Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.2 (alanine aminotransferase)
 26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Slc/ddY mice (10 male, 10 female per group) were given a single p.o. intubation of tris (1,3-dichloro-2-propyl) phosphate (TDCPP) in olive oil and were observed for 14 days. LD50 values of male and female mice were 2.67 (2.52 approximately 2.83) and 2.25 2.25 (2.12 approximately 2.39) g/kg, respectively. The animals revealed ataxic gait, hyperactivity, and convulsion. Slc/ddY mice (12 male, 12 female er group) were administered diet containing 1.33, 0.42, 0.13, 0.04, and 0.01% of TDCPP for 3 months. Male and female mice of the 1.33% group showed emaciation, rough hair, and tremor; and all animals died within one month. Hematological studies showed slight anemia in males of the 0.42% group and females of the 0.42% and 0.13% groups. They also exhibited a tendency to increase ALP and GPT levels. The animals of the 0.42%, 0.13% and 0.04% groups exhibited tendency to increase liver weights and kidney weights in both sexes. Histopathologically, very slight focal necrosis was recognized in the liver in only 2 females of the 0.42% group. The NOEL under this condition is 0.01% in the diet of tris (1,3-dichloro-2-propyl) phosphate (male: 13.2 mg/kg/day, female: 15.3 mg/kg/day).
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PMID:[Acute and subacute toxicity studies of tris (1,3-dichloro-2-propyl) phosphate on mice]. 263 31

Studies were carried out on the effect of various cadmium doses, which were given to growing rats in diet. A 42-day biological experiment was carried out on male growing Wistar rats. The animals divided into groups were given diets containing cadmium in amounts of 50, 100 and 200 ppm and diet with no adding cadmium. The diets contained 20% of protein in equal amounts from wheat gluten and casein. It was demonstrated that cadmium had a significant influence on diet intake and growth of rats. The absorption from diets containing 50, 100 and 200 ppm of cadmium was about 30 to 48%. The more cadmium was absorbed, the most was in blood and rat liver. Anaemia was noted in animals, which were given diets with cadmium. Rats had a low level of haematocrit and haemoglobin in plasma. It was shown that cadmium intake caused a significant decrease in plasma albumin concentration and increase of plasma alanine aminotransferase and aspartate aminotransferase activity.
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PMID:[Effect of various cadmium doses in the diet on the body of growing rats]. 263 83

In order to assess the safety of cefmetazole, preclinical multiple-dose parenteral studies, varying from one to three months in length, were conducted in Sprague-Dawley rats and beagle dogs. Although the largest doses used were in multiples of several times the weight-adjusted doses intended for humans, cefmetazole was generally well tolerated. The principal adverse effect noted in the adult rats receiving the largest doses (2000 and 2500 mg/kg/day) of cefmetazole was slight elevation of serum alanine aminotransferase. Infant rats injected subcutaneously with 300 mg/kg/day or more of cefmetazole for 35 consecutive days had reversible reductions in testicular weight and maturation of spermatogenesis, but not lasting discernible effect on reproductive function. The most consistent effects of longterm multiple dosing with cefmetazole in dogs consisted of vomiting and retching during dosing and reversible haematological changes (mild regenerative anaemia, positive Coombs' test, clinically-silent thrombocytopenia) in a number of the dogs. These findings supported the interpretation that cefmetazole was acceptably safe for clinical studies in humans.
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PMID:Preclinical safety studies of cefmetazole. 272 19

Consumption of edible oils contaminated with Argemone mexicana seed oil is known to cause various clinical manifestations. In the present study, the effect of dietary intake of argemone oil on histopathological changes, haematological indices and selected marker parameters of toxicity was investigated to observe the exact sites and mode of action of argemone oil in rats. Histopathological changes in the liver showed increased fibrosis, hyperplasia of bile ducts and congestion in a few portal tracts. Lungs of argemone oil-fed animals indicated congestion and thickening of interalveolar septa. Alveolar spaces were disorganised and irregular. Kidneys showed vascular and glomerular congestion and patchy tubular lesions. At 30 days only mild congestion was noted in the myocardium. Cardiac muscle fibres showed degenerative changes at 60 days which were more marked in the auricular wall. Haematological examination showed appearance of anaemia in experimental animals. Hepatic alkaline phosphatase, alanine transaminase and aspartate transaminase activities were inhibited by 30, 29 and 29% after 30 days of argemone intake along with concomitant enhancement in serum by 27, 29 and 66%, respectively. Liver showed decrease in glutathione (32-63%) content along with significant stimulation of lipid peroxidation (49-105%) in argemone-intoxicated animals. These results suggest that liver, lungs, heart and kidneys are the target tissues of argemone oil toxicity and that membrane destruction may be a possible mode of action.
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PMID:Biochemical toxicology of argemone oil. IV. Short-term oral feeding response in rats. 279 30

A phase II study of bronchial artery infusion of mitomycin C (MMC) was performed in 14 patients with non-small cell lung cancer (6 patients with adenocarcinoma, 6 patients with squamous cell carcinoma and 2 patients with large cell carcinoma). MMC at a dose of 20 mg was infused into the bronchial artery (total dose 20-60 mg, mean 27 mg). Among the 14 patients, one with adenocarcinoma of the lung showed partial response. The response rate for bronchial artery infusion of MMC was thus 7.1%. The toxic effects included anemia (35.7%), leukopenia (28.6%), thrombopenia (14.3%), elevation of GPT (14.3%), anorexia (14.3%), nausea (7.1%) and eruption (7.1%).
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PMID:[Phase II study of bronchial artery infusion of mitomycin C in non-small cell lung cancer]. 302 79

The marmoset, a small non-human primate, has rarely been used in toxicological studies. A short-term toxicity study was performed on common marmosets (BW = 330 +/- 32 g). Fifteen male marmosets received oral administration of DAB at a dose level of 56 mg/kg/day and 4 control animals received corn oil alone for a period of 15 days. Hematological, biochemical, histopathological and bone marrow examinations were carried out on the 5th, 10th and 15th day of treatment. Body weight decreased continuously and two animals died on day 10. Decreases in RBC, Hb and Ht and increases in MCV and WBC were observed. Uric acid and glucose were increased and AlP and LAP were decreased. Aldolase, GOT and GPT were increased by day 10, and thereafter recovery of aldolase to the control level and decreases of GOT and GPT were observed. Relative organ weights of the liver, kidney, spleen and adrenal were increased. Histologically, C-cell hyperplasia of the thyroid and slight changes of the liver were noted. Marrow total cell counts were not changed, but the G/E ratio was reduced. Thus, macrocytic anemia, an increase of marrow erythroblasts due to anemia and changes of biochemical parameters indicating liver injury were observed in marmosets; these findings were similar to those in rats in the previous experiments.
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PMID:Short-term toxicity study of 4-dimethylaminoazobenzene in marmosets. 310 51

Fifty-nine children treated with acute lymphoblastic leukemia (ALL) were evaluated for abnormalities of liver function in order to monitor chemotherapy-induced hepatotoxicity. Twenty-one patients (36%) had elevations of alanine aminotransferase (ALT) in a pattern consistent with either drug-induced hepatocellular injury or non-A, non-B (NANB) hepatitis. These 21 patients (Group 1) were compared with the other 38 children (Group 2) with regard to a number of clinical and laboratory characteristics. Patients in Group 1 were older (P = 0.002) and had lower platelet counts (P less than 0.001) and hemoglobin values (P = 0.075) at diagnosis than Group 2 patients. The median number of units of blood products transfused was significantly greater in Group 1 patients (9.0 versus 1.0 units, P less than 0.001). The two groups were similar with regard to chemotherapy regimens. Children with ALL who present at an older age and who have more marked anemia and thrombocytopenia require more blood transfusions and are more likely to develop elevated ALT values in a pattern consistent with acute or chronic NANB hepatitis. These findings suggest a predominant role of NANB posttransfusion hepatitis--rather than or in addition to chemotherapy-induced hepatic injury--as a cause for elevated ALT values in children with ALL. In view of the potentially serious consequences of NANB hepatitis, a change in transfusion support practices may be warranted.
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PMID:Elevated serum transaminase values during therapy for acute lymphoblastic leukemia correlate with prior blood transfusions. 313 78

Acute toxicity of cefodizime sodium (THR-221) was examined in mice of both sexes, rats of both sexes (including 5-day-old young), and male dogs. The LD50 values of THR-221 (mg/kg) were as follows: (1) mice: intravenous, 7200 for males and 5000 for females; intraperitoneal, 10500 for males and 11000 for females; subcutaneous, 17500 for males and 16500 for females; and oral, 28000 for males and 29000 for females. (2) rats (adult): intravenous, 7000 for males and 8200 for females; intraperitoneal, 9500 for males and 8800 for females; subcutaneous, 17000 for males and 15500 for females; oral, more than 20000 for both sexes; and intramuscular, more than 3200 for both sexes. (3) 5-day-old rats: subcutaneous, 5278 for males and 5314 for females. (4) male dogs: intravenous, more than 5000. Major changes in general conditions observed in mice and rats were decreased spontaneous activity, lying prone, respiratory changes, staggering gait, clonic or clonic-tonic convulsions, and cyanosis, and in the animals dosed orally, diarrhea or salivation was also noted. The changes in 5-day-old rats were respiratory changes, agony, loss of reflex to an external stimulus, and congestion at the injection site, and those in dogs were vomiting, dryness of the nose, and soft or mucous stools. Autopsies on the mice and rats which died revealed hemorrhage on the brain surface. In addition, the following were seen: intraperitoneal retention of fluid and dark red spots on the abdominal wall (i.p.), subcutaneous retention of fluid or jellylike material and hemorrhage at the injection site (s.c.), and retention of fluid and dark red spots on the mucosa in the digestive tract (mice p.o.). In 5-day-old rats which died, the subcutaneous tissue at the injection site showed hemorrhage macroscopically and inflammatory changes microscopically. Hematological and blood chemical tests performed in dogs showed an increase in white blood cells and changes suggesting anemia, increases in GOT, LDH and ALP activities, and slight changes in urea nitrogen and inorganic phosphorus. In one animal given a low dose of 2500 mg/kg, an increase in GPT activity was also seen. However, these changes were all transient. Microscopic findings in dogs were slight inflammatory changes in the subcutaneous tissue around the injection site.
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PMID:[Acute toxicity study of cefodizime sodium]. 317 86

The present experiment was performed to see the influence of phlebotomy on hematology, serum chemistry, and pathology data in rats. When normal rats received a single phlebotomy of 2 or 3 ml blood, erythrocyte count and hematocrit were slightly reduced along with a persistent depression of the blood pressure. In repeated phlebotomy studies, 0.25 to 2 ml each of blood was removed from each rat every other day for 10 days. Normal rats from which 0.5 ml and more of blood was withdrawn showed decreases in erythrocyte count and serum iron level concomitant with an increase in reticulocyte count. Similar findings were obtained in rats with CCl4 liver damage or gentamicin nephrotoxicity, except that those rats hardly exhibited anemia because of a simultaneous occurrence of hemoconcentration. Histopathological findings of the liver and kidney were not different between animals with and without phlebotomy. In phenylhydrazine-treated rats receiving repeated phlebotomy, one rat in the 1-ml phlebotomy and two rats in the 2-ml phlebotomy died from severe anemia. Surviving rats receiving 2-ml phlebotomy showed higher serum GOT and GPT activities together with fatty deposition and/or focal necrosis of hepatocytes. It is concluded that every-other-day phlebotomy of up to 0.25 ml each does not significantly influence the physiological condition of normal or diseased rats.
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PMID:The influence of single or repeated phlebotomy on the physiological condition of normal and diseased rats. 359 1

Cefuzonam (L-105, CZON), a new parenteral cephalosporin, was evaluated for its efficacy and safety in 22 children with bacterial infections (Table 1). The results obtained are summarized below. MICs of CZON to 26 strains of isolated organisms are shown in Table 2. MICs to all 14 strains of Haemophilus influenzae and 6 strains of Streptococcus pneumoniae were less than 0.05 microgram/ml. The MIC to 2 strains of Staphylococcus aureus was 0.39 microgram/ml and that to another was 0.78 microgram/ml. Two strains of Escherichia coli showed MICs of less than 0.05 and 0.10 microgram/ml, respectively. The MIC to 1 strain of Enterococcus faecalis was 6.25 micrograms/ml. The CZON was administered in 3 or 4 divided doses at a daily dosage ranging from 58.5 to 85.7 mg/kg by 30-minute drip infusion or intravenous injection to 22 patients (9 cases of pneumonia, 9 cases of tonsillitis, 2 cases of bronchitis, 1 case each of suppurative parotitis and acute pyelonephritis) and the following clinical results were obtained; excellent: 12 cases; good: 7 cases; fair: 3 cases. The overall efficacy rate was 86% (Table 4). Diarrhea was observed in four patients, and was resolved with or without discontinuation of the medication within a week. Anemia was noted in 2 cases. Leucopenia and neutropenia was observed in 1 case. There were a moderate rises in S-GOT and S-GPT activities in 1 patient (Table 4), and they necessitated the cessation of the CZON therapy. The S-GOT and S-GPT activities became normal after the drug treatment was stopped.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Clinical evaluation of cefuzonam in children]. 359 88


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