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)

Effects of histidine deficiency on muscle carnosine and anserine levels and on activities of enzymes associated with histidine catabolism and protoporphyrin synthesis were investigated. Male Sprague-Dawley (150 g) rats were tube-fed isonitrogenous, isocaloric, defined diets containing 0%, low (0.013%) or adequate (0.45%) histidine for 8-13 days. While histidine-deficient animals maintained body weight, muscle and plasma histidine and carnosine concentrations decreased rapidly and remained low following a 3-day histidine repletion period. Hepatic histidine ammonia-lyase and histidine-pyruvate transaminase activities were decreased in histidine-deficient animals, whereas formiminotransferase activity was unchanged. Hematocrit levels and hemoglobin concentrations declined progressively during histidine depletion and the activity of erythrocyte and hepatic delta-aminolevulinic acid dehydratase also decreased relative to controls. Evidence is presented indicating that decreased histidine catabolism combined with carnosine and hemoglobin degradation can provide sufficient histidine to explain the slow onset of negative nitrogen balance associated with histidine deficiency and that impaired protoporphyrin synthesis may partially explain the anemia observed in the absence of dietary histidine.
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PMID:Metabolic effects of histidine-deficient diets fed to growing rats by gastric tube. 649 66

Eleven adult Basenji dogs with immunoproliferative small intestinal disease (IPSID) were studied. Two items of history related to the digestive tract were characteristic: (i) chronic intractable diarrhea in most dogs, and (ii) progressive emaciation. Anorexia was intermittent in only a few dogs. In addition, skin lesions of various degrees of severity were observed, including alopecia of pinnae and ventrum, hyperpigmentation and hyperkeratosis of pinnae, and necrosis and ulcerations of margins of pinnae. The cause of the skin lesions was not determined; however, hypothyroidism did not appear to contribute to the skin changes. Standard hematologic and serum chemical values were not consistently abnormal. However, a poorly regenerative anemia, mild neutrophilia, and increased aspartate aminotransferase and alanine aminotransferase activities were generally observed in severely affected dogs. The Pelger-Huet anomaly was identified in dog 3. Maldigestion and malabsorption as determined by the N-benzoyl-L-tyrosyl-p-aminobenzoic acid and d-xylose test was documented to varying degrees in dogs with IPSID. Maldigestion was correlated with functional pancreatic exocrine insufficiency. Severe malabsorption was documented in only 3 dogs. Serum gastrin values were evaluated in these dogs because of a prior observation of parietal cell hyperplasia and gastric ulceration. Hypergastrinemia was documented in 3 dogs. Additional studies will be necessary to determine whether an acid hypersecretory state contributes to the pathogenesis of IPSID in Basenjis.
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PMID:Clinical and laboratory characterization of Basenjis with immunoproliferative small intestinal disease. 660 87

Twenty-one male rabbits were divided into three groups: rabbits of two groups were given pelleted food containing cadmium chloride at a dose level of 300 micrograms Cd/g over periods of 44 or 19 weeks. Rabbits of the last group were given ordinary commercial pelleted food and served as controls. Cadmium increased urinary protein and amino acid by week 19 and increased it to a remarkably high level by week 44. After cessation of cadmium exposure, rabbits of the first group (44 weeks exposure group) showed only little recovery from cadmium health effects: proteinuria and aminoaciduria were slightly improved. Depressed hepatic functions were also slightly improved, but did not return to the control level in 24 weeks. Fat and bone metabolism also remained depressed below the control level. Anemia did not also readily recover. On the other hand, rabbits of the second group (19 weeks exposure) recovered from the effects of cadmium: proteinuria and aminoaciduria in most animals disappeared soon after the end of cadmium exposure, plasma GPT fell after 1 week, and hemoglobin and hematocrit returned to normal in 6-11 weeks. The above results show that after cessation of cadmium exposure, mild cadmium-induced health effects were reversible in a short period, while more severe effects were not readily reversible. High performance liquid chromatographic (HPLC) profiles of renal and hepatic cadmium-thionein (Cd-MT) during and after exposure to cadmium showed no correlation to the degree of cadmium health effects, and therefore, did not help to elucidate mechanisms of the recovery from cadmium-induced health effects, probably because cadmium not bound with metallothionein (non-MT-Cd) is responsible for inducing renal effects.
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PMID:Reversibility of cadmium-induced health effects in rabbits. 673 56

The oral toxicity of a mixture of 2,4,6-trinitrotoluene and hexahydro-1,3,5-trinitro-1,3,5-triazine (1:0.62, w/w) compounds typically found in munitions plant effluents, was evaluated in mammalian species. Single-dose oral LD50s of the mixture were 574 and 594 mg/kg in male and female rats and 947 and 1130 mg/kg in male and female mice, respectively. Long dispersion periods during preparation or ultraviolet irradiation of the mixture lowered the LD50s. In repeated-exposure studies, dogs were given 0.50, 5.0 or 50 mg/kg X d by capsule for up to 90 d. Rats and mice were fed the mixture in the diet at 0.005, 0.05, or 0.5% for 90 d; mice were also fed at 0.25%. Mortality resulted at the highest dose level in each species. All three species showed depression of body weight or body weight gain, depressed food intake, moderate to severe anemia, and alterations in the spleen (hemosiderosis), liver (hepatomegaly), and testes (atrophy) at the highest dose levels. Cholesterol was elevated in rats and dogs after 90 d. Several species differences were also noted. Uric acid values were elevated in rats but not in dogs, serum glutamic-pyruvic transaminase (SGPT) activity was low in dogs but unchanged in rats, and rats developed hypoplasia of the uterus but dogs did not. Signs of anemia were present at the intermediate dose levels. The lowest dose level in all three species was designated at a "no observable effects" level, based on the absence of clearly treatment-related effects. In a 4-wk study, the irradiated mixture fed to rats at 0.003, 0.03, or 0.3% in the diet was less toxic than the unirradiated mixture.
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PMID:Short-term oral toxicity of a 2,4,6-trinitrotoluene and hexahydro-1,3,5-trinitro-1,3,5-triazine mixture in mice, rats, and dogs. 710 80

Erythema multiforme major and disseminated intravascular coagulation developed in a dog 24 hours after exposure to a d-limonene-based insecticidal dip. Clinical signs included severe lethargy and weakness, ulceration of the oral mucosa, and erythematous serpiginous, annular, and arciform lesions on the head, trunk, and limbs. Clinicopathologic abnormalities included leukocytosis with neutrophilia, normocytic normochromic anemia, thrombocytopenia, prolongation of prothrombin and partial thromboplastin times, increased fibrin degradation products, hypoproteinemia, hyponatremia, hypochloremia, azotemia, high serum alanine aminotransferase and alkaline phosphatase activities, and high serum bilirubin concentration. Despite intensive supportive care, the dog developed severe intrathoracic and abdominal hemorrhage and died. Necropsy revealed severe diffuse epidermal necrosis and widespread hemorrhage within organs. Insecticidal dips containing d-limonene have the potential to induce various toxic effects, including, possibly, erythema multiforme major, and should be used cautiously.
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PMID:Erythema multiforme major and disseminated intravascular coagulation in a dog following application of a d-limonene-based insecticidal dip. 759 26

This study was designed to evaluate the interaction between protein malnutrition, gossypol treatment and blood parasitosis (Trypanosoma brucei) in the Wistar rat. Haematological and serum biochemical changes were evaluated in the rats, which were placed on two planes of nutrition--low protein (LP) and normal protein (NP)--and either treated with gossypol or infected with Trypanosoma brucei, or both. Higher parasitaemia occurred in gossypol-treated NP rats than in the corresponding LP group. Gossypol treatment and trypanosomal infection, either alone or in concert, caused an anaemia that was both macrocytic and hypochromic. Both treatments together also caused increases in serum alkaline phosphatase and alanine aminotransferase activities, which were accompanied by depressed serum albumin concentrations, suggestive of hepatic dysfunction in affected rats. These results suggest that, with adequate protein intake, the growth and infectivity of trypanosomes is not inhibited by gossypol but that protein malnutrition has a beneficial effect of reduced parasitaemia. Unfortunately, this beneficial effect is counteracted by gossypol enhancement of hepatic dysfunction caused by trypanosomes.
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PMID:The effects of protein malnutrition and experimental infection with Trypanosoma brucei on gossypol treatment in the rat: haematological and serum biochemical changes. 759 58

Functional abnormalities of the liver uncovered during preoperative routine evaluation were analyzed in 109 donor candidates for 100 cases of living-related liver transplantation (LRLT) performed during the period from June, 1990 to May, 1994 at the Second Department of Surgery, Kyoto University Hospital. High serum transaminase (GOT, GPT) levels were noted in 10 (9.2%) cases among 109 candidates, high alkaline phosphatase in 4 (3.7%), hyperbilirubinemia in 3 (2.8%), anemia in 3 and high choline esterase in 3 cases. Positive hepatitis C antibody (HCV) was also noted in 1 case. Fatty liver was detected in 10 (9.2%) cases, cholecystitis in 2 cases, 1 case each of cyst and calcification in the liver by diagnostic imaging (ultra sonograph and/or computed tomography). These abnormalities of the liver necessitated replacing the initial candidate with the other parent in 9 cases, including 1 case without any functional abnormality whose graft liver was too large to fit the recipient abdominal cavity. There were 14 cases of ABO blood type incompatible combination. Switching the initial candidate due to these abnormalities mentioned above resulted in incompatible combinations in 4 of these 14 cases. Although the advantages of the LRLT are the superior viability of the donor graft and the genetic histocompatibility between recipient and donor, to optimize the advantage of LRLT, all donor candidates should be strongly advised to make every effort preoperatively to improve their physical condition in preparation for the LRLT protocol, since many of these abnormalities are typically reversible.
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PMID:Analysis of functional abnormalities uncovered during preoperative evaluation of donor candidates for living-related liver transplantation. 774 84

Gemcitabine (GEM) is a novel deoxycytidine analogue which has shown promising antitumor activity in solid tumor models and a broad range of schedule-dependent MTDs (12-4560 mg/m2) in preliminary clinical studies. The present phase I trial evaluated escalating doses of weekly GEM using a 30-min infusion at a starting dose-level of 300 mg/m2/wk x 3 every 28 days. At least 3 patients entered each dose-level step and 3 more cases were treated when significant toxicity was seen. A total of 39 patients with various advanced solid tumors and prior chemotherapy entered this study. Six escalation steps (102 courses) were tested to define the MTD at 1,370 mg/m2/wk. No definite dose-effect relationships were observed for myelosuppression up to 1,095 mg/m2/wk. However, increased severity of leucopenia (dose-limiting) and greater non-hematologic toxicity as well as a higher number of toxic treatment delays, requiring subsequent dose attenuation in 6 out of 12 patients, were observed at 1,370 mg/m2/wk. In all, 6 out of 11 patients experiencing WHO grade > or = 3 toxicity (11/21 events recorded in 11/18 courses) were treated at the MTD. Clinically significant toxicity included (patients with WHO grade 2-3): leucopenia (44%), thrombocytopenia (26%), anemia (23%), fever (69%), emesis (38%) and AST/ALT rise (26%). Mild proteinuria, ankle edema, skin rash, hair loss and mucositis were seen in < or = 5%.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Weekly gemcitabine in advanced or metastatic solid tumors. A clinical phase I study. 786 Feb 27

The effects of protein malnutrition on haematological and serum biochemical values were evaluated in gossypol-treated rats which were simultaneously fed with ethanol. Gossypol caused anaemia, leucopenia and thrombocytopenia in malnourished animals, suggesting a depression of bone marrow activity. Gossypol also caused a significant elevation of serum alkaline phosphatase and alanine aminotransferase activities and increases in the concentrations of Mg++ and Ca++ with reduced albumin, regardless of the nutritional status. These changes were more severe with malnutrition. Ethanol alone caused a thrombocytopenia but no other significant haematological changes. However, it appeared to cause derangement of lipid and protein metabolism as reflected in serum cholesterol and urea. The toxic effects seen in gossypol-treated rats were significantly reduced in animals simultaneously given ethanol. As the livers of gossypol-treated rats were significantly heavier than in these animals, it seems possible that ethanol consumption enhances the ability of the liver to metabolize gossypol, thereby reducing its accumulation and consequently its toxicity. However, further studies are needed to determine the mechanisms responsible.
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PMID:Haematological and serum biochemical changes in the rat due to protein malnutrition and gossypol-ethanol interactions. 788 58

Four patients with cryptococcal meningitis have been treated with fluconazole in the past two years at the Department of Neurology, National Cheng Kung University Medical Center. There were three women and one man. Two patients had a history of anemia and one had undergone a splenectomy due to hypersplenism. Two patients were healthy before the onset of meningitis. After receiving fluconazole 300 mg per day for 8 to 13 weeks, three patients were cured without clinical evidence of recurrence during follow-up lasting from 2 to 17 months. One patient died from pneumothorax as a complication of subclavian vein cannulation. During the treatment course, there was no side effect except for one patient who had transient elevation of the GOT and GPT values which reversed spontaneously without a change in dosage. In the three successfully treated cases, the cryptococcal antigen titers began to decrease after the first week of treatment. Our preliminary experience shows that fluconazole alone is an effective and safe drug for the treatment of cryptococcal meningitis.
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PMID:[Clinical experience with fluconazole monotherapy in cryptococcal meningitis: report of four cases]. 790 3


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