No abstract available.
Animals ; Ethanol* ; Metabolism* ; Phenobarbital* ; Rats* ; Trichloroethylene*

OBJECTIVES: To evaluate the effects on the formation of benzidine-hemoglobin, and benzidine metabolite-hemoglobin adducts, caused by pretreatment with the known xenobiotic metabolism effectors, ethanol and phenobarbital, in rats administered Direct Black 38 dye. METHODS: The experimental rats were divided into three groups: a control group, an ethanol group and a phenobarbital group. Rats were pretreated with ethanol (1g/kg) or phenobarbital (80mg/kg) 24 hours prior to the oral administration of Direct Black 38 (0.5mmol/kg), with the control group being administered the same amount of distilled water. Blood samples were obtained from the vena cava of 5 rats from each group prior to, and at 30 min, 3 h, 6 h, 9 h, 12 h, 24 h, 48 h, 72 h, 96 h, and 144 h following the oral administration of Direct Black 38. Directly after sampling the blood was separated into hemoglobin and plasma, with the adducts being converted into aromatic amines by basic hydrolysis. Hydrolyzed benzidiene, monoacetylbenzidine and 4-aminobiphenyl were analyzed by reverse-phase liquid chromatography with an electrochemical detector. The quantitative amount of the metabolites was expressed by the hemoglobin binding index (HBI). RESULTS: In the ethanol group, benzidine-, monoacetylben-zidine-, and 4-aminobiphenyl-HBI were increased to a greater extent than those in the control group. These results were attributed to the ethanol inducing N-hydroxylation, which is related to the formation of the hemoglobin adduct. In the phenobarbital group, all the HBIs, with the exception of the benzidine-HBI, were increased to a greater extent than those of the control group. These results were attributed to the phenobarbital inducing N-hydroxylation related to the formation of the hemoglobin adduct. The N-acetylation ratio was only increased with the phenobarbital pretreatment due to the lower benzidine-HBI of the phenobarbital group compared to those of the control and ethanol groups. The N-acetylation ratios for all groups were higher than 1 for the duration of the experimental period. Although the azo reduction was unaffected by the ethanol, it was inhibited by the phenobarbital. The ratio of the benzidine-HBI in the phenobarbital group was lower than those of the ethanol the control groups for the entire experiment. CONCLUSION: Our results indicate that both ethanol and phenobarbital increase the formation of adducts by the induction of N-hydroxylation, but also induced N-acetylation. Phenobarbital decreased the formation of benzidine-HBI due to the decrease of the azo reduction. These results suggest that the effects of ethanol and phenobarbital need to be considered in the biochemical monitoring of Direct Black 38.
Administration, Oral ; Amines ; Animals ; Chromatography, Reverse-Phase ; Ethanol* ; Hydrolysis ; Metabolism ; Phenobarbital* ; Plasma ; Rats* ; Water

Anticonvusant therapy with any of several agents, especially phenytoin, phenobarbital, and primidone causes disturbances in bone mineral metabolism. Anticonvulsants stimulate the hepatic microsomal mixed-oxidase enzymes and hence increase the rate of clearance of vitamin D and its metabolism. The severity of clinical manifestations in any given individual appears to be a function of the combined effects of variety of factors including drug type and total drug dose, dietary vitamin D intake, sunlight exposure, and physical activity level. We report a case of osteomalacia associated with long term carbamazepine therapy in a 21-year-old male with less exposure to sunlight.
Anticonvulsants ; Carbamazepine* ; Humans ; Male ; Metabolism ; Motor Activity ; Osteomalacia* ; Phenobarbital ; Phenytoin ; Primidone ; Sunlight ; Vitamin D ; Young Adult

OBJECTIVES: The effects of ethanol and phenobarbital,which are known to affect metabolism of xenobiotics, on the formation of benzidine-and its metabolites-plasma protein adducts in rats administered benzidine were evaluated. METHODS: The experimental rats were divided into the control,ethanol and phenobar-bital groups. The experimental groups (ethanol and phenobarbital group)were pretreated with ethanol (1g/kg)or phenobarbital (80mg/kg)24 hours prior to the oral administration of benzidine (0.5mmol/kg). Blood samples were obtained from the vena cava from 5 rats in each group; and at 30 min,3 h,6 h,9 h,12 h,24 h,48 h,72 h,96 h,and 144 h after the administration of benzidine using heparin treated syringes.The plasma protein levels were separated immediately after taking blood samples. The adducts were underwent basic hydrolysis to convert them into aromatic amines. The hydrolyzed benzidine, monoacetylbenzidine, and 4-aminobiphenyl were analyzed by reverse-phased liquid chro-matography with an electrochemical detector. The quantitative amount of the metabolites was expressed by the plasma protein binding index(PBI). RESULTS: Similar to the hemoglobin adducts,the levels of the plasma protein adducts of the ethanol and phenobarbital groups (benzidine-, monoacetylbenzidine-, and 4-amino-biphenyl-PBI)were higher than those of the control group. These results are attributable to the fact that ethanol and phenobarbital induced to the plasma protein adduct formation. The N-acetylation ratio in the control group was highest at 72 h with 2.34.In the ethanol group,it was highest at 72 h with a ratio of 2.46 and was highest in the phenobarbital group at 72 h with a ratio of 2.43. The N-acetylation ratio of the plasma protein adducts was relatively lower than that of the hemoglobin adducts.The level of the plasma protein adduct increased more rapidly than the hemoglobin adducts in all experimental groups regardless of the pretreatment,and decreased rapidly after reaching the maximum level. CONCLUSION: The above results indicate that ethanol and phenobarbital increased the level of plasma protein adduct formation. The plasma protein adducts tended to decrease more rapidly than the hemoglobin adducts in the body after benzidine exposure. This results in this study result suggests that the effects of ethanol or phenobarbital need to be considered in the biochemical monitoring,and that the level of the plasma protein adducts be a more proper biomarker than the hemoglobin adducts for assessing the short term exposure to a benzidine and benzidine based dye.
Administration, Oral ; Amines ; Animals ; Environmental Monitoring* ; Ethanol* ; Heparin ; Hydrolysis ; Metabolism ; Phenobarbital* ; Plasma* ; Protein Binding ; Rats* ; Xenobiotics

The simultaneous administration of two or more drugs may result in interactions that increase or decrease the intended effects of one or both drugs. These interactions are often the result of induced alterations in the metabolism of the drugs. A wide variety of unrelated chemical agents are also capable of enhancing the activity of drug-metabolizing enzymea in the smooth-surfaced endoplasmic reticulum of the liver, and this accelerated metabolism alters the duration and intensity of action of a variety of pharmacological agents. Phenobarbital is a well known drug which promotes the metabolism of durgs in the liver. Some volatile or intravenous anesthetics were reported that enhance hepatic microspmal metabolism for themselves or for other drugs. Of these, Chang and Glazko (1974) reported that ketamine pretreatment did not influence the demethylation rate of drug metabolism and the liver weight in rats. However many opposite opinions have been expressed that ketamine enhanced mierosomal drug metabolism. Marietta et al (1975 and 1976) reported that the demethylating enzyme fraction of the ketamine-pretreated group was double of that of the control group in vitro. Thus we have made a study to evaluate the enhancement of drug metabolism induced by ketamine hydrochloride. Our experimental mice were divided into 4 groups, preteated with saline, phenobarbital, ketamine or carbon tetracbloride for 3 days. On the 1 st, 3 rd, 5th, 7th and 14th day after the pretreatment, we selected 10 mice randomly in each group, and hexobarbital(100mg/kg) was administered intraperitonealy. Then we evaluated the sleeping time, liver weight and microscopic findings of liver tissue. The results are as follows: 1) On the 1 st, 3 rd and 5th day after the pretreatment, the duration of hexobarbital induced hypnosis was significantly shorter in the ketamine-pretreated group than that in the control group, but not as long as that in the phenobarbital-pretreated group. 2) There was no remarkable change of the liver weight in the ketamine pretreated group. On the 1st and 3rd day after the pretreatment, liver weight was significanty increased in the phenobarbital and carbon tetrachloride pretreated groups. 3). Microscopic findings of liver showed no remarkable change in the ketamine-pretreated group, but there were significant cholestasis and hydrophic degeneration in the phenobarbital-and carbon tetrachloride-pretreated group respectively. In conclusion, it may be indicated that ketamine enhances hepatic microsomal drug metabolism because of shortening of the duration of hexobarbital-induced hypnosis.
Anesthetics, Intravenous ; Animals ; Carbon ; Carbon Tetrachloride ; Cholestasis ; Endoplasmic Reticulum ; Hexobarbital ; Hypnosis* ; In Vitro Techniques ; Ketamine ; Liver ; Metabolism ; Mice ; Phenobarbital ; Rats

BACKGROUND: The adverse effects of antiepileptic drugs (AEDs) on bone metabolism have been reported in epilepsy patients, however the underlying mechanisms have yet to be completely understood. The purpose of this study was to determine whether or not there is an abnormality in bone mineral density (BMD) in epilepsy patients with long-term AED treatment, and also to investigate the underlying mechanisms related to those abnormalities. METHODS: BMD was measured by densitometer using dual-energy X-ray absorptionmetry (Lunar PIXI) at the right calcaneus in both patients who had already taken AEDs longer than 6 months, and in patients with newly diagnosed epilepsy. A total of 80 patients (45 women and 35 men) were recruited for the former group, and 29 (11 women and 18 men) for the latter group. In the latter group, BMD and markers for bone metabolism were measured before and after 6 months of AED treatment including serum parathyroid hormone (PTH), total and ionized calcium, osteocalcin, 25-(OH) vitamin D, and urine pyrilinks. RESULTS: BMD decreased in epileptic women compared to the control group (p=0.021). Decreased BMD was most prominent in patients with phenytoin or phenobarbital. Osteocalcin and PTH levels increased after 6 months of AED therapy (p=0.002 and p<0.0001, respectively). CONCLUSIONS: BMD decreased in patients with epilepsy, especially in women even in premenopausal age, in those who are taking phenytoin or phenobarbital. AEDs increase bone turnover, which may relate to these alterations in bone mass and bone metabolism.
Anticonvulsants* ; Bone Density* ; Calcaneus ; Calcium ; Epilepsy ; Female ; Humans ; Metabolism* ; Osteocalcin ; Osteoporosis ; Parathyroid Hormone ; Phenobarbital ; Phenytoin ; Vitamin D

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

Benign idiopathic neonatal convulsion is a rare disorder which has no family history of convulsion and develops before and after the 5th day in a healthy full-term neonate. Its characteristics appear focal, or multifocal clonic seizures but rare tonic seizures lasting about several minutes. It reveals non-specific findings in neurologic examination, neuroimaging and EEG(electroencephalography) so that it should be differentiated from those diseases such as eletronic imbalance, inborn errors of metabolism, other neonatal epileptic syndromes. We report two healthy full-term female neonates presented with multifocal clonic seizures before and after the 5th day after birth. They had no family history of convulsion, fetal asphyxia, fetal and maternal problems and the neurologic examination and neuroimagings were normal. The convulsions were controlled by intravenous phenobarbital injection. They had no more convulsions ever since and showed normal development at the follow-up performed one year later. We experienced a rare disorder, benign neonatal convulsion in healthy full-term neonates. We hope this report will help its diagnosis and treatment and prevent unnecessary long- term anticonvulsant medication.
Asphyxia ; Epilepsy, Benign Neonatal ; Female ; Follow-Up Studies ; Humans ; Infant, Newborn ; Metabolism, Inborn Errors ; Neuroimaging ; Neurologic Examination ; Parturition ; Phenobarbital ; Seizures

PURPOSE: This study aimed to investigate the relationship between the SUVmax of primary breast cancer lesions and the molecular subtypes based on the recommendations of the St. Gallen consensus meeting 2013.METHODS: Clinical records of patients who underwent F-18 FDG PET/CT for initial staging of invasive ductal carcinoma (IDC) of SUVmax was correlated with the molecular subtypes defined by the St. Gallen Consensus Meeting 2013, i.e., luminal A-like (LA), luminal B-like HER2 negative (LBHER2−), luminal Blike HER2 positive (LBHER2+), HER2 positive (HER2+), and triple negative (TN), and with the clinicohistopathologic characteristics.RESULTS: The molecular subtype was LA in 38 patients, LBHER2− in 72, LBHER2+ in 21, HER2+ in 30, and TN in 22. The mean SUVmax in the LA, LBHER2−, LBHER2+, HER2+, and TN groups were 4.5 ± 2.3, 7.2 ± 4.9, 7.2 ± 4.3, 10.2 ± 5.5, and 8.8 ± 7.1, respectively. Although SUVmax differed significantly among these subtypes (p < 0.001), the values showed a wide overlap. Optimal cut-off SUVmax to differentiate LA from LBHER2−, LBHER2+, HER2+ and TN were 5.9, 5.8, 7.5, and 10.2 respectively, with area under curve (AUC) of 0.648, 0.709, 0.833, and 0.697 respectively. The cut-off value of 5.9 yielded the highest accuracy for differentiation between the LA and non-LA subtypes, with sensitivity, specificity, and AUC of 79.4 %, 57.9 %, and 0.704 respectively.CONCLUSION: The SUVmax showed a significant correlation with the molecular subtype. Although SUVmax measurements could be used along with immunohistochemical analysis for differentiating between molecular subtypes, its application to individual patients may be limited due to the wide overlaps in SUVmax.
Area Under Curve ; Breast Neoplasms ; Breast ; Carcinoma, Ductal ; Consensus ; Glucose ; Humans ; Metabolism ; Phenobarbital ; Positron-Emission Tomography and Computed Tomography ; Sensitivity and Specificity

The present work was to study induction of cytochrome P450 (CYP)3A and CYP2H1 gene by reverse transcriptase polymerase chain reaction (RT-PCR) and quantitative RTPCR in Bantam, Bantamized White Leghorn and White Leghorn chicks. Out of 18 chicks total 3 from each group (Bantam, Bantamized White Leghorn and White Leghorn) were treated intraperitoneal with phenobarbital at the dose rate of 12 mg/100 g (body weight) while the control group was treated with the saline. Total RNA was extracted from the liver samples using Tri Reagent based method. First strand cDNA was synthesized using one step RT-PCR kit. The PCR was performed and the product was subjected to agarose gel electrophoresis. Quantitative RT-PCR was conducted to quantify gene expression level of CYP3A and CYP2H1 genes. Relative expression ratio of CYP3A and CYP2H1 genes was calculated using relative expression software tool (REST). It was found that CYP3A is up regulated by factor of 1.34, 14.51 and 1.00 in Bantam, Bantamized White Leghorn and White Leghorn chicks, respectively. In Bantam and Bantamized White Leghorn chicks CYP2H1 gene was up regulated by factor 1.50 and 80.87, respectively but down regulated by a factor of 1.97 in White Leghorn chicks. The PCR efficiency ranged from 1.30 to 1.70, 0.86 to 1.70 and 0.91 to 1.58 for CYP3A, CYP2H1 and beta-actin, respectively in Bantam, Bantamized White Leghorn and White Leghorn chicks.
Animals ; Chickens/*metabolism ; Cytochrome P-450 CYP3A/*biosynthesis/genetics ; Cytochrome P-450 Enzyme System/*biosynthesis/genetics ; Gene Expression Regulation/drug effects ; Phenobarbital/*pharmacology ; Reverse Transcriptase Polymerase Chain Reaction