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)

Late Phase II clinical study with bropirimine (U-54461S), a novel oral antitumor agent that has interferon inducing and anti-proliferative activities, was conducted in patients with bladder CIS at 38 institutions nationwide. To investigate the efficacy and safety of the treatment, bropirimine was administered to the patients at the dose of 750 mg every two hours, three times a day, for three consecutive days with four-day drug withdrawal, based on the results of the preceding clinical studies up to early phase II. Among the 48 patients registered, 41 patients were evaluable for antitumor efficacy. Complete response (CR) was observed in 17 of them, no change (NC) in 18 patients, and progressive disease (PD) in 6 patients; so the efficacy rate was 41.5%. Classified by patient background, the efficacy rates were 58.3% (7/12) in patients with primary bladder CIS, 34.5% (10/29) in those with secondary bladder CIS, 45.5% (10/22) in those with Grade 3, and 23.8% (5/21) in those previously given chemotherapeutic agents or BCG by intravesical or other routes. Adverse drug reactions frequently observed were influenza-like symptoms such as fever and generalized malaise and gastrointestinal symptoms like anorexia and nausea/vomiting; these symptoms were all Grade 2 or milder. Abnormalities in laboratory tests, such as an elevation in GOT/GPT, neutropenia, and leukopenia were observed. These adverse effects were all tolerated by the patients. From the above results, bropirimine was considered to be a useful oral agent for the treatment of bladder CIS.
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PMID:[Bropirimine (U-54461S) late phase II clinical study for carcinoma in situ of the bladder. Japan Bropirimine Study Group]. 902 Sep 49

An open label trial of GM-CSF plus high-dose interferon (IFN) alpha 2b was performed in eight patients with chronic hepatitis B infection and 16 patients with chronic hepatitis C, who either failed to clear virus with 6 months of daily high-dose IFN (5 MU daily) therapy (n = 22) or were considered untreatable because of advanced disease and leukopenia (n = 2). The dose of GM-CSF used was 500 micrograms subcutaneously twice weekly. The dose of IFN used was 5 MU daily. Both agents were administered for 4 months. Five of the eight hepatitis B patients and five of the 16 hepatitis C virus patients responded to combined therapy having previously failed IFN therapy alone. The hepatitis B virus responders had low entry ALT, AST, and gamma GPT levels as compared to the non-responders. No such differences for responders and non-responders were seen with the hepatitis C virus patients. These data suggest that the combination of GM-CSF and IFN may be more effective at achieving viral clearance than IFN alone.
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PMID:A preliminary experience with GM-CSF plus interferon in patients with HBV and HCV resistant to interferon therapy. 909 87

We compared the severity of clinical symptoms and laboratory test results of tsutsugamushi disease patients in Oita Prefecture according to the serotype of infected R. tsutsugamushi. Of the 45 patients, except one with the Karp-type, who were suffering in Oita Prefecture between 1992 and 1994, 20 were the Irie-type and 24 were the Hirano-type. There was no apparent difference with regard to clinical symptoms between the two groups of patients. Laboratory tests showed that CRP increased almost equally in the two groups. The ESR level was slightly higher in the Irie-type patients than in the Hirano-type, but did not differ significantly between the two groups. Both leukocyte count in the acute stage and platelet count decreased in the Hirano-type, as compared with those of normal ranges in the Irie-type. GPT values elevated in proportion to the day of illness in the acute stage. This trend continued after the initiation of specific chemotherapy in the Hirano-type. The median GOT, GPT and LDH values were 71, 65 and 709 IU/l for the patients in the Hirano-type, as compared with 37, 36.5 and 546.5 for the patients in the Irie-type, respectively. Above results show that the Hirano-type rickettsiae produces a more severe illness than the Irie-type ricketsia. Platelet count had a significant correlation with ESR, suggesting the pathophysiologic changes leading to disseminated intravascular coagulation, a symptom of severe tsutsugamushi disease. There may be common causes in leukopenia and thrombopenia, as being suggested by the significant correlation between leukocyte count and platelet count.
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PMID:[Analysis of clinical severity of tsutsugamushi disease according to the serotype of pathogenic rickettsia]. 916 83

We employed a bile duct ligation (BDL) model of cholestatic liver injury to test the hypothesis that this form of preexisting hepatic dysfunction alters the kinetics of circulating TNF-alpha and IL-6 after Escherichia coli endotoxemia, thereby augmenting mortality and lung injury by a TNF-alpha:leukotriene (LT) axis of inflammation. Male rats were catheterized 13 d after BDL or sham surgery and studied while awake 18 to 24 h later. Cholestasis after BDL was confirmed by baseline serum bilirubin (BDL = 7.34 +/- 0.72 mg/dl, mean +/- SEM, n = 17 versus Sham = 0.25 +/- 0.07, n = 20; p < 0.005) and histopathology. Sham and BDL animals received E. coli lipopolysaccharide serotype O55:B5 (LPS, 5 mg/kg i.v.) or 0.9% NaCl (NS) ending at t = 0 and were monitored over 24 h for vital signs and hemodynamics. In parallel studies, lipoxygenase inhibition was performed using diethylcarbamazine or the 5-lipoxygenase activating-protein inhibitor MK-886. Blood was collected at baseline and at t = 1.5, 3.5, and 24 h for formed elements and for serum endotoxin, TNF-alpha, IL-6, bilirubin, and alanine aminotransferase (ALT). Organs were evaluated at 24 h for histopathology, including neutrophil (PMN) densities and wet/dry weight (W/D) ratios. Cholestasis reduced survival after otherwise nonlethal endotoxemia, with seven of 11 BDL + LPS rats dying within 24 h versus no deaths in BDL + NS (n = 6), Sham + LPS (n = 14), or Sham + NS (n = 6) animals (p < 0.01). Despite equivalent serum endotoxin between groups, circulating TNF-alpha was 8-fold higher in BDL + LPS than in Sham + LPS rats at 1.5 and 3.5 h (p < 0.001), whereas serum TNF-alpha did not differ between BDL + NS and Sham + NS rats. IL-6 likewise was increased differentially by 1.5 h in BDL + LPS animals (11.98 +/- 2.42 ng/ml) versus Sham + LPS rats (3.05 +/- 0.58 ng/ml, p < 0.05). Hypothermia, bradycardic hypotension, and leukopenia were most severe and prolonged in BDL + LPS rats, which also had significantly higher ALT values, W/D ratios, and organ PMN counts. LT inhibition failed to reduce BDL-related differences in serum cytokines or survival after endotoxemia. Thus, cholestasis augments inflammatory responses to gram-negative endotoxemia, sensitizing the host to enhanced fluid flux in multiple organs and to mortality by a LT-independent mechanism.
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PMID:Cholestatic liver injury increases circulating TNF-alpha and IL-6 and mortality after Escherichia coli endotoxemia. 960 37

Administration of ground-up tick tissue stabilate (0.75 tick equivalent) by the subcutaneous route to crossbred calves aged 1 week to 1 month led to the development of acute theileriosis. Haematological studies revealed significant progressive decreases in haemoglobin concentration, packed cell volume and red blood cell count, whereas the total leukocyte count showed an initial non-significant leukocytosis followed by a significant leukopenia. Analysis of serum revealed significant increases in levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, creatinine kinase and gamma-glutamyltransferase, and in the concentrations of uric acid, blood urea nitrogen and bilirubin. The concentrations of total protein, albumin, glucose, cholesterol and calcium showed non-significant decreases, while phosphorus decreased significantly during the terminal stages of the disease.
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PMID:Haematological and biochemical studies on experimental Theileria annulata infection in crossbred calves. 977 80

Scrub typhus, a mite-transmitted zoonosis caused by Orientia tsutsugamushi, is a disease endemic to Taiwan. Serious complications in scrub typhus were more common in the past 4 years than reported previously. Between August 1993 and July 1997, 33 cases of scrub typhus were admitted at Tri-Service General Hospital. Symptoms and signs were: fever (100%), chills (39%), cough (24%), headache (21%), diarrhea (18%), dyspnea (18%), eschar (60%), adenopathy (33%), and rash (21%). Nineteen percent (6/32) had obvious leukopenia (WBC < 4000/ mm3), 34% (11/32) had leukocytosis(WBC > 10,000/mm3) and 44% (14/32) had thrombocytopenia (platelet count < 100,000/mm3). Elevation of aspartate aminotransferase (AST) and elevation of alanine aminotransferase (ALT) were 81% (26/32) and 75% (24/32), respectively. Serious complications included pneumonitis 36% (12/33), acute respiratory distress syndrome (ARDS) 15% (5/33), acute renal failure 9% (3/33), myocarditis 3% (1/33) and septic shock 3% (1/33). One patient died of ARDS due to delay in diagnosis. Other patients recovered after appropriate antibiotic and intensive supportive treatments. Emerging virulent strains of O. tsutsugamushi in Taiwan might be biologically plausible. Scrub typhus should be considered in a patient with fever, varying degree of respiratory distress, particularly if there is an eschar or a history of environmental exposure in endemic areas. Prompt diagnosis, timely antimicrobial therapy and intensive supportive care are important for ARDS and other life-threatening complications.
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PMID:Serious complications in scrub typhus. 1049 65

A toxicity study was made on Lepidium sativum L. seeds used in Saudi traditional medicine for the treatment of various ailments. Lepidium sativum L. seed fed to Wistar albino rats at 2% (w/w) was non-toxic, Ten percent (w/w) was toxic but not fatal and 50% (w/w) of the diet for 6 weeks was lethal and caused depression in growth rate and entero-hepato-nephrotoxicity. Organ lesions accompanied by anemia and leukopenia were correlated with alterations in serum AST and ALT activities and concentrations of total protein, cholesterol, urea, and other serum constituents.
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PMID:Effects of various levels of dietary Lepidium sativum L. seeds in rats. 1059 49

The demonstrated utility of the nucleoside analog ribavirin in the treatment of certain viral diseases can be ascribed to its multiple distinct properties. These properties may vary in relative importance in differing viral disease conditions and include the direct inhibition of viral replication, the promotion of T-cell-mediated immune responses via an enhanced type 1 cytokine response, and a reduction of circulating alanine aminotransferase (ALT) levels associated with hepatic injury. Ribavirin also has certain known toxicities, including the induction of anemia upon chronic administration. To determine if all these properties are linked, we compared the D-nucleoside ribavirin to its L-enantiomer (ICN 17261) with regard to these properties. Strong similarities were seen for these two compounds with respect to induction of type 1 cytokine bias in vitro, enhancement of type 1 cytokine responses in vivo, and the reduction of serum ALT levels in a murine hepatitis model. In contrast, ICN 17261 had no in vitro antiviral activity against a panel of RNA and DNA viruses, while ribavirin exhibited its characteristic activity profile. Importantly, the preliminary in vivo toxicology profile of ICN 17261 is significantly more favorable than that of ribavirin. Administration of 180 mg of ICN 17261 per kg of body weight to rats by oral gavage for 4 weeks generated substantial serum levels of drug but no observable clinical pathology, whereas equivalent doses of ribavirin induced a significant anemia and leukopenia. Thus, structural modification of ribavirin can dissociate its immunomodulatory properties from its antiviral and toxicologic properties, resulting in a compound (ICN 17261) with interesting therapeutic potential.
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PMID:The ribavirin analog ICN 17261 demonstrates reduced toxicity and antiviral effects with retention of both immunomodulatory activity and reduction of hepatitis-induced serum alanine aminotransferase levels. 1077 Jul 62

A study was undertaken to investigate the effect of immunosuppression by cyclophosphamide or methylprednisolone on the clinicopathological alterations in respiratory absidiosis in rabbits. Infected rabbits showed respiratory distress that was more severe in immunosuppressed groups. Leukocytosis due to neutrophilia was observed in the non-immunosuppressed group in the initial stages, whereas leukopenia was observed in both the immunosuppressed groups initially, owing to polymorphopenia in the cyclophosphamide-treated group and to lymphopenia in the methylprednisolone-treated group, followed by leukocytosis in both groups. Total serum proteins increased significantly in the non-immunosuppressed group but were significantly decreased in the immunosuppressed groups. Serum creatinine increased significantly in all the infected groups from 20 days post inoculation (DPI) onwards. Blood urea nitrogen increased significantly in the initial stages only in the methylprednisolone-treated group. AST and ALT also showed significant increases in the infected animals. Total serum immunoglobulins and circulating immune complexes increased gradually in all three infected groups, except for an initial significant drop in the immunosuppressed rabbits. Re-isolation of fungus was only achieved from the lungs of infected rabbits up to 15 DPI in the non-immunosuppressed group and 30 DPI in the immunosuppressed groups. Pathological lesions in all the infected groups were found mainly in the lungs and consisted of pyogranulomas. The lesions were most severe in the cyclophosphamide-treated group and least severe in the non-immunosuppressed group.
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PMID:Effect of immunosuppression on the clinicopathological changes in experimental zygomycosis in rabbits. 1083 67

A pilot dose-escalation study of recombinant human interleukin 12 (rhIL-12) was conducted in Japanese patients with advanced malignancies. Cohorts of three patients received escalating doses of rhIL-12 that increased from 50 to 300 ng/kg/day s.c. three times a week for 2 weeks followed by 1-week rest. The same dosage and schedule was repeated for two additional courses. Sixteen previously treated patients were registered, and 15 were evaluated. Common toxicities were fever and leukopenia; the abnormality of laboratory tests included elevations in aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, C-reactive protein, and beta2-microglobin. Dose-limiting toxicity was the grade 3 elevation of aminotransferases, and was observed in two of six patients at the 300-ng/kg dose level after the first course in one patient and after the third course in the other. Leukopenia was observed at all of the dose levels; two of six patients at 300 ng/kg experienced grade 3 leukopenia. Thus, 300 ng/kg was determined to be the maximum acceptable dose. Peak plasma levels of rhIL-12 decreased in the second courses, but the areas under the curve were almost the same in the first and second courses. Biological effects included increases of plasma levels of IFN-gamma, tumor necrosis factor-alpha, IL-6, IL-10, and neopterin. In two patients with renal cell carcinoma, complete response and partial response of metastatic tumors were observed with 50 and 300 ng/kg; the responses lasted for 5 and 3.5 months, respectively. Although immunological response to rhIL-12 varies depending on administration route and schedule and on patients' physiological conditions, the recommended dose for Phase II studies is 300 ng/kg s.c. three times a week for 2 weeks followed by 1-week rest.
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PMID:A dose-escalation and pharmacokinetic study of subcutaneously administered recombinant human interleukin 12 and its biological effects in Japanese patients with advanced malignancies. 1091 7


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