정신분열병에 대한 리스페리돈의 효과 및 안정성

이민수,김용구,김영훈,연병길,오병훈,윤도준,윤진상,이철,정희연,강병조,김광수,김동언,김명정,김상훈,김희철,나철,노승호,민경준,박기창,박두병,백기청,백인호,손봉기,손진욱,양병환,양창국,우행원,이정호,이종범,이홍식,임기영,전태연,정영조,정영철,정인과,정인원,지익성,채정호,한상익,한선호,한진희,서광윤 大韓神經精神醫學會 1998 신경정신의학 Vol.37 No.1

연구목적 : 본 시험의 목적은 임상시험 시작전에 연구자들을 대상으로 PANSS Workshop을 통하여 PANSS, ESRS에 대한 국내에서의 표준화 작업을 구축하고 새로운 정신병 치료제인 리스페리돈의 효과와 안정성을 재확인하여 리스페리돈 사용에 대한 적정화를 이루는데 있다. 연구방법 : 1996년 4월부터 1996년 9월까지 국내 39개 대학병원 정신과에 입원중인 혹은 증상이 악화되어 입원하는 정신분열병 환자 377명을 대상으로 다시설 개방 연구를 시행하였다. 1주일간의 약물 배설기간을 가진후, 리스페리돈을 8주간 투여하였고, 기준점, 1주, 2주, 4주, 그리고 8주후에 평가되었다. 용량은 제1일에는 리스페리돈 1mg씩 1일 2회, 제2일에는 2mg씩 1일 2회, 제3∼7일에는 3mg씩 1일 2회 투여하였다. 이후 환자의 임상상태에 따라 임의로 증량할 수 있으며, 최대 일일 16mg을 초과하지 않도록 하였다. 추체외로 증상을 조절하기 위한 투약을 허용하였다. 임상증상 및 부작용의 평가는 PANSS(Positive and Negative Syndrome Scale), CGI(Clinical Global Impression) 그리고 ESRS(Extrapyramidal Symptom Rating Scale)을 사용하였다. 연구결과 : 377명중 343명(91%)이 8주간의 연구를 완결하였다. 치료 종결시점인 8주후 PANSS 총점수가 20% 이상 호전된 경우를 약물 반응군으로 정의할때, 약물반응군은 81.3%였다. 리스페리돈에 반응하는 예측인자로는 발병연령, 이전의 입원 횟수, 유병기간이 관련 있었다. 리스페리돈은 1주후부터 PANSS양성, 음성, 및 일반정신병리 점수상에 유의한 호전을 보여 효과가 빨랐다. CGI의 경우도 기준점에 비해 1주후부터 유의한 감소를 나타내었다. ESRS의 경우, 파킨슨 평가점수는 기준점과 비교해 투여 1주, 2주, 4주후 유의하게 증가되었다가 8주후 기준점과 차이가 없었다. Dystonia 평가점수는 1주후만 유의한 증가를 보였으며, dyskinesia 평가점수는 유의한 차이가 없었다. 혈압, 맥박수의 생명징후 및 일반 혈액학 검사, 생화학적 검사, 심전도 검사에서 유의한 변화는 없었다. 결 론 : 이상의 다시설 개방 임상 연구를 통해 리스페리돈은 정신분열병 환자에서 양성증상뿐만 아니라 음성증상 및 전반적인 증상에도 효과적인 것으로 사료된다. 보다 명확한 평가를 위해서는 다른 항정신병약물과의 이중맹검 연구가 필요할 것으로 생각되며, 또한 장기적 치료에 대한 평가도 함께 이루어져야 하겠다. Objective : The purpose of this study was to investigate the efficacy and safety of risperidone in the treatment of Korean schizophrenic patients. Method : This multicenter open study included 377 schizophrenic patients drawn from 39 university hospitals. After a wash-out period of 1 week, the schizophrenic patients were treated with risperidone for 8 weeks and evaluated at 5 points ; at baseline, and 1, 2, 4 and 8 weeks of treatment. The dose was increased from 2mg/day(1mg twice daily) to 6mg/day(3mg twice daily) during the first week and adjusted to a maximum of 16mg/day over the next 7 weeks according to the patient's clinical response. Medication to control extrapyramidal symptoms was permitted. The psychiatric and neurological status of the patients was assessed by PANSS, CGI, and ESRS scales. Results : 343(91%) of 377 patients completed the 8-week trial period. Clinical improvement, as defined by a 20% or more reduction in total PANSS score at end point, was shown by 81.3% of patients. The predictors of response to risperidone were associated older age, shorter duration of illness, fewer previous hospitalization. Risperidone had rapid onset of action ; a significant decrease of the total PANSS and three PANSS factor(positive, negative, general), and CGI was already noticed at the end of first week. For the ESRS, parkinsonism rating scores were significantly increased until week 4 comparing with baseline. Dystonia rating scores were significantly increased until week 1, and dyskinesia rating scores were not significantly changed during the study. Laboratory parameters including vital sign, EKG, hematological, and biochemical values showed no significant changes during the trial. Conclusions : This study suggests that risperidone is generally safe and effective against both the positive and negative symptoms in our group of patients.

Risk Factors for Acute Exacerbations in Elderly Asthma: What Makes Asthma in Older Adults Distinctive?

Kyoung-Hee Sohn,Woo-Jung Song,Jong-Sook Park,박흥우,Tae Bum Kim,Choon-Sik Park,조상헌,Elderly Asthma Cohort in Korea Group 대한천식알레르기학회 2020 Allergy, Asthma & Immunology Research Vol.12 No.3

Purpose: Asthma in the elderly (EA; ≥ 65 years of age) is increasing, adding a heavy socioeconomic burden to the healthcare system. However, little is known about risk factors associated with acute exacerbations in EA patients. The objective of this study was to investigate risk factors for acute exacerbation in EA compared to non-elderly asthma (NEA). Methods: We combined data from 3 adult asthma cohorts under a unified protocol and database. Asthmatic patients with regular follow-up during a 1-year period were selected from the cohorts to identify the risk factors predicting acute exacerbations in EA compared to NEA. Results: We selected a total of 1,086 patients from the merged cohort. During the observation period, 503 and 583 patients were assigned to the EA and NEA groups, respectively. The exacerbation rate was 31.0% in the EA and 33.2% in the NEA group. Multivariate logistic regression analysis revealed fixed airway obstruction, chronic rhinosinusitis (CRS), and male sex as independent risk factors for exacerbation in the EA group. In the NEA group, exacerbation increased along with an increase in eosinophil count. Bayesian analysis of the interactions among clinical factors revealed that forced expiratory volume in 1 second/forced vital capacity was directly related to exacerbation in the EA group, and eosinophil count was related to exacerbation in the NEA group. Conclusions: We suggest that fixed airway obstruction and CRS as the important clinical factors predicting acute exacerbations in EA, whereas in NEA, eosinophil count was the strong predictor of exacerbation.

Lipid-Overloaded Enlarged Adipocytes Provoke Insulin Resistance Independent of Inflammation

Kim, Jong In,Huh, Jin Young,Sohn, Jee Hyung,Choe, Sung Sik,Lee, Yun Sok,Lim, Chun Yan,Jo, Ala,Park, Seung Bum,Han, Weiping,Kim, Jae Bum American Society for Microbiology 2015 Molecular and cellular biology Vol.35 No.10

<P>In obesity, adipocyte hypertrophy and proinflammatory responses are closely associated with the development of insulin resistance in adipose tissue. However, it is largely unknown whether adipocyte hypertrophy <I>per se</I> might be sufficient to provoke insulin resistance in obese adipose tissue. Here, we demonstrate that lipid-overloaded hypertrophic adipocytes are insulin resistant independent of adipocyte inflammation. Treatment with saturated or monounsaturated fatty acids resulted in adipocyte hypertrophy, but proinflammatory responses were observed only in adipocytes treated with saturated fatty acids. Regardless of adipocyte inflammation, hypertrophic adipocytes with large and unilocular lipid droplets exhibited impaired insulin-dependent glucose uptake, associated with defects in GLUT4 trafficking to the plasma membrane. Moreover, Toll-like receptor 4 mutant mice (C3H/HeJ) with high-fat-diet-induced obesity were not protected against insulin resistance, although they were resistant to adipose tissue inflammation. Together, our <I>in vitro</I> and <I>in vivo</I> data suggest that adipocyte hypertrophy alone may be crucial in causing insulin resistance in obesity.</P>

Effects of Three Thiazolidinediones on Metabolic Regulation and Cold-Induced Thermogenesis

Sohn, Jee Hyung,Kim, Jong In,Jeon, Yong Geun,Park, Jeu,Kim, Jae Bum Korean Society for Molecular and Cellular Biology 2018 Molecules and cells Vol.41 No.10

Insulin resistance is closely associated with metabolic diseases such as type 2 diabetes, dyslipidemia, hypertension and atherosclerosis. Thiazolidinediones (TZDs) have been developed to ameliorate insulin resistance by activation of peroxisome proliferator-activated receptor (PPAR) ${\gamma}$. Although TZDs are synthetic ligands for $PPAR{\gamma}$, metabolic outcomes of each TZD are different. Moreover, there are lack of head-to-head comparative studies among TZDs in the aspect of metabolic outcomes. In this study, we analyzed the effects of three TZDs, including lobeglitazone (Lobe), rosiglitazone (Rosi), and pioglitazone (Pio) on metabolic and thermogenic regulation. In adipocytes, Lobe more potently stimulated adipogenesis and insulin-dependent glucose uptake than Rosi and Pio. In the presence of pro-inflammatory stimuli, Lobe efficiently suppressed expressions of pro-inflammatory genes in macrophages and adipocytes. In obese and diabetic db/db mice, Lobe effectively promoted insulin-stimulated glucose uptake and suppressed pro-inflammatory responses in epididymal white adipose tissue (EAT), leading to improve glucose intolerance. Compared to other two TZDs, Lobe enhanced beige adipocyte formation and thermogenic gene expression in inguinal white adipose tissue (IAT) of lean mice, which would be attributable to cold-induced thermogenesis. Collectively, these comparison data suggest that Lobe could relieve insulin resistance and enhance thermogenesis at low-concentration conditions where Rosi and Pio are less effective.

Perilipin 1 (Plin1) deficiency promotes inflammatory responses in lean adipose tissue through lipid dysregulation

Sohn, Jee Hyung,Lee, Yun Kyung,Han, Ji Seul,Jeon, Yong Geun,Kim, Jong In,Choe, Sung Sik,Kim, Su Jung,Yoo, Hyun Ju,Kim, Jae Bum American Society for Biochemistry and Molecular Bi 2018 The Journal of biological chemistry Vol.293 No.36

<P>Lipid droplets are specialized cellular organelles that contain neutral lipid metabolites and play dynamic roles in energy homeostasis. Perilipin 1 (Plin1), one of the major lipid droplet-binding proteins, is highly expressed in adipocytes. In mice, Plin1 deficiency impairs peripheral insulin sensitivity, accompanied with reduced fat mass. However, the mechanisms underlying insulin resistance in lean Plin1 knockout (Plin1(-/-)) mice are largely unknown. The current study demonstrates that Plin1 deficiency promotes inflammatory responses and lipolysis in adipose tissue, resulting in insulin resistance. M1-type adipose tissue macrophages (ATMs) were higher in Plin1(-/-) than in Plin1(+/+) mice on normal chow diet. Moreover, using lipidomics analysis, we discovered that Plin1(-/-) adipocytes promoted secretion of pro-inflammatory lipid metabolites such as prostaglandins, which potentiated monocyte migration. In lean Plin1(-/-) mice, insulin resistance was relieved by macrophage depletion with clodronate, implying that elevated pro-inflammatory ATMs might be attributable for insulin resistance under Plin1 deficiency. Together, these data suggest that Plin1 is required to restrain fat loss and pro-inflammatory responses in adipose tissue by reducing futile lipolysis to maintain metabolic homeostasis.</P>

Effects of Disease Resistant Genetically Modified Rice on Soil Microbial Community Structure According to Growth Stage

Sohn, Soo-In,Oh, Young-Ju,Ahn, Jae-Hyung,Kang, Hyeon-jung,Cho, Woo-Suk,Cho, Yoonsung,Lee, Bum Kyu The Korean Society of Environmental Agriculture 2019 한국환경농학회지 Vol.38 No.3

BACKGROUND: This study investigated the effects of rice genetically modified to be resistant against rice blast and rice bacterial blight on the soil microbial community. A comparative analysis of the effects of rice genetically modified rice choline kinase (OsCK1) gene for disease resistance (GM rice) and the Nakdong parental cultivar (non-GM rice) on the soil microbial community at each stage was conducted using rhizosphere soil of the OsCK1 and Nakdong rice. METHODS AND RESULTS: The soil chemistry at each growth stage and the bacterial and fungal population densities were analyzed. Soil DNA was extracted from the samples, and the microbial community structures of the two soils were analyzed by pyrosequencing. No significant differences were observed in the soil chemistry and microbial population density between the two soils. The taxonomic analysis showed that Chloroflexi, Proteobacteria, Firmicutes, Actinobacteria, and Acidobacteria were present in all soils as the major phyla. Although the source tracking analysis per phylogenetic rank revealed that there were differences in the bacteria between the GM and non-GM soil as well as among the cultivation stages, the GM and non-GM soil were grouped according to the growth stages in the UPGMA dendrogram analysis. CONCLUSION: The difference in bacterial distributions between Nakdong and OsCK1 rice soils at each phylogenetic level detected in microbial community analysis by pyrosequencing may be due to the genetic modification done on GM rice or due to heterogeneity of the soil environment. In order to clarify this, it is necessary to analyze changes in root exudates along with the expression of transgene. A more detailed study involving additional multilateral soil analyses is required.

인체 모낭기관배양에서 substance P 가 모발성장에 미치는 영향

이원수,손인범 대한피부과학회 2001 대한피부과학회지 Vol.39 No.2

Background: In vitro, some neuropeptides, including substance P(SP), act as a growth factor. The cyclic growth of the richly innervated hair follicle offers a model for probing such functions in a complex, developmentally regulated tissue interaction system under the physiologic condition. Dissecting the role of neuropeptides in this system may also reveal as yet obscure neural mechanisms of hair growth control. Objective: The purpose of this study was to investigate the effect of SP on human hair growth using a recently described model in which isolated hair follicles are grown in vitro. Methods:After the healthy human hair follicles without any visible damage were collected, they were cultured in DMEM with several combination of supplements including insulin, hydrocortisone, sodium selenite, human transferrin, fetal bovine serum at 37℃ in an atmosphere of 5% CO_2 /95% air incubator, and SP was added to the media. The culture media were supplemented with final concentration of 10^(-6),10^(-7),10^(-8) M SP dissolved in DMEM. The results were evaluated by measuring linear hair fiber growth and hair follicle morphology on light microscopy and electron microscopy and by measuring radioisotope uptake of [methyl-^3H] thymidine and [U-^14C] leucine of hair follicle. Results: The following results were obtained from this study. 1. SP did not have an statistically significant effect on the rate of linear hair growth in cultured hair follicles. However, it prolonged the anagen stage of hair cycle. 2. We could not find morphological differences of hair follicles cultured in SP groups compared with those cultured in control group. 3. DNA and protein synthesis in hair follicles increased steadily for 5 days of culture. Conclusion: From the results, we can conclude that SP has growth-stimulatory effect and especially prolongs the duration of anagen phase without affecting the rate of linear hair growth.

Effects of Disease Resistant Genetically Modified Rice on Soil Microbial Community Structure According to Growth Stage

( Soo-in Sohn ),( Young-ju Oh ),( Jae-hyung Ahn ),( Hyeon-jung Kang ),( Woo-suk Cho ),( Yoonsung Cho ),( Bum Kyu Lee ) 한국환경농학회 2019 한국환경농학회지 Vol.38 No.3

BACKGROUND: This study investigated the effects of rice genetically modified to be resistant against rice blast and rice bacterial blight on the soil microbial community. A comparative analysis of the effects of rice genetically modified rice choline kinase (OsCK1) gene for disease resistance (GM rice) and the Nakdong parental cultivar (non-GM rice) on the soil microbial community at each stage was conducted using rhizosphere soil of the OsCK1 and Nakdong rice. METHODS AND RESULTS: The soil chemistry at each growth stage and the bacterial and fungal population densities were analyzed. Soil DNA was extracted from the samples, and the microbial community structures of the two soils were analyzed by pyrosequencing. No significant differences were observed in the soil chemistry and microbial population density between the two soils. The taxonomic analysis showed that Chloroflexi, Proteobacteria, Firmicutes, Actinobacteria, and Acidobacteria were present in all soils as the major phyla. Although the source tracking analysis per phylogenetic rank revealed that there were differences in the bacteria between the GM and non-GM soil as well as among the cultivation stages, the GM and non-GM soil were grouped according to the growth stages in the UPGMA dendrogram analysis. CONCLUSION: The difference in bacterial distributions between Nakdong and OsCK1 rice soils at each phylogenetic level detected in microbial community analysis by pyrosequencing may be due to the genetic modification done on GM rice or due to heterogeneity of the soil environment. In order to clarify this, it is necessary to analyze changes in root exudates along with the expression of transgene. A more detailed study involving additional multilateral soil analyses is required.

九鍼歌 譯釋

손인철 ( In Chul Sohn ),안성훈 ( Seong Hun Ahn ),김유리 ( Yu Lee Kim ),양승범 ( Seung Bum Yang ),김재효 ( Jae Hyo Kim ) 경락경혈학회 2012 Korean Journal of Acupuncture Vol.29 No.3

Objectives : The purpose of this study is to make nine classical needles understood easily through interpreting Nine Classical Needles in Rhymes. Methods : The principle of classification and clinical application of Nine Classical Needle was sorted out referring to 「The beginning of Nine Classical Needles in Rhymes」and 「The presciption and treatment of Nine Classical Needles in Rhymes」which is the chapter of 『Golden Mirror of Medicine』. Results & Conclusions : The Nine Classical Needles, which were designed to get harmonious interaction between human beings and the nature, have been representative medical appliance in Korean Medicine. The needles consist of shear needle, round-pointed needle, spoon needle, lance needle, stiletto needle, round-sharp needle, filiform needle, long needle, and big needle. Nine Classical Needles in Rhymes was formed in a poem format to help us easily memorize the essential contents of Nine Classical Needles. 「The beginning of Nine Classical Needles in Rhymes」dealt with the reasons of making needles and organization principles about Nine Classical Needles. 「The prescription and treatment of Nine Classical Needles in Rhymes」sorted main treatment applications of nine needles, helping understand needles as medical appliance.

During Adipocyte Remodeling, Lipid Droplet Configurations Regulate Insulin Sensitivity through F-Actin and G-Actin Reorganization

Kim, Jong In,Park, Jeu,Ji, Yul,Jo, Kyuri,Han, Sang Mun,Sohn, Jee Hyung,Shin, Kyung Cheul,Han, Ji Seul,Jeon, Yong Geun,Nahmgoong, Hahn,Han, Kyung Hee,Kim, Jiwon,Kim, Sun,Choe, Sung Sik,Kim, Jae Bum American Society for Microbiology 2019 Molecular and cellular biology Vol.39 No.20

<P>Adipocytes have unique morphological traits in insulin sensitivity control. However, how the appearance of adipocytes can determine insulin sensitivity has not been understood. Here, we demonstrate that actin cytoskeleton reorganization upon lipid droplet (LD) configurations in adipocytes plays important roles in insulin-dependent glucose uptake by regulating GLUT4 trafficking.</P><P>Adipocytes have unique morphological traits in insulin sensitivity control. However, how the appearance of adipocytes can determine insulin sensitivity has not been understood. Here, we demonstrate that actin cytoskeleton reorganization upon lipid droplet (LD) configurations in adipocytes plays important roles in insulin-dependent glucose uptake by regulating GLUT4 trafficking. Compared to white adipocytes, brown/beige adipocytes with multilocular LDs exhibited well-developed filamentous actin (F-actin) structure and potentiated GLUT4 translocation to the plasma membrane in the presence of insulin. In contrast, LD enlargement and unilocularization in adipocytes downregulated cortical F-actin formation, eventually leading to decreased F-actin-to-globular actin (G-actin) ratio and suppression of insulin-dependent GLUT4 trafficking. Pharmacological inhibition of actin polymerization accompanied with impaired F/G-actin dynamics reduced glucose uptake in adipose tissue and conferred systemic insulin resistance in mice. Thus, our study reveals that adipocyte remodeling with different LD configurations could be an important factor to determine insulin sensitivity by modulating F/G-actin dynamics.</P>