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 bronchosecretolytic agent ambroxol added to histidine-tryptophan-ketoglutarate (HTK) solution has recently been shown to protect cold stored rat hepatocytes. The aim of the present study was to confirm these observations in a rat liver transplantation model. Before orthotopic liver transplantation, donor livers from 30 syngeneic Wistar rats were assigned to three groups (n = 10): (A) in situ flush (ISF) and 1/2-h cold storage (CS) with HTK solution, (B) ISF and 3-h CS with HTK, and (C) ISF and 3-h CS with HTK + 10(-3) mol/L ambroxol. The efficacy of the drug was evaluated by postoperative survival (> 14 days) and liver enzyme release (ALT), bile flow, histomorphological injury, and malondialdehyde (MDA) level in the grafts 15 min after reperfusion. After 1/2-h CS with HTK solution (A), 90% of the transplanted rats survived. In comparison with donor conditions, bile flow in the reperfused grafts decreased to 87 +/- 5.3%, whereas postoperative ALT levels slightly increased. After 3-h HTK preservation (B), the survival rate decreased to 60%, while ALT values markedly increased and bile flow after reperfusion declined to 82 +/- 6.6%. Ambroxol added to HTK solution (C) enhanced bile flow to 106 +/- 3.4%(p < .05), and reduced ALT and MDA levels and histomorphological injury of the transplanted livers, so that its beneficial effect in organ preservation has been confirmed in the transplant model. However, survival rate was not improved by the agent, probably because of the low cold ischemia tolerance of the Wistar rat livers used.
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PMID:Protective effects of ambroxol in hypothermic liver preservation: a transplant study. 1099 99

Previous morphological studies failed to show appreciable injury of biliary epithelial cells (BEC) after cold ischemia of rat liver, although recent evidence indicated that BEC integrity and function were impaired in this model. We tested the hypothesis that analysis of bile for enzymes, such as lactate dehydrogenase (LDH), alanine transaminase (ALT), and aspartate transaminase (AST), can be used for assessing cold ischemic injury of BEC. Furthermore, we examined whether biliary gamma-glutamyltransferase (GGT) reflects warm ischemic injury of BEC and whether normothermic reperfusion aggravates the negative effect of cold ischemia on BEC integrity and function. Rat livers were reperfused after different periods of cold or warm ischemia using a blood-free perfusion model. Compared with controls, perfusate LDH, ALT, and AST levels and parameters of hepatocyte function, including hepatocyte tight junction permeability, were not significantly altered by 18-h cold ischemia. On the other hand, 9-h cold ischemia markedly increased biliary LDH, ALT, and AST levels. However, only LDH release into the bile was strongly dependent on the time of cold storage. Biliary GGT, LDH, and glucose levels decreased during the reperfusion period following 18-h cold ischemia. The results suggest that biliary LDH can be used for assessing injury of BEC in cold-preserved livers and that normothermic reperfusion does not aggravate preservation-induced injury of BEC after cold ischemic storage.
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PMID:Bile analysis as a tool for assessing integrity of biliary epithelial cells after cold ischemia--reperfusion of rat livers. 1103 93

The aim of this study is to assess the effect of accumulation of marginal liver graft criteria on the immediate outcome of liver transplantation (LT). The last 325 consecutive LT performed in 293 patients were analyzed retrospectively with respect to donor acceptance criteria. A marginal liver score was elaborated on the basis of the following features: donor > 60 years, ICU stay > 4 days, cold ischemia times > 13 h, hypotensive episodes < 60 mmHg > 1 h, bilirubin > 2.0 mg/dl, ALT > 170 U/l, and AST > 140 U/l were scored with the value 1. The use of dopamine doses > 10 microg/kg per min and peak serum sodium > 155 mEq/l were labeled with value 2. The cut-off point at 6 months after LT revealed 42 deaths (14%), with 65 graft losses (20%) and 32 (9%) retransplants. Recipient survival was not affected by the combined effect of marginal criteria. However, recipients transplanted with marginal livers with score 3 or more showed a decrease in graft survival (log-rank 6.21; P = 0.045) and an increase in delayed non-function rate (10 out of 33 vs 4 out of 156; P = 0.03). The use of marginal liver donors with more than three risk factors must be carefully reviewed or refused because of the cumulative dysfunction of these grafts.
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PMID:A proposal for scoring marginal liver grafts. 1111 5

In situ split-liver transplantation is a new surgical technique where the bipartition of a single liver allows procurement of a right graft (segments I, IV, V-VIII) for an adult recipient (75% of the total liver volume), and a left graft (segments II and III) for a child recipient. The present study was designed to assess the effects of ischemia-reperfusion on right grafts obtained by in situ split-liver transplantation. To this aim, hepatic glutathione and conventional plasmatic markers of allograft function (alanine and aspartate aminotransferase, total bilirubin, prothrombin time, lactate dehydrogenase, gamma-glutamyltranspeptidase, and alkaline phosphatase) were evaluated in four adult recipients. At the time of reperfusion, a marked glutathione decrease was found in the segment VI in three cases, whereas the amount of glutathione in segment IV was related to the duration of cold ischemia in all cases. Upon reperfusion, a marked increase in plasmatic alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase was found. A recovery in prothrombin time was observed from the first day in three cases. An increasing trend in total bilirubin, gamma-glutamyltranspeptidase, and alkaline phosphatase was noted from the second day after transplant. This preliminary study suggests a possible relationship between the duration of cold ischemia, amount of glutathione in segment IV of the right graft, and the trend in plasmatic markers of allograft damage during in situ split-liver transplantation in adult recipients.
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PMID:Effects of ischemia-reperfusion on hepatic glutathione and plasmatic markers of graft function during in situ split-liver transplantation in adult recipients. 1111 71

Reperfusion injury can cause liver dysfunction after cold storage and warm ischemia. Recently it has been suggested that more than 50% of hepatocytes and sinusoidal endothelial cells (SEC) are undergoing apoptosis during the first 24 hours of reperfusion. The aim of our study was to quantify apoptotic and necrotic hepatocytes and apoptotic SEC after 60 or 120 minutes of warm, partial no-flow ischemia and 0 to 24 hours reperfusion in male SD rats. Apoptotic cells were identified by TUNEL assay in combination with morphological criteria. After 60 minutes of ischemia and 1 hour of reperfusion there was a significant increase of apoptotic hepatocytes (0.7 +/- 0.1% vs. 0.3 +/- 0.1% in controls) and SEC (1.5 +/- 0.6% vs. 0.3 +/- 0.1% in controls). The number of apoptotic SEC and hepatocytes was not different from controls at 6 hours or 24 hours of reperfusion. In contrast, the number of necrotic hepatocytes was quantified as 12 +/- 2% at 1 hour, 34 +/- 6% at 6 hours, and 57 +/- 11% at 24 hours. These results correlated with the increase in plasma ALT levels at these time points. Longer (120 min) ischemia times did not affect the number of apoptotic cells but increased hepatocellular necrosis to 58 +/- 4% at 6 hours reperfusion. No significant increase in caspase-3 activity and processing was detectable in any of these livers. Moreover, the caspase inhibitor Z-Asp-cmk (2 mg/kg IV) had no significant effect on reperfusion injury. Our results suggest that only a small minority of SEC and hepatocytes undergo apoptosis after 60 to 120 minutes of warm ischemia followed by 0 to 24 hours of reperfusion. Oncotic necrosis appears to be the principal mechanism of cell death for both cell types.
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PMID:Mechanism of cell death during warm hepatic ischemia-reperfusion in rats: apoptosis or necrosis? 1139 50

Evaluation of graft quality remains a major problem in liver transplantation. The aim of this retrospective analysis was to examine the impact of donor criteria on postoperative graft function. Between June 1986 and September 1993 324 liver transplantations were performed at our institution. Criteria for exclusion from analysis were postoperative thrombosis of graft vessels, retransplantation, death prior to the 5th postoperative day or missing donor criteria. For the eligible 255 transplantations the impact of the following donor criteria were examined: age (range 1-62 years, median 28 years), size/body weigt index, duration of intensive care, cause of death, circulatory condition, need for vasopressive support and liver function tests (bilirubin, GOT, GPT, GGT, LDH, ALP, prothrombin time (PT), creatinine, sodium). The following intraoperative factors were also assessed: type of protective solution, cold ischaemic time (CIT), anhepatic period and blood transfusions. Graft function during the first 5 postoperative days was categorized into four groups: (1) good function (GOT max < 1000 U/l, spontaneous PT > 50%, bile production > 100 ml/day); (2) fair function (GOT 1000-2500 U/l, clotting factor support < 2 days, bile < 100 ml/day); (3) poor function (GOT > 2500 U/l, clotting factor support > 2 days, bile < 20 ml/day); (4) primary non-function (retransplantation required within 7 days). A univariate analysis revealed duration of intensive care (P = 0.001), circulatory condition (P = 0.005), anhepatic period (P = 0.0004), blood transfusions (P = 0.03) and CIT (P = 0.039) as significant risk factors for postoperative graft function. Entering these factors in a multivariate regression model we identified creatinine (P = 0.007), duration of intensive care (P = 0.009) and the size/body weight index (P = 0.03) as donor-related factors of high significance. Analysis of the intraoperative data revealed the anhepatic period as the factor of highest significance (P = 0.0004) together with CIT (P = 0.02) and intraoperative blood transfusions (P = 0.008). A doubling of the number of days of intensive care resulted in a threefold increased risk of postoperative graft failure. Prolonged intensive care is a variable representing multiple risk factors. Accepting donors with a longer history of hypotension or who show signs such as elevated creatinine should be carefully considered. In patients with expected surgical difficulties resulting in an extended anhepatic period and a higher blood loss, transplantation of organs retrieved from donors with a long duration of intensive care and a long CIT should be avoided.
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PMID:Influence of donor criteria on postoperative graft function after orthotopic liver transplantation. 1127 36

To obtain "exact" laboratory data which show or reflect the pathophysiological conditions of patients, preanalytical, analytical and postanalytical processes should be checked. However, it is difficult to know the preanalytical situation or out of laboratories. We realize preanalytical issue is one of the weak points in current laboratory medicine. I reported the results of analyses on the issues concerning abnormal laboratory data produced by inadequate handling of samples and sample collection. Five issues are described as follows: 1) The effect of detergents on fecal occult blood test. Immunological methods were affected markedly to moderately by various sanitizers and detergents tested. In collecting feces for immunological fecal occult blood test, contact of feces with toilet flush water dissolving sanitizers should be inhibited. 2) Blood storage and potassium(K) release. Causes of slight elevation of K in serum are sometimes unknown. Addition of injection drugs in vitro showed that various drugs induced K release from erythrocytes. Cold storage of blood is well-known to bring elevation of K level, however, the detailed mechanism is still unknown. We developed a simple method to measure K flux activity of erythrocytes and the decreased activity was shown in patients with chronic renal insufficiency and the aged as well as the aged erythrocytes. 3) Thawed serum and concentration difference. Frozen serum samples were thawed without mixing and various layers contained different concentrations in 60 items tested. Comparing the concentration before freezing, the upper layer contained 1/2 and the bottom 2 times more. T3 and FT4 showed exceptionally smaller difference, significance of which is unknown. 4) Two syringe method in blood collection. Blood samples drawn in the first half and the latter half were comparatively measured for APTT, PT and TT. Blood amount of 1 ml or more showed no differences. TT showed elevation in the first half in 0.5 ml-sample. The effects of local treatment by warming, tapping and congestion were examined. In some cases, tissue factor level elevated by such physical pretreatment. However, in usual blood collection in human, two syringe method is not necessarily employed. 5) Heat-inactivation and cold storage of serum. Preheating sera at 56 degrees C for 30 min reduced markedly the levels of ALT, ALP, CK, ChE, ATIII and alpha 2-PI. In seroimmunology, some complement components are markedly affected and rheumatoid factor of IgM classes was also affected. In about a half of HCV-Ab positive sera, CH50 levels were decreased by the cold storage(cold activation). We reported previously the non-participation of C1q in this phenomenon. In such sera, temperature management is important. Scientific data on the storage and collection of samples should be informed not only to laboratory staffs but to nurses and doctors in order to provide "exact" data.
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PMID:[Analyses of preanalytical issues on samplings and samples]. 1130 17

Clinical features of tsutsugamushi disease (scrub typhus) were analyzed, based on 416 cases reported in Japan in 1998. Three major clinical symptoms: eschar, fever and rash were found in 87%, 98% and 92% of the cases, respectively. Elevated levels of CRP, GOT, GPT and LDH were observed in 96%, 85%, 78% and 91%, respectively. These clinical and laboratory findings were observed in the majority of the cases and considered important for diagnosis. Disseminated intravascular coagulation developed in 21 cases, indicating that scrub typhus can be life threatening. Lymphadenopathy was observed in 51% of the cases. Enlarged lymph nodes were limited to the local sites in 75% of these lymphadenopathy cases and most of these sites were adjacent to eschars. Most eschars were scabbed and located in the abdomen and the lower half of the body, especially the feet. This suggests that these parts are frequently exposed to tsutsugamushi mites. Furthermore, the skin is soft in these parts and covered by cloth. These factors may make it possible for mites to keep biting without being noticed for several hours, long enough for rickettsial transmission. Interestingly, eschar and rash were absent in 14% and 8% of the cases, respectively. This result suggests that the cases without the unique symptoms may have been misdiagnosed as common cold or other febrile illnesses. One hundred and fifty-four suspected cases were not scrub typhus cases by the serological tests. The three major clinical symptoms were present in approximately a half of these negative cases, eschar being observed in approximately 70%. This may suggest the presence of new type of scrub typhus can not be diagnosed by the present laboratory tests. Clinical features of scrub typhus in Japan were well revealed, and information obtained in the present study is useful for improving clinical diagnosis. It should, however, be stressed that there were cases that could not be correctly diagnosed only by the clinical symptoms, suggesting that it is important to improve the serological tests.
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PMID:[Tsutsugamushi disease (scrub typhus) in Japan: clinical features]. 1142 84

Emotional stress affects cellular integrity in many tissues including the heart. Much less is known about the effects of social stress. We studied the effect of emotional (immobilization with or without cold exposure) or social (intermale confrontation) stress in mice. Tissue injury was measured by means of the release of enzyme activities to blood plasma: lactate dehydrogenase (LDH), creatine kinase (CK), aspartate transaminase (AST), and alanine transaminase (ALT). Tape-immobilization increased all these activities in the plasma. AST-ALT ratio was also increased in these animals. Electrophoretic analysis of CK isoenzymes showed the appearance of CK-MB. These results indicate that the heart was injured in immobilized mice. Analysis of LDH isoenzymes and measurement of alpha-hydroxybutyrate dehydrogenase (HBDH) activity suggests that other tissues, in addition to the heart, contribute to the increase in plasma LDH activity. Restraint in small cylinders increased plasma LDH, CK, AST, and ALT activities, but to lower levels than in tape immobilization. Because the decrease in liver glycogen and the increase in plasma epidermal growth factor (EGF) were also smaller in restraint than in the tape-immobilization model of emotional stress, we conclude that the former is a less intense stressor than the latter. Cold exposure during the restraint period altered the early responses to stress (it enhanced liver glycogen decrease, but abolished the increase in plasma EGF concentration). Cold exposure during restraint enhanced heart injury, as revealed by the greater increase in CK and AST activities. Intermale confrontation progressively decreased liver glycogen content. Plasma EGF concentration increased (to near 100 nM from a resting value of 0.1 nM) until 60 minutes, and decreased thereafter. Confrontation also affected cellular integrity in some tissues, as indicated by the rise in plasma LDH activity. However, in this type of stress, the heart appeared to be specifically protected because there was no increase in plasma CK activity, and both AST and ALT increased, but the AST-ALT ratio remained constant. Habituation to restraint (1 h/d, 4 days) made mice resistant to restraint-induced tissue injury as indicated by the lack of an increase in plasma LDH, CK, AST, or ALT activities. Similar general protection against homotypic stress-induced injury was observed in mice habituated to intermale confrontation.
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PMID:Acute stress-induced tissue injury in mice: differences between emotional and social stress. 1189 86

Histological changes which appear as a result of reperfusion injury of cold-preserved rat liver were studied at intervals of 0 hr, 3 hr, 24 hr and 48 hr of cold storage. The isolated livers were stored in a UW solution (University of Wisconsin), which is used in human liver transplantations. Computer image analysis of light microscopic sections (methyl green-pyronin stained) was used for the study and quantification of injured cells. The method of TUNEL was performed to prove possible apoptosis of sinusoidal endothelial cells and heptocytes. Bile production during reperfusion and ALT, AST, LDH and ACP were measured in the reperfusion medium at the end of the 90 min reperfusion. It has been confirmed that prolongation of the cold storage of liver results in extensive changes in the liver structure and increased injury of liver cells. Sinusoidal endothelial cells were damaged more and earlier than hepatocytes. It has been shown that methyl green-pyronin stained sections are advantageous for the study of these morphological changes, allowing the strongest view of these changes. The appearance of TUNEL positive cells and an increase in the levels of biochemical parameters, e.g. AST or ALT, indicate earlier cell injury. The methodology described in this article can be used for the study of reperfusion injury of the liver and for the study of this phenomenon in other experiments.
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PMID:[Reperfusion injury in the isolated rat liver after hypothermic preservation]. 1192 82


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