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)

CB3717 is a quinazoline antifolate whose cytotoxic activity is mediated by inhibition of thymidylate synthase (TS). A phase I clinical trial commenced in September 1981 and 99 patients have received 296 treatments. Doses were dissolved in 0.15 mol/L NaHCO3 (pH 9.0) at a concentration of 4 mg/mL infused over one hour or in a total volume of 1 L infused over 12 hours. Doses were repeated every 3 weeks. The starting dose of 140 mg/m2 was escalated to 600 mg/m2. Renal toxicity, detected by a decrease in the 51Cr EDTA clearance, was dose-related and occurred in seven of ten patients receiving greater than 450 mg/m2. Reversible hepatic toxicity often associated with malaise occurred in 223 of 288 assessable courses (77%). Fifty-nine courses (20%) were associated with increases in alanine transaminase (ALT) levels to greater than 2.5 times the upper limit of the normal laboratory range. Increases in alkaline phosphatase levels also occurred, but were less marked. The severity and prevalence of these elevations were unaffected by the duration of the infusion. A self-limiting rash appeared in 12 patients and a radiation recall reaction was seen in two. Leukopenia developed in 17 patients (WBC less than 3 X 10(9)/L), and thrombocytopenia occurred in six patients (platelets less than 100 X 10(9)/L). The mean leucocyte nadir occurred on day 10 and was followed by recovery at 11 to 19 days. Neither the incidence nor the severity of any of these latter toxicities was dose related. The maximum tolerated dose was in the region of 600 mg/m2 with renal toxicity being dose limiting, although the inter-patient variation did not allow a precise definition. Seventy-six patients were evaluable for response. Responses occurred at doses greater than or equal to 200 mg/m2 and were ovary, one complete response (CR), one partial response (PR), seven minor responses (MR) in 30 cases; breast, two PRs and one MR in eight cases; adenocarcinoma of the lung, one MR in 5 cases; mesothelioma, one PR in five cases; and colon, two MRs in four cases. CB3717 has activity in heavily pretreated patients. The recommended phase II dose for good-risk patients is 400 mg/m2 using the one-hour infusion schedule of administration.
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PMID:A phase I evaluation of the quinazoline antifolate thymidylate synthase inhibitor, N10-propargyl-5,8-dideazafolic acid, CB3717. 373 49

Sprague-Dawley rats and cultured rat hepatocytes exposed to bromobenzene (BB) and carbon tetrachloride (CCl4) display rapid and significant increases and decreases in hepatic phospholipase C (PLC) and sn-glycerol-3-phosphate acyltransferase (GPAT) activities, respectively. Primary cultures of adult rat hepatocytes were used to determine if the BB- and CCl4-dependent alterations in phospholipid metabolism were related to the hepatotoxicity of these agents. Cultured hepatocytes exposed to BB and CCl4 exhibited a rapid (1 to 5 min). PLC-mediated reduction (20 to 80%) in [32P]phosphatidylserine content. Other phospholipids were also reduced; however, phosphatidylserine was preferentially degraded by hepatotoxin-activated PLC. A time course of CCl4-and BB-induced cellular events showed that these agents (1) rapidly activate liver cell PLC activity; (2) accelerate 86Rb release; (3) decrease GPAT acyltransferase activity; and (4) cause a release of intracellular enzymes (GOT and GPT). All of these BB- and CCl4-mediated effects on the functional integrity of liver cells were blocked or reduced by agents (EDTA and chlorpromazine) that reduce the BB- and CCl4-dependent rise in PLC activity. Therefore, BB- and CCl4-dependent alterations in the functional and structural integrity of liver cells may be a result of accelerated phospholipid degradation and a corresponding inability of the cell to repair injured membranes by generating new phospholipids.
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PMID:The role of phospholipid metabolism in bromobenzene- and carbon tetrachloride-dependent hepatocyte injury. 647 78

The usefulness of the direct virus detection by polymerase chain reaction (PCR) and reverse transcription/polymerase chain reaction (RT PCR) for blood donor screening was investigated, including the following viruses: cytomegalovirus (CMV), hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency type 1 virus (HIV1). Hepatitis C viraemia was detected by RT PCR in 97% of anti-HCV-positive haemophiliacs, in 48% of anti-HCV-positive hepatitis patients, in only 21% of anti-HCV-positive blood donors from North-West Germany, and not at all in 945 blood donors with elevated serum ALT. In order to compare HIV1 detection by PCR and by p24 antigen determination, we tested 34 anti-HIV1-positive AIDS patients for p24 antigen, HIV1 RNA and HIV1 provirus DNA. 97% had HIV1 provirus DNA, 35% had HIV RNA, but only 30% had p24 antigen. A multiplex PCR specific for HBV, HCV and HIV1 (RNA and DNA) was developed for the investigation of a blood donor population from Namibia, where HBV and HIV1 infections occur more frequently than in German blood donors. The prevalence of anti-HIV1 antibodies in this population was 0.6%. HIV1 RNA was never detected in the plasma of 2,569 anti-HIV1-negative donors. HIV1 provirus DNA was present in 75% of the 16 anti-HIV1-positive individuals. None of these anti-HIV1-positive blood donors was also positive for p24 antigen. CMV infections and reactivations in 130 immunocompromised heart transplant patients and in 420 healthy anti-CMV-positive blood donors were monitored using cytochemical detection of CMV early antigen, and PCR. CMV DNA was neither detected in the plasma nor in the leucocytes of any anti-CMV-positive blood donor. During the course of CMV reactivation in immunocompromised heart transplant patients, CMV DNA was always detectable first in granulocytes and afterwards in the plasma. The cytochemical demonstration of CMV early antigen was typically delayed by several days and was observed in only 11% of those blood samples which contained CMV DNA in leucocytes. The determination of CMV DNA in leucocytes proved to be the most sensitive method to detect viraemia. Thus, CMV detection in leucocytes is the method of choice for the monitoring of transplant patients. This method is also promising for blood donor screening. The sensitive routine monitoring of blood donations for virus infections by multiplex PCR is practicable. However, nucleic acid must be extracted both from the plasma and from the cellular compartments of blood in order to detect HIV and CMV provirus DNA. Lysate from EDTA blood is a suitable material for this purpose. The determination of the surrogate marker serum ALT activity is of no use in hepatitis C screening, and determination of p24 antigen is not required in HIV1 screening.
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PMID:[Molecular biological screening of viruses important to transfusion medicine]. 948 64

We conducted a multicenter clinical evaluation of the second versions of the manual AMPLICOR and the semiautomated COBAS AMPLICOR tests for hepatitis C virus (HCV) RNA (Roche Molecular Systems, Inc., Pleasanton, Calif.). The performance characteristics of these HCV RNA tests for diagnosis of active viral infection were determined by comparison to anti-HCV serological test results, alanine aminotransferase levels, and liver biopsy histology results. A total of 878 patients with clinical or biochemical evidence of liver disease were enrolled at four hepatology clinics. A total of 1,089 specimens (901 serum and 188 plasma) were tested with the AMPLICOR test. Sensitivity compared to serology was 93.1% for serum and 90.6% for plasma. The specificity was 97% for serum and 93.1% for plasma. A total of 1,084 specimens (896 serum and 188 plasma) were tested with the COBAS test. Sensitivities for serum and plasma were the same as with the AMPLICOR test. The specificity was 97.8% for serum and 96.6% for plasma. Of the 69 specimens with false-positive and false-negative AMPLICOR test results relative to those of serology, alternative primer set (APS) reverse transcription (RT)-PCR analysis showed that the AMPLICOR test provided the correct result relative to the specimens containing HCV RNA in 64 (92.7%) specimens. Similarly, 66 of 67 (98.5%) false-positive and false-negative COBAS test results were determined to be correct by APS RT-PCR analysis. There were no substantive differences in clinical performances between study sites, patient groups, specimen types, storage conditions (-20 to -80 degrees C versus 2 to 8 degrees C), or anticoagulants (EDTA versus acid citrate dextrose) for either test. Both tests showed >99% reproducibility within runs, within sites, and overall. We conclude that these tests can reliably detect the presence of HCV RNA, as evidence of active infection, in patients with clinical or biochemical evidence of liver disease.
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PMID:Prospective multicenter clinical evaluation of AMPLICOR and COBAS AMPLICOR hepatitis C virus tests. 1168 22

The efficacy of two chelating agents (Tiron and calcium disodium EDTA) in the treatment of beryllium induced blood biochemistry and hepatic histopathological alteration was investigated at different duration in female albino rats. Single administration of beryllium nitrate at a dose of 50 mg/kg (im) showed significant decrease in haemoglobin percentage, blood sugar level, protein contents and activity of alkaline phosphatase. On the contrary significant elevation was found in the activity of transaminases (AST and ALT). Tiron was found to be more effective than CaNa2EDTA in reducing the beryllium induced haematological alterations and histopathological lesions in liver. These findings were further confirmed by AAS thus, in which reduced beryllium body burden was seen in liver and blood with Tiron.
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PMID:Comparative effectiveness of Tiron (4,5-dihydroxy benzene 1,3-disulphonic acid disodium salt) and CaNa2EDTA with time after beryllium poisoning. 1255 11

Each of 102 Nordic routine clinical biochemistry laboratories collected blood samples from at least 25 healthy reference individuals evenly distributed for gender and age, and analysed 25 of the most commonly requested serum/plasma components from each reference individual. A reference material (control) consisting of a fresh frozen liquid pool of serum with values traceable to reference methods (used as the project "calibrator" for non-enzymes to correct reference values) was analysed together with other serum pool controls in the same series as the project samples. Analytical data, method data and data describing the reference individuals were submitted to a central database for evaluation and calculation of reference intervals intended for common use in the Nordic countries. In parallel to the main project, measurements of commonly requested haematology properties on EDTA samples were also carried out, mainly by laboratories in Finland and Sweden. Aliquots from reference samples were submitted to storage in a central bio-bank for future establishment of reference intervals for other properties. The 25 components were, in alphabetical order: alanine transaminase, albumin, alkaline phosphatase, amylase, amylase pancreatic, aspartate transaminase, bilirubins, calcium, carbamide, cholesterol, creatine kinase, creatininium, gamma-glutamyltransferase, glucose, HDL-cholesterol, iron, iron binding capacity, lactate dehydrogenase, magnesium, phosphate, potassium, protein, sodium, triglyceride and urate.
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PMID:The Nordic Reference Interval Project 2000: recommended reference intervals for 25 common biochemical properties. 1522 94

The objective of this article is to present a series of 12 cases with the chronic lead poisoning produced after a short but intensive professional exposure (in average 12-14 hours per day, 41.6 days) at mineral dust and oxides containing lead (technical revision of a oven and of a furnace network by mechanical and welding operation). After the first case with saturnine colic, all the workers of the same team (n=12) were hospitalised (average time was of 14 days) with clinical examination and by specific toxicological indicators. Particularly, for clinical picture were uncharacteristic and oligosymptomatic complaints. Occupational exposure was augmented by the level of Pb-blood (46.8-286 mg/100 ml are ranges), Pb-urine (221-637 mg/l are ranges), d-aminolevulinic urinary acid (22.9-99.1 mg/l are ranges) and increased urinary coproporphyrins (+ +, + + +) exceeding biological limits and high urinary discharge of lead induced by CaNa2-EDTA treatment. The biological effects of lead intoxication consist in the occurrence of stippled basophilic erythrocytes (2 cases with 46,000/1 mil erythrocytes), the anemia (only 4 cases with haematocrit L 40%) and the liver cytolytic syndrome (the increase of GPT, GOT and of g-GT). These changes and the polyneuropathic syndrome (the decrease of motor and sensitive speed velocity) were judged by toxic combination between ethanol and lead.
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PMID:[Chronic lead poisoning like a group pathology. Clinical report of 12 cases]. 1568 76

The aim of the present study was to evaluate pharmacological and toxicological properties of 1-buthyltelurenyl-2-methylthioheptene (compound 1). In vitro, compound 1 at 1 microM was effective in reducing lipid peroxidation induced by Fe/EDTA. Compound 1 presented neither thiol peroxidase nor thiol oxidase activity and did not change delta-ALA-D (delta-aminolevulinate dehydratase) activity (10-400 microM). Calculated LD(50) of compound 1, administered by oral route, was 65.1 micromol/kg. Rats treated with compound 1 did not reveal any motor impairment in the open field. Hepatic, renal and cerebral lipid peroxidation in treated rats did not differ from those in control rats. Conversely, 0.5 micromol/kg of compound 1 decreased lipid peroxidation in spleen. Delta-ALA-D activity in liver and spleen was inhibited in rats treated with the higher dose of compound 1 but no significant differences were detected in renal delta-ALA-D activity. AST (aspartate aminotransferase) and ALT (alanine aminotransferase) activities as well as urea and creatinine levels were increased by high doses of compound 1 (50-75 micromol/kg). Compound 1 induced a significant decrease in plasma triglyceride levels but none of the doses tested changed the cholesterol level. This is a promising compound for more detailed pharmacological studies involving organotellurium compounds.
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PMID:Evaluation of antioxidant activity and potential toxicity of 1-buthyltelurenyl-2-methylthioheptene. 1671 63

The effects of various types of anticoagulants on plasma biochemistry were studied in man and various animals but limited informations are existing for camel plasma biochemistry. Eleven clinically healthy one-humped camels were blood sampled in different tubes containing different anticoagulants and plain tubes for harvesting plasma and serum. The concentrations of glucose, cholesterol, triglyceride, total bilirubin, urea, creatinine, total protein, albumin, calcium, inorganic phosphorus, magnesium, and chloride and the activity of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), creatine kinase (CK) and gamma glutamyl transferase (GGT) were measured. Except for the amounts of AST, ALT, CK, total bilirubin, and inorganic phosphorus, other measured parameters were significantly lower in citrated plasma than in serum. Most parameters did not show any difference, but significant increase for CK activity and significant decrease for GGT, cholesterol, creatinine and chloride were seen when heparin was used as anticoagulant. Using EDTA as an anticoagulant caused a significant difference in the amounts of some measured parameters in plasma except glucose, AST, ALT, GGT, cholesterol, albumin, total protein, bilirubin, and triglyceride in comparison with serum.
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PMID:Plasma biochemistry of one-humped camel (Camelus dromedarius): effects of anticoagulants and comparison with serum. 1837 99

The present investigation was an attempt to evaluate the ameliorative effect of curcumin on aflatoxin-induced toxicity on serum and blood of mice. Aflatoxin was obtained by growing Aspergillus parasiticus in SMKY liquid medium. Pure curcumin (97% purity) was purchased from Hi-Media Laboratories Pvt. Ltd., Mumbai, India. Young adult male albino mice were orally administered with low dose and high dose (750 and 1500 microg/kg body weight) with and without curcumin (2 mg/0.2 mL olive oil/animal/day) for 45 days. On 46th day the animals were sacrificed by cervical dislocation. For serum parameters blood was collected in non-EDTA containing vails from heart of the dissected mice. Serum parameters are creatinine, protein, AST and ALT. The results revealed dose dependent increase in creatinine, AST and ALT and decrease in protein in serum parameters of mice. Treatment with curcumin along with aflatoxin ameliorates aflatoxin-induced changes in serum parameters.
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PMID:Ameliorative effect of curcumin on aflatoxin-induced toxicity in serum of mice. 1864 53


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