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)

Although several studies suggest that hepatic graft failure after cold ischemia results from nonparenchymal cell damage, other data indicate that hepatocellular ATP content is significantly correlated with the transplantation success rate. In this study, we have conducted a systematic investigation of various aspects of cell viability and function of isolated hepatocytes stored at 4 degrees C for 24 and 48 hr in either University of Wisconsin solution or Hanks' HEPES buffer, a control solution clinically unsuitable for organ preservation. After 24 hr, hepatocytes stored in Hanks' HEPES buffer had viability (measured by trypan blue exclusion and ALT and lactic dehydrogenase leakage), transport function (measured by 22Na+ and [3H]taurocholate uptake) and cell size similar or only slightly altered when compared with freshly isolated and University of Wisconsin solution-stored hepatocytes. ATP content was decreased in both groups; however, the reduction was much greater in Hanks' HEPES buffer-stored cells. Furthermore, ATP regenerating capacity was greatly reduced in Hanks' HEPES buffer- stored but not in University of Wisconsin solution-stored hepatocytes. By 48 hr viability and function of Hanks' HEPES buffer-stored hepatocytes were decreased; University of Wisconsin solution afforded partial protection. When examined by light and electron microscopy, cells stored in both University of Wisconsin solution and Hanks' HEPES buffer for 24 hr appeared essentially normal except for the presence of numerous membrane blebs in the Hanks' HEPES buffer group. Tissue sections of livers preserved in Hanks' HEPES buffer but not in University of Wisconsin solution revealed the presence of extensive amounts of blebs in the sinusoidal lumen and loss of endothelial elements.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Functional and morphological features of isolated hepatocytes preserved in University of Wisconsin solution. 186 Jun 90

Verapamil, a calcium channel blocker, improves myocardial preservation during cold cardioplegia and protects against renal damage during periods of warm and cold ischemia. To determine if verapamil could prevent ischemic damage to livers during and after cold storage, harvested rat livers were flushed with either University of Wisconsin (UW) solution or UW solution with 25 mg/liter verapamil. Twenty rats were used in each group. After 24 hr of storage at 4 degrees C, livers were perfused with oxygenated blood through the portal veins for 2 hr at 37 degrees C and pH 7.4. Liver enzymes, electrolytes, and perfusate flow rate were determined at 30-min intervals. At 90 min of perfusion, the verapamil group of livers had less elevation of AST (110 +/- 17 IU/liter vs 172 +/- 25 IU/liter, P less than 0.05), ALT (115 +/- 21 IU/liter vs 210 +/- 34 IU/liter, P less than 0.05), and LDH (962 +/- 170 IU/liter vs 1452 +/- 253 IU/liter, NS). Verapamil livers produced more bile than controls (6.9 +/- 1.9 microliters/g vs 2.3 +/- 1.7 microliter/g, P less than 0.05) and maintained a higher portal flow rate throughout the perfusion. Both groups showed similar reduction in liver weights after storage (3.9 +/- 0.9% vs 2.8 +/- 0.7%) and required the same amount of bicarbonate for correction of acidosis during perfusion (2.6 +/- 0.2 mM vs 2.8 +/- 0.2 mM). Light microscopic exam after perfusion showed hepatocyte damage in 30% of control livers, but 0% of verapamil livers. We conclude that verapamil-treated rat livers showed less damage and better function upon reperfusion after 24 hr of cold storage. This agent may be clinically useful as an additive to the UW preservation solution for livers.
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PMID:Verapamil improves rat hepatic preservation with UW solution. 205 66

In order to investigate whether or not transferrin is involved in the uptake of 67Ga by inflamed liver (acute inflammatory tissues) the uptake of 67Ga by the liver of mice treated with carbon tetrachloride (CCl4) was studied. The serum GPT value reached its maximum on the 1st day after the CCl4 treatment. The uptake of 67Ga by the liver also reached its maximum on the 1st day after the CCl4 treatment and the amount uptaken into inflamed liver was about 6 times that uptaken into normal liver. On the other hand, the uptake of 125I-transferrin into inflamed liver on the 1st day after CCl4 treatment was only about 1.6 times that into normal liver. Moreover, cold Fe3+ decreased the uptake of 67Ga by normal liver but increased the uptake of 67Ga by inflamed liver. These results show that transferrin plays an important role in the uptake of 67Ga by normal liver but not by inflamed liver, i.e. 67Ga in the transferrin-unbound form is preferentially taken up by inflamed liver.
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PMID:67Ga in transferrin-unbound form is taken up by inflamed liver of mouse treated with CCl4. 208 40

The effect of cold milk drink on selected biochemical and haematological parameters in calves blood during the milk nutrition period was observed in farm conditions, as compared with the current feeding regime. The test group was offered cold sour milk drink (one 1 MKS Laktosan acidulated with addition of 22 ml formic acid to a pH of 4.6) at the temperature of 16 degrees C after four-day-adaption till the calves average age of 61 days. The control group was given MKS Laktosan in the usual way, using the same amount of the drink and time of serving it. During the test the performance was recorded, as well as haemoglobine content, total protein, haematocrit, urea, glucose, cholesterol, transaminase (ALT and AST) activities and alkaline blood reserves. In the studied parameters no significant differences were found between the test and control group (P greater than 0.05). The average daily gains of live weight during the period of milk nutrition was 0.762 kg in the test group and 0.667 kg in the control group.
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PMID:[Determination of the effects of feeding cold soured milk to calves under normal conditions]. 210 Apr 25

To evaluate the epidemiology and incidence of community-acquired pneumonia (CAP) a retrospective study of 573 cases which had been diagnosed during a 3 1/2 year period was carried out. There was a male predominance (2.09/1) with mean age of 53.33 years. The diagnostic delay (days) was 1.5. The mean hospital stay was 13.39 days. The most common underlying disease was COLD (27%). 34% of patients had received previous therapy. The most common clinical features were cough, fever, and mucous sputum. The most common radiological pattern was alveolar (81%). There was increased ESR and moderately high GOT and GPT. The microbiological diagnosis was achieved in 35.4%, with positive sputum culture (mostly pneumococcus) in 26.8% an positive blood culture in 5.9%. Ten patients died (1.7%). The following factors predicted a poor prognosis: age 75 years, underlying disease, bilateral radiological involvement and leukocytosis with neutrophilia.
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PMID:[Community-acquired pneumonia: 573 cases]. 210 56

To assess the validity of determining the origin of plasma lactate from the ratio of lactate and glucose specific activities (SA) during infusion of labeled glucose, normal subjects received infusions of [6-3H]- and [6-14C]glucose for 4 h after a 12 h fast, and, on another day, cold glucose labeled with both tracers during 4-6 h of hyperinsulinemia (approximately 650 microU/ml). Basally, less lactate was derived from plasma glucose when measured with [6-3H]glucose (27 +/- 2%) than with [6-14C]glucose (40 +/- 2%, P less than 0.001). Insulin did not increase the percent of lactate derived from plasma glucose when measured with [6-3H]glucose (29 +/- 2%) but did increase when measured with [6-14C]glucose (60 +/- 4%). The arterialized blood (A) [3H]lactate SA was 30-40% higher (P less than 0.01) than deep venous blood (V) [3H]lactate SA, whereas A and V [14C]lactate SA were similar. During conversion of alanine to lactate with glutamic-pyruvic transaminase (GPT) and lactate dehydrogenase (LDH) in vitro, 32 +/- 2% of 3H in [3-3H]alanine was found in water and 68 +/- 2% in lactate. During infusion of [6-3H]- and [6-14C]glucose, the ratio of [14C]alanine to lactate SA (0.88 +/- 0.05) was less than the ratio of [3H]alanine to lactate SA (0.31 +/- 0.03, P less than 0.001). In conclusion 1) loss of 3H relative to 14C from position 6 in glucose occurs during lactate formation in extrahepatic tissues possibly due to the GPT reaction (alanine conversion to pyruvate), and 2) even under supraphysiologic hyperinsulinemic conditions not all of plasma lactate originates from plasma glucose.
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PMID:Measurement of lactate formation from glucose using [6-3H]- and [6-14C]glucose in humans. 220 8

In hepatic preservation by simple perfusion and hypothermic storage, a portal and hepatic washout before revascularization would avoid receptor hyperkaliema. In this report we study the effectiveness of this washout with Haemaccel at room temperature. Large-White pigs were used and eight livers were perfused "in situ" via the portal wein with Hartmann's solution containing 10,000 IU of heparin at 4 degrees C, and afterwards, via portal and arterial routes with C2 solution at 4 degrees C. After a cold ischemia time of less than 31/2 hours a liver washout via the portal vein and hepatic artery with Haemaccel before portal revascularization was done. The high concentrations of glucose, K+, GOT, GPT and LDH in the effluents obtained during the washout are attributed to Haemaccel hyperosmolarity. A portal and arterial hepatic washout associated with free drainage of the first 50-100 ml of portal venous blood after hepatic portal revascularization through the infrahepatic inferior vena cava (IH-IVC), prevents hyperkaliemia from occurring after a portal and arterial revascularization in the orthotopic liver transplant (OLT) in pigs.
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PMID:Washout of the pig liver with Haemaccel after hypothermic preservation. 237 95

The activities of alanine-, aspartate- and branched-chain amino-acid transaminases, glutamine synthetase, glutamate dehydrogenase and adenylate deaminase in white adipose tissue of adult male rats have been determined in animals submitted to 12-h cold exposure (4 degrees C) or to 24-h food deprivation. Starvation resulted in small changes in glutamate dehydrogenase and alanine transaminase when expressed per unit of protein weight, inducing an increase in branched-chain amino-acid transaminase and glutamine synthetase. Cold exposure showed the same effects as starvation with respect to glutamate dehydrogenase and alanine transaminase, but induced increases in glutamine synthetase and aspartate transaminase. It is concluded that starvation increases the handling of some amino acids by white adipose tissue and the detoxification of the ammonia thus evolved. The changes observed suggest a different pattern of amino-acid metabolism enzyme changes with either cold or starvation.
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PMID:Amino-acid metabolism enzyme activities in rat white adipose tissue. 243 May 32

A review of the relevant literature strongly suggests that several medical and laser treatments presently used in glaucoma therapy, and other potential treatments under investigation, reduce IOP, at least, in part, by stimulating endogenous PG synthesis. There are four lines of evidence leading to this conclusion. (1) PGs are potent ocular hypotensive agents. (2) Adrenergic and cholinergic agonists stimulate PG synthesis by ocular tissues in vitro. (3) Epinephrine and ALT cause elevation of PG levels in the aqueous humor in vivo. (4) PG synthesis inhibitors such as indomethacin or flurbiprofen block, or partially inhibit, the reduction of IOP produced by epinephrine, para-aminoclonidine, forskolin, vanadate, verapamil, arachidonic acid, and ALT in rabbits, cats, monkeys, and/or humans. This last finding has great clinical importance with regard to the efficacy of such treatment modalities as epinephrine and ALT, since it indicates that these modalities may be less effective in reducing IOP in glaucoma patients who are taking systemic PG synthesis inhibitors - such as aspirin or indomethacin - for arthritis, cerebrovascular disease, arteriosclerotic coronary vascular disease, headache, or the common cold. Other surgical procedures for glaucoma such as cyclocryotherapy or other cyclodestructive procedures may also reduce IOP in part by stimulating local PG synthesis. Since PGs are produced in various ocular tissues and some of these PGs are highly potent ocular hypotensive agents, their potential role in mediating the reduction of IOP produced by medical or surgical modalities of glaucoma therapy must always be considered. Furthermore, these considerations support the concept that topical application of an appropriately selected PG, or its derivative, may provide a more direct means of lowering IOP than some of the currently used procedures or therapeutic agents.
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PMID:The role of endogenous prostaglandins in clinically-used and investigational glaucoma therapy. 250 30

A recent study from our laboratory revealed that cotreating mice with the alpha-adrenoreceptor antagonists phentolamine and idazoxan markedly diminished bromobenzene-induced hepatotoxicity. Subsequent studies also revealed that such cotreatment does not alter the pharmacokinetic disposition of bromobenzene in mice nor its bioactivation to reactive metabolites. In the present study, the possible role of hypothermia in the phentolamine antagonism of bromobenzene-induced hepatotoxicity was investigated. Bromobenzene alone caused a significant, dose-related hypothermia. The high dosage regimen (10 mg/kg per dose) of phentolamine or idazoxan that had been found to be hepatoprotective in earlier studies potentiated this hypothermia and more than doubled the net decrease in core body temperature experienced by the animals. Placing mice receiving bromobenzene in an environment with an ambient temperature of 10 degrees C likewise increased the hypothermia experienced by animals receiving bromobenzene. The magnitude of the net change in core body temperature elicited by exposure to cold was similar to but slightly less than the net change produced by cotreatment with either alpha-adrenoreceptor antagonist and the magnitude of the hepatoprotection this procedure provided against bromobenzene hepatotoxicity was equivalent to that observed with phentolamine cotreatment. In contrast, a lower dosage regimen of either adrenoreceptor antagonist (2.5 mg/kg per dose) resulted in no additional hypothermia yet still produced a near maximal antagonism of bromobenzene-induced hepatotoxicity. Further, increasing the ambient temperature to 30 degrees C completely reversed the phentolamine-induced (10 mg/kg per dose) increase in hypothermia, but did not affect phentolamine's antagonism of the bromobenzene-induced changes in hepatic glutathione levels, serum alanine aminotransferase activity, or 24-hr mortality. Therefore, we conclude that while the hepatoprotective intervention of phentolamine can be mimicked by an exposure to cold that results in hypothermia, it is clear that alpha-adrenergic antagonists diminish the hepatotoxicity induced by bromobenzene by a mechanism that is independent of hypothermia.
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PMID:Antagonism of bromobenzene-induced hepatotoxicity by the alpha-adrenoreceptor blocking agents phentolamine and idazoxan: role of hypothermia. 256 19


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