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:2.6.1.1 (aspartate aminotransferase)
21,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The adverse effects caused by antibiotics and the interactions between other drugs based on the results of clinical studies on children recently conducted in Japan, as well as the results of previous studies in the literature were reviewed. Adverse effects of beta-lactam, macrolide and azalide antibiotics commonly observed in children included gastrointestinal symptoms such as diarrhea and loose stool, and hypersensitivity such as rash and fever. The incidences were 1-6% and 0.2-1.6%, respectively. Eosinophilia, thrombocytosis, and elevation of serum glutamate oxaloacetate transaminase and serum glutamate pyruvate transaminase were common abnormal laboratory findings. Although many of the antibiotics used in children are relatively safe, cautions should be given because developing children tend to have adverse effects unique or common in children, in addition to those commonly seen in adults.
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PMID:Adverse effects of antibiotics. 912 46

Congenital intrahepatic arteriovenous fistulae, a rare hepatic vascular anomaly, in an 8-mo-old female beagle dog was investigated. The animal showed anorexia, repeated vomiting, hemorrhagic diarrhea, and jaundice for approximately 2 wk. There was mild to severe increase of serum alkaline phosphatase, glutamic-oxalacetic transaminase, glutamic pyruvic transaminase, total cholesterol, total bilirubin, and gamma-glutamyl transpeptidase. Macroscopically, the main abdominal organs showed hemorrhagic edema together with bloody ascites. Other characteristic findings were severe hepatic atrophy (right medial, quadrate, left medial, and lateral lobes) with multiple vascular cysts and compensatory hypertrophy of the other lobes. The cystic vessels seemed to extend from the proper hepatic arteries and their branches but were indistinguishable from the portal vein. Histopathologically, the atrophied hepatic lobes were characterized by wide, fibrous septa containing severe hyperplasia and anastomosis of the arteriolae and venulae and proliferation of bile ducts.
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PMID:Congenital intrahepatic arteriovenous fistulae in a young beagle dog. 932 40

Ten patients with asymptomatic human immunodeficiency virus (HIV) infection were treated for typhoid fever at King Edward VIII Hospital, Durban, South Africa, from 1993 through 1995. The mean age was 23.7 years (range, 8-33 years), with a female-to-male ratio of 9 to 1 and mortality and morbidity rates of 20% and 10%, respectively. Common presenting manifestations were fever (100%), relative bradycardia (50%), and diarrhea (40%). With respect to epidemiologic and clinical characteristics, we noted no significant differences among these 10 HIV-positive and 32 HIV-negative patients treated for typhoid fever during the same period. However, we found hepatic dysfunction in the form of an isolated increase in aspartate aminotransferase (p < 0.01) and abnormal urinary findings suggestive of glomerulonephritis (p = 0.01) more frequently in HIV-positive patients.
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PMID:Typhoid fever and asymptomatic human immunodeficiency virus infection. A report of 10 cases. 941 66

The toxicity of Rhazya stricta leaves for Najdi sheep is described in 9 sheep assigned as untreated controls, Rhazya-treated at 0.25 g/kg/d and Rhazya-treated at 1 g/kg/d. The oral use of 1 g/kg/d caused body weight depression, ruminal bloat, diarrhea, dyspnea and weakness of the hind limbs. Enterohepatonephropathy, pulmonary congestion, hemorrhage and emphysema, lymphocytes in vital organs, and congestion of the blood vessels of the heart were associated with increases in serum AST and LDH, in elevated bilirubin and urea concentrations, and decreased total protein, albumin and calcium concentrations, and leucopenia and anemia.
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PMID:Toxicity of Rhazya stricta to sheep. 955 56

Clinical, epidemiological features of acute viral hepatitis of 331 hospitalized adult patients were evaluated. HA, HB, HC, and non A-C H were diagnosed in 36.6%, 34.1%, 10.6%, and 18.7%, respectively. Age of HA cases was significantly lower than that of other cases. Only HA showed seasonal variation. Acquisition of HA was often associated with visits in endemic areas when compared with all other types, while HB, HC, and non A-C H were rather associated with iatrogenic events (blood transfusion, surgical procedures, and hospitalization). Symptoms of fever and diarrhea, and high ESR were more frequent in HA than in other types, while signs of weight loss and high levels of ALT, AST, and S.T.B, and decreased PT index were significantly more frequent in HB. Cholestasis course was found in 1.7%, 0.9%, and 3.2% of patients with HA, HB, and non A-C H, respectively. Fulminant course was found only in 0.9% of HB patients. Factors as sex and age had no effect on severity of acute phase in HA, HC, and non A-C H, while only the age of patients was inversely associated with severity of acute phase in H B.
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PMID:Clinical, laboratory, and serological findings of adult Hungarian hospitalized acute hepatitis patients, and possible source of the infection. 955 66

The safety of tacrine (Cognex), a centrally active, reversible acetylcholinesterase inhibitor approved in 1993 for the treatment of mild to moderate dementia of the Alzheimer type, was evaluated in 2,706 patients with Alzheimer disease (AD) in clinical trials and in 9861 patients with AD in a treatment investigational new drug (TIND) program. More than 190,000 patients in the United States received tacrine during the first 2 years following marketing approval. The most common tacrine-associated adverse events were elevated liver transaminase levels [alanine aminotransferase (ALT) and, to a lesser degree, aspartate aminotransferase] and peripheral cholinergic events involving primarily the digestive system (nausea, vomiting, diarrhea, dyspepsia, anorexia, and weight loss). Based on clinical trial experience, potentially clinically significant (>3 x upper limit of normal) ALT elevations occurred in 25% of patients, requiring routine monitoring early in treatment. The elevations were almost always asymptomatic, rarely accompanied by significant increases in bilirubin, and related to time on drug rather than to dose (90% occurred within the first 12 weeks of treatment). Gastrointestinal events were related to dose and generally of mild to moderate intensity. Tacrine-associated events, including ALT elevations, were reversible. Cholinergic events were manageable with dosage adjustment. Tacrine was not associated with permanent liver injury in clinical trials or a TIND setting.
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PMID:Safety of tacrine: clinical trials, treatment IND, and postmarketing experience. 965 Nov 38

Preclinical schedule dependency suggests that prolonged maintenance of low plasma levels of topotecan, a specific inhibitor of the nuclear enzyme topoisomerase I, results in optimal antitumor activity. The pharmacokinetics and pharmacodynamics of topotecan, administered as single agent in second-line therapy as a continuous low-dose infusion for 21 days, were evaluated in nine patients with small cell lung cancer (SCLC). Topotecan was administered i.v. as a 21 day continuous infusion every 28 days via an ambulatory pump. Dosages ranged from 0.4 to 0.6 mg/m2/day. Plasma levels of topotecan, the sum of topotecan, and its hydroxy acid congener and the N-desmethyl metabolite were determined at 1, 7, 14 and 21 days during infusion, using a validated high-performance liquid chromatography method with fluorescence detection. Myelosuppression was the most important toxicity. All patients experienced anemia, being severe (grade 3/4) in 55% of all courses. Other adverse effects were relatively mild and reversible, and included nausea, vomiting, diarrhea and fatigue. Three patients achieved a partial response. Mean steady-state concentrations of topotecan (C(ss)) in the first course were 0.46+/-0.17 and 0.47+/-0.19 ng/ml after doses of 0.4 and 0.5 mg/m2/day, respectively. Steady-state levels of the total of topotecan and hydroxy acid (C(ss,tot)) were 1.28+/-0.25 (range 0.93-1.58) and 1.57+/-0.19 (range 1.43-1.70) ng/ml at doses of 0.4 and 0.5 mg/m2/day, respectively. The percentage of the administered topotecan dose excreted in the urine within 24 h was 40+/-14 and 1.2+/-1.0% for total topotecan and N-desmethyltopotecan, respectively. During the second course, C(ss,tot) was significantly higher (p=0.032, paired t-test), which suggests altered topotecan disposition. A sigmoidal relationship was found between C(ss,tot) and the percent decrease in platelets (r=0.76, p=0.018). We conclude that topotecan administered as a 21 day continuous low-dose infusion has activity as single-agent, second-line therapy in patients with SCLC. There was considerable interpatient and intrapatient variability in systemic exposure to topotecan. Differences in organ function might contribute to this variation. Serum aspartate aminotransferase and albumin levels were predictive of topotecan pharmacokinetics.
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PMID:Continuous infusion of low-dose topotecan: pharmacokinetics and pharmacodynamics during a phase II study in patients with small cell lung cancer. 966 May 38

The safety and efficacy of one-year administration of propiverine hydrochloride (BUP-4 tablets) were assessed in facilities affiliated with the Department of Urology of Yokohama City University School of Medicine. Changes in subjective symptoms showed significant improvement in mean frequency of urination in the daytime from 10.3 +/- 4.0 times before administration to 7.1 +/- 2.9 times 1 year after the start of administration, in mean frequency of voiding at night from 4.2 +/- 1.7 times to 2.1 +/- 1.1 times and in mean incidence of urinary incontinence from 2.9 +/- 2.1 times to 0.7 +/- 1.0 times. The final degree of overall improvement rate was 82.0% (41/50 cases). Adverse effects were observed 26 times in 22 patients, the incidence being 15.6% (22/141 cases). They consisted of digestive symptoms in 9.9% (6 events of dry mouth, 4 of constipation, 2 of abdominal discomfort, 2 of diarrhea and 1 of gastritis), urinary tract symptoms in 3.5% (4 of dysuria and 1 of residual urine), abnormal laboratory findings in 1.4% (increase in glutamic-oxaloacetic transaminase, glutamic-pyruvic transaminase or lactate dehydrogenase levels) and others (1.4%). These results provide further evidence of the safety and efficacy of propiverine hydrochloride (BUP-4 tablets) even when administered for a long-term in the treatment of patients with pollakiuria and urinary incontinence.
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PMID:[Long-term administration study of propiverine hydrochloride (BUP-4 tablets) in pollakiuria and urinary incontinence]. 980 79

AG331 (N6-[4-(morpholinosulfonyl)benzyl]-N6-methyl-2, 6-diaminobenz-[c,d]-indole glucuronate) is a lipophilic thymidylate synthase inhibitor with activity in solid tumor models. On the basis of preclinical data supporting regimens of frequent drug administration, we performed a Phase I trial of AG331 as a 5-day continuous infusion repeated every 3 weeks. Twenty-nine patients were entered at doses ranging from 25 to 1000 mg/m2/day. The major side effects were mild to moderate fatigue, nausea, vomiting, diarrhea, and fever. At doses >/=400 mg/m2, acute reversible elevation of bilirubin, aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyltranspeptidase was observed. All patients who received >/=600 mg/m2/day experienced elevated alanine aminotransferase. Elevated liver function tests were evident by day 3 of the infusion and had resolved by day 8 in the majority. This toxicity was dose limiting at 1000 mg/m2/day, at which dose two of two patients developed grade 4 reversible hyperbilirubinemia in addition to the enzyme elevations. Serum and urine samples were analyzed by a novel high-pressure liquid chromatography method for the determination of the pharmacokinetics of AG331. Over the 50-1000 mg/m2/day dose range, mean total clearance ranged from 11.6 to 30.0 liters/h/m2, and volume of distribution at steady state ranged from 279.5 to 758.7 liters/m2. These parameters were dose independent over the dose range tested. The harmonic mean terminal half-life of AG331 was 20.2 h. Less than 5% of an AG331 dose is eliminated unchanged in the urine. Both the administered dose and exposure to the drug were related to the changes in bilirubin and aminotransferase blood levels. Evidence for inhibition of thymidylate synthase was obtained at doses ranging from 100 to 1000 mg/m2 in seven patients; plasma deoxyuridine concentrations at end-infusion were 1.8-3.8-fold higher than pretreatment values. Because of the nature of toxicity on this schedule, more extensive Phase II evaluation is not recommended, although an AG331 dose of 800 mg/m2/day for 5 days is tolerable. Exploration of less frequent dose administration is under way.
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PMID:Phase I trial of the thymidylate synthase inhibitor AG331 as a 5-day continuous infusion. 981 17

The effects on goats of Calotropis procera latex given by different routes of administration were investigated. The administration of latex at 1 ml/Kg body weight via the oral route or at 0.005 ml/Kg body weight/day via the intravenous or intraperitoneal route caused death of the goats between 20 minutes and 4 days. When the small dose of latex (0.005 ml/Kg body weight/day) was given by the oral route or intramuscular route no death among the goats occurred. Nervous signs, frequent urination, frothing at the mouth, dyspnoea and diarrhoea were the main features in goats given latex by the oral, intravenous or intraperitoneal route. Lameness was observed in goats given latex via the intramuscular route. Lesions were widespread congestion and haemorrhage, pulmonary cyanosis, enterohepatonephropathy, peritonitis (in goats receiving latex via i.p. route) and haemorrhagic myositis at the site of latex injection. These changes were accompanied by increases in the activities of serum GDH, LDH, ALP, GGT and AST and in the concentrations of cholesterol, urea and creatinine and decreases in the level of total protein.
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PMID:Studies on laticiferous plants: toxic effects in goats of Calotropis procera latex given by different routes of administration. 985 66


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