PURPOSE: Oxcarbazepine (OXC) is chemically related to carbamazepine (CBZ). OZC exerts less liver enzyme induction than CBZ and is completely metabolized by reduction to the active metabolite, 10, 11-dihydro-10-hydroxy-5H-dibenzo (b,f) azepine-5-carboxamide (MHD). It was known that OXC had no significant pharmacokinetic interactions with other antiepileptic drugs. But it is not thoroughly studied yet because of short duration of clinical application. We investigated whether the plasma concentration of OXC metabolite (MHD) is changed by valproic acid compared with OXC monotherapy and studied the correlation of the dose of OXC with the plasma concentration of its active metabolite (MHD). METHODS: The patient with OXC monotherapy (19 cases) and patients with OXC and valproic acid(16 cases) were incluses. We analyzed the level of its metabolites MHD by HPLC RESULTS: The plasma concerntration of MHD in OXC monotherapy is 15.5+/-3.2 microgram/ml and that of the MHD in polytherapy with valproic acid is 16.4+/-3.4 microgram/ml at the same dose of OXC. The plasma concentration of MHD is ranged from 7.4 microgram/ml at 600 mg/day of OXC to 27.0 microgram/ml at 1800 mg/day of OXC and highly correlated with OXC dose per body weight (r=0.72-84). CONCLUSION: There is no significant change or difference of MHD plasma concentraion between OXC monotherapy and polytherapy with valproic acid at the same dose of OXC. THe plasma concentration of MHD is highly correlated with OXC dose per body weight.
Anticonvulsants ; Body Weight ; Carbamazepine ; Chromatography, High Pressure Liquid ; Enzyme Induction ; Humans ; Liver ; Plasma* ; Valproic Acid

Nucleoside phosphorylases (NPases) were found to be induced in Enterobacter aerogenes DGO-04, and cytidine and cytidine 5'-monophosphate (CMP) were the best inducers. Five mmol/L to fifteen mmol/L cytidine or CMP could distinctly increase the activities of purine nucleoside phosphorylase (PNPase), uridine phosphorylase (UPase) and thymidine phosphorylase (TPase) when they were added into medium from 0 to 8 h. In the process of enzymatic synthesis of adenine arabinoside from adenine and uracil arabinoside with wet cells of Enterobacter aerogenes DGO-04 induced by cytidine or CMP, the reaction time could be shortened from 36 to 6 h. After enzymatic reaction the activity of NPase in the cells induced remained higher than that in the cells uninduced.
Cytidine ; pharmacology ; Cytidine Monophosphate ; pharmacology ; Enterobacter aerogenes ; enzymology ; Enzyme Induction ; Pentosyltransferases ; biosynthesis ; Vidarabine ; biosynthesis

OBJECTIVETo study the stereoselectivity of R-(+) and S-(-)-propranolol glucuronidation and metabolic interaction between R(+)- and S-(-)-propranolol.

METHODSA RP-HPLC analytical method was developed for determination of R-(+)-and S-(-)-propranolol glucuronide (PG) incubated with rat hepatic microsome induced with phenobarbital (PB). The method was applied to investigate the stereoselectivity metabolism of racemic propranolol glucuronidation in vitro.

RESULTIn control and PB group, the concentration of R-(+)-PG produced at different substrates was higher than that of S-(-)-PG. Compared with the control, the V(max) and Cl(int) for R(+)-and S-(-)-propranolol increased significantly the K(m) for R(+)-propranolol was elevated, while that for S-(-) propranolol was decreased.

CONCLUSIONThere is a stereoselectivity in glucuronidation of propranolol in rat hepatic microsome induced with PB and R-(+)-propranolol is preferred. Metabolic interaction between R-(+)-and S-(-)-propranolol exists with a concentration-dependent mode.

Animals ; Enzyme Induction ; Microsomes, Liver ; enzymology ; Phenobarbital ; pharmacology ; Propranolol ; analogs & derivatives ; metabolism ; Rats ; Rats, Sprague-Dawley ; Stereoisomerism

PURPOSE: It is known that serum thyroid hormones and lipid profiles are affected by the different biotransformation pathways of antiepileptic drugs (AEDs). The aim of this study was to evaluate thyroid functions and lipids in epileptic patients taking AEDs. METHODS: We prospectively examined serum thyroid hormone concentrations and lipid profiles in 45 patients with epilepsy and compared them with 45 healthy age- and sex-matched controls. We measured serum free T4 (FT4), thyroid stimulating hormone (TSH), thyroid peroxidase antibody (TPO-ab), thyroid globulin antibody (TG-ab), total cholesterol, low density lipoprotein (LDL), high density lipoprotein (HDL) and triglycerides (TG). To analyze, the patient groups were divided into two groups:36 patients using hepatic enzyme inducing AEDs and 9 patients using non-enzyme-inducing AEDs. RESULTS: Mean age, sex and body mass index (BMI) were not different in both groups. The serum free T4 level of all patients was lower than that of the control group (p<0.05). The serum free T4 level of the patients taking hepatic enzyme inducing AEDs was lower than that of the control group. TSH, TPO-ab and TG-ab levels were not different in both groups. There was no correlation between free T4 levels and the duration of therapy in the patient group. For lipids, LDL, HDL, TG and total cholesterol, levels were not different in both groups. CONCLUSIONS: Hepatic enzyme inducing AEDs led to a decrease in free T4 levels but the TSH level remained normal. These findings seem to be not only due to liver enzyme induction but also hypothalamic interference of regulation of thyroid hormone production by the drugs. Lipid profiles were not significantly influenced by AEDs but further evaluation should be needed.
Anticonvulsants* ; Biotransformation ; Body Mass Index ; Cholesterol ; Enzyme Induction ; Epilepsy ; Humans ; Iodide Peroxidase ; Lipoproteins ; Liver ; Prospective Studies ; Thyroid Gland* ; Thyroid Hormones* ; Thyrotropin ; Triglycerides

PURPOSE: Neopterin is a degradation product derived from guanosin triphosphate (GTP) during biosynthesis of tetrahydrobiopterin. It is produced by human monocytes/macrophages upon stimulation with interferon-gamma from activated T lymphocytes. Therefore, increased neopterin concentration suggests the activation of cell-mediated immune response during viral infections, autoimmune diseases, allograft rejection, immunodeficiencies and certain types of malignancy. In these diseases, increased neopterin concentrations in serum and urine correlate to the stage of disease and predict worse prognosis. It has been proved that in various malignant disorders, higher neopterin concentrations are associated with more rapid disease progression and are a valuable predictor of stage and extension of the tumor. METHODS: Serum neopterin concentrations were measured by ELISA test in 20 patients with acute lymphocytic leukemia (ALL) at diagnosis and at complete remission after induction chemotherapy, and in 20 normal children that served as the control group. RESULTS: Serum neopterin levels were significantly (P=0.021) increased in the ALL group at diagnosis (9.48 nmol/L) compared to the control group (4.49 nmol/L). In the ALL group, serum neopterin levels were significantly (P=0.015) decreased at complete remission state (6.84 nmol/L) compared to the time of diagnosis (11.96 nmol/L). CONCLUSION: Neopterin was shown to be a valuable indicator of disease activity in childhood ALL and will contribute to predicting the treatment response.
Allografts ; Autoimmune Diseases ; Child ; Diagnosis ; Disease Progression ; Enzyme-Linked Immunosorbent Assay ; Humans ; Induction Chemotherapy ; Interferon-gamma ; Neopterin* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma* ; Prognosis ; T-Lymphocytes

Levoglucosan is the main product derived from pyrolysis of cellulose. A mutant Aspergillus niger CBX-209 could grow on levoglucosan well fermenting it into citric acid with a yield comparable to that on glucose. Levoglucosan hydrolase was absent by measuring glucose formation with the glucose oxidase and peroxidase coupling system. Cell extracts were partly purified by ammonium sulfate fractionation and ion-exchange chromatograph. Direct formation of glucose 6-phosphate from levoglucosan in the presence of ATP and MgCl2 was observed when it was reacted with partly purified enzyme by a combined strategy of enzymological and fast atom bombardment mass spectrometric analysis. These data showed that the mutant used a novel enzyme, levoglucosan kinase, to convert levoglucosan into glucose 6-phosphate. Levoglucosan kinase was an inductive enzyme.
Aspergillus niger ; metabolism ; Enzyme Induction ; Fermentation ; Glucose ; analogs & derivatives ; metabolism ; Glucose-6-Phosphate ; metabolism ; Phosphorylation ; Phosphotransferases ; biosynthesis ; Spectrometry, Mass, Fast Atom Bombardment

OBJECTIVETo study the effects of chrysotile on the activities of some enzymes for xenobiotics metabolism.

METHODSUICC chrysotile (UC) and China Mangya chrysotile (MC) asbestos fibers were used at different doses (0, 25, 50, 100, 200 mg/L) to study its effects on the activities of cytochrome P4501A1 and glutathione S-transferase (GST) in A549 cell line. Also, the effects of chrysotile on the activities of CYP1A1 and GST induced by benzo(a)pyrene were studied.

RESULTSThe activity of EROD increased slowly with the increasing dose of UC, as A549 cells were incubated with UC for 24 h, and EROD activity increased by 40% at a dose of 200 mg/L UC. However, activity of EROD decreased by 32% with 48 h incubation at the same dose, indicating that lower dose of UC and short time could induce the activity of EROD in A549 cells, whereas higher doses and long time could inhibit its activity. MC exhibited a multiphasic effects on the activity of EROD, whether at a dose of 25 mg/L for 24 h or 48 h all gave the strongest induction, 1.86 times or 1.28 times as controls, respectively. However, EROD activity decreased with the increases in MC doses and incubation time, with the lowest as 35% of the controls. The effect of UC on GST activity was not so obvious, with the highest as the increase in its activity by 20%. The highest induction of MC to GST activity was at a dose of 25 mg/L, 2, 5 times as that in controls. With the increases in its doses, effects of MC on GTS activity became inhibition from induction, like that on EROD activity. MC at a dose of 200 mg/L could lower the activity of GST by 18.7%. A549 cells were incubated with chrysotile fiber for 24 h firstly, and then incubated with benzo(a)pyrene to induce the activities of EROD and GST. The results showed that neither UC nor MC could affect the activity of EROD induced by benzo(a)pyrene. However, UC at a dose of 200 mg/L and MC at 100 mg/L could increase the activity of GST induced by benzo(a)pyrene.

CONCLUSIONChrysotile at different doses or its different types showed varied effects on the activities of EROD and GST in A549 cell lines, probably because of different physicochemical characteristics and surface activity of two kinds of asbestos.

Asbestos, Serpentine ; toxicity ; Cytochrome P-450 CYP1A1 ; metabolism ; Dose-Response Relationship, Drug ; Enzyme Induction ; Glutathione Transferase ; metabolism ; Humans ; Lung Neoplasms ; enzymology ; Tumor Cells, Cultured

The paper summarizes the interactions between luteolin (glucosides) and drug-metabolizing enzyme from the literature of recent years and our research work. The metabolism of luteolin is chiefly mediated by phase II metabolic enzyme. Its glucosides are firstly hydrolyzed into aglycone in intestinal tract, and then absorbed and metabolized. Luteolin has the effect on the induction of CYP3A, and on the inhibition of CYPIA, 1B and 2E. Also, luteolin is an effective inhibitor of CYP2B6, CYP2C9 and CYP2D6. Luteolin can induce and inhibit UGTs and SULTs. It can also inhibit multi ABC transport proteins. Understanding the interactions between luteolin (glucosides) and drug-metabolizing enzyme has an important significance in guiding clinical use of the drug.
ATP-Binding Cassette Transporters ; metabolism ; Animals ; Aryl Hydrocarbon Hydroxylases ; metabolism ; Drug Interactions ; Enzyme Induction ; Glucuronosyltransferase ; metabolism ; Humans ; Luteolin ; metabolism ; Microsomes, Liver ; metabolism ; Sulfotransferases ; metabolism

The aim of this study was to investigate whether serum levels of anti-Mullerian hormone (AMH) and inhibin B at ovulation triggering day correlate with the number of immature oocytes obtained from stimulated in vitro fertilization (IVF) cycles. Fiftynine consecutive cycles of ovarian hyperstimulation and IVF were selected from 45 women who had tubal (n=18) or unexplained infertility (n=27) and obtained at least one oocyte. Serum levels of AMH and inhibin B at ovulation triggering day were measured by enzyme-linked immunosorbent assay (ELISA). Univariate analysis and multiple regressions revealed that serum AMH or inhibin B levels were significantly correlated with immature oocyte count and the correlation coefficients were higher compared to the mature oocyte count. Serum AMH and inhibin B levels on triggering day seems to be more closely related with the immature oocyte count and thus could be good predictors to determine the immature oocyte count in IVF cycle.
Adult ; Anti-Mullerian Hormone/*blood ; Enzyme-Linked Immunosorbent Assay ; Female ; *Fertilization in Vitro ; Humans ; Inhibins/*blood ; *Oocyte Retrieval ; *Ovulation Induction ; Regression Analysis

OBJECTIVETo investigate the change in the antibiotic resistant spectrum of Pseudomonas aeruginosa (PA) isolated from burn wounds and the production of inducible beta-lactamase.

METHODSVITEK-AMS system (total automatic bacterial identification and drug sensitivity system) and E-test concentration gradient were employed to perform bacterial identification and antibiotic sensitivity tests. K-B method was applied to detect inducible enzyme.

RESULTSThe resistance of PA to Cephalosporin and Imipenem was increased in the past 4 years from June of 1996 to June of 2000. Whereas the resistance to Cefoperazone/Sulbactam was least. There was an obvious difference of the resistance of PA to antibiotics during the 4 years (P < 0.05). The resistant rate to Imipenem ranged from 20% to 40%. PA was able to produce inducible enzymes among 120 strains of wild type of PA occupying 72.5% with Imipenam as the inducing agent.

CONCLUSIONThe analysis of the antibiotic resistance of PA and the detection of inducible enzymes could be monitored from time to time and helpful in the correction of the use of antibiotics. Constant monitoring of antibiotic resistance might be beneficial to the prevention of outbreak of epidemics of PA infection in a burn unit.

Burns ; microbiology ; Cephalosporins ; pharmacology ; Drug Resistance, Bacterial ; Enzyme Induction ; Humans ; Imipenem ; pharmacology ; Microbial Sensitivity Tests ; Pseudomonas aeruginosa ; drug effects ; isolation & purification