Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.3.1.109 (AST)
 6,066 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A study was conducted comparing the effects of initial arterialization vs. initial portal revascularization in unstored warm ischemic (for 30 min) livers, livers stored for 4 hr at 0 degrees C in Collins solution and livers rendered warm ischemic for 1 hr before removal and replacement as autografts. All livers that received initial arterialization showed uniform diffuse perfusion, whereas those with initial portal perfusion were patchy and well perfused only in the right lobe. In the experimental animal, initial arterialization using an end-to-end method was much easier and required less retraction. The energy charge and ATP levels dropped sharply during brief warm ischemia but returned rapidly to normal on revascularization. Although the decline in energy charge was less in stored livers, the return to normal was slower and incomplete. Plasma levels of AST indicated much greater damage in the stored livers and were lowest in recipients in unstored livers that were arterialized first. After longer warm ischemia, energy charge values declined and only completely returned to 60% of preoperative values within 2 hr of grafting. Despite this, the survival rate of these animals was very poor and only one survived overnight. Seven of the 12 survived the procedure, but in five death occurred within 30 min of full revascularization. In this group, AST levels rose sharply after revascularization to a mean level of 1,000 U.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The relevance of the order of revascularization in liver grafting. 231 60

Oxygen free radicals have been implicated in the pathogenesis of postischemic liver injury. High-dose superoxide dismutase (SOD), a radical scavenging enzyme, has been investigated in a rat model of liver ischemia reperfusion by biochemical monitoring. Blood vessels to the median and left lobe were clamped for 1 h and then reperfusion was allowed. The indices used were serial venous blood levels of AST, ALT, calcium, and ATP determination in liver tissue. In SOD-treated animals (7,5000 U i.v.) a significant attenuation of the rise in enzyme levels was observed as well as the absence of the decrease in calcium level in the early phase after reperfusion as compared with control rats, and furthermore ATP restoration was significantly increased.
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PMID:Effect of superoxide dismutase on liver ischemia-reperfusion injury in the rat: a biochemical monitoring. 322 31

It has been shown that the nutritional state of the donor may affect the outcome of liver transplantation. However, many donors staying in the intensive care unit for a long period are in a reduced nutritional state. In this study, we investigated the effects of various methods of nutritional repletion on the outcome of liver transplantation in pigs. Donor pigs were divided into three groups according to the nutritional pretreatment given for 7 days before harvesting: group I were fasted and received intravenous administration of saline; group II were fed orally; group III were fasted, but given 20% glucose intravenously. Donor livers were stored for 4 hr in cold Euro-Collins' solution and transplanted. The serum AST level 24 hr after reperfusion remained at a lower level in group III compared with those in groups I and II. Bile production of the liver after transplantation was also well recovered in group III. The glycogen content of the liver at harvesting, which was completely consumed in group 1, was well preserved in groups II and III. These storages in both groups were rapidly consumed 1 hr after reperfusion. On the other hand, ATP content of the liver in groups I, II, and III, which were at a similar level at harvesting, were markedly decreased 4 hr after cold preservation and, 1 hr after reperfusion, recovered to 26%, 48%, and 73% of that before preservation, respectively. The mean survival time in group III was 37.2 days, significantly longer than 5.8 +/- 0.7 and 9.8 +/- 2.0 days in groups I and II, respectively (P < 0.01). These results show that the favorable outcome of liver transplantation depends on the glycogen storage in the donor liver, and also on ATP generation after reperfusion. Furthermore, it was suggested that ATP generation was affected by some unknown factor related to the method of nutritional repletion.
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PMID:The effects of nutritional repletion on donors for liver transplantation in pigs. 765 57

Pravastatin, lovastatin, and simvastatin, drugs which lower cholesterol by inhibiting 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, have been linked to skeletal myopathies in humans and rats. The myotoxicity of these three drugs was compared, after 48 hr exposure, in cultures of primary neonatal rat skeletal myotubes. Measurements included HMG CoA reductase activity ([14C]acetate incorporation into cholesterol), indicators of membrane damage (CPK, LDH, and AST), cell viability (mitochondrial dehydrogenase metabolism of MTT), protein synthesis ([3H]leucine incorporation), and energy status (ATP). All three drugs inhibited cholesterol synthesis to the same extent in rat hepatocytes (IC50s approximately 0.07 microM). Lovastatin- and simvastatin-induced inhibition of cholesterol synthesis in myotubes was unchanged compared to that of hepatocytes, but pravastatin was 85-fold less potent (IC50 = 5.9 microM). Protein synthesis and ATP levels were the most sensitive indicators of toxicity. Pravastatin (IC50 = 759 microM) was > 100-fold less inhibitory of protein synthesis than lovastatin (IC50 = 5.4 microM) or simvastatin (IC50 = 1.9 microM). Addition of mevalonic acid (the immediate product of the HMG CoA reductase reaction), as 100 microM mevalonic acid lactone, reversed the toxicity of all three drugs. Removal of serum for 24-72 hr did not alter the toxicity of any of the drugs compared to cultures containing 10% serum, suggesting that differences in protein binding did not account for the differences in toxicity of the drugs. These results indicate that pravastatin is less myotoxic than lovastatin or simvastatin in this in vitro system using neonatal rat skeletal muscle cells, and this differential toxicity is correlated with the selective decrease in inhibition of HMG CoA reductase by pravastatin in nonhepatic tissues.
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PMID:In vitro myotoxicity of the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, pravastatin, lovastatin, and simvastatin, using neonatal rat skeletal myocytes. 787 72

Since an occlusion of the vascular inflow to the liver is a useful technique in liver surgery, a relation between ischemia and regeneration in the liver is particularly important. The purpose of this study was to evaluate the effect of ischemic duration on liver regeneration after massive hepatectomy. Animals were subjected to segmental liver ischemia. After 30, 60, or 90 min, nonischemic liver lobes were resected (70% hepatectomy). Hepatectomy without prior liver ischemia was performed in the control group. On the 1st, 3rd, 5th, and 7th days following hepatectomy, a BrdU labeling index was calculated as a marker of liver regeneration. AST, ALT, and liver adeninenucleotides were also measured. Although 30 min of liver ischemia resulted in higher peak AST and ALT levels, liver regeneration and ATP levels were significantly higher than those in control animals. Ninety minutes of liver ischemia resulted in significantly lower liver regeneration and ATP levels compared with the other treatment paradigms. Liver regeneration and ATP levels were almost identical to those in control animals, in rats with 60 min of ischemia preceding hepatectomy. We conclude that livers regenerative capacities can tolerate significant ischemia and that relatively brief periods of ischemia can even accelerate liver regeneration.
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PMID:Duration of liver ischemia and hepatic regeneration after hepatectomy in rats. 788 25

Need of oxygen by the liver during hypothermic perfusion was evaluated using isolated perfusion model. Livers were perfused by a continuous perfusion system with oxygen saturated perfusate or nitrogen saturated perfusate, or simply stored for 12 hours at 5 degrees C. Quality of individual liver was assessed at one hour after normothermic reperfusion. Tissue edema was significant in all experimental groups, but the extent of which was much higher in nitrogen and simple cold storage groups. AST, ALT, LDH and PNP in the perfusate at the end of normothermic reperfusion were significantly higher in nitrogen and simple storage groups and those of oxygen group were similar to the control. Tissue adenine nucleotide and purine catabolite concentration in oxygen group was almost identical to the control at the end of hypothermic preservation, while ATP and energy charge in nitrogen and simple cold storage groups were significantly low. Conjugated dienes before and after reperfusion showed no difference in any groups, indicating no involvement of free radical injury on reperfusion in this asanguineous perfusion model. These results suggest that continuous supply of oxygen is necessary for liver preservation even though the temperature is lowered to inhibit cellular metabolism.
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PMID:Evaluation of oxygen necessity during hypothermic liver perfusion. 803 Dec 17

The red blood cell metabolic parameters ATP, ADP, sigma AN, ATP/ADP, ATP/ATP, energy charge, PAD, 2,3-DPH, Pn were studied in 106 patients with generalized meningococcus infection (GMI) and meningitis of other etiology over their natural history. There was a typical adaptative red blood cell response that featured glycolytic stimulation on hypoxia that ran with impaired red blood cell energy metabolism (RBCEM), negative energy balance. It was the most pronounced at the peak of disease. RBCEM changes occurred in the presence of antioxidative disorders of red blood cells as lowered PAD levels. When early complications, such as shock, brain edema, death developed, there was a high incidence of signs of erythrocytic biochemical disadaptation. The RBCEM changes were associated with the magnitude of cytolysis, i.e. serum AST and AST/ALT levels. The significance of the metabolic changes found in the red blood cells in the pathogenesis and clinical picture of GMI and purulent meningitis is discussed in the paper.
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PMID:[Erythrocyte metabolism in meningococcal infection and purulent meningitis]. 899 64

We describe a 76-year-old male patient who developed a life-threatening acute hepatotoxicity possibly caused by flutamide, an antiandrogen drug given during the previous 10 months, in the scenario of a brief moderate hypotension secondary to atrial flutter. There was a sudden increase of liver enzyme levels AST = 4.521 IU/L, ALT = 1.716 IU/L (normal values 0-37 and 0-40 respectively), prothrombin activity decreased to 16%, and also felt the platelet count, with significant haemorrhages. We hypothesize this was triggered as a consequence of the transient diminished supply of oxygen to the subclinically flutamide-damaged hepatocytes by the well-known mechanism of the cytochrome P450 (3A and 1A)-mediated formation of electrophilic metabolites, and the inhibitory effect of flutamide on mitochondrial respiration and ATP formation.
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PMID:[Hepatoxicity caused by flutamide increased by hypotensive situation?]. 901 17

The possibility of resuscitating livers after warm ischaemia has been recently suggested. The aim of the present investigation was to analyse the effects of anoxia on the morphology of hepatic cells, to determine whether these effects are reversible after providing a resuscitation period between warm ischaemia (WI) and cooling, and to study the behaviour of the resuscitated liver in the recipient organism. Ten female, Large-White pigs acted as donors for 10 recipient animals of the same kind who received an orthotopic liver graft. Recipients were divided into two groups depending on whether the livers they received had undergone a resuscitation period (Group I (n=5) where animal livers were subjected to 5 min warm ischaemia (WI) without resuscitation, and Group II (n=5) where the livers were subjected to 5 min WI followed by 5 min resuscitation). Morphological and ultrastructural studies of liver cells were performed using light and electron microscopy. ATP, ADP and AMP levels were determined in liver biopsies by high performance liquid chromatography (HPLC). Plasma AST and bilirubin levels in the two groups were compared 24 h after transplantation. After 5 min of anoxia, hepatocytes showed two morphological patterns in response to WI. Some were appreciably condensed with dark mitochondria, peroxisomes and some cytoplasmic vacuoles. Others showed electronlucent organelles, inflamed mitochondria with broken cristae and disorganized endoplasmic reticulum. Hepatocytes showed globular microvilli and bleb formation with migration towards the sinusoids. One hour after the revascularisation of the resuscitated livers, the hepatocytes showed nearly normal morphological characteristics. However, the hepatocytes of non-resuscitated organs continued to show alterations. Kupffer cells were activated in the livers of both experimental groups. Ultrastructural changes and total tissue adenine nucleotide (TAN) levels recovered completely in resuscitated livers soon after transplant. These results suggest that when short WI periods are followed by equivalent periods of resuscitation, the hepatocytes of transplanted livers recover from the effects of anoxia.
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PMID:A histopathological study of anoxic-resuscitated liver allografts. 904 50

Muscle ATP loss with exercise has implications both to the causes of fatigue and muscle damage. To study this at the single muscle fibre level, five trained thoroughbred horses performed consecutive 90 second gallops on an inclined treadmill followed by a final gallop to fatigue. Biopsies of the m. gluteus medius were taken at rest, post-exercise and during 24 hour recovery. Blood lactate was 20.0 mmol litre-1 or more, and plasma NH3 300-800 mumol litre-1, following the final gallop. Minimal changes occurred in the plasma markers, CK and AST. ATP loss with exercise was 32.2 (SD 12.2) per cent. Following exercise single fibre ATP contents showed a much broader distribution than at rest, with contents in some close to zero. Following five and 24 hour recovery, however, frequency distribution curves were close to those seen at rest. There was no difference in the ATP contents of types I, IIa and IIb at rest of with exercise or recovery. The results pointed to marked heterogeneity between individual fibres in their biochemical response with exercise, independent of fibre type.
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PMID:ATP loss with exercise in muscle fibres of the gluteus medius of the thoroughbred horse. 949 49


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