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:2.6.1.1 (aspartate aminotransferase)
21,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endotoxin administration causes liver injury. Patients with alcoholic liver disease frequently have portal vein and systemic endotoxemia, and some investigators have suggested that endotoxin plays an etiologic role in alcoholic liver injury. Many of the metabolic effects of endotoxin are mediated by the cytokine tumor necrosis factor (TNF). It was the purpose of this study to determine whether TNF plays a role in ethanol-enhanced endotoxin liver injury. Rats were fed either a diet in which 36% of the calories were from ethanol or an isocaloric control diet. After 6 weeks, groups of 10 rats were intravenously injected with either saline, 1 mg/kg endotoxin, or 30 micrograms/kg of a prostaglandin E1 (PGE1) analogue + 1 mg/kg endotoxin 24 hr prior to sacrifice. Ethanol/endotoxin-treated rats had significantly higher liver enzyme levels (ALT: 1064 +/- 355 IU/liter, AST: 2024 +/- 515 IU/liter) compared with isocaloric/endotoxin controls (ALT: 237 +/- 54 IU/liter, AST: 602 +/- 80 IU/liter). Ethanol/endotoxin rats also had significantly higher peak serum TNF concentrations (992 +/- 200 units/ml) compared with isocaloric/endotoxin controls (344 +/- 96 units/ml). Pretreatment of ethanol/endotoxin rats with PGE1 caused significant attenuation of liver injury (ALT: 267 +/- 64 IU/liter, AST: 612 +/- 77 IU/liter) and a diminished serum TNF response. In contrast to chronic ethanol administration, acute gavage with 2 mg/kg ethanol (30% w/v) followed by intravenous injection of 2 mg/kg endotoxin produced significantly lower peak serum TNF concentrations (401 +/- 76 units/ml) than gavage with distilled water (1152 +/- 208 units/ml).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Tumor necrosis factor in alcohol enhanced endotoxin liver injury. 153 Jan 27

A 63 year old woman with liver failure received a transplant from a 21 year old male diagnosed as brain dead following a motor accident. After the operation, bile production was virtually absent and aspartate transaminase (AST) values rose dramatically 40 h postoperatively. Primary non-function of the graft was diagnosed, and the patient put on an urgent list for retransplantation. At the same time a continuous intravenous infusion of PGE1 was administered. Aspartate transaminase levels decreased within 9 h and reached normal levels by the sixth postoperative day, when bile production began to increase. Liver function subsequently returned to normal.
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PMID:Successful reversal of primary graft non-function in a liver transplant patient treated with prostaglandin E1. 155 May 25

The effect of prostaglandins (PG) in patients with fulminant and subfulminant viral hepatitis was studied. Seventeen patients presented with FHF secondary to hepatitis A (N = 3), hepatitis B (N = 6) and non-A, non-B (NANB) hepatitis (N = 8). Fourteen of the 17 patients had stage III or IV hepatic encephalopathy (HE). At presentation, the mean AST was 1844 +/- 1246 units/liter, bilirubin 232 +/- 135 mumol/liter, PT 34 +/- 18 and PTT 73 +/- 26 sec, and coagulation factors V and VII were 8 +/- 4 and 9 +/- 51%, respectively. Twelve of 17 patients responded to PGE1 rapidly, with a decrease in AST from 1540 +/- 833 to 188 +/- 324 units/liter, a decrease in prothrombin time from 27 +/- 7 sec to 12 +/- 1 sec, PTT from 61 +/- 10 sec to 31 +/- 2 sec, and an increase in factor V from 9 +/- 4% to 69 +/- 18% and factor VII from 11 +/- 5% to 71 +/- 20%. Five responders with NANB hepatitis relapsed upon discontinuation of therapy, with recurrence of HE and increases in AST and PT but improvement was observed upon retreatment. After four weeks of intravenous therapy, oral PGE2 was substituted. Two patients have recovered completely and remain in remission six and 12 months following cessation of therapy. Two additional patients continue in remission after two and six months of PGE2. No relapses have been seen in patients with hepatitis A virus (HAV) or hepatitis B virus (HBV) infection. Liver biopsies in the 12 surviving patients have returned to normal. These results suggest efficacy of PGE for FHF. Further investigation is warranted.
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PMID:Treatment of fulminant viral hepatic failure with prostaglandin E. A preliminary report. 190 42

Primary nonfunction following orthotopic liver transplantation is characterized by rapidly rising serum transaminases, minimal bile production, and severe coagulopathy, which can progress to hypoglycemia, hepatic encephalopathy, and acute renal failure. Untreated it has a mortality of over 80% and to date the only treatment has been retransplantation. As a result of the beneficial effect of Prostaglandin E1 infusion in patients with fulminant hepatic failure, this trial was conducted to determine whether PGE1 would be of value in primary nonfunction. We have encountered 16 cases of primary nonfunction in 94 liver transplants, an incidence of 17%. Initially in the program, there were 6 occurrences of nonfunction that did not receive PGE1; 3 underwent retransplantation (2 survivors), 2 died awaiting another liver, and in one recovery of hepatocellular function occurred with supportive care but the patient died of cytomegalovirus infection. Ten patients received PGE1 within 4-34 hr of transplantation. Within 12 hr of treatment, 8 patients responded with a significant fall in the AST (129 U/hr) whereas, in the untreated group, the AST continued to rise (267 +/- 102 U/hr) at the same rate as prediagnosis (337 +/- 95 U/hr). At the conclusion of the infusion (4-7 days) in the 8 responders, there were significant decreases in AST (4386 +/- 546 U/L to 102 +/- 21 U/L), prothrombin time (22 +/- 2 to 12 +/- .4 sec) and partial thromboplastin time (45 +/- 3-29 +/- 4 sec), and significant increases in coagulation factor V (26 +/- 8 to 95 +/- 12%) and factor VII (10 +/- 5 to 61 +/- 4%). No serious side effects occurred, although 2 patients developed diarrhea, and abdominal cramps. Two patients treated with PGE1 were retransplanted at 10-36 hr and were considered nonresponders. Graft survival was 80% in the PGE1-treated group and 17% in the untreated group (P less than 0.05) and patient survival was 90% and 33%, respectively. This study suggests a potential benefit of PGE1 in the treatment of primary nonfunction.
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PMID:Treatment of primary liver graft nonfunction with prostaglandin E1. 267 5

The effect of PG on patients with fulminant and subfulminant viral hepatitis (FHF) was studied. 17 patients presented with FHF secondary to hepatitis A (n = 3), hepatitis B (n = 6), and non-A, non-B (NANB) hepatitis (n = 8). 14 of the 17 patients had stage III or IV hepatic encephalopathy (HE). At presentation the mean aspartate transaminase (AST) was 1,844 +/- 1,246 U/liter, bilirubin 232 +/- 135 mumol/liter, prothrombin time (PT) 34 +/- 18, partial thromboplastin time (PTT) 73 +/- 26 s, and coagulation Factors V and VII 8 +/- 4 and 9 +/- 5%, respectively. Intravenous PGE1 was initiated 24-48 h later after a rise in AST (2,195 +/- 1,810), bilirubin (341 +/- 148), PT (36 +/- 15), and PTT (75 +/- 18). 12 of 17 responded rapidly with a decrease in AST from 1,540 +/- 833 to 188 +/- 324 U/liter. Improvement in hepatic synthetic function was indicated by a decrease in PT from 27 +/- 7 to 12 +/- 1 s and PTT from 61 +/- 10 to 31 +/- 2 s, and an increase in Factor V from 9 +/- 4 to 69 +/- 18% and Factor VII from 11 +/- 5 to 71 +/- 20%. Five responders with NANB hepatitis relapsed upon discontinuation of therapy, with recurrence of HE and increases in AST and PT, and improvement was observed upon retreatment. After 4 wk of intravenous therapy oral PGE2 was substituted. Two patients with NANB hepatitis recovered completely and remained in remission 6 and 12 mo after cessation of therapy. Two additional patients continued in remission after 2 and 6 mo of PGE2. No relapses were seen in the patients with hepatitis A virus and hepatitis B virus infection. Liver biopsies in all 12 surviving patients returned to normal. In the five nonresponders an improvement in hepatic function was indicated by a fall in AST (3,767 +/- 2,611 to 2,142 +/- 2,040 U/liter), PT (52 +/- 25 to 33 +/- 18 s), and PTT (103 +/- 29 to 77 +/- 44 s), but all deteriorated and died of cerebral edema (n = 3) or underwent liver transplantation (n = 2). These results suggest efficacy of PGE for FHF, and further investigation is warranted.
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PMID:Biochemical and clinical response of fulminant viral hepatitis to administration of prostaglandin E. A preliminary report. 279 44

Prostaglandins (PGE1) and dibutyryl cyclic AMP (dBc AMP) induce similar morphological changes in astrocytes obtained in primary cultures. PGE1 and dBc AMP increased 2 enzymes of GABA and glutamate metabolism, GABA-T and AAT, but did not modify GDH and GLN-S. Prostaglandins probably affect the cAMP content of glial cells and act in the same way as dBc AMP on glial cell differentiation.
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PMID:Effect of prostaglandins and dibutyryl cyclic AMP on the morphology of cells in primary astroglial cultures and on metabolic enzymes of GABA and glutamate metabolism. 625 71

The liver has been judged relatively resistant to ischemia, but prolonged inflow occlusion at normothermic conditions can produce evidence of reversible or irreversible hepatocellular damage. Cytoprotective agents have been used both experimentally and clinically to afford extended viability of hepatocytes under reduced perfusion. One agent, prostaglandin E1, has been described clinically as effective in sustaining liver function under ischemic conditions. We have sought to verify this observation in an experimental model using prolonged normothermic inflow occlusion. Twenty miniature pigs were anesthetized and subjected to subtotal normothermic hepatic inflow occlusion (portal vein, hepatic artery, choledochal vessels) to allow for sufficient splanchnic decompression. Half of the animals received pretreatment with prostaglandin E1 (alprostadil) 500 micrograms intravenously. Inflow occlusion was maintained for 2 hours followed by reperfusion and killing 24 hours later. As a measure of functional preservation, the tissue adenine nucleotides adenosine monophosphate, diphosphate, and triphosphate (AMP, ADP, ATP) were measured in ischemic liver by freeze-clamping and high-performance liquid chromatography during occlusion and after reperfusion. Cytosolic enzyme determinations (aspartate transaminase, alanine transaminase, lactate dehydrogenase) were also made before occlusion and after reperfusion. As a possible indicator of cellular injury, blood ionized Ca++ was measured before inflow occlusion and after reperfusion. Although no difference was found in levels of AMP and ADP between prostaglandin E1 and control animals, ATP levels rose significantly higher during recovery in prostaglandin E1 animals at 60 minutes and 24 hours after reperfusion (13.97 +/- 1.29 and 13.60 +/- 0.91 mumoles/gm dry weight prostaglandin E1 vs. 9.25 +/- 0.97 and 9.80 +/- 0.85 mumoles/gm dry weight co control, P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effect of prostaglandin E1 on liver adenine nucleotides and cytoplasmic enzymes in a porcine model of normothermic hepatic ischemia. 759 Jun 75

Acute hepatic failure was induced in 50 male rabbits by D-galactosamine HCl (1 g per kg bw), and the effects of prostaglandin E1 on this model were investigated. Twelve hours after the administration of D-galactosamine HCl, a continuous infusion of prostaglandin E1 (2 micrograms.kg-1.h-1 or 20 micrograms.kg-1.h-1) was started. Ten animals in each group were observed until the time of death and mean survival times were compared between the groups. Five animals in each group were used for the determination of regional blood flows and brain water content. After the injections of D-galactosamine HCl, serum aspartate transaminase and alanine transaminase activity rose markedly and prothrombin time was prolonged. The administration of prostaglandin E1 did not affect these levels. However, the survival time in the prostaglandin E1 20 micrograms.kg-1.h-1 group (48.2 +/- 10.4 h) was significantly longer (p < 0.005, p < 0.01) than those in the untreated group (24.9 +/- 5.0 h) and the prostaglandin E1 2 micrograms.kg-1.h-1 group (28.1 +/- 5.8 h). Prostaglandin E1 20 micrograms.kg-1.h-1 inhibited elevations of blood urea nitrogen and creatinine and significantly inhibited the decrease of urine volume and urinary sodium excretion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of prostaglandin E1 on experimental acute hepatic failure in rabbits: prostaglandin E1 prevents the development of multiple-organ failure. 805 85

Although the liver is relatively resistant to normothermic ischemia, prolonged periods of inflow occlusion have produced evidence of hepatocyte injury. We have developed an animal model of liver ischemia using the pig and maintaining subtotal inflow (hepatic artery and portal vein) occlusion, allowing mesenteric portal decompression via patent portal veins through the caudate lobe, obviating the need for portosystemic shunting. This produced biochemical [aspartate transaminase (AST), lactate dehydrogenase (LDH)] and histopathologic evidence, using a microscopic grading system, of hepatocyte necrosis after 2 hr of normothermic ischemia. By administration of prostaglandin E1 (PGE1) prior to and during inflow occlusion, we have produced a statistically significant reduction in LDH (1085.9 +/- 413.5 U/liter compared to 669.1 +/- 161.4 U/liter) and AST (236.5 +/- 80.4 U/liter compared to 85.1 +/- 39.7 U/liter) (P < 0.05) between control and PGE1 animals 24 hr after reperfusion. Moreover, using the blinded microscopic grading system for hepatocellular necrosis, we have found significantly less (2.86 +/- 0.90 compared to 1.57 +/- 1.13, P < 0.01) necrosis when control and PGE1 animals were compared. Our experimental model supports the hypothesis that PGE1 exerts a cytoprotective effect during prolonged normothermic hepatic ischemia but does not aid in elucidating a mechanism for this effect.
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PMID:Evidence for cytoprotection by prostaglandin E1 with normothermic hepatic ischemia. 815 23

Fulminant hepatic failure (FHF) is a severe, life-threatening disorder. Previous studies have suggested that intravenous prostaglandin treatment may improve survival in FHF. The present study was performed to further investigate the possible benefit of intravenous prostaglandin E1 (PGE1) for patients with FHF. A total of 18 patients, all excluded as candidates for hepatic transplantation, were studied. Thirteen of 18 participated in a randomized, double-blind, placebo-controlled trial. PGE1 was administered by continuous infusion at a dose of 10 to 40 microg/h as tolerated. After 48 hours of blinded treatment, 3 of 7 patients randomized to placebo were converted to open-label PGE1 for lack of biochemical and/or clinical improvement. Mean values for alanine transaminase, aspartate transaminase, total bilirubin, prothrombin time, factor V percent, factor VII percent, hepatic encephalopathy score, days from onset of symptoms to initiation of treatment, and cause of FHF were similar between treatment groups. Ten of 18 patients (55%) enrolled in this trial survived. However, survival was not different between PGE1-(60%) and placebo (50%) treated patients. The greatest predictor of survival was the number of days from onset of symptoms to hospitalization, which was significantly (P = .002) shorter for survivors (3.3 v 12.4 days), regardless of PGE1 treatment. Six of 8 patients (75%) who began PGE1 therapy and 4 of 5 placebo-treated patients (80%) hospitalized within 10 days of onset of symptoms survived. By contrast, all 5 patients who were hospitalized and subsequently began PGE1 treatment 10 days or longer after the onset of symptoms died. We conclude that early recognition and hospitalization is the most important factor in reduction of mortality from FHF. It is unclear whether PGE1 treatment is beneficial when administered during this period. However, it is apparent that PGE1 was not effective for treatment of FHF if treatment started more than 10 days after onset of this clinical syndrome.
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PMID:Treatment of fulminant hepatic failure with intravenous prostaglandin E1. 972 81


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