administration of AAV-TPP1 were evaluated for the development of non-neuronal pathology. Affected treated dogs exhibited progressive cardiac pathology reflected by elevated plasma cardiac troponin-1, impaired cardiac function and development of histopathological myocardial lesions. Progressive increases in the plasma activity levels of alanine aminotransferase and creatine kinase indicated development of pathology in the liver and muscles. The treatment also did not prevent disease-related accumulation of lysosomal storage bodies in the heart or liver. These studies indicate that optimal treatment outcomes for CLN2 disease may require delivery of TPP1 systemically as well as directly to the central nervous system.
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PMID:Extraneuronal pathology in a canine model of CLN2 neuronal ceroid lipofuscinosis after intracerebroventricular gene therapy that delays neurological disease progression. 2807 62

Pazopanib is a tyrosine kinase inhibitor that is generally used for the treatment of metastatic renal cell cancer and advanced soft tissue sarcoma. It can cause various degrees of hepatotoxicity. Our study aimed to investigate the effect of taxifolin on pazopanib-induced liver toxicity. A total of 18 rats were divided into three groups: the pazopanib (PP), pazopanib plus taxifolin (TPP), and control (C) group. Taxifolin was administered to the TPP (n=6) group with a dose of 50 mg/kg. Distilled water was orally admnistered to the C (n=6) and PP (n=6) groups as a solvent. Subsequently, pazopanib 200 mg/kg was administered to the TPP and PP groups via the stomach. This procedure was repeated once a day for four weeks. Then, all rats were sacrificed, and their livers were removed. Malondialdehyde (MDA), total glutathione (tGSH), total oxidant status (TOS), and total antioxidant status (TAS) levels were evaluated. MDA and TOS levels were higher in the PP group compared with the levels of the other parameters (p<0.001). tGSH and TAS levels were lower in the PP group than in the TPP and C groups (p<0.001), and the AST, ALT, and LDH levels were higher. Furthermore, liver tissue damage, including hemorrhage, hydropic degeneration, and necrosis was observed in the PP group. Administration of taxifolin before pazopanib significantly improved degenerative changes. Our study demonstrated that the administration of taxifolin is significantly effective in preventing pazopanib-induced hepatotoxicity in rats.
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PMID:Protective effects of taxifolin on pazopanib-induced liver toxicity: an experimental rat model. 3323 95