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)

In order to study the experimental infection of HGV in rhesus monkey, the monkeys were infected using the plasma from a donor with HGV RNA positive. The second generation monkeys were infected with the sera of the first generation monkeys infected after 6 weeks, and also the third generation monkeys were infected with the sera of the second generation monkeys. HGV RNA were detected by RT-nPCR. The results showed that in sera of infected monkeys HGV RNA were positive after 1 week of inoculation, and were consecutively positive for up to 28 weeks at longest. The level of ALT raised a little in monkey No. 1 and higher than 100 U/L in No. 5. The liver biopsy showed viral hepatitis--like histological changes. Comparing the sequence of HGV 5'LTR from sera of the infected monkeys and the blood donor, the homogeneity, to strain HGU44402 was 98.33% and 95.83% to strain HGU36380 was 92.50% and 89.17%, respectively. The results suggested that the rhesus monkey is sensitive to HGV and is suitable for establishment of an animal model.
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PMID:[Study on the experimental infection of hepatitis G virus in rhesus monkey]. 1252 30

Although actinomycin D has been used to prevent protein synthesis in experiments of several hours' duration, its effects on the synthesis of adaptive enzymes which are induced over a period of several days have received less attention. Treatment of young rats with doses of actinomycin D, which permitted survival for a period of 5 days, resulted in marked increases in the activities of four hepatic enzymes known to be induced by cortisol: alanine transaminase, tyrosine transaminase, serine dehydrase, and tryptophan pyrrolase. Actinomycin D also induced responses of two of these enzymes in adrenalectomized rats.
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PMID:INDUCTION OF SEVERAL ADAPTIVE ENZYMES BY ACTINOMYCIN D. 1419 8

BACKGROUND: There are several reports that indicate a linkage between exposure to power frequency (50 - 60 Hz) magnetic fields with abnormalities in the early embryonic development of the chicken. The present study was designed to understand whether power frequency electromagnetic fields could act as an environmental insult and invoke any neurochemical or toxicological changes in developing chick embryo model. METHODS: Fertilized chicken eggs were subjected to continuous exposure to magnetic fields (50 Hz) of varying intensities (5, 50 or 100 microT) for a period of up to 15 days. The embryos were taken out of the eggs on day 5, day 10 and day 15. Neurochemical (norepinephrine and 5-hydroxytryptamine) and amino acid (tyrosine, glutamine and tryptophan) contents were measured, along with an assay of the enzyme glutamine synthetase in the brain. Preliminary toxicological investigations were carried out based on aminotransferases (AST and ALT) and lactate dehydrogenase activities in the whole embryo as well as in the liver. RESULTS: The study revealed that there was a significant increase (p < 0.01 and p < 0.001) in the level of norepinephrine accompanied by a significant decrease (p < 0.01 and p < 0.001) in the tyrosine content in the brain on day 15 following exposure to 5, 50 and 100 microT magnetic fields. There was a significant increase (p < 0.001) in glutamine synthetase activity resulting in the significantly enhanced (p < 0.001) level of glutamine in the brain on day 15 (for 100 microT only). The possible mechanisms for these alterations are discussed. Further, magnetic fields had no effect on the levels of tryptophan and 5-hydroxytryptamine in the brain. Similarly, there was no effect on the activity of either aminotransferases or lactate dehydrogenase in the whole embryo or liver due to magnetic field exposure. CONCLUSIONS: Based on these studies we conclude that magnetic field-induced changes in norepinephrine levels might help explain alterations in the circadian rhythm, observed during magnetic field stress. Also, the enhanced level of glutamine can act as a contributing factor for developmental abnormalities.
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PMID:Biological effects of power frequency magnetic fields: Neurochemical and toxicological changes in developing chick embryos. 1475 60

Transamination of tryptophan belongs to minor pathways of amino acid metabolism. The present paper describes conditions for application of dinitrophenylhydrazine method, originally prepared for alanine aminortansferase and aspartate aminotransferase assay, to the measurement of tryptophan transamination catalysed by any of the enzymes mentioned above. The method was tested using purified pig heart AST. While the free enzyme showed a characteristic absorption profile with the maxima at 360 and 430 nm, the course of transamination of tryptophan was confirmed by the measurement of UV-VIS spectral changes of the coenzyme in the active site of the enzyme in the presence of the amino acid substrate only, when tryptophan caused a shift of the peak from 360 nm to 330 nm due to a change of the pyridoxal form to the pyridoxamine form (= the first step of ping-pong transaminating reaction). A general limitation of dinitrophenylhydrazine method is the interference of hydrazones formed from the coenzyme pyridoxal-5'-phosphate and from the oxo- substrate 2-oxoglutarate, showing the absorption maxima at 492 nm and 388 nm, respectively with the hydrazones formed by the oxo- products (pyruvate and/or oxaloacetate in the case of ALT/AST, the absorption maxima at 443 nm in our measurements). In the case of tryptophan transamination, indolepyruvate as the oxo- product of a catalysed reaction forms dinitrophenylhydrazone, which has, besides a maximum at 435 nm, a distinct peak at 542 nm, convenient for the product concentration measurement. This is favourable for resolution from other (interfering) hydrazones. Suitable conditions for tryptophan transamination in tissue and enzyme preparations were found. Reaching optimal conditions for tryptophan transamination measurements in vitro is generally limited by low solubility of the amino acid in water solutions: With AST preparation, the velocity of catalysed reaction at 5-50 x 10(-3) M tryptophan concentration was of 1st order to the amino acid substrate. Km for tryptophan was found > or = 2 x 10(-1) M. Therefore the enzyme activity measurement at two different tryptophan concentrations is recommended for unknown samples. Tryptophan transamination by purified pig AST was compared with that catalysed by preparations obtained from mammalian tissues.
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PMID:Tryptophan metabolism via transamination. In vitro aminotransferase assay using dinitrophenylhydrazine method. 1520 68

Histidine-tryptophan-ketoglutarate solution (HTK) and University of Wisconsin solution (UW) have been shown to have similar outcomes in cadaveric kidney, pancreas, and liver transplantation. Our institution changed from UW to HTK as the primary preservation solution for liver, kidney and pancreas transplantation. This study compares the perioperative and first year outcomes of liver transplantation using UW or HTK. Primary use of HTK began on May 1, 2003. We reviewed the records of all adult liver transplant recipients from July 1, 2002 to December 31, 2004. Recipients were compared based on organ preservation solution (UW n = 204, HTK n = 174). Outcomes included 1-, 6- and 12-month graft and patient survival and 1-, 7-, 14-, and 30-day liver function and serum creatinine. During the entire study period, the two groups were managed similarly in operative technique, immunosuppressive regimens, and donor liver criteria. Over 30 months, 378 adult patients underwent liver transplantation. There were no significant differences between UW and HTK in 1-, 6-, or 12-month graft or patient survival. The HTK group had a higher day 1 median AST, ALT, and total bilirubin, but the two groups were similar thereafter. An anticipated difference in infused volume between UW and HTK was demonstrated. In conclusion, to our knowledge, this is the first reported large case series from North America comparing HTK and UW in liver transplantation with 2- to 12-month follow-up. There were no significant differences between HTK and UW in this population when comparing 1 month graft function and first-year graft and patient survival.
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PMID:Comparison of histidine-tryptophan-ketoglutarate solution (HTK) and University of Wisconsin solution (UW) in adult liver transplantation. 1644 7

The potential of short-term oxygenated perfusion after cold storage (CS) to reverse deleterious priming of nonheart beating donors grafts should be investigated, addressing the respective role of oxygenation and nutrients or metabolic charge. Livers were retrieved 30 min after cardiac arrest of male Wistar rats and preserved with histidine tryptophan ketoglutarate (HTK)-solution for 18 h by CS. After 16 h, some livers were put on an oxygenated machine-preservation-circuit for the last 2 h and conditioned by cold perfusion with either HTK (conHTK), HTK supplemented with adenosine, phosphate and glucose (conHTK+) or Williams-E solution (conWE). Upon warm reperfusion, postconditioning with any of the solutions led to a significant (three- to fivefold) reduction of parenchymal damage (ALT, GLDH-release) compared with CS. Metabolic recovery (bile production) was also significantly enhanced compared with CS, with best results found after conHTK. The beneficial effect of postconditioning with HTK was associated with a significantly mitigated cleavage of caspase 12 and 3. We conclude from these data that conditioning of predamaged livers is possible even after CS by short-term oxygenated perfusion in the cold and, under these conditions, not depending on energetic support or nutritive stimulation.
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PMID:Possibility of conditioning predamaged grafts after cold storage: influences of oxygen and nutritive stimulation. 1682 84

In recent years, it has been reported that sodium valproate occasionally can cause renal tubular impairment. This study was designed to demonstrate the renal tubular and glomerular functions in rats given sodium valproate as monotherapy, as well as to determine any reversibility of dysfunctions. Female rats were randomly allocated to three groups: group 1 received sodium valproate 500 mg/kg/d intraperitoneal for six weeks; after the same injection period, group 2 was housed for another six weeks, after which laboratory investigations were completed; and group 3 served as a control group made up of 20 healthy rats living in same condition without any treatment. Serum ALT, total protein, uric acid, ALP, phosphorus, sodium levels, and urine Ca/cr ratio were significantly different between groups 1 and 3 (p < 0.025), but this difference was not seen between groups 2 and 3. On the other hand, other parameters such as TRP, Ccr, NAG, and MDA were not significantly different among the three groups ( p > 0.025) These results suggest that SV does not have a significant dose- or time-related side effect on renal functions. Minor biochemical dysfunctions related to long-term sodium valproate therapy is reversible, and the minimal renal fibrosis that showed histopathologically is not clinically important. The renal tissues of rats are known to show similar metabolic and histological patterns with human renal tissues. No renal dysfunction was expected in humans because there were no clinically statistically significant renal side effects in this study.
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PMID:Effects of sodium valproate on renal functions in rats. 1705 Feb 43

University of Wisconsin (UW) solution has been recognized as the gold standard in liver preservation, but its limitations are becoming obvious, such as risk of biliary complications and its high cost. Alternatively, the effects of histidine-tryptophan-ketoglutarate (HTK), such as improved biliary protection and low cost, have been observed. This systematic review is conducted to compare the efficacy and safety of these 2 solutions. Databases from 1966 to June 2006 were searched. Randomized clinical trials (RCTs) and cohort studies comparing HTK and UW solutions for liver transplantation were included. Ten articles including 11 comparisons (1,200 patients) met the inclusion criteria, containing 2 RCTs and 9 cohort studies. No marked differences existed between the 2 groups in patient and graft survival rates, acute rejection, primary nonfunction, primary dysfunction, delayed graft function, and ALT and AST levels after transplantation. The only positive result was observed in the bile production after deceased donor liver transplantation (DDLT), which was statistically significantly higher in HTK group than that of UW group (95% confidence interval, 18.65-57.47; P=0.0001). Although the difference in biliary complications between the 2 groups did not reach statistical significance, HTK was thought to be more effective for biliary tract flush and prevention of biliary complications in some studies. There was no statistically significant difference of effects (except bile production) between HTK and UW. But trends were documented in some studies for the superiority of HTK in biliary tract flush, prevention of biliary complications, and cost saving. Adequately powered RCTs with longer follow-up periods are required to evaluate the long-term effect of these 2 solutions.
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PMID:Histidine-tryptophan-ketoglutarate solution vs. University of Wisconsin solution for liver transplantation: a systematic review. 1766 93

Liver, pancreas, and kidney allografts preserved in histidine-tryptophan-ketoglutarate (HTK) and University of Wisconsin (UW) solutions have similar clinical outcomes. This study compares HTK and UW in a large number of standard criteria donor (SCD) and extended criteria donor (ECD) livers at a single center over 5 years. All adult, cadaveric liver and liver-kidney transplants performed between July 1, 2001 and June 30, 2006 were reviewed (n = 698). There were 435 livers (62%) categorized as ECD for severe physiologic stress and 70 (10%) because of old age. Recipient outcomes included perioperative death or graft loss and overall survival. Liver enzymes were analyzed for the first month post-transplant. Biliary complications were assessed through chart review. Overall, 371 donor livers were preserved in HTK (53%), and 327 were preserved in UW (47%). There were no statistically significant differences in any of the primary outcome measures comparing HTK and UW. The HTK group overall had a higher day 1 median aspartate aminotransferase and alanine aminotransferase, but the two groups were similar in function thereafter. HTK was superior to UW in protection against biliary complications. Kaplan-Meier graft survival curves failed to demonstrate a significant difference in SCD or ECD livers. In conclusion, HTK and UW are not clinically distinguishable in this large sample of liver transplants, although HTK may be protective against biliary complications when compared to UW. These findings persisted for both SCD and ECD livers. Given the lower cost per donor for HTK, this preservation solution may be preferable for general use.
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PMID:Comparison of histidine-tryptophan-ketoglutarate solution and University of Wisconsin solution in extended criteria liver donors. 1830 80

Short-term machine perfusion after liver retrieval from non-heart-beating donors has been considered a beneficial means to reverse deleterious priming of the predamaged organ. In this study, the possible impact of different temperatures during aerobic perfusion was addressed, focusing on liver metabolic functions, structural integrity, and vascular activation. Livers retrieved 30 minutes after cardiac arrest of male Wistar rats (200-300 g) were preserved with histidine-tryptophan-ketoglutarate (HTK) solution for 18 hours by simple cold storage (CS) or subjected to short-term resuscitation (STR) with oxygenated (pO(2) > 500 mm Hg) machine perfusion with HTK at 4 degrees C, 12 degrees C, or 22 degrees C for 2 hours with subsequent CS for 16 hours at 4 degrees C. Upon reperfusion in a normothermic perfusion circuit, STR significantly improved enzyme leakage (alanine aminotransferase, glutamate dehydrogenase) and metabolic recovery (tissue levels of ATP) providing best values at 12 degrees C or 22 degrees C. Moreover, a hugely increased gene expression of the adhesion molecule ICAM-1 as well as major histocompatibility complex (MHC) class II antigen was seen after CS, but significantly alleviated by STR at 4 degrees C or 12 degrees C. However, mRNA for both surface proteins rose significantly after STR at 22 degrees C compared with CS. In conclusion, STR by oxygenated perfusion is beneficial to the predamaged graft, facilitating later transportation and supervision of the graft compared with continuous machine preservation. However, increased perfusion temperature should be recommended only up to the limit of 12 degrees C to prevent overactivation of surface antigen expression.
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PMID:Short-term resuscitation of predamaged donor livers by brief machine perfusion: the influence of temperature. 1910 Mar 81


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