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)

Therapy of renal anaemia in haemodialysis patients with chronic renal failure by application of recombinant human erythropoietin leads to an increase of the haematocrit. Rejuvenation of the erythrocyte population results in a decrease of the median density (D50), an increase of cell age-dependent enzyme activities, such as aspartate aminotransferase, and elevated concentrations of purine nucleotides in the erythrocytes. After density gradient separation of erythrocyte populations into cell age-dependent fractions, the concentrations of adenosine-5'-triphosphate, guanosine-5'-triphosphate and guanosine-5'-diphosphate were be found to be elevated by 25-100% in all cell fractions from haemodialysis patients, compared with a healthy control group. Therapy of haemodialysis patients with recombinant human erythropoietin leads to further increase (65%) of ATP in the younger (low density) cells, but not in the older (high density) cells. The elevated concentrations of ATP and total adenine nucleotides during recombinant human erythropoietin therapy possibly result in improved deformability of erythrocytes. The data point to an enhancement of the proportion of younger erythrocytes, but not to an improvement of the reduced life span of erythrocytes of haemodialysis patients during therapy with recombinant human erythropoietin.
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PMID:Changed purine nucleotide concentrations and enzyme activities in erythrocytes of haemodialysis patients undergoing erythropoietin therapy. 144 58

The objective of this study was to determine the probabilities of specific morbid events or death among patients with end-stage renal disease (ESRD) treated by hemodialysis. A prospective cohort study was performed between March 1988 and September 1989 in 18 hemodialysis centers in 13 Canadian cities, representing about one third of the hemodialysis population in Canada. The inception cohort consisted of 496 patients entering hemodialysis who had survived 1 month. The few new hemodialysis patients who received erythropoietin (EPO) in the last 3 months of the study were excluded. Survival curves were compared using the Cox proportional hazards regression model. Older age and history of cardiovascular disease were independently associated with a greater probability of death. Age and history of cardiovascular disease were also associated with a greater probability of nonfatal circulatory events (myocardial infarction, angina requiring hospitalization, or stroke), while a serum albumin level less than or equal to 30 g/L (3.0 g dL) was associated with an increased probability of pulmonary edema. The probability of surviving 12 months without receiving a blood transfusion was 47.2% for males and 27.5% for females. The incidence of non-A, non-B hepatitis, as estimated by unexplained elevations in serum aspartate aminotransferase (AST) values, was not different between patients receiving and not receiving blood transfusions. The probability of hospitalization for any cause was greater for patients with grafts for vascular access than for those with fistulae, for those with a history of cardiovascular disease, for those with a serum albumin level less than or equal to 30 g/L, and for those with renal disease due to diabetes or vascular disease. Hospitalization due to circulatory disease was more likely among those with a history of cardiovascular disease and among those with a lower serum albumin level. Hospitalization for infectious disease was more likely among those with a lower serum albumin level and less likely among those with a fistula for vascular access. Among all patients receiving hemodialysis treatment for more than 6 months, there were 14.8 hospital days per year.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Canadian Hemodialysis Morbidity Study. 155 66

Renal anemia is the result of reduced erythropoietin (EPO) biosynthesis in the diseased kidney and also in part the result of a reduced life span of red blood cells (RBCs). An increase in density and a decrease in enzyme equipment (aspartate aminotransferase; GOT) of RBCs reflect cell age. In the following study, the density distribution (median density D50; determined by Percoll density gradients) and GOT activities of RBCs were measured in patients on acetate (HDA; n = 15) and bicarbonate (HDB; n = 51) hemodialysis. Hemoglobin (Hb) concentrations were: in the HDB group, 9.1 +/- 3.4 g/dl; in the HDA group, 6.2 +/- 1.2 g/dl, and, in a control (C) group of healthy persons, 14.0 +/- 1.5 g/dl. 14 HDB patients with severe anemia received EPO therapy during 1 year. D50 were found as follows: group C, 1.0674 +/- 0.0016 g/ml; HDB, 1.0674 +/- 0.0015 g/ml, and HDA, 1.0660 +/- 0.0012 g/ml (HDA vs. group C: p less than 0.05; HDA vs. HDB: p less than 0.05. D50 were elevated in the subgroups of HDA and HDB patients with severe anemia (Hb less than 8 g/dl). During activated erythropoiesis by EPO therapy, D50 decreased from 1.06739 +/- 0.0015 to 1.0656 +/- 0.0014 g/ml. The GOT activities in RBCs demonstrated a rejuvenation of the RBC population in the HDB group (6.4 +/- 2.5 U/g Hb) and HDA group (5.9 +/- 3.1 U/g Hb) compared to group C (3.9 +/- 1.3 U/g Hb).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Red blood cell density distribution in uremic patients on acetate and bicarbonate hemodialysis. 196 10

The aim of this study was to evaluate the effect of treatment with subcutaneous injections of recombinant human erythropoietin (rhEpo), 20-40 IU kg-1 body weight, 3 times a week, on resting blood pressure, blood pressure response during submaximal exercise, some haematological parameters, and subjective side-effects in 15 healthy male subjects. RhEpo increased both haemoglobin (Hb) concentration and haematocrit (Hct) significantly, the values for Hb being 152 +/- 4.2 g l-1 before treatment and 169 +/- 9.3 g l-1 (mean values +/- SD) after 6 weeks of rhEpo treatment (P less than 0.001). The corresponding values for Hct were 44.5 +/- 1.5% and 49.7 +/- 1.9% (P less than 0.001), respectively. The systolic and diastolic blood pressure values at rest were unchanged after rhEpo treatment. A marked increase in systolic blood pressure was observed during submaximal exercise at 200 W, the initial and final values being 177 +/- 14.2 mmHg and 191 +/- 19.5 mmHg (P less than 0.01), respectively. Heart rate during exercise at 200 W was significantly lower after rhEpo treatment than before it: 144 +/- 15 beats min-1 compared to 136 +/- 8 beats min-1 (P less than 0.001). The leucocyte count remained unchanged after rhEpo treatment, but there was a significant decrease (P less than 0.05) in the number of lymphocytes. Reticulocyte and platelet counts were unchanged. Serum (S) ferritin decreased from 87.3 +/- 41.8 mmol l-1 to 59.3 +/- 27.8 mmol l-1 after rhEpo treatment (P less than 0.001). Serum-Na, S-K, S-Ca, S-creatinine, S-bilirubin, S-aspartate aminotransferase (ASAT), S-alanine aminotransferase (ALAT), and S-lactate dehydrogenase (LD) were unchanged after rhEpo treatment. No subjective side-effects were reported. In conclusion, low doses of rhEpo increased Hb levels and Hct by more than 10% after 6 weeks. Blood pressure at rest was unchanged, but rhEpo induced a markedly accentuated blood pressure reaction during exercise. A minor decrease in the lymphocyte count was observed, but electrolyte and creatinine levels remained unchanged after rhEpo treatment.
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PMID:Effect of recombinant human erythropoietin treatment on blood pressure and some haematological parameters in healthy men. 199 37

Renal anemia is caused in part by a reduced life span of red blood cells (RBCs) and by reduced erythropoietin biosynthesis in the damaged kidney. The RBC age can be determined by density gradient centrifugation and estimation of cell-age-dependent enzyme activities, as aspartate aminotransferase. The RBC age distribution influences the median density (D50) of RBCs and the blood rheology in coherence with the hematocrit. In our study, the median density was determined by Percoll density gradient centrifugation in 18 healthy subjects (D50 = 1.0674 +/- 0.0016 g/ml) and in 14 hemodialysis patients (D50 = 1.0674 +/- 0.0016 g/ml in the course of recombinant human erythropoietin (rhEPO) therapy. During the first 4 weeks of therapy, a strong rejuvenation of RBCs was observed whereby the D50 reached a minimum after 2 weeks (D50 = 1.0655 +/- 0.0022 g/ml; p less than 0.05 vs. value before therapy) and a steady state after 4 weeks (D50 = 1.0658 +/- 0.0013 g/ml; p less than 0.1 vs. value before therapy). In 5 of the patients with elevated plasma parathyroid hormone (i-PTH) concentrations greater than 10 pmol/l, a significantly (p less than 0.05) reduced amount of younger RBCs (D50 = 1.0675 +/- 0.0016 g/ml) was observed in the first 2 weeks of rhEPO therapy as compared to patients with i-PTH less than 10 pmol/l (D50 = 1.0677 +/- 0.0019 g/ml). Thus, erythropoiesis in the early phase of rhEPO therapy is strongly influenced by elevated plasma i-PTH concentrations. Therefore, a gradual increase in rhEPO doses is preferable before therapy at elevated doses with an uncontrolled increase in RBC amount.
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PMID:Erythropoiesis and erythrocyte age distribution in hemodialysis patients undergoing erythropoietin therapy. 224 89

It has been shown previously that erythropoietin expression in vitro by hepatoma cells increases in response to hypoxia. To verify whether hypoxia of the tumor might result in hepatic release of erythropoietin in vivo, serum erythropoietin concentrations were measured immunoenzymatically in 12 patients (5 women, 7 men) who underwent transarterial chemoembolization for hepatocellular carcinoma. Peripheral blood samples were collected at baseline, and after 6 hours and 1, 2, 3, and 7 days after the procedure. In a second set of experiments, performed in three male patients also undergoing chemoembolization for hepatocellular carcinoma, paired blood samples were collected after catheterization of the hepatic veins and of the right antecubital vein. None of the patients had erythrocytosis. In comparison with a baseline mean value +/- SEM of 100.6 +/- 12.6 micrograms/L, serum erythropoietin concentrations were the following; +6 hours, 55.4 +/- 18.0 (P < .001); +1 day, 102.4 +/- 24.7 (P = NS), +2 days, 183.0 +/- 31.1 (P < .05); +3 days, 155.0 +/- 26.0 (P < .05); +7 days, 153.3 +/- 27.4 (P < .05) (matched Student's t-test). The ratio of hepatic vein/antecubital vein serum erythropoietin concentrations increased from 0.85 at baseline to 1.30 at +2 days, paralleling the increase of aspartate transaminase (r = .914, P < .005). After chemoembolization, no correlation was found between serum erythropoietin and alpha-1-fetoprotein concentrations. The concentration of the latter, stable initially, decreased 7 days after the procedure.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hepatic release of erythropoietin induced by transarterial chemoembolization in patients with hepatocellular carcinoma. 760 7

There is little quantitative information about the influence of weight change before and during hemodialysis on the concentration of proteins, lipoproteins, lipids, enzymes and other dialysis-resistant compounds in blood. We studied the concentration of 12 such compounds before and at the end of high-flux hemodialyses, 1.5 h after the start and 1, 2 and 3 h postdialysis and have developed formulae for roughly predicting the near steady-state 2-3 h postdialysis concentration. For hemoglobin, albumin, total protein and total cholesterol, the relationship of mean change in concentration to weight loss in groups was linear, and the % increase in concentration correlation correlated with % weight reduction (r = 0.64-0.81 and p = 0.002-0.0002). Correlations with ultrafiltration rate were comparable. By 3 h postdialysis values were relatively stable; the average fall in concentration for theses 4 compounds was 25% from end dialysis. The simplest formula we found which roughly predicts the % increase in concentration from predialysis to 3 h postdialysis is to multiply the % loss in body weight in kg during dialysis by 3.3. More accurate formulae were developed using combined and specific regression equations relating % weight loss during dialysis to % concentration rise. Mean values for alkaline phosphatase, triglycerides, lipoprotein (a), high-density lipoprotein cholesterol, calcium, apolipoprotein B, bilirubin and aspartate aminotransferase also rose appreciably during dialysis with significant increases for the first five. With major interdialytic weight gain, the reduction in predialysis concentrations of hemoglobin and cholesterol may be enough to inappropriately modify treatment decisions about anemia (e.g. erythropoietin) or hypercholesterolemia, and to cause false concern about the concentration of albumin for nutrition and prognosis. Major weight gain may also contribute to concentration changes in numerous other compounds resistant to dialysis.
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PMID:Prediction of reduction in predialysis concentrations due to interdialysis weight gain. 853 51

Augmentation of gamma-gene synthesis by using recombinant human erythropoietin (r-Hu-EPO) represents a new approach to the therapy of beta-thalassemia. A prospective study was conducted in 26 transfusion-dependent beta-thalassemia major patients. r-Hu-EPO (Eprex/Cilag, Switzerland) was given to the patients at an initial dose of 500 IU/kg s.c. 3 times a week for at least 2 months during which no transfusion was applied. A sustained hemoglobin (Hb) level greater than 8 g/dl was considered as a response to EPO treatment. In the patients whose Hb levels remained under 8 g/dl or did not increase in comparison to pretreatment levels within 4 weeks, the dose of r-Hu-EPO was increased to 1,000 IU/kg 3 times a week and applied for another 4 weeks. Only 16 cases also received oral iron supplementation. The whole blood and reticulocyte counts, the biochemical tests including BUN, creatinine, AST, ALT, alkaline phosphatase and ferritin were done and the percentages of HbF and F cells were analyzed regularly. At the end of the 2nd month, 6 cases qualified to continue with the trial. At the end of the 6th month, r-Hu-EPO therapy was ceased in 3 cases of the 6 since their Hb levels had decreased below 7 g/dl. Only 3 cases (11.5%) continued with the r-Hu-EPO therapy without transfusion for up to 12 months. In conclusion, r-Hu-EPO may be useful in some selected transfusion-dependent patients with beta-thalassemia major. Selection criteria should include a mild beta-genotype of coinheritance of alpha-thalassemia, splenectomy and pretreatment reticulocyte response of the patients as well as the patients' compliance.
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PMID:Recombinant erythropoietin trial in children with transfusion-dependent homozygous beta-thalassemia. 940 97

This study was constructed to investigate the relationship between renal anaemia and erythropoietin (EPO) concentrations in chronic renal failure (CRF) patients and to evaluate the possible role of the liver. Serum EPO levels were measured in blood samples from 20 CRF patients on hemodialysis (HD), 20 liver cirrhosis (LC) patients, 20 patients having both CRF and LC and undergoing HD, and 20 normal control subjects. Blood cell counts, iron indices (iron, total iron-binding capacity (TIBC) and ferritin), renal function (blood urea nitrogen (BUN) and creatinine), hepatic function (ALT, AST, ALP and bilirubin) investigations were carried out for all the subjects enrolled in this study. CRF patients without LC had serum EPO concentration of 6.21 +/- 0.53 mU/ml (mean +/- SE), which was significantly higher than that in patients having both CRF and LC (4.32 +/- 0.52) (p < 0.01). Both groups showed significantly lower values than the controls (12.75 +/- 0.70) (p < 0.001). LC patients with intact kidneys had significantly higher EPO level (22.70 +/- 1.70) (p < 0.001). No correlation was found between EPO level and any of the hematologic or iron indices.
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PMID:Assessment of erythropoietin levels and some iron indices in chronic renal failure and liver cirrhosis patients. 1068 46

The cytokine erythropoietin protects the heart from ischaemic injury, in part by preventing apoptosis. But appropriate dose of erythropoietin for the protection of injured heart has not been studied. While we were researching the cardiac protective effects of erythropoietin in acute myocardial infarction, we experienced two cases of accidental nearly ten times overdose administration of erythropoietin up to 318,000 units instead of 33,000 units on the second day of three scheduled days of treatment. So a total of 384,000 units of erythropoietin were administered during three days. In case 1, the ALT level soared up to 386 U/l on the second day of administration and decreased slowly. It was back to normal state 3 months later. The AST level increased slowly up to 391 U/l and normalized 3 months later. Haemoglobin level was elevated up to 15.7 g/dl (14.7 g/dl at admission) and, 3 months later, normalized to 14.8 g/dl. In case 2, the ALT level was elevated up to 98 U/l on the second day of administration and decreased slowly. Three months later, the ALT level was normalized. The AST level also increased slowly up to 71 U/l and normalized 3 months later. Haemoglobin level was elevated up to 15.6 g/dl (13.8 g/dl at admission) and, 3 months later, normalized to 13.6 g/dl. In these two cases reported, these patients, even after massive overdose, tolerated it relatively well and the only side-effects we found were elevated liver enzyme and haemoglobin levels.
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PMID:Accidental ten times overdose administration of recombinant human erythropoietin (rh-EPO) up to 318,000 units a day in acute myocardial infarction: report of two cases. 1644 99


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