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)

The role of platelet-activating factor as a potential mediator of hepatic inflammatory injury associated with liver ischemia/reperfusion was investigated using a partial no-flow model in rats in vivo. Platelet-activating factor levels of livers from sham-operated rats and from animals experiencing hepatic reperfusion for less than 6 hr were very low. They were observed to increase significantly after 12 hr of reperfusion and reached peak levels after a 24-hr reperfusion period, a time when maximal hepatic injury and inflammation occurred. Treatment of experimental rats with WEB2170, a platelet-activating factor receptor antagonist, attenuated the hepatic injury and inflammation, as evidenced by decreases in plasma ALT and in hepatocyte necrosis and neutrophil infiltration. Both inactivation of Kupffer cells with gadolinium chloride and inhibition of the formation of reactive oxygen species with allopurinol reduced platelet-activating factor production in the liver, whereas induction of neutropenia had no effect, suggesting that interaction of Kupffer cells with oxygen-derived free radicals may be a plausible mechanism for hepatic platelet-activating factor accumulation. It is concluded that platelet-activating factor contributes to the inflammatory consequences of ischemia/reperfusion underlying late-phase hepatic injury.
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PMID:Inflammation and platelet-activating factor production during hepatic ischemia/reperfusion. 142 62

Eighteen immuno-compromised children (malignancies, hematological diseases, collagen diseases) with neutropenia and infections were treated with imipenem/cilastatin sodium (IPM/CS), and the efficacy and the safety of the drug were evaluated. 1. Responses to IPM/CS were excellent in 13 patients, good in 1, and fair in 4. None of the patients displayed a poor response to the treatment thus the efficacy rate was 77.8%. 2. Of 5 patients with sepsis, 4 had excellent or good responses. IPM/CS was effective against sepsis caused by Enterococcus faecalis and Pseudomonas aeruginosa. 3. In patients with severe neutropenia (WBC less than 100/mm3), the efficacy rate was 70%. 4. As for side effects, elevations of GOT and GPT were observed in 1 patient with liver cirrhosis. These results indicate that IPM/CS is safe and effective in immuno-compromised children with neutropenia and infections.
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PMID:[Clinical evaluation of imipenem/cilastatin sodium against infections in compromised children (malignancy, hematological disease, collagen disease)]. 143 90

Role of platelet-activating factor (PAF) as a potential mediator of hepatic pathophysiology was investigated using a rat model of obstructive jaundice. Over a 1-wk course of bile duct ligation, a sixfold increase in tissue levels of PAF (1.57 +/- 0.43 ng/g vs. control 0.24 +/- 0.08 ng/g) occurred in the liver, whereas no change was observed in PAF levels in plasma. Concomitantly, endotoxin was detected in portal blood drawn from jaundiced rats, and antagonism of the putative effect of endotoxin by neomycin plus polymyxin B reduced local PAF concentrations in livers from jaundiced animals. Induction of neutropenia failed to alter the elevated hepatic PAF concentrations. Moreover, a large quantity of PAF was released spontaneously from Kupffer cells isolated from livers derived from jaundiced rats but not from endothelial cells or hepatocytes from the same animals. An in vitro study using cultured Kupffer cells from normal rats indicated that Kupffer cells secreted a significant amount of PAF in response to lipopolysaccharide challenge; pretreatment of cells with polymyxin B prevented this stimulated PAF release. Treatment of animals with either of two PAF receptor antagonists (BN 52021 and WEB 2170) partially prevented the increase in tissue levels of eicosanoids and O2-derived free radicals and partially alleviated liver injury as judged by the appearance of glutamate-pyruvate transaminase in the plasma of jaundiced rats. The present study indicates 1) that endogenous PAF may be an important signaling mediator for the hepatic inflammatory alterations associated with short-term bile duct ligation and 2) that the interaction of Kupffer cells with portal endotoxin is the mechanism by which PAF is produced locally.
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PMID:Role of platelet-activating factor in hepatic responses after bile duct ligation in rats. 144 33

Bacteriological and clinical studies have been performed on meropenem (MEPM, SM-7338), a newly developed carbapenem antibiotic, in the pediatric field. 1. Antibacterial activities of MEPM against 24 clinical isolates were determined. MEPM showed excellent activity against Gram-positive bacteria including Staphylococcus aureus and Gram-negative bacteria, especially Escherichia coli and Branhamella catarrhalis. Against Haemophilus influenzae, MEPM had a higher activity than imipenem and flomoxef, but had a lower activity than piperacillin and cefoperazone. 2. Clinical efficacies of MEPM were evaluated in 32 cases with bacterial infections. A poor efficacy was observed in 1 patient with phlegmon but excellent or good efficacies were obtained in other 31 patients with tonsillitis (1), pneumonia (17), UTI (12), or SSSS (1). The overall efficacy rate was 96.9%. All strains except 1 of S. aureus were eradicated by the administration of MEPM, and a high eradication rate of 95.8% (23 out of 24 strains) was obtained. 3. No side effects were observed in 35 evaluated cases. As abnormal laboratory test results, elevated GOT, elevated GPT, eosinophilia and neutropenia were noted in 4, 4, 4 and 2 patients, respectively. 4. Influences on blood coagulation parameters were studied. PIVKA II was elevated upon administration of MEPM in some cases, but no changes in ATT, TT, HPT or Fbg were observed during the treatment. Based on the above results, it has been concluded that MEPM is a safe and effective drug to use in the treatment of pediatric infections. The usual recommended dosage and administration should be 10 to 20 mg/kg of MEPM at a time, using intravenous drip infusion, 3 times a day.
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PMID:[Bacteriological and clinical studies on meropenem in the pediatric field]. 150 6

The clinical trial of KRN 8601 was conducted in patients with neutropenia induced by chemotherapy for lung cancer. Thirty-six patients were treated with KRN 8601 subcutaneously for 14 days once daily at the dose of 50 or 100 micrograms/m2, and the effects were compared with the control phase without KRN 8601 treatment. Both the elevation of neutrophil count and shortened period of neutropenia were observed by the administration of KRN 8601. The efficacy rate was 75% (18/24) at 50 micrograms/m2 and 100% (10/10) at 100 micrograms/m2. A side effect observed was fever in one patients, and in 2 patients, abnormal GOT, GPT and LDH elevation were observed in each. We concluded that KRN 8601 was clinically effective and safe at the dose of 50 micrograms/m2 or 100 micrograms/m2 for neutropenia induced by chemotherapy for lung cancer.
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PMID:[Clinical trial of KRN 8601 in patients with neutropenia induced by chemotherapy for lung cancer]. 218 94

Clinical studies of imipenem/cilastatin sodium (IPM/CS) were conducted in 40 pediatric patients. 29 out of the 40 patients were treated for infections and 11 for prophylaxis. The following results were obtained. 1. The response rate in 29 patients with infections was 79.3%. Among the 29 patients, 16 patients who presented with malignant diseases showed the response rate of 68.8%. The response rate was lower in patients with severe infections than in those with mild or moderate infections, and a lower response rate was associated with severe neutropenia. However, there were no differences in the response rates between patients who had previously been treated and those who had been untreated with other antibiotics. The response rate in 6 patients from whom causative organisms were isolated was 83.3% and that in the remaining 23 patients was 78.3%. 2. The response rate in 11 patients to whom IPM/CS was administered prophylactically was 63.6%. 3. As for side effects, a rash was observed in 1 patient and hematuria in another, and the abnormal laboratory test results observed were elevations of GOT and GPT in 1 patient. However, they were not clinically significant. From the above results, it appears that IPM/CS may be used as a drug of the first choice for the treatment of patients with severe infections in which the causative organisms are unknown, and for the prophylaxis of infection in patients with neutropenia.
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PMID:[Clinical study of imipenem/cilastatin sodium in children with severe infections]. 234 51

Forty-two patients with small cell lung cancer were treated with a combination of carboplatin, ifosfamide and etoposide. Vincristine was given on day 14 of each course, the courses being repeated every 28 days for a maximum of six. Thoracic radiotherapy was given 4 weeks after the last course of chemotherapy but no prophylactic cranial radiotherapy was administered. Thirty patients had clinically limited state disease, the remaining patients having contralateral neck lymphadenopathy and/or pleural effusions. Elevated enzyme levels (alkaline phosphatase, LDH, ALT, GGT) were noted in 69% of patients. Twenty-four patients (57%) achieved a complete response (CR) when assessed one month after the end of treatment. A further 21% of patients had a partial response (PR). Median duration of CR was 14 months and of PR 8 months. Cerebral metastases were the sole site of relapse in 13% of the CR patients. Myelosuppression was severe with a median nadir of neutropenia of 0.2 x 10(9) cells 1-1. However, 74% of the patient group received all six courses of chemotherapy and only 16 courses (7%) were delayed because of toxicity. There were three deaths associated with treatment-related neutropenia. The median survival of the total group was 14 months, with an actuarial 2 year survival of 37% and a minimum follow-up of 18 months. [A recent analysis, March 1989, demonstrated a 33%, 2 year actual survival.]
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PMID:Carboplatin, ifosfamide and etoposide with mid-course vincristine and thoracic radiotherapy for 'limited' stage small cell carcinoma of the bronchus. 255 90

Adult wild-trapped opossums were infected with Leishmania donovani (Khartoum strain, WR 378) and evaluated as an animal model of visceral leishmaniasis. All infected opossums died within 32 days. Loss of body fat, hepatomegaly, and petechiae of skin and abdominal musculature were seen at necropsy. Microscopically, numerous amastigote-laden macrophages were seen in histologic sections of liver, spleen, and lymph nodes; fewer parasite-laden macrophages were in the bronchial-associated lymphoid tissues and renal glomeruli. Hematological findings included thrombocytopenia (terminal), neutropenia, and lymphopenia. Blood lymphocyte blastogenesis in response to concanavalin A and phytohemagglutinin was decreased markedly at day 24 post-infection (PI). Serum antibodies (1:40 dilution) to promastigotes of L. donovani were detected in five of eight infected opossums tested on days 10 and 24 PI. Total bilirubin concentrations and alanine aminotransferase and aspartate aminotransferase activities were increased after day 25 PI. Activated partial thromboplastin times and one-stage prothrombin times were prolonged before death. Concurrently, factors V, VIII, and XII activities were decreased.
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PMID:Experimental visceral leishmaniasis in the opossum. 276 21

A pharmacokinetic and clinical study of ceftizoxime (CZX), a newly developed cephem antibiotic intended for parenteral use, was conducted in premature and newborn infants, and resulted in the following findings. 1. Pharmacokinetics (1) Average serum half-lives (T 1/2) following a one shot intravenous dose of 20 mg/kg of CZX to mature and premature newborn infants in age groups of 0-3, 4-7, 8-14, and 15-30 days were: 4.14, 3.01, 2.57, and 1.98 hours (for mature infants) and 5.26, 4.59, 3.71, and 2.64 hours (for premature infants), respectively, decreasing with ages in days of the infants. (2) Average T 1/2's after a one shot 10 mg/kg dose was similar to that after a 20 mg/kg dose. Serum concentrations of CZX were dose-dependent. (3) T 1/2 after 1-hour intravenous drip infusion revealed a same trend after one shot injection. (4) Urinary in the first approximately 6 hours recoveries following a 20 mg/kg one shot dose to mature and premature newborn infants were as follows: 35% (0-3 days old) and 45-55% (4 days old and older) in mature infants and 30% (0-3 days old) and 45% (4 days old and older) in premature infants. 2. Therapeutic effectiveness (1) The subjects examined were 112 newborn infants consisting of 83 with infections and 29 who received CZX for prophylaxis. The 83 infants had 86 cases of infections, which were classified as A, when the causative organisms were identified and as B, when the causative organisms were not identified. Rates of therapeutic effectiveness were 95.0% for group A and 95.7% for group B. Bacteriological effectiveness were studied on 41 strains isolated from group A, and were as high as 89.5% for Gram-positive organisms and 95.5% for Gram-negative organisms. The rate of successful prophylaxis for the 29 infants was 96.6%. (2) Side effects did not occur among the 120 newborn infants. Laboratory tests with abnormalities included leukopenia, neutropenia, eosinophilia, thrombocytosis and increased GOT or GPT. These pharmacodynamic and clinical findings have fully substantiated the satisfactory therapeutic usefulness of CZX in both the treatment and prevention of neonatal infections in the usual dose of 20 mg/kg, which is to be given b.i.d. for infants up to 3 days old; b.i.d. or t.i.d. for infants 4 to 7 days old, and t.i.d. or q.i.d. for infants 8 days old and older. The drug can be given in a daily dose as high as 120 mg/kg when infection is severe.
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PMID:[Pharmacokinetic and clinical studies on the use of ceftizoxime in premature and newborn infants. The Chemotherapy Research Group for Mother and Child]. 305 Jan 88

Flomoxef (FMOX, 6315-S), a newly synthesized antibiotic which belongs to the oxacephem group, was clinically evaluated for its efficacy and safety in 17 patients with ages ranging from 1 month to 9 year-8-month who had bacterial infections. The results obtained were summarized as follows. 1. A pharmacokinetic study following 20 mg/kg FMOX administration by intravenous bolus injection showed that the half-life of FMOX (beta phase) was 39.8 minutes and the urinary excretion of FMOX in the first 6 hours was 76.5%. 2. FMOX was administered to 3 patients with pneumonia, 8 patients with bronchopneumonia, 2 patients with tonsillitis, 2 patients with pyelonephritis, one patient each with cervical lymphadenitis, and pustulosis associated with severe varicella at daily dosage levels of 61.9 approximately 87.2 mg/kg, divided into 3 or 4 administrations by intravenous bolus injection or by 30 minutes drip infusion. The clinical results of these 17 patients were as follows; excellent: 14 patients, good: 2 patients, poor: 1 patient. The efficacy rate was 94.1%. 3. No clinical adverse reaction was observed in any of the 17 patients. Neutropenia, eosinophilia, a slight elevation of GPT and slight elevations of GOT & GPT were observed in 1, 1, 1, and 2 patients, respectively. No abnormality in coagulation system was observed in any of 10 evaluable patients. 4. MICs of FMOX against 13 strains isolated from patients were as follows. MIC against 2 out of 3 strains of Streptococcus pneumoniae was 0.20 micrograms/ml and that of the remaining 1 strain was 0.39 micrograms/ml.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Clinical studies of flomoxef in the field of pediatrics]. 343 Jul 17


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