Pharmacotherapy of bipolar disorder is a rapidly evolving field. Mood stabilizers and anticonvulsants have varying biochemical profiles which may predispose them to different adverse effects and drug-drug interactions. Several of the new anticonvulsants appear less likely to have the problems with drug-drug interaction. To provide more effective combination pharmacotherapies, clinicians should be allowed to anticipate and avoid pharmacokinetic and pharmacodynamic drug-drug interactions. We reviewed the role of cytochrome P450 isozymes in the metabolism of the drugs and their interactions. The drug-drug interactions of several classes of drugs which used as mood stabilizers and new anticonvulsants, some of which may have psychotropic profiles, are discussed mainly in this article. Finally, potential pharmacokinetic interactions between the benzodiazepines and other coadministered drugs are discussed briefly.
Anti-Anxiety Agents* ; Anticonvulsants ; Benzodiazepines ; Bipolar Disorder ; Cytochrome P-450 Enzyme System ; Drug Therapy ; Isoenzymes ; Metabolism

Phosphoinositide-specific Phospholipase C (PI-PLC) is a second messenger of signal transducer on cell membrane. In the previous study, PLC of bovine brain has been purified three isozymes. In this paper, uterus and seminal vesicle have been purified. Two peaks of PI-PLC activity were resolved when bovine uterus and seminal vesicle proteins were chromatographed on a DEAE and phenyl TSK 5PW HPLC column. Each two peak was compared with PI-PLC I, II and III from bovine brain and we got the retention time on HPLC. The peak fractions with PLC activity were tested homogeneity with brain PLC monoclonal antibodies (Mab). Mab-labeled affigels were bounded in the range of 73.8%~97.5% with PLC I, II and III. Homogeneity of fractions were revealed that DEAE F-1 and phenyl F-1-I were highest level of PLC III in uterus and seminal vesicle and DEAE F-2 and phenyl F-2-I were mixed PLC I and II.
Antibodies, Monoclonal ; Brain* ; Cell Membrane ; Chromatography, High Pressure Liquid ; Isoenzymes* ; Phospholipases* ; Second Messenger Systems ; Seminal Vesicle Secretory Proteins ; Seminal Vesicles* ; Transducers ; Type C Phospholipases* ; Uterus*

Mental illnesses were understood for centuries as affliction of spirit or mind. There were many efforts to reveal the nature of mind. In the past century, however, physicians recognized that psychiatric disorders are primarily diseases of the brain and that many mental illnesses are caused by abnormalities in the brain. For the evolution and development of psychiatry in the New Millenium, understanding the relationship between the brain and mind is inevitable. To understand the nature of mind, we must understand the nature of brain. The more we know the brain, the better understood are the truth of mind and it's disorders.
Brain Diseases* ; Brain*

Four cases of intracerebral hemorrhage remote from the site of initial supratentorial craniotomy are presented. Traumatic cases are excluded in this report and all cases developed after uneventful elective craniotomy. Two patients had ruptured aneurysm and the other two had giant supratentorial tumors, one craniophayrngioma and one ependymoma. All patients were operated on supine position and no patient had preoperative hypertension. Two had hematoma in the sucortical white matter, one in the cerebellar hemisphere and the other one showed hematoma both in the cerebellar hemisphere and the supratentorial subcortical area. The size of hematoma ranged from 8-20cc in volume. No definite cause could be found except one in which the blood pressure was transiently elevated during induction of anesthesia. A possible cause might be the sudden changes of blood pressure during induction and recovery from anesthesia, overdrainage of CSF, continuous CSF drainage and sudden changes in intracranial dynamics by removal of a huge intracranial mass. One patient with intracerebellar hemorrhage needed emergency suboccipital craniectomy for removal of the hematoma. One patient shows no improvement due to aspiration pneumonia and subsequent lung abscess. Although rare, these conditions may occur after any craniotomy and surgeons should always be alert to the possibilities of such comlication, especially when intracranial pressure(ICP) was elevated.
Anesthesia ; Aneurysm, Ruptured ; Blood Pressure ; Cerebral Hemorrhage ; Craniotomy ; Drainage ; Emergencies ; Ependymoma ; Hematoma* ; Hemorrhage ; Humans ; Hypertension ; Lung Abscess ; Pneumonia, Aspiration ; Supine Position ; Supratentorial Neoplasms

OBJECTIVE: A Comparison of QTc prolongation for various antipsychotics and an analysis of QTc prolongation for the various types of serotonin transporter polymorphism were performed. METHOD: EKG was checked, followed by QTc measurement as Bazett's correction, and the serotonin transporter polymorphism was examined in 110 chronic schizophrenia patients were performed EKG before 24 weeks ago. We defiened QTc prolongation as over 450ms. The risk factor of sudden cardiac death were defiend as QTc prolongation and or 60ms in delta value. RESULT: The prevalence of QTc prolongation in this study was 7.3%, and the prevalence of over 60ms was 4.5%. Patients who had the risk factors were 10(9.1%). 6/52 who prescribed atypical antipsychotics and 2/58 who prescribed haloperidol showed QTc prolongation. The prevalence who had the risk factor of sudden cardiac death were 16% in atypical antipsychotics group, 3.4% in haloperidol group. QTc prolongation were observed more frequently in l/l type than s/s type. l allele frequency were 50% in QTc prolongated group, 19% in not prolongated group. l allele had an association with QTc prolongation(p<0.01). CONCLUSION: The prevalence of QTc prolongatin was frequent in chronic schizophrenia patients who were prescribed atypical antipsychotics. It has strong association with l allele of 5-HTTLPR.
Alleles ; Antipsychotic Agents ; Death, Sudden, Cardiac ; Electrocardiography ; Gene Frequency ; Haloperidol ; Humans ; Prevalence ; Risk Factors ; Schizophrenia ; Serotonin Plasma Membrane Transport Proteins

OBJECTIVE: In this study we examined the effects of quetiapine on the immobilization stress-induced brain-derived neurotrophic factor (BDNF) and corticotropin-releasing factor (CRF) expression in rat brain. We also assessed the antidepressant activity of quetiapine. METHOD: We used in situ hybridization to examine the effects of chronic administration of quetiapine in gene transcription. This study also examined the influence of quetiapine in an animal model of depression, the forced swimming test (FST). RESULTS: 1) Repeated immobilization stress (2 hr daily for 3 weeks) decreased mRNA levels of BDNF in the hippocampus (p<0.01), parietal cortex (p<0.01) and pyriform cortex (p<0.05). 2) Repeated immobilization stress increased mRNA levels of CRF in the hypothalamic paraventricular nucleus (PVN)(p<0.01). 3) Chronic quetiapine (10 mg/kg) treatment (daily for 3 weeks) alone significantly increased BDNF mRNA expression in the dentate gyrus of hippocampus when compared to controls under basal conditions (p<0.01), whereas no such effect was observed in the neocortex. 4) Chronic pretreatment of quetiapine also markedly increased the stress-induced decrease of BDNF mRNA expression in the hippocampus (p<0.01) and neocortex (p<0.01). 5) Moreover, the stress-induced elevation of CRF mRNA expression was blocked by chronic quetiapine pretreatment in PVN (p<0.01) although chronic quetiapine treatment alone did not significantly reduce CRF mRNA levels in comparison to controls under basal condition. 6) When rats received acutely quetiapine, quetiapine did reduce the immobility time at 10 mg/kg, as compared with the control group (p<0.05). CONCLUSION : These results suggest that quetiapine has not only potentially an antidepressant effect but also a neuroprotective action in schizophrenia and this effect may be related to its antipsychotic effect in patients with schizophrenia.
Animals ; Antipsychotic Agents ; Brain* ; Brain-Derived Neurotrophic Factor* ; Corticotropin-Releasing Hormone ; Dentate Gyrus ; Depression ; Hippocampus ; Humans ; Immobilization* ; In Situ Hybridization ; Models, Animal ; Neocortex ; Paraventricular Hypothalamic Nucleus ; Physical Exertion ; Rabeprazole ; Rats* ; RNA, Messenger ; Schizophrenia ; Quetiapine Fumarate

OBJECTIVES: Thioredoxin peroxidase(TPx), which does not exhibit similar activity and amino acid sequence homology to conventional antioxidant enzymes has been purified from S cerevisiae and bovine brain. Natural killer enhancing factor-A(NKEF-A)/ proliferation associated gene(PAG), natural killer enhancing factor-B(NKEF-B)/TPx and MER5 which has sequence homology to yeast TPx has been recently characterized biochemically, Prosperi has reported that the level of PAG in HL-60 cells was increased after serum stimulation and decreased after differentiation induced by DMSO treatment. It is well known that thioredoxin, the electron donor to thioredoxin peroxidase, also implicated in cell proliferation via protein kinase C pathway. Disturbed balance of reactive oxygen species and antioxidant in tumor tissue could enhance the cancer promotion This study was designed to investigate the distribution of NKEF-A/FAG, NKEF-B/TPx and MER5 in various tissues, and the expression of NKEF-A/PAG, NKEF-B/TPx and MER5 in human cancers. METHODS: We used antibodies against the purified recombinant protein of NKEF-A/PAG and NKEF-B/TPx and C-terminus amino acids(SP-TASKEYFEKVHO) of MER5, We separated cytosole and mitochondria from rat liver and prepared crude extract from these. We prepared crude extract of various tissues from rat and cancer tissue from lung, stomach and breast and paired normal tissue. Immunoblot analysis of these crude extracts was performed. RESULTS: 1) NKEF-A/PAG and NKEF-B/TPx existed in cytosolic fraction as Cu, Zn-SOD and MER5 mainly exist mainly in mitochondrial fraction as Mn-SOD. Although the level of NKEF-AIPAG, NKEF-B/TPx and MER5 was different, all tissues exhibited NKEF-A/PAG, NKEF-B/TPx and MER5 immunoreactive bands. The adrenal gland had relatively strong band of MEK. 2) The expression of NKEF-A/PAG in HL-60 cell was increased after serum stimulation and decreased after cell differentiation induced by DMSO treatment. 3) The expression of NKEF-A/PAG was increased in lung and breast cancer tissues compaired to paired normal tissues but was not changed in stomach cancer tissues and the expression of NKEF-B/TPx and MER5 was not changed in lung, stomach and breast cancer tissues compaired to paired normal tissues. 4) The level of NKEF-A/PAG, NKEF-B/TPx and MER5 was not different among various lung cancer cell lines. CONCLUSION: The NKEF-A/PAG, NKRF-B/TPx and MER5 are present in the cytosol and mitochondria of various tissues. The NKEF-A/PAG, in particular, is associated with cell proliferation and differentiation and overexpressed in lung and breast cancer.
Adrenal Glands ; Animals ; Antibodies ; Brain ; Breast ; Breast Neoplasms ; Cell Differentiation ; Cell Line ; Cell Proliferation ; Complex Mixtures ; Cytosol ; Dimethyl Sulfoxide ; HL-60 Cells ; Humans* ; Liver ; Lung ; Lung Neoplasms ; Mitochondria ; Peroxidases* ; Peroxiredoxins ; Protein Kinase C ; Rats ; Reactive Oxygen Species ; Saccharomyces cerevisiae ; Sequence Homology ; Sequence Homology, Amino Acid ; Stomach ; Stomach Neoplasms ; Superoxide Dismutase ; Thioredoxins* ; Tissue Donors ; Yeasts

OBJECTIVE: Heart rate variability(HRV) is helpful to diagnosis autonomic disturbance and sympathetic-parasympathetic imbalance in patients with myocardial infarction and diabetes mellitus. Patients with liver cirrhosis demonstrate reduced blood pressure despite increased heart rate and increased cardiac output, indicating a fall in peripheral vascular resistance. Autonomic disturbance may contribute to this phenomenon. The aim of the present study is to evaluate the degree of autonomic disturbance and the circadian rhythm of autonomic nervous system by estimating HRV with 24 hour-Holter recorder, METHODS: 24 hour-HRV with Del Mar Avionics 563 Holter recorder and cardiovascular reflex tests were carried out on 32 patients with liver cirrhosis and 20 control subjects. We evaluated the presence of autonomic disturbance, and assessed quantitatively the autonomic disturbance. RESULTS: 1) Among cardiovascular reflex tests, Valsalva test, standing test and deep breathing test were showed a significantly decreased response in liver cirrhosis compared with control groups. 2) The standard deviation of 24hours average R-R intervals were showed a significantly decrease in liver cirrhosis than control groups(P<0.0001). The HRV of low frequency(LF. P<.D.001), high frequency(HF, P<0.0001) and total power spectral density (P<0.0001) in liver cirrhosis were statistically lower than control. 3) The LF/HF ratio of patients with liver cirrhosis was showed higher than control at night CONCLUSION: Non-invasive assessment of 24 hour-HRV has a few advantages in the diagnosis and degree of autonomic disturbance, evaluation of diurnal variation of autonomic tone.
Autonomic Nervous System ; Blood Pressure ; Cardiac Output ; Circadian Rhythm ; Diabetes Mellitus ; Diagnosis ; Heart Rate* ; Heart* ; Humans ; Liver Cirrhosis* ; Liver* ; Myocardial Infarction ; Reflex ; Respiration ; Vascular Resistance

Meckel Gruber syndrome consisting of an occipital encephalocele, polycystic kidney disease and polydactyly is a rare autosomal recessive disorder with a recurrence risk of 25%. Targeted ultrasonography in late embryonic or early fetal stages of pregnancy has great importance in diagnosis and management of affected pregnancy in high risk groups due to incomplete genetic mapping of meckel syndrome gene (MKS). We present a case of prenatal diagnosis at 14 weeks' gestational age of Meckel Gruber syndrome in a woman, who experienced same disorder in her previous pregnancy.
Diagnosis ; Encephalocele ; Female ; Gestational Age ; Humans ; Polycystic Kidney Diseases ; Polydactyly ; Pregnancy ; Prenatal Diagnosis ; Recurrence ; Ultrasonography

From retrospective review of medical charts of patients diagnosed as bilateral vestibulopathy during the past seven years, this study investigated incidence, etiologies, symptoms, vestibular function test findings; electronystagmography (ENG) studies, rotatory chair testing, and posturography, and post-vestibular rehabilitation (VRT) follow-up results. we have an incidence of 1.2% of all the 3423 patients who have undergone vestibular function test. Ototoxicity was the first known etiology and we had a lot of patients of idiopathic bilateral vestibulopathy. Most patients in our study had experiences of sudden onset vertigo rather than slowly progressive symptoms. The most frequently complained symptoms were dysequilibrium and oscillopsia. Post-VRT courses were better in patients whose initial gain of vestibulo-ocular reflex(VOR) was high or ascending type.
Electronystagmography ; Follow-Up Studies ; Humans ; Incidence ; Rehabilitation ; Retrospective Studies ; Vertigo ; Vestibular Function Tests