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)

Iron overload is found clinically in such conditions as hemochromatosis and sideroblastic anemia, and after long term repeated transfusion in aplastic anemia. An animal model of iron overload was successfully developed in rats and rabbits by repeated intraperitoneal injections of ferric nitrilotriacetate (Fe3+-NTA). This procedure induced a diabetic state with hyperglycemia, ketonemia, glycosuria and ketonuria. Blood venesection on these rats reduced the iron load in the liver and pancreas, and ameliorated the general diabetic symptoms. A single injection of Fe3+-NTA in rats induced a temporary elevation in plasma iron concentration, lipid peroxidation in the perfused liver homogenate expressed by malondialdehyde (MDA) formation, blood GOT, GPT, ALP and gamma-GTP sequentially. Fe3+-NTA uptake in the liver caused membrane lipid peroxidation, and subsequently produced a transit liberation of liver cell enzymes, although the incorporated liver Fe3+-NTA was only 1% of the injected dosage (7.5 mg iron/kg BW) at 3 hr after injection. The direct toxic effect of Fe3+-NTA to living cells was examined using cultured normal rat liver parenchymal cells (RL-34). Marked cytolysis was found in cells exposed to more than 25 micrograms of iron through Fe3+-NTA/ml. At 50 micrograms iron of Fe3+-NTA/ml, most cells were lethally injured and the remaining cells were piled up and aggregated at 15 days. They grew on soft agar culture, and when inoculated subcutaneously to five newly born rats a subcutaneous tumor developed in all animals within three weeks. Lung metastases were found in three of five inoculated rats. A spin trapping technique with electron spin resonance (ESR) on Fe3+-NTA employing 5, 5-dimethyl-l-pyrroline-N-oxide (DMPO) yielded a spin adduct with three doublets (DMPO-Z) which corresponded to singlet oxygen. By ESR in the presence of H2O2, the Fe3+-NTA solution strongly generated hydroxyl radical. The production of active oxygen species by Fe3+-NTA solution may explain the toxicity and carcinogenicity of Fe3+-NTA. The majority of stainable iron in the iron overloaded tissue was hemosiderin (Hs). We tried to purify the Hs from multi-transfused human spleen by the method of Weir et al. The purified Hs did not show a DMPO-OH adducts in the presence of H2O2 and DMPO on ESR measurement. The Hs iron was solubilized with several biological ligands in an acidic state in the presence of a reducing reagent like glutathione. Solubilized Hs iron produced iron chelate complexes which resulted in OH radicals production in the presence of H2O2 in acidic conditions below pH 5.5.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Pathogenesis and mechanism of iron overload: ferric nitrilotriacetate, hemosiderin, active oxygen, and carcinogenesis]. 268 76

The author found marked differences in isoferritin patterns between the ferritins of hepatocytes and Kupffer cells in normal adult rats of the Wistar strain. This fact was considered to be a phenomenon of the heterogeneities recognized widely between these two cells from the embryological, morphological and physiological viewpoint. Accordingly, the iron metabolism of hepatocytes and Kupffer cells was studied separately in cells obtained from the livers of rats which had received iron dextran previously. Especially, the concentrations of iron and ferritin and isoferritin patterns in these cells were followed by rats given the different amounts of iron (25, 50, 150 and 200 mg given to the rats) 48 hours previously and also in time course experiment (2, 10 and 30 days) by the rats given 100 mg iron. Serum iron concentration and TIBC were increased markedly 48 hours after administrations of more than 100 mg iron. However RBC count, Hb concentration and Ht showed no changes related to iron administration. In the conditions settled by the author, there were no serious increases in the serum enzyme activities of GOT, GPT, LDH and gamma-GTP. Isoferritin patterns obtained from hepatocytes and Kupffer cells maintained the same characteristics except for a slight shift to the alkaline side in each peak with the respective controls in the rats receiving 100 mg iron. In this experiment, ferritin and iron concentrations in hepatocytes and whole liver showed similarly positive increases in a dose dependent manner, while the concentrations of both compounds in Kupffer cells arrived at their maximums with 100 mg iron and were decreased by larger administrations of iron. In the time course experiment, ferritin concentration increased in hepatocytes, Kupffer cells and whole liver, and arrived at the maximum at 2 days in Kupffer cells and at 10 days in the other two specimens. However the iron concentrations reached their maximums at 2 days respectively and returned almost to the control levels afterwards in all specimens. These results indicated the characteristics of iron metabolism in two kinds of cells, and suggested the differences in the structure and the metabolism of their ferritins.
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PMID:[Iron metabolism in the hepatocytes and Kupffer cells of rats receiving large amounts of iron dextran]. 275 89

The effects of recombinant human interleukin-1 beta (rhIL-1 beta) on various serum constituents were studied following subcutaneous injection (12.5 or 125 micrograms/kg) in female Wistar rats. Protein electrophoresis and the determination of the serum concentrations of carboxypeptidase N (CPN), aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, aldolase, total proteins, iron, urea, creatinine, and several amino acids were performed 12, 24, and 72 hr after injection. With both doses of rhIL-1 beta, iron, albumin, CPN, and lysine were significantly decreased whereas alpha 2-globulin, urea, and creatinine were significantly increased 12 hr after administration. Iron and CPN were still low after 24 hr but returned to normal levels after 72 hr. With the higher dose of rhIL-1 beta, only alanine and phenylalanine levels were increased after 12 and 72 hr, taurine after 12 hr, and methionine after 24 hr. There were no biochemical or histological signs of hepatotoxicity. The findings indicate that rhIL-1 beta produces a reversible alteration of various biochemical plasma constituents without any apparent signs of cytotoxicity. Moreover, the decrease in CPN observed may influence the degradation of inflammatory peptides.
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PMID:Recombinant human interleukin-1 beta decreases serum carboxypeptidase N and modifies serum amino acid concentrations in rats. 278 29

Acute iron intoxication is a frequent, sometimes life-threatening, form of poisoning. Present therapy, in severe cases, includes oral and intravenous administration of the potent iron chelator, deferoxamine. Unfortunately, high dose intravenous deferoxamine causes acute hypotension additive with that engendered by the iron poisoning itself. To obviate this problem, we have covalently attached deferoxamine to high molecular weight carbohydrates such as dextran and hydroxyethyl starch. These macromolecular forms of deferoxamine do not cause detectable decreases in blood pressure of experimental animals, even when administered intravenously in very large doses, and persist in circulation much longer than the free drug. These novel iron-chelating substances, but not deferoxamine itself, will prevent mortality from otherwise lethal doses of iron administered to mice either orally or intraperitoneally. Further reflecting this enhanced therapeutic efficacy, the high molecular weight iron chelators also abrogate iron-mediated hepatotoxicity, suppressing the release of alanine aminotransferase. We conclude that high molecular weight derivatives of deferoxamine hold promise for the effective therapy of acute iron intoxication and may also be useful in other clinical circumstances in which control of free, reactive iron is therapeutically desirable.
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PMID:Acute iron poisoning. Rescue with macromolecular chelators. 279 68

Three hundred and seventy-three female and 213 male nonalcoholic subjects, aged 60-100 y, who had participated in a nutritional status survey of elderly people in the Boston area were grouped according to usual alcohol intake: 0-4, 5-14, or 15+ g/d. The age- and sex-adjusted mean intake of calories, fat, protein, carbohydrate, and 10 micronutrients and the mean levels of 14 nutrient and 22 nonnutrient biochemical indices were compared for the three categories of alcohol intake. The mean micronutrient intakes were also adjusted for total caloric intake and the mean nutrient biochemical concentrations were also adjusted for the corresponding nutrient intakes. The results suggest that caloric intake and blood concentrations of retinol, iron, ferritin, HDL cholesterol, AST, and ALT increased with increasing alcohol intake whereas folate and phosphorus intakes and blood measures of riboflavin, copper, zinc, urea nitrogen, and creatinine decreased with increasing alcohol intake.
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PMID:Moderate alcohol intake and nutritional status in nonalcoholic elderly subjects. 280 94

Metabolic and hormonal responses of eight adult male collared peccaries (Tayassu tajacu) to an ad libitum diet intake, or 25% of an ad libitum intake, were examined. Blood samples for hematological, serum-biochemical and hormonal profiles were collected at three week intervals during the nine week experiment starting 4 August 1983. Males fed on the restricted diet lost an average of 26% of their body weight during the trial, compared to a slight weight gain for those fed ad libitum. Characteristics of the red and white blood cell populations were not influenced by diet intake, with the exception of mean corpuscular volume, which was consistently lower amongst males fed on the restricted diet. Restricted food intake resulted in significantly elevated serum values for urea nitrogen, urea nitrogen:creatinine, urea index, alpha globulin:beta globulin, gamma globulin:albumin, nonesterified fatty acids, alkaline phosphatase and lactate dehydrogenase isozymes (LD1 and LD2). Restricted food intake resulted in significantly lowered serum values for total alpha globulin, alpha-1 globulin, total beta globulin, beta-1 globulin, beta-2 globulin, glucose, triglycerides, calcium, magnesium, sodium, chloride, copper and triiodothyronine. Serum levels of creatinine, total protein, albumin, alpha-2 globulin, uric acid, total bilirubin, cholesterol, aspartate aminotransferase, alanine aminotransferase, gamma glutamyltransferase, lactate dehydrogenase, phosphorus, calcium:phosphorus, potassium, iron, zinc and thyroxine were unaffected by diet intake level. Semen evaluation indicated spermatogenesis was not affected by dietary restriction despite reductions in scrotal circumference and ejaculate gel volume. Serum testosterone levels were significantly lower among males fed on the restricted diet after nine weeks. These data suggest male libido might be depressed during poor range conditions, while maintenance of spermatogenesis might permit them to take immediate advantage of improved range conditions. Blood analysis of metabolic and hormonal function can provide useful information for predicting the adult male's nutritional and reproductive condition.
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PMID:Physiological responses of the adult male collared peccary, Tayassu tajacu (Tayassuidae), to severe dietary restriction. 286 11

1. An automated blood serum chemistry analytical system designed for human usage was employed to establish the levels of 26 different components present in sera obtained from various experimental groups of channel catfish. 2. Comparisons of samples from feral and commercial production pond fish during warm months indicated statistically significant differences in the serum levels of sodium, CO2, urea nitrogen, direct bilirubin, cholesterol, creatinine and protein. 3. Laboratory acclimated and production pond fish exhibited differences in serum electrolytes (sodium, potassium, chloride, phosphorus), serum metabolites (urea nitrogen, creatinine, triglycerides), serum enzymes [gamma-glutamyl transferase, glutamate-oxaloacetate transaminase (GOT), lactate dehydrogenase (LDH), alkaline phosphatase, and amylase], and serum iron. 4. Seasonal (temperature?) differences in production pond fish were noted for 12 serum components including potassium, magnesium, CO2, glucose, creatinine, albumin, iron, alkaline phosphatase, and glutamate-pyruvate transaminase (GPT). 5. Comparisons of samples obtained from laboratory-acclimated fish before and 18 hours after acute handling and transport stress revealed significant differences in only three serum parameters: glucose, LDH, and creatine phosphokinase (CPK). 6. These studies suggest that "normal" values established by any method of sera analysis may be different in the same species depending on the diet, season, and presence of environmental stressors.
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PMID:Blood serum chemistry measurements of normal and acutely stressed channel catfish. 289 33

We determined the recovery time courses of muscle oxidases and liver enzymes after iron administration to iron-deficient rats. Female 21-day-old Sprague-Dawley rats were fed an iron-deficient (3 mg Fe/kg) or a control (50 mg Fe/kg) diet for 3 wk. The deficient rats were then injected with 50 mg Fe as iron dextran/kg body wt (Fe-T) or saline (Fe-) intraperitoneally. At 16, 40, 64, 112, and 180 h after injection, blood and tissue samples were taken to determine hemoglobin concentration (Hb), gastrocnemius glycolytic enzyme and oxidase activities, and liver amino acid catabolic enzyme activities. No changes were observed in any parameter across time in either the Fe- or control (Fe+) rats. In the Fe- rats, Hb, pyruvate + malate (P + M), 2-oxoglutarate (2-OG), and succinate oxidases (SO) were depressed to 33, 36, 44, and 7% of Fe+, respectively (P less than 0.05). At 16 h, Fe-T values were significantly elevated compared with Fe- rats but still only 40, 48, 55 and 10% of controls, respectively. Glutamate dehydrogenase (GDH) and alanine aminotransferase (AAT) of Fe- rats were 174 and 134% of control values (P less than 0.05). By the 180-h time point, Hb, P + M, 2-OG, and SO of Fe-T rats increased to 99, 84, 89, and 43% of Fe+ values, whereas GDH and AAT activities declined to 111 and 106% of controls. Glycolytic enzymes showed no systematic changes with iron deficiency or after iron administration.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reciprocal changes of muscle oxidases and liver enzymes with recovery from iron deficiency. 292 6

Seventy-four patients with beta-thalassemia major were studied to test the hypothesis that a deficiency of protein C (PC) and antithrombin III (AT III), both antithrombotic proteins, could contribute to the pathogenesis of CNS thromboembolic lesions. In 70 patients, PC levels were found to be significantly lower than normal, whereas AT III activity was found to be lower only in 41 patients. The lowest values of PC and AT III were found in older splenectomized patients, a low PC value only was found in chronic hepatitis patients. Prothrombin time and fibrinogen were found to be particularly abnormal in patients with chronic hepatitis and without spleen. A relatively poor correlation was observed between PC and AT III (p less than 0.02). PC correlated with age (p less than 0.001), transfusional iron (p less than 0.001) and ferritin (p less than 0.001). It also correlated with serum albumin (p less than 0.001), prothrombin time (p less than 0.001) and fibrinogen (p less than 0.02) and with serum transaminases (GPT) (p less than 0.001). The same indexes correlated less significantly with AT III activity. Nevertheless, only 2 of our patients had CNS thromboembolic complications. It is probable that low clotting factors, hyperfibrinolysis and thrombocytopenia (which are common in chronic liver disease) could have the opposite effect on hemostasis from that of low levels of anticoagulant proteins such as PC and AT III.
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PMID:Protein C and antithrombin III in polytransfused thalassemic patients. 310 18

The relationship between the number of units of blood transfused and indicators of iron status in 37 patients with sickle cell anaemia (Hb SS), SC disease (Hb SC) or S beta-thalassaemia has been studied. The correlation coefficient between serum ferritin and the number of units transfused was good (r = 0.86), provided that ferritin samples taken within one week following a crisis were excluded. The relationship of transfusion history to serum ferritin in the steady state showed a similar relationship to that previously observed for other multiply transfused patients. The serum ferritin taken within 7 days of a painful crisis was significantly greater than the serum ferritin from the same patients in the steady state (p less than 0.025). The serum alanine transaminase did not rise as consistently as the serum ferritin during crises; it correlated with the serum ferritin but not the transfusion burden in the steady state. Transferrin iron saturation correlated less clearly with transfusion history than serum ferritin (r = 0.62). Patients who had received exchange transfusions were less likely to be iron-overloaded (ferritin increment per unit of blood = 9.9 +/- 3.8 micrograms/l) than patients who had received an equivalent number of units by conventional transfusion (ferritin increment per unit of blood transfused = 25.1 +/- 2.42 micrograms/l).
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PMID:Transfusion and exchange transfusion in sickle cell anaemias, with particular reference to iron metabolism. 312 Apr 72


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