• Journal of Korean Neurosurgical Society
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• 제30권8호
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• pp.976-980
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• 2001

Objectives : For Parkinsonian patients who had not reacted favorably on drug therapy are good candidate for ventroposterolateral pallidotomy, although not curative. We studied these patients after unilateral pallidotomy, to confirm the effectiveness and safety of this procedure. Methods : We evaluated the 17 patients with idiopathic Parkinson's diesease who had undergone unilateral posteroventral pallidotomy. All patients responded to levodopa initially. Mean age was 55 years(38-75years), and mean duration of disease was 9.8 years(3-20years). Pre-and postoperative evaluation at 3 month intervals included Unified Parkinson's Disease Rating scale(UPDRS) scoring, Hoehn and Yahr(H & Y) staging, and neuropsychological examinations. Results : Pallidotomy significantly improved parkinsonian symptom(tremor, rigidity, bradykinesia, dyskinesia, sensory symptom). Nine of 10 patients who showed dyskinesia preoperatively significant improvement. The mean dose of levodopa in 9 patients was lowered. The mean H & Y score and UPDRS score were improved in on and/or off time in 15 patients. Among patients who were not improved, one patient worsened, and the others showed no change. The mean overall UPDRS off score changed from 76 preoperatively to 44(33%) at 6 months and from 70 to 52(25%) at 1 year. Transient surgical morbidity was showen in four patients and included dysarthria, hypotonia and confusion. Conclusion : We conclude that pallidotomy is safe and effective in patients who have levodopa-reponsive parkinsonism with severe symptom fluctuation. Unilateral pallidotomy also considered helpful to ipsilateral symptom. Unilateral pallidotomy can improve all of parkinsonian's symptom and allow to reduce the levodopa medication. Most of patients show satisfactory results.

• 생물정신의학
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• 제7권2호
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• pp.140-146
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• 2000

P450 CYP2D6 enzyme(=debrisoquine hydroxylase) is known to metabolize many neuroleptics and some genetic polymorphisms in the CYP2D6 gene were reported to be associated with tardive dyskinesia(TD). We investigeted the association of two genetic polymorphisms in the CYP2D6 gene, $CYP2D6^*4$ and $CYP2D6^*10$, with TD in Korean schizophrenic subjects. Subjects consisted of 71 Korean schizophrenics and TD was evaluated using the Abnormal Involuntary Movement Scale (AIMS). There were no statistically significant differences in the demographic variables of age, male to female percentage and the current antipsychotic(CPZ equivalent) dose between the group with TD and the group without TD. But the duration of antipsychotic drug exposure was significantly higher in the group without TD(p=0.000, by independent t-test). The mean AIMS score in the group with TD was $11.2{\pm}6.6$(S.D.). Genotypings for the presence of $CYP2D6^*4$ and $CYP2D6^*10$ were done using PCR amplifications and endonuclease digestions. There were no statistically significant genotypic and alleleic associations between TD and $CYP2D6^*4$(by chisquare tests), and between TD and $CYP2D6^*10$(by chi-square tests). These results indicate that the $CYP2D6^*4$ and $CYP2D6^*10$ polymorphisms have no significant roles in the causation of TD.

• Biomolecules & Therapeutics
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• 제23권6호
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• pp.590-596
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• 2015

The emergence and use of synthetic cannabinoids have greatly increased in recent years. These substances are easily dispensed over the internet and on the streets. Some synthetic cannabinoids were shown to have abuse liability and were subsequently regulated by authorities. However, there are compounds that are still not regulated probably due to the lack of abuse liability studies. In the present study, we assessed the abuse liability of three synthetic cannabinoids, namely JWH-030, JWH-175, and JWH-176. The abuse liability of these drugs was evaluated in two of the most widely used animal models for assessing the abuse potential of drugs, the conditioned place preference (CPP) and self-administration (SA) test. In addition, the open-field test was utilized to assess the effects of repeated (7 days) treatment and abrupt cessation of these drugs on the psychomotor activity of animals. Results showed that JWH-175 (0.5 mg/kg), but not JWH-030 or JWH-176 at any dose, significantly decreased the locomotor activity of mice. This alteration in locomotor activity was only evident during acute exposure to the drug and was not observed during repeated treatment and abstinence. Similarly, only JWH-175 (0.1 mg/kg) produced significant CPP in rats. On the other hand, none of the drugs tested was self-administered by rats. Taken together, the present results indicate that JWH-175, but not JWH-030 and JWH-176, may have abuse potential. More importantly, our findings indicate the complex psychopharmacological effects of synthetic cannabinoids and the need to closely monitor the production, dispensation, and use of these substances.

• Journal of Microbiology and Biotechnology
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• 제30권2호
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• pp.279-286
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• 2020

A novel compound named 'kanakugiol' was recently isolated from Lindera erythrocarpa and showed free radical-scavenging and antifungal activities. However, the details of the anti-cancer effect of kanakugiol on breast cancer cells remain unclear. We investigated the effect of kanakugiol on the growth of MCF-7 human breast cancer cells. Kanakugiol affected cell cycle progression, and decreased cell viability in MCF-7 cells in a dose-dependent manner. It also enhanced PARP cleavage (50 kDa), whereas DNA laddering was not induced. FACS analysis with annexin V-FITC/PI staining showed necrosis induction in kanakugiol-treated cells. Caspase-9 cleavage was also induced. Expression of death receptors was not altered. However, Bcl-2 expression was suppressed, and mitochondrial membrane potential collapsed, indicating limited apoptosis induction by kanakugiol. Immunofluorescence analysis using α-tubulin staining revealed mitotic exit without cytokinesis (4N cells with two nuclei) due to kanakugiol treatment, suggesting that mitotic catastrophe may have been induced via microtubule destabilization. Furthermore, cell cycle analysis results also indicated mitotic catastrophe after cell cycle arrest in MCF-7 cells due to kanakugiol treatment. These findings suggest that kanakugiol inhibits cell proliferation and promotes cell death by inducing mitotic catastrophe after cell cycle arrest. Thus, kanakugiol shows potential for use as a drug in the treatment of human breast cancer.

• Journal of Pharmaceutical Investigation
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• 제39권1호
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• pp.65-71
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• 2009

The aim of the present study was to evaluate the bioequivalence of two domperidone maleate tablets, Motilium-$M^{(R)}$ Tablet (Janssen Korea Ltd., reference product) and $Toriem^{(R)}$ Tablet (Daewon Pharm. Co., Ltd., test product). Domperidone was extracted by liquid-liquid extraction using tert-butyl methyl ether and separated in less than 3 min on $C_{18}$ reverse-phase column using an isocratic elution. A tandem mass spectrometer, as detector, was used for quantitative analysis in positive mode by a multiple reaction monitoring mode to monitor the m/z $426.1{\rightarrow}119.1$ and the m/z $837.4{\rightarrow}158.2$ transitions for domperidone and the internal standard (roxithromycin), respectively. Calibration curves, from $0.05{\sim}50$ ng/mL of domperidone, showed correlation coefficients (r) higher than 0.9941. Intra day and inter day precision (C.V. %) for quality control were ranged from 10.04 to 16.09% and from 10.87 to 18.69%, respectively. The lower limit of quantification (LLOQ) of domperidone was 0.05 ng/mL. The method described is precise and sensitive and has been successfully applied to the study of bioequivalence of domperidone in 24 healthy Korean volunteers. Twenty-four healthy male Korean volunteers received a single dose of each medicine ($2{\times}12.72\;mg$ domperidone maleate) in a $2{\times}2$ crossover study. There was a one-week washout period between the doses. Plasma concentrations of domperidone were monitored for over a period of 24 hr after the administration. $AUC_{0-t}$ (the area under the plasma concentration-time curve) was calculated by the linear trapezoidal rule. $C_{max}$ (maximum plasma drug concentration) and $T_{max}$ (time to reach $C_{max}$) were compiled from the plasma concentration-time data. The 90% confidence intervals for the log transformed data were within acceptable range of log 0.8 to log 1.25 (e.g., $log\;0.92{\sim}log\;1.05$ for $AUC_{0-t}$, $log\;0.81{\sim}log\;1.05$ for $C_{max}$). The major parameters, $AUC_{0-t}$ and $C_{max}$ met the criteria of KFDA for bioequivalence indicating that $Toriem^{(R)}$ tablet is bioequivalent to Motilium-$M^{(R)}$ tablet.

• Journal of Pharmaceutical Investigation
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• 제39권1호
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• pp.73-78
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• 2009

A simple LC-MS/MS method of rabeprazole in human plasma was developed and validated. Rabeprazole and Internal standard (I.S), omeprazole, were extracted from human plasma by liquid liquid extraction, chromatographic separation of rabaprazole in plasma was achieved at $45^{\circ}C$ with a Shiseido UG120 $C_{18}$ column and methanol-10 mM ammonium acetate buffer (pH 9.42 with ammonium water), as mobile phase. Rabeprazole produced a protonated precursor ion [$(M+H)^+$] at m/z 360.10 and corresponding product ion at m/z 242.21. Internal standard produced a protonated precursor ion [$(M+H)^+$] at 346.09 and corresponding product ion at m/z 198.09. This method showed linear response over the concentration range of $1{\sim}500\;ng/mL$ with correalation coefficient greater than 0.99. The lower limit of quantitation (LLOQ) using 0.2 mL plasma was 1 ng/mL, which was sensitive enough for pharmacokinetics studies. The method was specific and validated with a limit of quantitation of 1 ng/mL. The intra-day and inter-day precision and accuracy were acceptable for all samples including the LLOQ. The applicability of the method was demonstrated by analysis of plasma after administration of a single 10 mg dose to 36 healthy subject. From the plasma rabeprazole concentration versus time curves, the mean $AUC_t$ (The area under the plasma concentration-time curve from time 0 to 12 hr ) was $691.36{\pm}321.88\;ng{\cdot}hr/mL$, $C_{max}$ (maximum plasma drug concentration) of $353.21{\pm}131.52\;ng/mL$ reached $3.4{\pm}1.1\;hr$ after adiministration. The mean biological half-life of rabeprazole was $1.37{\pm}0.75\;hr$. Based on the results, this simple method could readily be used in pharmacokinetics studies.

• 한국식품과학회지
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• 제48권4호
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• pp.329-334
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• 2016

천연 녹차추출물인 epigallocatechin gallate (EGCG)의 메추리알 장조림에서 천연식품첨가제로서의 적용 가능성을 탐색하고자 S. Enteritidis에 대한 항미생물 활성을 냉장온도($4^{\circ}C$)와 일반실내온도($25^{\circ}C$)에서 평가하였다. 순수배양액에서의 실험결과 첨가된 EGCG의 농도($200-800{\mu}g/mL$)에 따라 $4^{\circ}C$에서 5일에서 16일 사이에서 그리고 $25^{\circ}C$에서 1일부터 6일 사이에서 S. Enteritidis균이 검출한계 이하로 억제되는 것이 관찰되었다. 이와 대조적으로 간장소스에서의 실험에서는 $25^{\circ}C$에서 첨가된 EGCG의 농도와 관계없이 S. Enteritidis균이 억제되지 않았으며, $4^{\circ}C$에서는 $400{\mu}g/mL$ 이상의 농도일 때 16일에 S. Enteritidis균이 검출한계 이하로 억제되는 것이 관찰되었다. 메추리알 장조림의 경우, $25^{\circ}C$에서 간장소스의 결과와 동일하게 어떠한 EGCG의 항미생물 활성이 나타나지 않았지만, $4^{\circ}C$에서 $400{\mu}g/mL$의 EGCG 농도 첨가 시 16일에 S. Enteritidis 균이 검출한계 이하로 억제되는 것이 확인되었다. 따라서, 메추리알 장조림 완제품에서 EGCG는 $4^{\circ}C$ 이하의 저온유통체계(cold chain system)하에서 S. Enteritidis과 같은 식중독세균을 제어할 수 있는 적합한 천연 식품첨가제로서 활용될 수 있을 것으로 기대된다.

• 대한한의학회지
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• 제29권2호
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• pp.182-192
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• 2008

Objective: The purpose of this study was to evaluate on the antimicrobial effect on the periodontal pathogens and anti-inflammatory effect of Eriobotryae folium. Eriobotryae folium are constituent herbs of Gagamgamroum, which has been used for a long time in oriental medicine as a herbal medicine for treating halitosis and toothache. Method: Eriobotryae folium was prepared by extracting medicinal herb with water. We investigated antimicrobial activity by the minimum inhibitory concentration (MIC) test. We also investigated inhibition of $IL-1{\beta}-induced$ collagenase (mmp-1), stromelysin-1 (mmp-3), interleukin-6 gene expression in human gingival fibroblasts using RTPCR analysis. Result: The antimicrobial effects of Eriobotryae folium was evaluated with MIC against periodontopathogens; Porphyromonas gingivalis 2561, W50, A7A1-28, 9-14K-1, Prevotella intermedia 28, and Actinobacillus actinomycetemcomitans Y4. MICs of Eriobotryae folium were 1.25 mg/ml, 2.5 mg/ml, 0.625 mg/ml, 1.25 mg/ml, 10 mg/ml and 10 mg/ml. The anti-inflammatory effect of Eriobotryae folium was evaluated with influence of herbs on the $IL-1{\beta}-induced$ expression of mmp-1, mmp-3, and interleukin-6. $IL-1{\beta}$ increased mmp-1, mmp-3, and interleukin-6 mRNA levels. Eriobotryae folium significantly inhibited $IL-1{\beta}-induced$ mmp-1, mmp-3, and interleukin-6 gene expressions in a dose-dependent manner. Conclusion: These results suggested that Eriobotryae folium might reduce the excessive proteolytic capacity of the gingival fibroblast during inflammation and could be developed as a new drug for periodontitis.

• The Korean Journal of Pain
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• 제30권3호
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• pp.176-182
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• 2017

Background: Current evidence suggests that intravenous magnesium sulfate might be effective for reducing migraine pain. In a recent pilot study, we showed that intravenous caffeine citrate could reduce the severity of migraine headache. The objective of this study is to investigate the efficacy of intravenous caffeine citrate vs. magnesium sulfate for management of acute migraine headache. Methods: We conducted a prospective quasi-experimental study from January until May 2016 in two educational medical centers of Shahid Beheshti University of Medical Sciences (Shoahadaye Tajrish Hospital and Imam Hossein Hospital), Tehran, Iran. The study included patients who were referred to the emergency department and met the migraine diagnosis criteria of the International Headache Society. Patients were allocated into 2 groups receiving either 60 mg intravenous caffeine or 2 g intravenous magnesium sulfate. The pain scores, based on the visual analog scale, were recorded on admission, as well as one and two hours after receiving the drug. A Chi-Square test and student t-test were used for analysis of baseline characteristics. A Mann-Whitney U test and Wilcoxon singed rank test were used to analyze differences in the visual analogue scale (VAS) score between and within the groups respectively. Results: In total, 70 patients (35 patients in each group) with the mean age of $33.1{\pm}11.3years$ were included (64.3% female). For the Caffeine citrate group, the median pain score decreased from 9.0 (2.0) to 5.0 (4.0) after one hour and to 3.0 (4.0) after two hours. For the magnesium sulfate group, the pain score decreased from 8.0 (2.0) to 2.0 (2.0) after one hour and to 0.0 (1.0) after two hours. Both intravenous caffeine citrate and intravenous magnesium sulfate reduced pain scores significantly but the magnesium sulfate group showed more improvement than the Caffeine citrate group after one hour (P < 0.001) and after two hours (P < 0.001). Conclusions: It is likely that both intravenous caffeine and intravenous magnesium sulfate can reduce the severity of migraine headache. Moreover, intravenous magnesium sulfate at a dose of 2 g might be superior to intravenous caffeine citrate 60 mg for the short term management of migraine headache in emergency departments.

• 대한약리학회지
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• 제27권2호
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• pp.197-205
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• 1991

Adriamycin (Doxorubicin HCl)의 혈관밖 유출에 따른 조직의 손상, 특히 피부괴양 및 괴사 기전을 규명하기 위한 연구의 일환으로 흰쥐 피부세포를 이용한 in vitro 실험에서 adriamycin에 의한 산소라디칼 생성 및 그와 관련된 세포독성 기전으로 지질과산화를 검토하였다. Adriamycin은 흰쥐 태자 피부의 배양세포에서 lactic dehydrogenase(LDH) 유리를 용량 및 시간 의존적으로 증가 시켰으며, NADPH 및 NADH 첨가 조건에서 $superoxide\;anion(O^-\;_2{\cdot})$ 생성을 현저히 증가시켰다. Adriamycin은 지질과산화 반응의 척도인 malondialdehyde(MDA) 생성을 역시 NADPH, NADH 존재하에서 용량의존적으로 증가시켰고, 산소라디칼 제거물질들인 superoxide dismutase (SOD), catalase 및 thiourea와 항산화물질인 butylated hydroxytoluene(BHT), ${\alpha}-tocopherol$은 MDA 생성증가를 현저히 억제하였다. 1, 3,-bis(2-chloroethyl)-1-nitrosourea(BCNU)를 처리하여 산화성 공격에 대한 방어기전의 하나인 glutahione 체계를 억제할 경우 adriamycin에 의한 MDA 생성은 더욱 현저히 증가하였고, 이는 역시 항산화 물질들에 의하여 억제되었다. 이상의 연구성적에서 adriamycin은 산소라디칼 생성의 증가와 그에 따른 지질과산화를 촉진하므로서 피부세포에 손상을 줄 것으로 사료되었다.