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Hepatic Enzymes (hepatic + enzyme)

Distribution by Scientific Domains

Medical Sciences	91%

Terms modified by Hepatic Enzymes

hepatic enzyme activity

Selected Abstracts

Effect of Labour and Delivery on Plasma Hepatic Enzymes in the Newborn

JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 1 2000
Dr. Max Mongelli
Abstract Objective: To study the relationship between cord blood hepatic enzymes and obstetric and neonatal outcome in a Chinese population. Materials and Methods: The study group consisted of 288 low-risk Chinese women with singleton term pregnancies. The following enzymes were assayed in cord blood: lactate dehydrogenase (LDH), glutamyl transferase (GGT), aspartate aminotransferase (AST) and alanine transferase (ALT). These were correlated to maternal and neonatal characteristics. Results: A strong correlation was noted between cord blood AST and LDH (R = 0.582, p < 0.01), which was absent amongst those infants delivered by elective cesarean section. LDH, AST and ALT were negatively correlated with cord arterial pH and base excess (BE). GGT was inversely related only to gestational age (R = - 0.18, p < 0.01). Both LDH and AST were weakly correlated with the duration of the first and second stages of labour. LDH was most closely linked to arterial pH, whereas AST was related to both arterial BE and duration of the second stage. Conclusions: The reference values are comparable to those published for Caucasian populations. There are moderate elevations in LDH and AST associated with the onset of labour and changes in acid-base status. [source]

Mutational Spectrum and Linkage Disequilibrium Patterns at the Ornithine Transcarbamylase Gene (OTC)

ANNALS OF HUMAN GENETICS, Issue 6 2006
L. Azevedo
Summary Ornithine transcarbamylase (OTC; EC 2.1.3.3) is a hepatic enzyme involved in ammonia elimination via the urea cycle. Since the sequence of the OTC gene was reported many types of mutations continue to be found in OTC deficiency patients, continuing to increase the already wide mutational spectrum known for this gene. In this study we present the clinical, biochemical and molecular features of thirteen late-onset OTC deficiency patients. Mutations were identified in all these patients, among which six were novel point substitutions (L59R, A137P, L148S, Y176L, L186P, and K210N) and one was a 2-bp deletion at exon 4 (341-342delAA). In addition, a de novo genomic deletion of maternal origin encompassing exons 1 to 5 was also identified by the analysis of LD patterns using intragenic polymorphic markers. This work exemplifies the potential value of population genetic studies for the detection of large deletions. [source]

Hyperhomocysteinemia in epileptic patients on new antiepileptic drugs

EPILEPSIA, Issue 2 2010
Vincenzo Belcastro
Summary Purpose:, Older enzyme-inducing antiepileptic drugs (AEDs) may induce supraphysiologic plasma concentrations of total (t) homocysteine (Hcy). The aim of the present study was to investigate the effect of new AEDs on plasma tHcy levels. Methods:, Patients 18,50 years of age, on AEDs monotherapy, with no other known cause of hyper-tHcy were enrolled. Plasma tHcy, folate, vitamin B12, and AEDs levels were determined by standard high-performance liquid chromatography (HPLC) methods. Methylenetetrahydrofolate-reductase (MTHFR) polymorphisms were checked using Puregene genomic DNA purification system (Gentra, Celbio, Italy). A group of healthy volunteers matched for age and sex was taken as control. Results:, Two hundred fifty-nine patients (151 on newer and 108 on older AEDs) and 231 controls were enrolled. Plasma tHcy levels were significantly higher [mean values, standard error (SE) 16.8, 0.4 vs. 9.1, 0.2 ,m; physiologic range 5,13 ,m] and folate lower (6.3, 0.1 vs. 9.3, 0.1 nm; normal > 6.8 nm) in patients compared to controls. Patients treated with oxcarbazepine, topiramate, carbamazepine, and phenobarbital exhibited mean plasma tHcy levels above the physiologic range [mean values (SE) 16 (0.8), 19.1 (0.8), 20.5 (1.0), and 18.5 (1.5) ,m, respectively]. Conversely, normal tHcy concentrations were observed in the lamotrigine and levetiracetam groups [both 11.1 (0.5) ,m]. Discussion:, Oxcarbazepine and topiramate might cause hyper-tHcy, most likely because of the capacity of these agents to induce the hepatic enzymes. Because literature data suggest that hyper-tHcy may contribute to the development of cerebrovascular diseases and brain atrophy, a supplement of folate can be considered in these patients to normalize plasma tHcy. [source]

Valproic Acid-Induced Hyperammonemic Encephalopathy with Triphasic Waves

EPILEPSIA, Issue 7 2000
Akira Kifune
Summary: Purpose: To examine a patient with valproic acid (VPA)-induced hyperammonemic encephalopathy accompanied by triphasic waves. Methods: A 61-year-old male patient with epilepsy experienced disturbance of consciousness after VPA dose was increased because of poor seizure control. The electroencephalogram (EEG) taken on admission revealed triphasic waves and high-amplitude ,-activity with frontal predominance. Although serum hepatic enzymes, such as AST and ALT, were normal, serum ammonium level was high at 96 ,g/dl (normal range, 3,47 ,g/dl). Serum amino acid analysis showed multiple minor abnormalities. Administration of VPA was discontinued immediately after admission, while other anticonvulsants were continued. Results: The patient's condition was improved on the fourth day of admission. An EEG, serum ammonium level, and amino acid profile were normal on the eighth day. Based on VPA administration, serum ammonium levels, and results of amino acid analysis, this patient had VPA-induced hyperammonemic encephalopathy. Conclusions: Our case indicates that caution is required if triphasic waves appear in VPA-induced hyperammonemic encephalopathy. [source]

Variable expression of CYP and Pgp genes in the human small intestine

EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 6 2003
M. Lindell
Abstract Background ,The small intestine is receiving increased attention for its importance in drug metabolism. However, knowledge of the intervariability and regulation of the enzymes involved, cytochrome P450 and P-Glycoproteins (CYP and Pgp), is poor when compared with the corresponding hepatic enzymes. Methods ,The expression of eight different CYP genes and the Pgp were determined by reverse transcription polymerase chain reaction (RT-PCR) in 51 human duodenum biopsies. And the variability and correlation of expression was analyzed. Results ,Extensive interindividual variability was found in the expression of most of the genes. Only CYP2C9, CYP3A4 and Pgp were found in all samples. CYP1A2, CYP2A6 and CYP2E1 exhibited the highest interindividual variability. No strong correlation of expression existed between the genes. But a highly significant correlation was found between CYP2D6/1A2, 2D6/2E1, 1A2/2E1 and 2B6/2C9. Acetylsalicylic acid and omeprazole significantly increased the expression of CYPs 2A6, 2E1 and 3A4, respectively. Conclusions ,Extensive interindividual variability is characteristic for the expression of drug-metabolizing CYP and Pgp genes in human duodenum, and external factors such as drugs may further increase the variability. It is possible that the large interindividual variability may lead to variable bioavailability of orally used drugs and hence complicate optimal drug therapy, especially for drugs with a small therapeutic window. Elucidation of factors contributing to clinically important variances warrants further investigation. [source]

An animal model of testicular toxicity by cyclosporine: evaluation and protection

FUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 2 2009
Ridha Ben Ali
Abstract CyclosporineA (CsA) improves the survival of patients who benefited from transplantation. However, its use is generally limited by its side effects. The aim of our study was to measure, in an experimental model, the changes of the testosterone plasma levels after 21 days of CsA treatment and to explain the mechanism of this modification. After treatment, the levels of CsA, testosterone, corticosterone, transaminases were measured. The cytotoxic effect of CsA was evaluated by microscopic observation. The experimental study showed that CsA had no effect on the plasmatic levels of hepatic enzymes - alanine aminotransferase, aspartate aminotransferase and gamma-glutamyl-transferase , because their plasma concentrations in treated rats did not differ from those of the sham group. The plasma concentration of corticosterone was not modified, the plasma level of testosterone decreased when the dose of cyclosporine was increased to 4 mg/kg/day. The photonic microscope observation showed that the number of Leydig cells was increased and the electronic microscope observation showed mitochondria alteration. The treatment by CsA and trimetazidine did not correct the alteration caused by CsA. N-benzyl-N'-(2-hydrox-3, 4-dimethyloxybenzyl)-pipeazine did not protect the mitochondrial function but partially protected mitochondria structure from the deleterious effect induced by CsA. The decrease of the plasma level of testosterone induced by CsA was due to the inhibition of the mitochondrial 20,22 desmolase which blocked the formation of the testosterone precursor and the destruction of the mitochondria structure. [source]

Metabolic differences between Asian and Caucasian patients on clozapine treatment

HUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 4 2007
Mythily Subramaniam
Abstract Objective To establish if there are ethnic differences in the various metabolic disturbances that are common with clozapine treatment. Method Forty subjects (20 Asians and 20 Caucasians) with a diagnosis of schizophrenia were recruited for the study. Clozapine blood levels as well as fasting blood glucose, lipid levels, and liver function tests were established. Other clinical parameters such as blood pressure and Body Mass Index (BMI) were recorded for each patient. Results The mean clozapine dose was significantly higher in the Caucasian subjects (432.5,±,194.7,mg) as compared to the Asian subjects (175.6,±,106.9,mg) (p,<,0.001) while the mean weight-corrected dose for Asian patients was lower (3.0,±,1.9 and 5.0,±,2.1,mg/kg, respectively, p,=,0.005). There were, however, no ethnic differences in the mean plasma clozapine concentration (415.3,±,185.8,ng/ml in Caucasians and 417.1,±,290.8,ng/ml in Asians). BMI were significantly higher in Caucasians, as were the number of subjects with hypertension; levels of hepatic enzymes were higher in the Asian group. Conclusions Not only are there pharmacokinetic differences between Asian and Caucasian patients receiving clozapine, but there may also be differential emergence of certain metabolic abnormalities like hypertension and weight gain in these two ethnic groups. However, the effects of life style including diet and exercise cannot be excluded. Copyright © 2007 John Wiley & Sons, Ltd. [source]

Pharmacokinetics and pharmacodynamics of prasugrel in subjects with moderate liver disease

JOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 5 2009
D. S. Small PhD
Summary Background and Objective:, Prasugrel is a thienopyridine antiplatelet agent under investigation for the prevention of atherothrombotic events in patients with acute coronary syndrome who undergo percutaneous coronary intervention. Patients with chronic liver disease are among those in the target population for prasugrel. As hepatic enzymes play a key role in formation of prasugrel's active metabolite, hepatic impairment could affect the safety and/or efficacy of prasugrel in such patients. Methods:, This was a parallel-design, open-label, multiple dose study of 30 subjects, 10 with moderate hepatic impairment (Child-Pugh Class B) and 20 with normal hepatic function. Prasugrel was administered orally as a 60-mg loading dose (LD) and daily 10-mg maintenance doses (MDs) for 5 days. Pharmacokinetic parameters (AUC0,t, Cmax and tmax) and maximal platelet aggregation (MPA) by light transmission aggregometry were assessed after the LD and final MD. Results and Discussion:, Exposure to prasugrel's active metabolite was comparable between healthy subjects and those with moderate hepatic impairment. Point estimates for the ratios of geometric least square means for AUC0,t and Cmax after the LD and last MD ranged from 0·91 to 1·14. MPA to 20 ,m ADP was similar between subjects with moderate hepatic impairment and healthy subjects for both the LD and MD. Prasugrel was well tolerated by all subjects, and adverse events were mild in severity. Conclusion:, Moderate hepatic impairment appears to have no effect on exposure to prasugrel's active metabolite. Furthermore, MPA results suggest that moderate hepatic impairment has little or no effect on platelet aggregation relative to healthy controls. Overall, these results suggest that a dose adjustment would not be required in moderately hepatically impaired patients taking prasugrel. [source]

Clinical drug interactions in outpatients of a university hospital in Thailand

JOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 6 2005
B. Janchawee PhD
Summary Background:, A clinical event is likely to occur in patients receiving a pair of drugs, that have the potential to cause an interaction. The occurrence of a clinical drug,drug interaction in outpatients of university hospitals in Thailand is unknown. Purpose:, To investigate the occurrence of a clinical event associated with drug,drug interactions in outpatients at a Thai university hospital. Methods:, A case,control study was established. The case was a sample group, randomly selected from a 1-year sample of outpatient prescriptions containing ,significance-1' potential drug,drug interactions, whereas the control was from the same year but with no potential drug interactions. Medical records of the cases and the controls were reviewed for an adverse event (AE) using a newly developed review form. The odds ratio of occurrence of the AE between the cases and the controls was determined. The AE was assessed for its possibility of being caused from a drug,drug interaction. Results:, The most common specific AE in both the cases and the controls was cough. An unplanned revisit to outpatient department or emergency room was found to be the most common general AE. The odds ratio of the occurrence of an AE in the cases, compared with the controls, was 1·495 (95% CI: 0·917,2·438). The possibility that the AEs resulted from drug interactions in the case group was nine ,probable' patients and 15 ,possible' patients, whereas that in the control group was eight ,possible' patients. The most common interacting drug pair was isoniazid,rifampin with an increase in serum hepatic enzymes as the corresponding AE. Conclusions:, Despite outpatients receiving drug pairs with a high potential for adverse interactions, the rate of occurrence of clinical drug interaction events was low. [source]

Effect of Labour and Delivery on Plasma Hepatic Enzymes in the Newborn

Haematological and biochemical abnormalities in canine blood: frequency and associations in 1022 samples

JOURNAL OF SMALL ANIMAL PRACTICE, Issue 7 2004
S. Comazzi
Submission of blood samples to referral laboratories is very common in veterinary practice. Internal reference ranges should take into account published ranges adapted to the methods and apparatus used and to the population under consideration. The aim of this study was to examine the results from 1022 consecutive canine blood tests, analysing the frequency and the main associations of abnormalities, and to compare the results in different age groups. Haemograms and serum biochemistry were compared with internal ranges and between age groups: younger than one year, one to eight years and older than eight years. Young dogs exhibited lower numbers of erythrocytes and lower values for haemoglobin concentration and packed cell volume. They also showed higher numbers of lymphocytes and higher concentrations of phosphorus and 71 per cent showed raised alkaline phosphatase. Neutrophilia, hypergammaglobulinaemia and hypoalbuminaemia occurred quite frequently in all dogs, and hypoalbuminaemia and hyperphosphataemia were commonly seen in uraemic patients. The simultaneous evaluation of cytolytic and hepatobiliary enzymes allowed better detection of liver damage, since only a very low percentage of dogs had simultaneous increases in all hepatic enzymes. [source]

Smoking and anaesthesia: the pharmacological implications

ANAESTHESIA, Issue 2 2009
B. P. Sweeney
Summary Anaesthetists are generally familiar with the peri-operative implications of cigarette smoking. Although there are a number of publications dealing with the wider pharmacological implications of cigarette smoking, the specific interactions which are of direct relevance to anaesthetists are less well known. This review gives an overview of those interactions which are of clinical relevance to anaesthetists and provides, where possible, an explanation of the mechanism. Recent improvements in the understanding of biotransformation of drugs, including streamlining of the classification of hepatic enzymes has allowed better understanding of drug interactions and enables the mechanistic prediction of those involving new drugs. [source]