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)

The viability of the graft after liver transplantation is considered to be expressed as the sum of the hepatocellular activity by re-flowing of the hepatic blood flow after transplantation and the hepatocellular injury derived from the cold ischemia of the liver which is indispensable for transplantation. In order to elucidate the hepatocellular injury in ischemic liver graft cold ischemic liver model without hepatectomy was prepared and liver functions, serum insulin, glucagon and cyclic AMP after glucagon loading were measured. The following results were obtained. 1) Influence of anoxia due to ischemia of the liver expressed by s-GOT, disappeared 2 days after operation but it lasted for long time by s-GPT. Re-elevation of s-GOT, s-GPT observed after 2 days or more was considered to be derived from the hepatocellular necrosis due to rejection. Incidentally, Al-phosphatase was useful for judging the rejection, but s-total bilirubin, s-total cholesterol and albumin were considered to be not useful as parameters for evaluating the viability of the graft. 2) The rejection and the hepatocellular necrosis had not influence on serum insulin, but serum glucagon corresponded to the hepatocellular necrosis and was useful index for the judgment of the hepatocellular damage in the graft. 3) The level of c-AMP after glucagon loading and the c-AMP response corresponded very well to the hepatocellular activity of the graft, and they were considered to be useful indices for evaluating the viability of the graft.
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PMID:[Experimental study of orthotopic liver transplantation in dog--with reference to change of hepatic function, serum insulin, glucagon, c-AMP after liver transplantation and the viability of the graft]. 284 4

The isolated perfused rabbit liver was used to determine how continuous hypothermic perfusion affected liver function. Rabbit livers were perfused for 0, 24, 48, and 72 hr at 5 degrees C with the UW perfusate containing hydroxyethyl starch (5 g%) dissolved in a solution containing gluconate (80 mM), adenosine (5 mM), glutathione (3 mM), phosphate (25 mM), and additives as described previously, and they were used successfully for kidney preservation. At the end of preservation the livers were perfused in an isolated circuit with a Krebs-Henseleit solution with addition of 4 g% bovine serum albumin and 10 mM glucose at 38 degrees C for 120 min. Bile was collected from the cannulated common duct. Biliary excretions of indocyanine green and liver enzymes lactate dehydrogenase, aspartate aminotransferase, and alanine aminotransferase, were determined both in the cold perfusate and the normothermic perfusate. Livers were also studied after pretreatment of the donor with chlorpromazine (CPZ) and/or methylprednisolone (MP). Bile production (ml/120 min, 100 g liver) upon reperfusion produced the most interesting data and decreased from a control value of 10.3 +/- 2.6 to 9.3 +/- 1.0 (24 hr), 5.3 +/- 0.7 (48 hr), and 4.1 +/- 1.5 (72 hr). Enzyme release was not predictive of the degree of preservation-induced damage. Pretreatment of rabbits with a combination of CPZ/MP improved bile flow at 48 and 72 hr (8.3 +/- 3.0 and 7.0 +/- 1.3, P less than 0.05). Pretreatment with either drug alone also improved function after 72 hr of preservation (7.1 +/- 1.8, CPZ; 8.2 +/- 3.5, MP).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of chlorpromazine and methylprednisolone on perfusion preservation of rabbit livers. 319 35

PAP of harvested livers is routinely used to minimize parenchymal anoxia during storage. PP is compared with PAP to evaluate the relative reliability of PAP. Sixty female Landrace pigs were used for 30 OLTs. Group 1 livers underwent PP, whereas group 2 livers were treated with PAP. The cold ischemic time was less than 120 minutes for both groups, with no warm ischemia. Intraoperative and 24-hour postoperative biochemical, coagulation, and histocytological data were analyzed. Morphological studies of cellular damage were based on the percentage of CVD and KP and classified as light, moderate, and severe damage. Data, at closing, were compared by using Fisher's test (group 1 v group 2,P = 0.003 for light damage and P = .04 for severe damage; first postoperative day for group 1 v group 2, P = .133 for light damage and P = .25 for severe damage. Blood samples at closing and 24 hours postoperatively showed significant differences between groups 1 and 2: At closing for groups 1 and 2, respectively: AST, 968.9 +/- 742.7 and 327.4 +/- 174.7 IU/L (P less than .001); ALT, 63.1 +/- 40.3 and 20.3 +/- 5.3 IU/L (P less than .001); AP, 292.2 +/- 107.1 and 139.5 +/- 45.3 IU/L (P less than .001); and 24 hours postoperatively for groups 1 and 2, respectively: AST, 1,664.9 +/- 917.8 and 419.3 +/- 230.9 IU/L (P less than .001): ALT. 180.4 +/- 28.9 and 66.4 +/- 17.5 IU/L (P less than .001); AP, 602.1 +/- 153.3 and 255.7 +/- 116.3 IU/L (P less than .01). Comprehensively, the results reflect a better perfusate distribution of the PAP livers compared with PP ones: uniform organ preservation, faster metabolic recovery, and reduced postoperative mortality.
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PMID:Comparison of combined portal-arterial versus portal perfusion during liver procurement. 327 50

The relationship between transplant viability and liver function has been examined. Wistar rat livers were preserved at 4 degrees C for increasing intervals and then transplanted into Wistar rat recipients. Two critical times were identified, the longest preservation period with 100% transplantation success (4 hr) and the shortest preservation period with 100% transplant failure (8 hr). The comparable critical times were also identified in livers preserved at 37 degrees C (1 hr and 2 hr). Liver functions were studied by the isolated perfused liver technique in other rat livers stored at 4 degrees C or 37 degrees C for the critical times. Two liver function tests, AST and LDH concentration in perfusate, discriminated between viable and nonviable livers across as well as within preservation groups. AST gave the best separation between viable and nonviable livers. Some functions such as ALT concentration in perfusate separated viable from non viable allografts only within preservation groups. Other liver functions were more sensitive to preservation temperature than allograft viability. Oxygen consumption after cold preservation for either critical time was about twice control levels. Urea production was far below control levels in warm-preserved livers but almost normal in cold-preserved livers. Our results indicate that AST release into perfusate can be used as a screening technique to optimize preservation methods, reserving transplantation for confirming the most promising results.
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PMID:Markers of allograft viability in the rat. Relationship between transplantation viability and liver function in the isolated perfused liver. 331 44

The antihistamine methapyrilene (MP) was widely used as a component of cold, allergy and sleep-aid medications in the 1970s until it was identified as a potent rat liver carcinogen. MP does not induce positive responses in most short-term genotoxicity assays, which suggests that it is carcinogenic by a non-genotoxic mechanism. We have evaluated the potential of MP to induce unscheduled DNA synthesis (UDS), a genetic end point and S-phase synthesis (SPS), and indicator of cell proliferation, in Fischer-344 (F344) rat and B6C3F1 mouse liver. We also examined the response of MP in hepatocytes from two species treated in vitro. MP failed to induce UDS in rat or mouse liver following in vivo treatment, or in hepatocytes from rat and adult human treated in vitro. Control rats and mice yielded less than 0.3% of cells in S-phase (%S). In contrast, MP induced significant elevations in SPS both in male F344 rat (6.3%S) and female B6C3F1 mice (1.4%S). In the male rat, sorbitol dehydrogenase (SDH), bilirubin, serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvate transaminase (SGPT) showed elevations of 9-, 10-. 17- and 28-fold over controls respectively, indicating that significant hepatotoxicity was induced by MP. This was confirmed by histopathologic examination, which revealed significant periportal and focal necrosis followed by an increased presence of mitotic figures. These results indicate that MP is not genotoxic in rat liver, but is a potent inducer of hepatic cell proliferation by inducing toxicity and subsequent regeneration, which may be an important mechanism of hepatocarcinogenesis.
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PMID:Examination of genotoxicity, toxicity and morphologic alterations in hepatocytes following in vivo or in vitro exposure to methapyrilene. 337 Jul 59

Rabbit livers were stored cold for periods of 6 or 24 hr and tested using the isolated perfused liver model. Five solutions were tested: Eurocollins (EC), Ross and Marshall's hypertonic citrate (HC), modified plasma protein fraction (Cambridge PPF), Ringer lactate, and the recently developed "University of Wisconsin" (UW) solution. After storage livers were perfused with an erythrocyte-free oxygenated Krebs-Henseleit solution containing 4% bovine serum albumin at 38 degrees C for 2 hr. Bile production proved to be the most sensitive index of liver function for discriminating between the various storage solutions and the different preservation times. After 6 hr of cold storage, bile production was similar to control liver bile production (9.8 +/- 2.4 ml/2 hr/100 g) in livers stored in HC (8.8 +/- 2 ml), PPF (9.9 +/- 2.2 ml), and UW (10.3 +/- 1.9 ml); it was slightly depressed in EC (6.7 +/- 2.5 ml, P = 0.06), and markedly depressed in Ringer lactate (4.3 +/- 0.8 ml, P less than 0.05). After 24 hr of cold storage bile production in UW-stored livers was near normal (9.3 +/- 0.7 ml) but significantly depressed (3.5-6.2 ml) in all other solutions tested. Release of enzymes into the normothermic perfusate was also measured (aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase). In this small series the differences between cold storage solutions did not always reach statistical significance although the trend was for less enzyme release in livers stored in UW solution. This technique permits rapid assessment and refinement of new storage methods and new solutions for liver preservation prior to testing in a large animal transplant model. The results suggest that UW solution is superior to other preservation solutions and would permit successful 24-hr storage of livers.
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PMID:A comparison of cold storage solutions for hepatic preservation using the isolated perfused rabbit liver. 340 5

In a set of 11 young heifers-crossbreds in the period of milk nutrition the influence of the temperature of milk nutrition the influence of the temperature of milk drink was studied as exerted on haematological data (haemoglobin and haematocrit), on the values of nitrogen metabolism (total protein and urea), on the components of energy (glucose and cholesterol) and on alkaline blood reserve. In these values we did not record any statistically significant differences between the groups. The subnormal values were demonstrated for cholesterol which we regard as a response to the lower content of fat in milk replacers. Furthermore, the activity of ALT and AST enzymes was examined. A significantly lower ALT and AST activity was recorded in calves administered cold Lactosan. It indicates a possibility of feeding milk replacers at the temperature of stable environment. The heifer calves were to get used to cold drinks by means of Rehyvet, the pH-value of the drink being 4.6.
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PMID:[The effect of the temperature of a milk drink on physiological indicators in the blood of calves]. 393 34

In a prospective study, 93 patients were observed up to nine months after open-heart surgery using hypothermia, hemodilution and cold cardioplegia. In the first two weeks frequent determinations were made of serum aminotransferase, alkaline phosphatases (ALP), lactic dehydrogenase isoenzymes, gamma glutamyltransferase (GT), total and free bilirubin and bile acids. Plasma hemoglobin was measured at the end of the operation. After the first period, aminotransferases, alkaline phosphatases and bilirubin were determined monthly. On the first postoperative day almost all of the patients showed abnormal aspartate aminotransferase (ASAT) activity and ASAT/ALAT (alanine aminotransferase) greater than 1, and about 25% had hyperbilirubinemia. The findings suggested early postoperative leakage of enzymes not only from the myocardium, but also from the liver. After two weeks the patients presented another pattern of liver dysfunction, with abnormal ALAT in 50%, ASAT/ALAT less than 1, and abnormal ALP and GT in 28 and 45%, respectively. Eight patients were judged to have post-transfusion hepatitis of non-A, non-B type. Six of them had abnormal aminotransferases for more than six months.
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PMID:Hepatic dysfunction after open-heart surgery. 615 78

Intracellular enzyme activities can be greatly influenced by alterations of pH, and non-physiologic pH may inhibit cell metabolism. The study was undertaken to examine the influence of pH values in preservation solution on ischemic tolerance time of the liver. BDE rat livers were used. Livers were preserved for 20 min or 2 h in warm ischemia after an initial perfusion with Ringer's solution at pH 9.0, 7.4, and 6.0. The values of total adenine nucleotide (TAN) and energy reserve (ER) in the livers were determined at the end of the preservation. After 20 min of warm ischemia, TAN values at pH 9.0 and 7.4 fell to 2.727 +/- 0.255 and 2.410 +/- 0.164 mumol/g, respectively (normal values: 3.414 +/- 0.270 mumol/g) and ER values to 0.786 +/- 0.186 mumol/g at pH 9.0 and to 0.446 +/- 0.095 mumol/g at pH 7.4 (normal values: 2.962 +/- 0.214 mumol/g). A similar trend was also observed after 2 h of warm ischemia. The preservation with a solution at pH 6.0 did not present any difference as compared to that at pH 7.4. Four-hour preservation in cold ischemia with Ringer's solution at pH 9.0 rendered higher values of TAN (2.635 +/- 0.085 mumol/g) and ER (0.336 +/- 0.026 mumol/g) than those in preservation at pH 7.4. No significant difference between TAN and ER values was found when 4-h preservation at pH 7.4 and 6.0 was compared. In another group an intermittent liver perfusion at 1-h interval was performed with chilled Ringer's solution; afterwards GOT, GPT, beta-glucuronidase, and acid phosphatase values in the effluents were evaluated. All of these enzymes showed higher concentration in the effluent with solution at pH 7.4 than that at 9.0. These results suggested that better intracellular energy reserve and organ viability can be maintained by preservation with alkaline solution. Furthermore, ER values seemed to be an excellent indicator of the organ viability during preservation. These were also confirmed by orthotopic hepatic transplantation in pigs. Livers were successfully preserved with alkaline Ringer's solution for up to 12 h. However, without change of pH, livers could not be preserved for more than 4.5 h.
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PMID:[Prolongation of ischemic tolerance time of donor livers by alkaline preservation solutions]. 647 1

Cardiac metabolism following hypothermic potassium cardioplegia was studied in 23 patients undergoing isolated aortic valve replacement. All had normal coronary arteries. Cardioplegia was induced by infusing 700-1 000 ml of cold Ringer's acetate containing 20 mekv K+ selectively into the left coronary artery. Simultaneous blood samples were taken from the radial artery, a central vein and from the coronary sinus before and after cardioplegia. The PO2, O2-saturation and content, PCO2, pH, lactate, glucose, potassium, myoglobin, total creatine kinase (CK), its isoenzyme CK-MB, aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) were assessed. Before bypass lactate was extracted by the heart. During the initial 10 to 20 min after cardioplegia there was a marked release of lactate in the coronary sinus. Myoglobin concentration and CK-MB serum activity peaked during the first 4 hours after the release of the aortic cross-clamping. In order to determine the best indicator of myocardial damage after cardioplegia, duration of extracorporeal circulation (ECC-time), aortic occlusion time (AOT), mean myocardial temperature (MMT) and the product of AOT and MMT, referred to as time-temperature area (TTA), were related to possible indicators of myocardial injury, such as enzyme and myoglobin release. The TTA was the best way of expressing the degree of exposure of the heart to ischaemia. The CK-MB to peak area (CK-MB max area) was the best indicator of the degree of ischaemic injury sustained by the heart during operation.
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PMID:Myocardial protection during aortic valve replacement. Cardiac metabolism and enzyme release following hypothermic cardioplegia. 737 90


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