• Asian Pacific Journal of Cancer Prevention
• /
• 제13권12호
• /
• pp.6429-6433
• /
• 2012

To explore a possible new treatment for human ovarian cancer, we studied the effects of sodium valproate on the growth of the HO8910 human cell line. HO8910 cells were cultured in vitro and treated with different concentrations of sodium valproate. Cell proliferation, cell cycling, and apoptosis were measured by flow cytometry, cell morphology under a microscope, and expression levels of WWOX and P27 by Western blotting and RT-PCR. Tumor xenografts were established to determine in vivo effects of sodium valproate. Our results showed that cell proliferation was decreased with increasing concentration of sodium valproate, with features of cytoplasmic retraction and floating cells. Moreover, cell cycle analysis revealed a higher apoptosis rate and $G_0/G_1$ phase in the sodium valproate experimental group than in the control group. In addition, protein expression levels of WWOX and P27 were elevated. Importantly, sodium valproate decreased in vivo xenograft tumor burden and up-regulated WWOX and P27 expression in nude mice. In conclusion, sodium valproate might play a role in inhibition and control of ovarian cancer cell line HO8910 by inhibiting cell proliferation, interfering with the cell cycle and promoting apoptosis, so that it may be effective in the clinical treatment of ovarian cancer.

• Journal of Pharmaceutical Investigation
• /
• 제26권2호
• /
• pp.113-117
• /
• 1996

This study was attempted to investigate the pharmacokinetic interaction between sodium valproate (4, 8, 16 mg/kg, i.v.) and phenytoin (4 mg/kg, i.v.) in rabbits. The plasma concentration and area under the curve (AUC) of phenytoin were increased significantly (p<0.05, p<0.01) when coadministered with sodium valproate (4, 8, 16 mg/kg) in rabbits. The volume or distribution and total body clearance of phenytoin were decreased significantly (p<0.05, p<0.01) when coadministered with sodium valproate (8, 16 mg/kg) in rabbit. From the results of this experiment, it is desirable that dosage regimen of phenytoin should be adjusted and therapeutic drug monitoring should be performed for reduction of side or toxic effect when phenytoin will be coadministered with sodium valproate in clinical use.

• Clinical and Experimental Pediatrics
• /
• 제45권10호
• /
• pp.1288-1291
• /
• 2002

저자들은 임신 1개월 전 전신강직간대성 발작이 있어 임신 중에 발작 조절을 위해 valproate를 복용한 산모의 아이에게서 양 팔꿈치의 구축을 동반한 fetal valproate syndrome의 특징을 지닌 1례를 경험하였기에 문헌 고찰과 함께 보고하는 바이다.

• Archives of Pharmacal Research
• /
• 제27권5호
• /
• pp.495-501
• /
• 2004

A series of N-substituted-1,3-isoindolinedione derivatives (2-16) were synthesized for the purpose of defining the effect of N-substitution on the anticonvulsant activity of these derivatives. The target compounds (2-16) were obtained by condensation of phthalic anhydride with the corresponding amine derivative. The structures of the synthesized derivatives (2-16) were confirmed by means of IR, $^1$H-NMR, $^{13}$ C-NMR, MS and elemental analyses. The anticonvulsant activity of all compounds (2-16) were evaluated by subcutaneous pentylenetetrazole seizure threshold test at doses of 0.2, 0.4 and 0.8 mmol/kg compared with sodium valproate as a positive control. Their neurotoxicity were determined by the rotorod test. Many of the present series of compounds showed good anticonvulsant activity at the tested doses, as compared to sodium valproate. Three of them (4, 6 and 11) exhibited 100 % protection against convulsions, neurotoxicity and death at all tested doses. Out of the series, two compounds (12 and 13) were completely inactive with 100% mortality. 3-(p-chlorophenyl)-4-(1 ,3-dioxo-2,3-dihydro-1 H-2-isoindolyl) butanoic acid derivative (11) has emerged as the most active compound which is 20 times more active than valproate with ED$_{50}$ 8.7, 169 mg/kg; TD$_{50}$ 413, 406 mg/kg and PI 47.5, 2.4. The results revealed the importance of the combination of baclofenic and phthalimide moieties (compound 11) as a promising anticonvulsant candidate.

• The Korean Journal of Physiology and Pharmacology
• /
• 제22권1호
• /
• pp.23-33
• /
• 2018

Cushing's syndrome (CS) is a collection of symptoms caused by prolonged exposure to excess cortisol. Chronically elevated glucocorticoid (GC) levels contribute to hepatic steatosis. We hypothesized that histone deacetylase inhibitors (HDACi) could attenuate hepatic steatosis through glucocorticoid receptor (GR) acetylation in experimental CS. To induce CS, we administered adrenocorticotropic hormone (ACTH; 40 ng/kg/day) to Sprague-Dawley rats by subcutaneous infusion with osmotic mini-pumps. We administered the HDACi, sodium valproate (VPA; 0.71% w/v), in the drinking water. Treatment with the HDACi decreased steatosis and the expression of lipogenic genes in the livers of CS rats. The enrichment of GR at the promoters of the lipogenic genes, such as acetyl-CoA carboxylase (Acc), fatty acid synthase (Fasn), and sterol regulatory element binding protein 1c (Srebp1c), was markedly decreased by VPA. Pan-HDACi and an HDAC class I-specific inhibitor, but not an HDAC class II a-specific inhibitor, attenuated dexamethasone (DEX)-induced lipogenesis in HepG2 cells. The transcriptional activity of Fasn was decreased by pretreatment with VPA. In addition, pretreatment with VPA decreased DEX-induced binding of GR to the glucocorticoid response element (GRE). Treatment with VPA increased the acetylation of GR in ACTH-infused rats and DEX-induced HepG2 cells. Taken together, these results indicate that HDAC inhibition attenuates hepatic steatosis through GR acetylation in experimental CS.

• Biomolecules & Therapeutics
• /
• 제1권1호
• /
• pp.93-97
• /
• 1993

We have previously reported that an NADPH-dependent succinic semialdehyde reductase was purified homogeneously from bovine brain by several chromatographic procedures, and was found to be a monomeric protein with a molecular mass of 28 kDa (Cho et al., Eur. J. Biochem. 1993). Since succinic semialdehyde is an important intermediate in the ${\gamma}$-aminobutyrate(GABA) shunt and GABA level is associated with various forms of human neurological disorders, we have investigated the effects of anticonvulsant drugs on the succinic semialdehrde reductase. Among the drugs tested, sodium valproate and diphenylhydantoin inhibited the enzyme activity, while some other drugs, barbiturate and chlorpromazine, had no inhibitory effects on the enzyme activity. The purified enzyme was also injected as an immunogen into Balb/c mice to obtain monoclonal antibodies (mob) and several mobs to the protein were produced from the fusion experiments.

• 생물정신의학
• /
• 제8권1호
• /
• pp.167-174
• /
• 2001

A 54-year old male patient who was suffering from bipolar I disorder for 19 years and was admitted to the National Bugok Mental Hospital due to a depressive episode, was referred to the Kosin University Gospel Hospital. On arrival at the emergency room, he had confused mentality with disorientation, memory impairment, hypomania, marked anxiety and hyperirritability. The change of neuromuscular activity such as ataxia, gait disturbance, tremor, shivering, myoclonus and epileptic seizures was also shown. In addition, the symptoms and signs of autonomic instability including diaphoresis, tachycardia, hypotension, fever and facial flushing were noticed. The above symptoms developed after the administration of sertraline successive to the discontinuation of fluoxetine without any washout period. The degree of severity seemed to be severe because he had epileptic seizures, fever and hypotension. He was recovered from the severe serotonin syndrome by the supportive symptomatic treatment with sodium valproate, clonazepam, lorazepam and cyproheptadine after cessation of the selective serotonin reuptake inhibitors during hospitalization. Therefore, this rare case of severe serotonin syndrome was reported and related literatures were also reviewed.

• Clinical and Experimental Pediatrics
• /
• 제51권12호
• /
• pp.1346-1349
• /
• 2008

배뇨 유발 반사발작은 매우 드물며, 문헌상에서 단지 8례가 보고되었으며, 발작기 뇌파로 진단한 예는 국내에서 보고된 바 없다. 7세 남아가 이차전신화 부분발작을 주소로 내원하였다. 발작은 단지 배뇨 수초 후에 시작되었으며 손의 자동증과 함께 비틀거리며 쓰러지면서 의식소실과 함께 이차적으로 전신 강직 발작을 하였다. 발작기 뇌파에서 왼측 전두부와 측두부에서 다극서파가 보이다가 오른쪽 전두부와 측두부로 퍼져나가는 소견을 보여 배뇨 유발성 이차 전신화 부분발작으로 진단되어 보고하는 바이다.

• 대한불안의학회지
• /
• 제8권2호
• /
• pp.161-166
• /
• 2012

Though infanticide, killing the baby after birth of the neonate and denial of pregnancy, are very rare psychiatric disorder, they have been receiving a lot of social concerns. We report and review infanticide and denial of pregnancy administration in a 19 year-old adolescent with bipolar disorder and borderline personality disorder. Patients with a young age, cognitive immaturity, an unwanted child, hid the pregnancy facts were consistent with the results of previous studies. In addition, the patient's impulsivity and emotional instability is affecting infanticide. After inpatient care with pharmacotherapy (escitalopram 20mg, alprazolam 1.5 mg, clonazepam 0.5 mg, valproate sodium 1,100-1,300 mg, and quetiapine 100-400 mg) and supportive psychotherapy, and there were significant improvement of clinical symptoms.

• 대한치과마취과학회지
• /
• 제11권1호
• /
• pp.51-54
• /
• 2011

Wolff-Hirschorn syndrome is a condition that is caused by a deletion of genetic material near the end of the short (p) arm of chromosome 4. The major features of this disorder include a characteristic facial appearance, delayed growth and development, intellectual disability, and seizures. A 9-year-old girl was brought to the clinic with a chief complaint of dental examination. The child was diagnosed as WHS at Samsung medical center. The child was under Sodium valproate, Atrovastatin medication for epilepsy, hyperlipidemia and had a history of heart surgery. So prophylactic antibiotics were recommended. The child was mentally retarded and had seizure so it was difficult to manage her behavior effectively. Thus dental treatment was carried out under general anesthesia. For prompt sedation induction we used 8% sevoflurane shortly. This report presents the case of a 9-year-old girl with WHS, who has received treatment for extensive caries under general anesthesia.