Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P17174 (aspartate aminotransferase)
 14,872 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The efficacy and toxicity of combined paclitaxel and gemcitabine was evaluated in 54 chemotherapy-naive patients with metastatic non-small cell lung cancer (NSCLC). Gemcitabine i.v. 1000 mg/m(2)was administered on days 1 and 8 and paclitaxel 200 mg/m(2)as a continuous 3-hour infusion on day 1. Treatment was repeated every 21 days. Patients had a median age of 53 years. ECOG performance status was 0 or 1 in 48 patients. 41 patients (75.9%) had initial stage IV disease; histology was mainly adenocarcinoma (46.3%). 2 patients (4.3%) achieved a complete response and 15 (31.9%) achieved a partial response giving an overall response rate of 36.2% (95% CI: 22.4-49.9%); 19 patients (40.4%) had stable disease and 10 (21.3%) had progressive disease. The median survival time was 51 weeks (95% CI: 46.5-59.3), with a 1-year survival probability of 0.48 (95% CI: 0.34-0.63). Grade 3/4 neutropenia and febrile neutropenia occurred in 15.2% and 2.2% of courses, respectively. Grade 3/4 thrombocytopenia was rare (1.8% of courses). Peripheral neurotoxicity developed in 25 patients (47.2%), mostly grade 1/2. Arthalgia/myalgia was observed in 30 patients (56.6%), generally grade 1 or 2. Grade 3 abnormal levels of serum glutamate pyruvate transaminase (SGPT) and serum glutamate oxaloacetate transaminase (SGOT) occurred in 5 patients (9.4%) and 1 patient (1.9%), respectively. Combined paclitaxel and gemcitabine is an active and well-tolerated regimen for the treatment of advanced NSCLC, and warrants further investigation in comparative, randomized trials.
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PMID:Combined paclitaxel and gemcitabine as first-line treatment in metastatic non-small cell lung cancer: a multicentre phase II study. 1133 67

Actinomycin-D (Act-D) is a rare cause of veno-occlusive disease (VOD). Between 1993 and 1998, we managed 6 patients, all male, median age 19 months (range 6-48 months) who received Act-D for Wilms' tumour (n=4), clear cell sarcoma (n=1) or rhabdomyosarcoma (n=1). VOD presented with a median platelet count of 12 x 10(9)/l, INR 3.8, fibrinogen 16 mg/l, fibrinogen degradation products (FDPs) > or =80 microg/l, aspartate aminotransferase (AST) 6922 IU/l, bilirubin 47 micromol/l. In 3 cases, transient liver dysfunction and thrombocytopenia without neutropenia had been observed after a previous course of Act-D. All six children developed encephalopathy, hepatomegaly, ascites, reversed portal flow and renal impairment. All received mechanical ventilation and two required haemofiltration. The treatment was supportive. Severe Adult Respiratory Distress Syndrome developed in 3 patients, all of whom died. 3 patients recovered. The outcome of VOD with multi-organ failure is poor. Intravascular coagulopathy precedes and characterises severe VOD during Act-D treatment.
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PMID:Veno-occlusive disease with multi-organ involvement following actinomycin-D. 1137 45

(1) A new group IIa sPLA2 inhibitor was compared with selective inhibitors of COX-1, COX-2 and an LTC4 antagonist for effects on local and remote tissue injuries following ischaemia and reperfusion (I/R) of the small intestine in rats. (2) In an acute model of ischaemia (30 min) and reperfusion (150 min) injury in the absence of inhibitors, there was significant intestinal haemorrhage, oedema and mucosal damage, neutropenia, elevated serum levels of aspartate aminotransferase (AST) and hypotension. (3) Preischaemic treatment with the inhibitor of sPLA2 (Group IIa), at 5 mg kg-1 i.v. or 10 mg kg-1 p.o. significantly inhibited I/R-induced neutropenia, the elevation of serum levels of AST, intestinal oedema and hypotension. (4) Pretreatment with the COX-2 inhibitor celebrex (10 mg kg-1 i.v.) and the LTC4 antagonist zafirlukast (1 mg kg-1 i.v.) also showed marked improvement with I/R-induced AST, oedema and neutropenia. Hypotension was only reduced by the LTC4 antagonist. The COX-1 inhibitor flunixin (1 mg kg-1 i.v.) did not effect improvement in the markers of tissue injury. (5) Histological examination of rat I/R injury showed that all of the drugs offered some protection to the mucosal layer damage compared to no drug treatment. Given i.v., the sPLA2 inhibitor was more effective than either the COX-1 or COX-2 inhibitors in preventing rat I/R injury. (6) These results indicate that a potent new inhibitor of sPLA2 (group IIa) protects the rat small intestine from I/R injury after oral or intravenous administration. COX-2 and LTC4 inhibitors also showed some beneficial effects against intestinal I/R injury. Our study suggests that sPLA2 (Group IIa) may have a pathogenic role in intestinal I/R in rats.
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PMID:Comparative protection against rat intestinal reperfusion injury by a new inhibitor of sPLA2, COX-1 and COX-2 selective inhibitors, and an LTC4 receptor antagonist. 1296 36

There are few extensive studies about clinicopathological findings of spontaneous canine babesiosis caused by a large form of the parasite found in Europe. To further characterize and describe clinicopathological findings in dogs affected with this large form of Babesia in northeastern Italy, we evaluated 23 Italian dogs with canine babesiosis by means of clinical history, physical examination, hematological, biochemical, hemostatic tests, serum electrophoresis and urinalysis. Seventeen dogs (74%) had recently traveled on a hunting trip (within 5-15 days of being presented to the clinic) to Bosnia and Herzegovina (n=7), to Croatia (n=8) and to Hungary (n=2). The duration of clinical signs ranged from 1 to 5 days prior to the arrival at the clinic. The main clinical signs were dehydration (100%), apathy (74%), anorexia or decrease appetite (70%) and fever (68%). The anemia was present in 74% of the dogs and classified as mild (35%), moderate (59%) and severe (6%). In all cases, the anemia was normocytic and normochromic. Only three dogs presented erythrocyte regeneration. Seventy percent of dogs had hemolytic anemia and 30% had non-hemolytic anemia. Sixty-nine percent of dogs showed leucopenia and 74% neutropenia. Leucocitosis, due to mature neutrophilia and lymphocytosis, was present in one dog. Activated lymphocytes were noted in 61% of dogs. In all dogs, thrombocytopenia and an elevated hyperfibrinogenemia were present. Significant prolonged activated partial thromboplastin time (aPTT) was only found in one case. In four dogs, both plasma fibrinogen/fibrin degradation products (FDPs) and D-Dimer were increased. Antithrombin (AT) was slightly decreased in 11 of the 23 dogs. In the majority of cases, mild elevation of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), creatinekinase (CK), total bilirubin and lactic acid and decrease of total iron and total iron binding capacity (TIBC) were present. In conclusion, the main clinicopathological findings were a mild to severe thrombocytopenia, a mild to moderate hemolytic anemia, neutropenia and hyperfibrinogenemia.
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PMID:Clinicopathological findings in naturally occurring cases of babesiosis caused by large form Babesia from dogs of northeastern Italy. 1611 10

E7070 is a novel sulfonamide anticancer agent that disrupts the G1/S phase of the cell cycle. The objectives of this phase I study of E7070 were to estimate the maximal tolerated dose (MTD), to determine the recommended dose for phase II, and to clarify the pharmacokinetic profile of E7070 and its relation to polymorphisms of CYP2C9 (*2, *3) and CYP2C19 (*2, *3) in Japanese patients. Patients received 1-2-h i.v. infusions of E7070 (400, 600, 700, 800 or 900 mg/m2) on day 1 of a 21-day cycle. Twenty-one patients received between one and eight cycles of E7070. The dose-limiting toxicities (DLT) comprised leukopenia, neutropenia, thrombocytopenia, elevation of aspartate aminotransferase, colitis, and ileus. The mean area under the plasma concentration-time curve (AUC) for successive dose levels increased in a non-dose-proportional manner. Two patients were heterozygous for the CYP2C9 mutation. For CYP2C19, eight patients were wild type and the remainder had heterozygous (n = 8) or homozygous mutations (n = 5). Regarding the CYP2C19 genotype, the AUC of patients with mutant alleles were higher than those of patients with wild type at a dose of 600 mg/m2 or more. The severity of toxic effects, such as myelosuppression, seemed to depend on the AUC. No partial responses were observed. One patient treated at a dose of 700 mg/m2 experienced a maximum tumor volume reduction of 22.5%. The MTD was estimated to be 900 mg/m2. A dose of 800 mg/m2 is recommended for further phase II studies. The pharmacokinetic/pharmacodynamic properties of E7070 seemed to be influenced by CYP2C19 genotype. The observed safety profile and preliminary evidence of antitumor activity warrant further investigation of this drug in monotherapy or in combination chemotherapy.
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PMID:Phase I pharmacokinetic and pharmacogenomic study of E7070 administered once every 21 days. 1623 5

The preventive effect of neutropenia on carbon tetrachloride (CCl4)-induced hepatotoxicity was examined in rats. In rats treated once with CCl4 (1 ml kg(-1), i.p.), the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), indices of liver cell damage, and the hepatic activity of myeloperoxidase (MPO), an index of tissue neutrophil infiltration, increased at 6 h after the intoxication and further increased at 24 h. The liver of CCl4 -treated rats showed an increase in the concentration of thiobarbituric acid reactive substances (TBARS), an index of lipid peroxidation, and decreases in superoxide dismutase (SOD) activity and reduced glutathione (GSH) concentration at 6 h after the intoxication followed by a further increase in TBARS concentration and further decreases in SOD activity and GSH concentration at 24 h with increased xanthine oxidase (XO) activity at 24 h. Neutropenic treatment with anti-rat neutrophil antiserum (2 ml kg(-1), i.p.) at 0.5 h after CCl4 intoxication attenuated the increases in serum ALT and AST activities and hepatic MPO activity and TBARS concentration and the decreases in hepatic SOD activity and GSH concentration found at 6 and 24 h after CCl4 intoxication and the increase in hepatic XO activity found at 24 h after the intoxication. This neutropenia reduced the necrotic and degenerative changes with inflammatory cell infiltration in the liver cell of CCl4 -treated rats. These results indicate that neutropenia prevents CCl4 -induced hepatotoxicity in rats by attenuating the disruption of hepatic reactive oxygen species metabolism mediated by neutrophils accumulating in the liver tissue.
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PMID:Preventive effect of neutropenia on carbon tetrachloride-induced hepatotoxicity in rats. 1627 9

A 2-year-old, Quarter Horse filly was referred to Michigan State University, Veterinary Teaching Hospital with a 2-3 day history of depression and partial anorexia progressing to severe, watery diarrhea with severe neurologic abnormalities, including repetitive muscle fasciculations, muscle stiffening, and collapse. Laboratory findings included severe polycythemia, neutropenia, metabolic acidosis, and electrolyte and fluid loss, consistent with watery diarrhea and endotoxic shock. Increased creatine kinase and aspartate transaminase activities were consistent with recent transport and the muscle abnormalities. Severe hyperammonemia (1369.0 micromol/L; control value, 15.3 micromol/L) was found, without other substantial laboratory evidence of hepatic dysfunction. The horse was euthanized because of poor prognosis and rapid clinical deterioration. Necropsy findings were unremarkable with the exception of severe diffuse colitis. Culture of colonic contents recovered >1000 colony-forming units of Clostridium perfringens. Based on these findings, marked hyperammonemia in this filly was attributed to changes in colonic flora leading to increased bacterial production of ammonia that was readily absorbed through the inflamed bowel wall, exceeding the hepatic capacity for deamination. Intestinal bacteria as a source of hyperammonemia in the absence of hepatic disease has been linked rarely to positive culture results for clostridial organisms.
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PMID:Diarrhea and hyperammonemia in a horse with progressive neurologic signs. 1678 24

The application of myeloablative Allo-SCT is limited by its associated morbidity and mortality. Reduced-intensity conditioning regimens attempt to diminish these, but are associated with a higher risk of disease relapse. Given the evidence of activity of clofarabine and cytarabine in myelodysplastic syndrome/acute myeloid leukemia (MDS/AML), we explored a novel reduced-intensity conditioning regimen based on this backbone. Patients received clofarabine 40 mg/m(2) i.v. on days -6 to -2, cytarabine 1 g/m(2) i.v. on days -6 to -2 and anti-thymocyte globulin (ATG) 1 mg/kg on day -4 and 2.5 mg/kg x 2 days on days -3 and -2. Seven patients were enrolled. Their median age was 54 years; three were with MDS and four with AML. The median duration of neutropenia was 14 days and that of thrombocytopenia was 22 days. Toxicities included hand-foot syndrome (57% grade 2), elevated alanine aminotransferase (ALT) (57% grade 3), elevated aspartate aminotransferase (AST) (86% grade 3) and hyperbilirubinemia (29% grade 3-5). No acute GVHD was observed. Enrollment to the trial was halted after three of the first seven patients expired on days +15, +26 and +32. Three of the four surviving patients have relapsed with a median TTP of 152 days. This regimen was not sufficiently immunosuppressive to ensure engraftment, and was associated with substantial morbidity and mortality.
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PMID:Allo-SCT conditioning for myelodysplastic syndrome and acute myeloid leukemia with clofarabine, cytarabine and ATG. 1913 40

A high intermittent dose regimen (group A: 10 mg kg(-1) on day 1, 5 mg kg(-1) on days 3 and 6) was compared with standard dosing (group B: 3 mg kg(-1) per day for 14 days) of liposomal amphotericin B (LAB) for empirical treatment of persistent febrile neutropenia. A total cumulative dose of 1275 mg (group A) and 2800 mg (group B) was administered. Infusion-related adverse drug events, mainly rigors/chills, occurred more frequently with group A (11/45, 24 % infusions) than with group B (12/201, 6 % infusions) (P=0.002), which extended the mean infusion time by 20 min (P=0.001). Creatinine levels were similar in the two regimens: the A : B ratio of the area under the curve for creatinine (AUC(CREATININE)) for days 2-7 was 1.09 (P=0.27) and for days 2-14 was 1.05 (P=0.51). Rises in creatinine were mild (clinical toxicity criteria 1) in all patients with elevations. Hypokalaemia tended to be less severe in group A with a lower proportion of hypokalaemic days [57/143 (39 %) vs 80/137 (58 %), P=0.21], a higher AUC(POTASSIUM) (A : B ratio of 1.06, P=0.12), a lower proportion of patients with hypokalaemia at the end of study (10 vs 61 %, P=0.01) and fewer potassium-supplemented days [12/210 (6 %) vs 41/210 (19.5 %), P<0.1]. There were mildly elevated median levels of serum bilirubin, alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase, which were similar for the two regimens and were usually associated with other co-existing co-morbid conditions. The AUC for these enzymes was also similar in the two groups. No patient had discontinuation of the study drug due to toxicity. Composite success was identical for each regimen (11/15 patients, 73 %). Three of the fifteen patients in group B and none in group A developed invasive fungal infections (IFIs). Beta-D-Glucan levels were similar in both groups for patients without an IFI [AUC(GLUCAN) of 362 and 683 (P=0.36) for groups A and B, respectively]. The rate of defervescence was similar for each regimen (P=0.75). This feasibility study suggests that a short intermittent high-dose course of 10/5/5 mg LAB kg(-1) on days 1, 3 and 6 may be as safe and effective as a standard 14 day course of 3 mg kg(-1) per day, with drug-acquisition cost savings and reduced drug exposure. A larger study is indicated for confirmation of this.
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PMID:A safety and feasibility study comparing an intermittent high dose with a daily standard dose of liposomal amphotericin B for persistent neutropenic fever. 1958 1

The aim of this study was to investigate the efficacy and safety of oral iron chelators, deferiprone in combination with desferrioxamine in comparison with desferrioxamine alone. A total of 70 transfusion-dependent thalassemia major patients were randomly selected to receive one of the following two treatments: deferiprone in combination with desferrioxamine (n=35, desferrioxamine+deferiprone group) or desferrioxamine alone (n=35, desferrioxamine-only group). Changes in serum ferritin, liver enzymes (alanine aminotransferase and aspartate aminotransferase), blood urea nitrogen, and creatinin were evaluated before the treatment and then six and 12 months after the treatment, and any side effect caused by iron chelators was reported during the study. Student's t-test and repeated measures were used to compare different mean values for quantitative data and Chi-square to compare qualitative data. Serum ferritin decreased more significantly in patients on desferrioxamine+deferiprone therapy compared to patients who only received desferrioxamine (P<0.017). Side effects of deferiprone, including neutropenia, severe gastrointestinal upset, and arthropathy occurred in eight, four, and two patients, respectively but none led to discontinuation of the treatment. Beta-thalassemia major patients with iron overload due to transfusion could be successfully treated with a combination of desferrioxamine and deferiprone. This regimen is more effective than desferrioxamine-only therapy in decreasing serum ferritin; therefore, it also could be more effective in reducing iron overload and related complications in beta-thalessemia major patients.
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PMID:Efficacy of combined desferrioxamine and deferiprone versus single desferrioxamine therapy in patients with major thalassemia. 1972 72


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