UNIPROT:P17174 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

Query: UNIPROT:P17174 (aspartate aminotransferase)
14,872 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been suggested that depletion of donor hepatic glycogen reserves deleteriously affects the resistance of the hepatic graft to ischemic episodes. In this study, performed in the pig model, we showed that it is possible to enhance the quality of the graft at the time of reperfusion by using a method which rapidly restores the donor hepatic glycogen reserves. With the aid of an isolated liver perfusion model, we compared grafts (n = 24) harvested from pigs fed (group N), fasted for 24h (group J), or fasted with a restoration of glycogen reserves (group P). After the grafts were subjected to 8 hours of cold ischemia, the release of alanine aminotransferase, aspartate aminotransferase and lactic dehydrogenase in the perfusate increased in group J (P < 0.05 vs group N); the increase was corrected in group P (P < 0.05 vs group J). When the grafts were subjected to 15 minutes warm ischemia prior to the liver harvest, the production of bile was reduced in group J (P < 0.05 vs group N); bile production was reestablished in group P (P < 0.05 vs group J). The clinical application of such a method of donor nutritional conditioning, in the hours which precede organ harvesting, may enhance the quality of the hepatic graft at the time of transplantation.
...
PMID:[Enhancement of the quality of hepatic graft by restoration of hepatic glycogen reserves in the donor]. 129 69

Thirty-three canine hearts were isolated after initial cardioplegia and preserved for 6 hours in 4 degrees C saline solution with intermittent infusion of cardioprotective solution every hour. Reperfusion was observed for 2 hours under normothermic cross-circulation. Hearts were divided into five groups depending on the agent(s) added to the K(+)-Mg2+ cardioplegic solution (K(+)-Mg(2+)-CP) infused. Control hearts (n = 6) received K(+)-Mg(2+)-CP solution alone; group I (n = 7) received lidocaine, 200 mg/L, added to the K(+)-Mg(2+)-CP solution; group II (n = 7) received betamethasone (250 mg/L) added to the formula for group I; group III (n = 6) received diltiazem (200 micrograms/L) added to the formula for group II; group IV (n = 7) received aprotinin (150 KIU/L) added to the formula of group III. Coronary sinus MB fraction of creatine kinase level was significantly decreased at 60 and 120 minutes of reperfusion in group II, as was mitochondrial aspartate aminotransferase level at 2 hours of reperfusion. Lysosomal enzyme release decreased in group IV. Myocardial adenosine triphosphate levels and total adenine nucleotides showed no significant difference among the groups at the end of reperfusion; however, myocardial adenosine diphosphate and adenosine monophosphate levels during reperfusion increased significantly in group I, and myocardial adenosine diphosphate and adenosine monophosphate levels at the end of reperfusion in groups I and IV were significantly higher than those of the control. Calcium overload, which was lowest in group II, was not completely prevented during reperfusion in any group. Left ventricular end-systolic pressure volume relationship in group II showed the "best" functional recovery. In addition, the ultrastructure of the left ventricular myocardium was well preserved in all groups. These results suggest that membrane stabilization with lidocaine and betamethasone affords beneficial effects on myocardial biochemical and functional viability. Diltiazem appears to be less effective in preventing calcium overload during ischemia-reperfusion, and protease inhibition with aprotinin (150 KIU/ml) seems to be highly effective in suppressing lysosomal enzyme activation-release and maintaining myocardial adenosine diphosphate and adenosine monophosphate levels.
...
PMID:Heart preservation: analysis of cardioprotective infusate characteristics. Membrane stabilization, calcium antagonism, and protease inhibition on myocardial viability: a biochemical, ultrastructural, functional study. 137 28

This study was designed to clarify the effects of changes in liver tissue glutathione (GSH) concentration on postischemic liver injury together with the effects of gamma-glutamylcysteine ethyl ester (GCE), a prodrug of GSH, and GSH. Rats were pretreated with GSH (50 mg/kg, i.v.), or GCE (50 mg/kg, i.v.), or untreated. In each rat, liver was isolated, and liver mitochondria were prepared after 2 h of ischemia or 1 h of reperfusion following 2 h of ischemia. Mitochondrial function was measured polarographically. Liver adenine nucleotide concentrations were also determined using high-performance liquid chromatography. Liver tissue GSH, an oxidized form of glutathione (GSSG) concentrations, and activities of GSH peroxidase and GSSG reductase were determined enzymatically. Liver hypoxanthine and xanthine concentrations were determined by HPLC. Liver tissue concentration of lipid peroxide was measured. Leakages of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and adenine nucleotides into the hepatic vein after reperfusion were also measured. Administration of GCE improved the recovery of mitochondrial function and maintained tissue GSH concentration concomitantly. Increases in liver lipid peroxide concentration after reperfusion, and leakage of liver cell enzymes and adenine nucleotides were mitigated by administration of GCE. Administration of GSH itself failed to maintain tissue GSH concentration and had no protective effects. From these results, it is concluded that in the postischemic process, free radical formation might be enhanced, and the radical scavenging system deteriorated. To enhance the radical scavenging system is a possible maneuver to prevent radical-related cell damage associated with reperfusion, because pharmacological reduction of breakdown of ATP to hypoxanthine and xanthine seems to be difficult. GCE maintained liver GSH concentrations and mitigated postischemic liver injury, concomitantly. Clinical use of GCE might be recommended.
...
PMID:The effects of gamma-glutamylcysteine ethyl ester, a prodrug of glutathione, on ischemia-reperfusion-induced liver injury in rats. 833 63

A comparative study of 24 hr preservation at 4 degrees C of excised rat livers with Euro-Collins and hydroxyethyl starch-free University of Wisconsin (UWm) solutions has been conducted based on the assessment of (1) the cellular energy status determined by 31P NMR spectroscopy and (2) cellular injury estimated from the loss of purine compounds (inosine, hypoxanthine, xanthine, and uric acid) during cold ischemia and reperfusion measured by HPLC, the leakage of intracellular enzymes, and the modifications of parenchyma established by light microscopy. Recovery of nucleosides di- and triphosphate was greater in the UWm group (80 +/- 6% vs. 58 +/- 6%) while inorganic phosphate formation was comparatively reduced. During hypothermic storage, the UWm groups generated a higher amount of inosine and hypoxanthine (in relation to the presence of adenosine in the protective solution) while no xanthine or uric acid was detected due to the inhibitory effect of allopurinol. Conversely, large quantities of xanthine and uric acid were found in the reperfusate of the EC group, pinpointing the cytotoxic role of oxygen-derived free radicals in the generation of cellular damage, as also illustrated by a higher aspartate aminotransferase leakage in the EC group (devoid of allopurinol and glutathione. Light microscopy indicated no histological alterations in the UWm group and mild alterations in the EC group that showed ballooning of hepatocytes (no lactobionate and raffinose in EC) and an alternation of clarifications and eosinophilic condensations. This study clearly confirms and illustrates the overall superiority of UWm solution in liver transplant preservation.
...
PMID:Twenty-four-hour hypothermic preservation of rat liver with Euro-Collins and UW solutions. A comparative evaluation by 31P NMR spectroscopy, biochemical assays, and light microscopy. 141 50

As efforts to assess the viability of liver grafts continue, the recent description of noninvasive measurement by fluorimetry or magnetic resonance spectrometry of adenine nucleotides has brought energy charge into focus again as an index of viability. Many previous studies have been conducted in human donor livers that have clinical relevance but which cannot be standardized, or in rats in which the hepatic artery is not anastomosed. In the present study, pig livers were definitively rendered ischemic for 1 or 2 hr. In one group the livers were then revascularized (intact) while in the other, the livers were removed during the final 20-30 min of the ischemic period and were subjected to autograft. There was a marked difference in survival between the intact and the autograft groups. One hour of ischemia in the intact group was associated with survival comparable to that of autograft controls (8-100 days); 2 hr of ischemia caused shortened survival, ranging from 2 to 18 days. In the recipients of autografts, survival after 1 hr of ischemia ranged from 3 to 16 days; after 2 hr of ischemia no autograft recipient survived overnight. The energy charge returned to the preoperative level after 2 hr of ischemia in both intact and autograft groups. The concentrations remained depressed after 2 hr of ischemia in autografted animals, thus being associated with survival. However, the patterns of total adenine nucleotide and adenosine triphosphate were not always similar to those of energy charge. The concentrations of aspartate aminotransferase were similarly elevated in all ischemic groups irrespective of duration or subsequent survival. There was, however, a close association between euglobulin lysis times (ELT) and survival. In the autograft recipients of livers subjected to 2 hr of ischemia that did not survive overnight the ELT remained significantly shortened. It is concluded that adenine nucleotide metabolism is important as an index of viability, but that concentrations of total and individual adenine nucleotides and the energy change all need to be computed. There does, however, appear to be an absolute relationship between survival and euglobulin lysis time that would be clinically useful in patients undergoing liver transplantation or hepatic vascular exclusion.
...
PMID:Energy charge as an indication of liver viability. A comparison of changes in livers that remained intact with those subjected to autografting. 154 44

Ischemic hepatitis is not an uncommon complication of reversible severe hypotension or cardiac failure. The prognosis usually is determined by the cause of the initial hypotension or cardiac failure, rather than the subsequent hepatic dysfunction. We report a retrospective analysis of nine patients with ischemic hepatitis in which previously unreported clinical and biochemical abnormalities are noted. The clinical and biochemical course of the patients were reviewed until recovery or death from ischemic hepatitis. All the patients had a rapid striking elevation of aspartate aminotransferase, and lactic dehydrogenase, with an equally rapid resolution of these parameters. Abnormal serum glucose levels occurred in six patients (none of whom had a prior carbohydrate intolerance). Insulin therapy was given to three patients for a limited period. Renal impairment was manifest in all nine patients, and it resolved spontaneously within 10 days. Altered mental status was detected in six patients; the changes reverted to normal within 7 days of their onset. A preexisting anemia (hemoglobin less than 11.0 g/dl) was noted on admission in four patients, and it did not appear to potentiate the manifestations of the hepatic ischemia. We conclude that ischemic hepatitis should be anticipated in all patients with a recent history of systemic hypotension. It should be considered in the differential diagnosis of patients with unexplained hepatitis; the early massive rise in lactic dehydrogenase, the rapid fall in transaminases, and the early mild/moderate renal failure strongly suggest ischemic hepatitis. Patients with ischemic hepatitis can manifest reversible renal failure, mental confusion, and hyperglycemia which may require insulin for its control.
...
PMID:Ischemic hepatitis: widening horizons. 848 Jul 56

To evaluate the effects of hepatic inflow occlusion without the shunt, the physiological differences were compared in three groups of rats in which the hepatoduodenal ligament was occluded for 15 min, 30 min, and 60 min. The survival rate significantly decreased in the 60 min occlusion group (53.6%) when compared with that of the 15 min and 30 min occlusion groups (95% and 91.6%, respectively). The significant differences in the changes in blood pressure (BP), the values of plasma potassium, histamine (HIS), norepinephrine (NE), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and the values of hematocrit (HT) were also observed between the 30 min and 60 min occlusion groups. The results indicate that, in rats, there is a high probability of an irreversible state to shock after 30 min hepatic inflow occlusion when veno-venous bypass is not applied. The values of plasma HIS and NE and the values of HT in portal blood were significantly greater than those in the general circulation. The results suggest that splanchnic congestion may have a greater influence than hepatic ischemia has in contributing to the deterioration of the physiological state.
...
PMID:Effects of hepatic inflow occlusion on changes in plasma potassium, histamine, and norepinephrine in rats. 162 73

We have previously shown the safety and efficacy of University of Wisconsin solution for hypothermic preservation of the human donor heart in a pilot group of 16 transplant recipients. The present study is a randomized clinical trial comparing University of Wisconsin solution to conventional preservation using crystalloid cardioplegia and saline storage within a 4-hour limit of ischemia. Heart transplant recipients (n = 42) were randomized into two groups: those receiving hearts preserved by University of Wisconsin solution, the UWS group (n = 22), and those receiving hearts preserved in the conventional manner, the CCS group (n = 20). Recipient age, gender, heart disease, and preoperative inotropic support and donor age, gender, and mean ischemic time in hours (UWS 2 hours 36 minutes, range 1 hour 36 minutes to 2 hours 53 minutes; CCS 2 hours 20 minutes, range 1 hour 20 minutes to 2 hours 44 minutes; p = not significant) were similar. Significant differences observed between the two groups included (1) mean time (minutes) from reperfusion to achieve a stable rhythm, (2) need for intraoperative defibrillations, (3) need for transient cardiac pacing, and (4) integrated postoperative creatinine kinase and aspartate aminotransferase release over 48 hours. There was no difference in postoperative electrocardiogram, endomyocardial biopsy, or hemodynamics. One UWS patient died of sepsis and another of a ruptured cerebral aneurysm. UWS is safe for donor organ arrest and preservation despite high viscosity and potassium concentration. When compared with CCS hearts, hearts preserved in UWS regained electrical activity more rapidly and had better myocardial protection as demonstrated by enzymatic analysis. Further investigation is required to determine the effects of UWS preservation on long-term survival, to determine the prevalence of rejection and graft atherosclerosis, and to test the ability of UWS to extend donor ischemic time in human cardiac transplantation.
...
PMID:University of Wisconsin solution versus crystalloid cardioplegia for human donor heart preservation. A randomized blinded prospective clinical trial. 173 83

This study was undertaken to determine whether or not prostaglandin I2 (PGI2) analog pretreatment could successfully preserve organ viability after warm hepatic ischemia in rats. Although 120-min ischemia of the liver did not permit survival in rats administered normal saline solution (NS group) before warm ischemia, the survival rate of PGI2 analogue (500 ng/kg/min)-treated rats (PG group) significantly improved to 57% (P less than 0.05). Recirculation following 120-min hepatic ischemia in the NS group resulted in no improvement of B-phosphorus of the ATP (B-ATP)/inorganic phosphate (Pi) ratio measured by 31P nuclear magnetic resonance, a marked increase in the serum aspartate aminotransferase (SAST) level, and an increase in the malondialdehyde (MDA) level in liver tissue. In the PG group, the B-ATP/Pi ratio was significantly improved (P less than 0.05), the elevation in SAST was also markedly suppressed (P less than 0.05), and the MDA level of the liver was lowered more than that in the NS group. Severe congestion and extensive vacuolization of hepatocytes from the peripheral to the midzonal areas were histologically exhibited with single-cell necrosis in the NS group. There were fewer histological alterations of the liver and these coincided with the changes in other parameters in the PG group. Our results indicate that PGI2 analog reduces warm ischemic injury of the liver and provides greater protection for organs to be transplanted.
...
PMID:The beneficial effect of a prostaglandin I2 analog on ischemic rat liver. 175 84

The effects of pretreatment with cyclosporine, allopurinol, or methylprednisolone on ischemia-reperfusion injury of the liver were investigated. A total of 32 adult mongrel dogs that received one of the pretreatments were divided into four groups and were subjected to 90 min liver ischemia. Serum activities of aspartate aminotransferase (s-AST) and lactate dehydrogenase, (s-LDH) as well as animal survivals were used as indicators of liver injury. The elevation of both s-AST and s-LDH was significantly suppressed by pretreatment with cyclosporine as much as by allopurinol. However a significant improvement in animal survival was obtained only in the cyclosporine-pretreated group. Pretreatment with methylprednisolone did not affect either the activities of s-AST and s-LDH or animal survivals when compared with the control group. These data suggest that cyclosporine is a potent protector against ischemic liver injury--as effective as allopurinol or methylprednisolone. Although the precise mechanism of the effect of cyclosporine on liver ischemia still remains unknown, these observations may be of use in liver transplantation.
...
PMID:Attenuation of ischemia-reperfusion injury of the liver in dogs by cyclosporine. A comparative study with allopurinol and methylprednisolone. 185 50

1 2 3 4 5 6 7 8 9 10 Next >>