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)

Stroma-free hemoglobin (SFH) is advocated as an oxygen-transporting resuscitation solution. Hemoglobin has been shown to enhance endotoxin lethality when given intraperitoneally. It is possible that SFH could interact with endotoxin when used as an oxygen-transporting resuscitation system for trauma victims with contaminating wounds. To assess the effects of these two agents when given intravascularly, rabbits were infused with SFH (1.75 gm/kg) or albumin (controls; 1.75 gm/kg) with and without endotoxin. Two doses of endotoxin were used. At 14.5 ng/kg of Salmonella enteritidis endotoxin, no effect was seen in the albumin group. However, 50% of the hemoglobin group died. At 14.5 micrograms/kg, the albumin group showed hematologic alterations, but all animals lived. All SFH-treated animals died at the higher endotoxin dose. SFH alone caused cardiac abnormalities (bradycardia in 100%, sinus arrhythmias in 30%, and ventricular arrhythmias in 20%), liver abnormalities (necrosis in 40% and 240% increase in alanine aminotransferase activity by 6 hours), and intravascular thrombi (30%). The only hemoglobin-induced abnormality that was more frequent in the presence of endotoxin was ventricular arrhythmias (up to 75% of animals). Thrombin times were approximately 20% larger in all SFH groups compared with the albumin groups. By 6 hours after infusion, endotoxin prolonged the thrombin time even further, despite the lack of fibrinogen consumption. This study shows that endotoxin and SFH exert synergistic toxicity when SFH is given in a clinically relevant dose for an oxygen-transporting resuscitation system. Only minute quantities of endotoxin are needed to produce this phenomenon. We hypothesize that this synergism is endotoxin enhancement of hemoglobin toxicity.
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PMID:Synergistic toxicity of endotoxin and hemoglobin. 352 17

F344/N rats and B6C3F1 mice were exposed to 0, 1, 3, or 6 ppm methyl isocyanate by inhalation for 6 hr on 4 consecutive days. Deaths of rats were observed following 3 ppm exposures, and mice died after exposures to 6 ppm. Deaths appeared to be related to severe respiratory distress. Survivors in high dose groups lost weight initially, then gained weight at rates equal to controls throughout a 91-day recovery period. Lung weights increased significantly in male and female rats exposed to 3 ppm, but no persistent changes in brain, kidney, thymus, spleen, liver, or testis weights were seen in either mice or rats. Blood and serum from male and female rats were taken for clinical pathology and hematology assessments on day 7 of postexposure, the day prior to the first observed deaths of these animals. No changes or only slight changes were seen in measures of serum alanine aminotransferase, sorbitol dehydrogenase, alkaline phosphatase, or in blood and brain cholinesterase activities. However, serum creatine kinase increased with dose in both males and females. Blood urea nitrogen, creatinine, and methemoglobin were unchanged. No changes were seen in counts of red blood cells or platelets, or in red cell indices. Hemoglobin concentrations and hematocrits were slightly elevated. No changes were noted in absolute leukocyte counts, but counts of segmented neutrophils increased and lymphocytes decreased.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The toxicity of inhaled methyl isocyanate in F344/N rats and B6C3F1 mice. II. Repeated exposure and recovery studies. 362 27

This study was performed to examine the relationship between postmortem biochemical values and cause of death. The follow samples were taken from 399 corpses: cerebrospinal fluid (CSF; n = 376, suboccipital), blood (n = 158, femoral vein), and urine (n = 101, at autopsy). (See Table 1 for causes of death) All samples were stored at -80 degrees C. A further 100 samples of blood were later taken and stored at +4 degrees C before testing. Biochemical determinations made were: glucose in CSF, blood, and urine (hexokinase method); lactate (LDH/GPT) and free acetone (HS-gas chromatography) in CSF; hemoglobin A1 in blood (microcolumn technique). In 34 cases fatal diabetic coma was considered verified by morphological and chemical findings. One hundred cases of sudden cardiac death were chosen as the main control group. In 32 of the 34 cases defined above, the value of the formula of Traub (glucose + lactate in CSF) exceeded 415 mg/dl. It is not influenced significantly by hyperglycemia or hyperlactatemia due to factors other than diabetes (i.e., carbon monoxide, asphyxia). After death the value rose till the 30th hpm, then remained stable for at least 1 week. Fatal coma was defined as the ketoacidotic form if free acetone in CSF ranged above 21 mg/l. In these cases, CSF glucose and free acetone correlated positively. Hemoglobin A1 remained stable after death. Its amount was independent from postmortem blood glucose, postmortem interval and total hemoglobin. Furthermore, the manner of storage (-80 degrees or +4 degrees C) had no significant influence on its values. In 29 of 34 cases of fatal coma, Hb A1 exceeded 12.1%. Analysis of urine glucose showed elevated levels (over 500 mg/dl) in diabetic comas. On conclusion, fatal diabetic coma seems indicated as the cause of death if measured values of postmortem biochemistry exceed the following limits: CSF-Traub 415 mg/dl, free acetone (CSF) 21 mg/l; Hb A1 12.1%; urine glucose 500 mg/dl. Most important are the Traub formula and hemoglobin A1. Usually, in fatal coma both values are elevated. If both of them are normal, diabetic coma can nearly be excluded. Combined evaluation of all values is absolutely necessary. Morphology must also always be taken into account. Consequently, a diagnosis of fatal coma can be obtained by a process of elimination.
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PMID:[Biochemical measurements of glucose metabolism in relation to cause of death and postmortem effects]. 376 99

During the course of testing chronic toxicity in rats several physiological and biochemical parameters were investigated. Many of the processes studied show a circadian and infradian rhythm, which can clearly be influenced from the second year onwards by age dependent alterations. The daily rhythm of the following processes were investigated: Hexobarbital sleeping time, aminophenazone demethylation, Hb (Hemoglobin), Hc (Hematocrit), GPT (Glutamate-pyruvate-transaminase) and total plasma proteins. The seasonal changes of total plasma proteins, Hexobarbital sleeping time and aniline hydroxylation were also examined. The results obtained indicate, that for comparison and interpretation of data on acute and chronic toxicity the knowledge of daily and seasonal changes is necessary and has to be considered for an exact planning of experiments.
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PMID:Planning of experiments for the testing of chronic toxicity in rats taking into account biorhythms. 693 52

A group of 1916 Russian men donors was studied for 15 electrophoretic blood protein systems, coded by 22 protein loci: Transferrin (Tf), Haptoglobin (Hp)--2 loci, Group-specific component (Gc), Hemoglobin (Hb)--2 loci, Lactatdehydrogenase (LDH)--2 loci, Malatdehydrogenase (MDH), Erythrocyte esterase (Est)--4 loci, Albumen (Alb), 6-phosphogluconatdehydrogenase (6 PGD), Phosphoglucomutase (PGM)--2 loci, Esterase D (Est D), Adenosindesaminase (ADA), Acid Erythrocyte phosphatase (AcP), Glutamic transaminase (GPT) and Glioxalase-I (GLO-I). Ten loci were defined as polymorphic, the level of heterozygosity for cumulative loci was 0,1435 +/- 0,003. Moscow population was compared to major human races for the set of genetic characters--heterozygosity, correlation coefficient of single locus heterozygosity, a genetic distance. It has been shown that the extent of relation of ethnic groups to Moscow population decreases as follows: Caucasoids, Mongoloids, Negroids.
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PMID:[Polymorphism and heterozygosity levels of the Russian population of Moscow: data for 22 gene loci coding blood proteins]. 719 52

To investigate the therapeutic effects of rice bran fiber (30 g/day) and cholestyramine (12 g/day) for Yusho, clinical signs and symptoms, and laboratory examinations were studied before, during and after 14 day-treatment in four patients with Yusho. The increases of bowel movements and abdominal distention were observed in two of these patients, although no effect was seen in physical findings. In peripheral blood cells, red blood cell counts decreased significantly, from 430 +/- 47 x 10(4)/mm3 (mean +/- SD) to 378 +/- 48 x 10(4)/mm3 (p < 0.01) after therapy. Hemoglobin as well as hematocrit levels were also reduced significantly afer the therapy. However, no significant effect of the treatment was observed in white blood cell counts or platelet counts. In biochemical parameters, a significant depression was observed in total cholesterol levels after the therapy (from 262 +/- 31 mg/dl to 179 +/- 33 mg/dl; p < 0.005). A significant elevations was observed in serum levels of alanine aminotransferase and sodium, while significant depressions were found in serum levels of cholinesterase, total protein, albumin, gamma-globulin, and potassium.
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PMID:[Effects of treatment with rice bran fiber and cholestyramine on clinical and laboratory findings in Yusho patients]. 839 85

Median values and confidence intervals for hematology and serum and plasma chemistry parameters were established for 29 male and female healthy New Guinea snapping turtles (Elseya novaeguineae) held at 24.5 degrees C and 30.0 degrees C. Creatine kinase, albumin, potassium, and phosphorus values were significantly higher at 24.5 degrees C than at 30.0 degrees C. Glucose, alkaline phosphatase, aspartate transaminase, alanine aminotransferase, total carbon dioxide, and chloride values were significantly higher at 30.0 degrees C than at 24.5 degrees C. Cholesterol and calcium values were significantly higher in females than in males. Hemoglobin, packed cell volume, and bilirubin were significantly higher in males than in females, and bile acid values were significantly higher in serum than in plasma.
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PMID:Hematology and clinical chemistry reference ranges for clinically normal, captive New Guinea snapping turtle (Elseya novaeguineae) and the effects of temperature, sex, and sample type. 952 32

The present study examined whether measurement of hemoglobin-acetaldehyde (HbA1-AcH) using an improved methodology may be useful as a biological marker of alcohol abuse. Red blood cell hemolysates of 182 patients consecutively admitted to the drug and alcohol treatment unit of our institution were analyzed for HbA1-AcH concentration using cation exchange HPLC. Mean HbA1-AcH of those who claimed to drink > or = 6 drinks/day [mean = 0.055 (% total hemoglobin), SD = 0.051] was significantly higher than the mean of those who drank < 6 drinks/day (mean = 0.026, SD = 0.0174). The greatest sum of sensitivity (67%) and specificity (77%) came with a cut-score of 0.030 area% of total hemoglobin. A cut-score of 0.080 produced a 100% specificity, but lowered the sensitivity to 20%. The Pearson product moment correlation (r) between HbA1-AcH and reported drinks per day was r = 0.30 (p < 0.001). There was no significant difference in the association of HbA1-AcH and reported drinking between males and females, and the small difference observed was shown to be entirely associated with differences in hemoglobin levels between the sexes. Cocaine use did not significantly alter the correlation between reported drinking and HbA1-AcH levels. Hemoglobin levels were shown to have a significant correlation with HbA1-AcH independent of drinking. HbA1-AcH was shown to have a better sensitivity and specificity than gamma-glutamyltransferase, ALT, AST, or mean corpuscular volume in this population. The results suggest that HbA1-AcH may be a useful marker to help detect alcohol abuse, especially in populations where other markers have been shown to fail.
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PMID:Evaluation of acetaldehyde-modified hemoglobin and other markers of chronic heavy alcohol use: effects of gender and hemoglobin concentration. 983 1

An increasing number of women is treated with adjuvant cyclophosphamide, methotrexate and 5-fluorouracil therapy for breast cancer. The effects of the chemotherapy on many laboratory tests are, however, inadequately known. This study investigates the effects of the treatment on various laboratory tests. Fifteen premenopausal women receiving adjuvant cyclophosphamide, methotrexate and 5-fluorouracil chemotherapy and optional radiotherapy were included in the study. Common hormonal, biochemical, hematological, protein and lipid laboratory tests were taken serially during a 10-month follow-up. Twelve women became amenorrheic. Their serum follicle stimulating hormone and luteinising hormone concentrations increased accordingly. Other serum hormones (testosterone, androstenedione, sex hormone-binding globulin, prolactin, dehydroepiandrosterone sulfate, cortisol, parathyroid hormone and thyroid hormones) changed only slightly. Hemoglobin concentration and white blood cell count decreased slightly. Serum alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase, creatine kinase, angiotensin-converting enzyme, amylase, glucose, potassium, phosphate, urea and triglycerides concentrations increased slightly whereas serum bilirubin, haptoglobin, and immunoglobulin A and M decreased slightly. Serum alpha1-antitrypsin fluctuated around the baseline concentration. Other test results remained at their pretreatment concentrations. With the exception of increases in serum gonadotrophins, the changes observed were slight and the mean concentrations remained within reference limits. Therefore, cyclophosphamide, methotrexate and 5-fluorouracil adjuvant treatment is unlikely to complicate the diagnosis of other diseases.
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PMID:Alterations in laboratory test results during adjuvant breast cancer treatment. 1095 29

Tocotrienols are added as antioxidants to food. As there have been no reports of toxicological evaluation, a 13-week oral toxicity study was performed in Fischer 344 rats of both sexes at dose levels of 0 (group 1), 0.19 (group 2), 0.75 (group 3) and 3% (group 4) of a preparation in powdered diet. Suppression of body weight gain was observed in group 4 males. On hematological examination, significant decrease in mean corpuscular volume (MCV) was observed in all treated males. Platelets were significantly reduced in group 3 and 4 males. Hemoglobin concentration, MCV, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration were significantly decreased in group 3 and 4 females and hematocrit in group 4 females. On serum biochemical examination, increase in the albumin/globulin ratio (A/G) and alkaline phosphatase in all treated males, elevated alanine transaminase in group 4 of both sexes and increases in asparagine transaminase and gamma-glutamyl transaminase in group 4 females were observed. With regard to relative organ weights, liver weights in group 4 of both sexes and adrenal weights in all treated males demonstrated an increase, and ovary and uterus weights in group 4 females were reduced. Histopathologically, slight hepatocellular hypertrophy in group 3 and 4 males, and reduction of cytoplasmic vacuolation in the adrenal cortical region in group 4 males were observed. Because of pathological changes in male liver and hematological changes in females, the no-observed-adverse-effect level (NOAEL) was concluded to be 0.19% in the diet (120 mg/kg body weight/day for male rats and 130 mg/kg body weight/day for female rats). As a decrease in MCV, an increase in the A/G, elevation of alkaline phosphatase and increase in adrenal weight were observed in all treated males, a no-observed-effect level (NOEL) could not be determined in this examination.
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PMID:Oral toxicity of a tocotrienol preparation in rats. 1143 87


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