씨름선수에서 체중 감량과 회복기의 Leptin과 PAI-1 변화

김용운,도경오,권태동,박덕일,장응찬,박소영,김종연,이석강 대한스포츠의학회 2000 대한스포츠의학회지 Vol.18 No.2

Obesity which is defined as accumulation of excess body fat, is central factor of insulin resistance syndrome. Recently, it is revealed tat adipose tissue is not simply an energy storage organ but it also secretes a variety of molecules which affect the metabolism of the whole body, those are leptin and plasminogen activator inhibitor-1(PAI-1). Therefore, leptin and PAI-1 are increased in the obese state. Leptin regulates energy homeostasis and satiety and PAI-1 regulates fibrinolytic system. For these reasons, elevated levels of leptin and PAI-1 are considered as link factors between obesity and insulin resistance syndrome. However, the exact regulating mechanism for serum levels of leptin and PAI-1 is not fully understood yet. In this study, to evaluate the regulating mechanisms of serum levels of leptin and PAI-1 according to the weight changes, we measured leptin, PAI-1, physical, metabolic, and endocrine parameters during 10 days of weight reduction and 10 days of regain period in 7 young athletes. The mean body weight change was -4.7 kg(5.0%) in the weight reduction period and -2.4 kg(2.5%) in the weight regain period compared to baseline value. Baseline level of leptin in athletes was 1.7±0.66 ng/ml, which was significantly correlated with body weight, BMI, percent body fat, body fat mass, triglyceride, insulin, and PAI-1. Baseline level of PAI-1 in athletes was 16.6±5.26 ng/ml, which was significantly correlated with body weight, BMI, triglyceride, insulin, and leptin. Leptin was decreased to 0.7±0.39(44% of the basaline value) in the weight reduction period, and increased to 1.9±0.64(119% of the baseline value) in the regain period. PAI-1 was decreased to 7.4±2.72(44% of the basaline value) in the weight reduction period, and increased to 22.8±7.33(138% of the baseline value) in the regain period. The changes of leptin during weight reduction period were significantly correlated with the changes of insulin(r=0.890, P<0.01) and triglycerides(r=0.874, P<0.01). The changes of PAI-1 during weight reduction period were significantly correlated with the changes of FFA(r=0.889, P<0.01) and triglycerides(r=0.869, P<0.05). The changes of both leptin and AAI-1 during weight regain period were significantly correlated with the changes of insulin(r=0.755 and 0.849, P<0.05, respectively). In summary, these results suggest that serum levels of leptin and PAI-1 were affected by weight cycling, the percentages of change were more greater than that of weight change, and rebound phenomena were occurred during weight regain period.

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.

Role of lactate in metabolism of skeletal muscle

Kyung-Oh Doh 한국자기학회 2020 한국자기학회 학술연구발표회 논문개요집 Vol.30 No.1

Effects of TGF-<FONT FACE= HJ중명조 >Ղ1 Ribbon Antisense on CCl<SUB>4</SUB>-induced Liver Fibrosis

Kyung-Oh Doh 대한생리학회-대한약리학회 2008 The Korean Journal of Physiology & Pharmacology Vol.12 No.1

Ribbon-type antisense oligonucleotide to TGF-<FONT FACE= HJ중명조 >Ղ1 (TGF-<FONT FACE= HJ중명조 >Ղ1 RiAS) was designed and tested to prevent or resolve the fibrotic changes induced by CCl₄ injection. When Hepa1c1c7 cells were transfected with TGF-<FONT FACE= HJ중명조 >Ղ1 RiAS, the level of TGF-<FONT FACE= HJ중명조 >Ղ1 mRNA was effectively reduced. TGF-<FONT FACE= HJ중명조 >Ղ1 RiAS, mismatched RiAS, and normal saline were each injected to mice via tail veins. When examined for the biochemical effects on the liver, TGF-<FONT FACE= HJ중명조 >Ղ1 mRNA levels were significantly reduced only in the TGF-<FONT FACE= HJ중명조 >Ղ1 RiAS-treated group. The results of immunohistochemical studies showed that TGF-<FONT FACE= HJ중명조 >Ղ1 RiAS prevented the accumulation of collagen and <FONT FACE= HJ중명조 >Ձ-smooth muscle actin, but could not resolve established fibrosis. These results indicate that ribbon antisense to TGF-<FONT FACE= HJ중명조 >Ղ1 with efficient uptake can effectively prevent fibrosis of the liver.

Validation of Heterodimeric TAT-NLS Peptide as a Gene Delivery Enhancer

Doh, Kyung-Oh The Korean Society for Microbiology and Biotechnol 2015 Journal of microbiology and biotechnology Vol.25 No.6

Cationic liposomes have been actively used as gene delivery vehicles despite their unsatisfactory efficiencies because of their relatively low toxicity. In this study, we designed novel heterodimeric peptides as nonviral gene delivery systems from TAT and NLS peptides using cysteine-to-cysteine disulfide bonds between the two. Mixing these heterodimeric peptides with DNA before mixing with lipofectamine resulted in higher transfection efficiencies in MCF-7 breast cancer cells than mixing unmodified TAT, NLS, and a simple mixture of TAT and NLS with DNA, but did not show an adverse effect on cell viability. In gel retardation assays, the DNA binding affinities of heterodimeric peptides were stronger than NLS but weaker than TAT. However, this enhancement was only observed when heterodimeric peptides were premixed with DNA before being mixed with lipofectamine. The described novel transfection-enhancing peptide system produced by the heterodimerization of TAT and NLS peptides followed by simple mixing with DNA, increased the gene transfer efficiency of cationic lipids without enhancing cytotoxicity.

Prevention of CCl4-induced liver cirrhosis by ribbon antisense to transforming growth factor-beta1.

Doh, Kyung-Oh,Jung, Hyun-Kyung,Moon, Ik-Jae,Kang, Hyun-Gu,Park, Jeong-Hoh,Park, Jong-Gu D.A. Spandidos 2008 International journal of molecular medicine Vol.21 No.1

<P>Transforming growth factor-beta1 (TGF-beta1) is an important mediator of tissue fibrosis, including liver cirrhosis. Ribbon-type antisense oligonucleotide to TGF-beta1 (TGF-beta1 RiAS) was designed and combined with cationic peptide derived from the nuclear localization signal of human immunodeficiency virus-1 Tat protein for enhanced cellular uptake. When Hepa1c1c7 cells were transfected with TGF-beta1 RiAS, the level of TGF-beta1 mRNA was reduced by >70%. TGF-beta1 RiAS, mismatched RiAS, and normal saline were each injected into mice via the tail vein, beginning the week after intraperitoneal CCl4 injection and continuing for 7 weeks, in order to determine whether TGF-beta1 RiAS prevents the fibrotic changes induced by the CCl4 injection. After 8 weeks of the experiment, all of the mice treated with TGF-beta1 RiAS survived, compared to 50% of the control group and 65% of the mismatched RiAS-treated group. Upon examining the biochemical effects on the liver, TGF-beta1 mRNA levels were reduced significantly only in the TGF-beta1 RiAS-treated group. Immunohistochemical studies showed a reduced accumulation of collagen and alpha-smooth muscle actin. Our experimental results suggest that ribbon antisense to TGF-beta1, with efficient uptake, effectively blocks the expression of TGF-beta1 and prevents fibrosis of the liver.</P>

What is the Key Step in Muscle Fatty Acid Oxidation after Change of Plasma Free Fatty Acids Level in Rats?

Doh, Kyung-Oh,Suh, Sang-Dug,Kim, Jong-Yeon The Korean Society of Pharmacology 2005 The Korean Journal of Physiology & Pharmacology Vol.9 No.3

The purpose of this study was to discern the critical point in skeletal muscle fatty acid oxidation by changing plasma free fatty acids (FFA) level in rat. In the study, 3 key steps in lipid oxidation were examined after changing plasma FFA level by acipimox. The rates of both palmitate and palmitoylcarnitine oxidation were decreased by decrease of plasma FFA level, however, carnitine palmitoyl transferase (CPT) 1 activity was not changed, suggesting CPT1 activity may not be involved in the fatty acid oxidation at the early phase of plasma FFA change. In the fasted rats, ${\beta}-hydroxy$ acyl-CoA dehydrogenase (${\beta}$-HAD) activity was depressed to a similar extent as palmitate oxidation by a decrease of plasma FFA level. This suggested that ${\beta}-oxidation$ might be an important process to regulate fatty acid oxidation at the early period of plasma FFA change. Citrate synthase activity was not altered by the change of plasma FFA level. In conclusion, the critical step in fatty acids oxidation of skeletal muscles by the change of plasma FFA level by acipimox in fasting rats might be the ${\beta}-oxidation$ step rather than CPT1 and TCA cycle pathways.

Insulin Resistance of Skeletal Muscle was Recovered by Leptin Injection in vivo, but not in vitro, in High-fat Diet Fed Rats

Doh, Kyung-Oh,Park, Jeong-Oak,Jeon, Jeong-Ryne,Kim, Jong-Yeon The Korean Society of Pharmacology 2005 The Korean Journal of Physiology & Pharmacology Vol.9 No.2

We examined the effect of leptin on the insulin resistance in skeletal muscles by measuring the glucose transport. Male Wistar rats were fed with chow or high-fat diets for 30 days. Three days before sacrifice, high-fat fed rats were subcutaneously injected with leptin (1 mg/kg body weight) for 3 days. The glucose transports in the epitrochlearis and soleus muscle were not different among the experimental groups under basal state, however these were decreased significantly in the high fat-diet rats under insulin-stimulation (p<0.01). Leptin treatment recovered the decreased glucose transport in the epitrochlearis (p<0.05) and soleus (p=0.08). Triglyceride concentration in the soleus muscle was increased significantly in the high fat-fed rats, compared to chow diet rats (p<0.01), and it was decreased significantly by leptin treatment (p<0.01). The glucose transport was measured under basal and $60{\mu}u/ml$ of insulin with or without 50 ng/ml of leptin. Leptin had no direct stimulatory effect on glucose transport under both basal and insulin-stimulated conditions in vitro. These results demonstrate that leptin injection to high fat diet fed rats recovered impaired insulin responsiveness of the skeletal muscles and muscle triglyceride concentration. However, there was no direct stimulatory effect of leptin on insulin sensitivity of the skeletal muscle in vitro.

What is the Key Step in Muscle Fatty Acid Oxidation after Change of Plasma Free Fatty Acids Level in Rats?

Kyung-Oh Doh,Sang-Dug Suh,Jong-Yeon Kim 대한생리학회-대한약리학회 2005 The Korean Journal of Physiology & Pharmacology Vol.9 No.3

The purpose of this study was to discern the critical point in skeletal muscle fatty acid oxidation by changing plasma free fatty acids (FFA) level in rat. In the study, 3 key steps in lipid oxidation were examined after changing plasma FFA level by acipimox. The rates of both palmitate and palmitoyl- carnitine oxidation were decreased by decrease of plasma FFA level, however, carnitine palmitoyl transferase (CPT) 1 activity was not changed, suggesting CPT1 activity may not be involved in the fatty acid oxidation at the early phase of plasma FFA change. In the fasted rats, β-hydroxy acyl-CoA dehydrogenase (β-HAD) activity was depressed to a similar extent as palmitate oxidation by a decrease of plasma FFA level. This suggested that β-oxidation might be an important process to regulate fatty acid oxidation at the early period of plasma FFA change. Citrate synthase activity was not altered by the change of plasma FFA level. In conclusion, the critical step in fatty acids oxidation of skeletal muscles by the change of plasma FFA level by acipimox in fasting rats might be the β-oxidation step rather than CPT1 and TCA cycle pathways.

Synthesis of NBD-Labeled DOTAP Analog to Track Intracellular Delivery of Liposome

( Kyung Oh Doh ),( Bieong Kil Kim ),( Tae Jin Lee ),( Jong Won Park ),( Young Bae Seu ) 한국미생물 · 생명공학회 2013 Journal of microbiology and biotechnology Vol.23 No.1

A DOTAP analog labeled by NBD on the head group (DTNBD) was designed and synthesized to label DOTAP liposome. The structure was confirmed by 1H NMR and FAB-MS, and the fluorescence of the newly synthesized DT-NBD was observed by fluorescent microscopy. The transfection efficiency of DOTAP liposome containing DT-NBD was comparable to commonly used NBD PE in COS7 and MCF7 cells. Furthermore, the level of cellular uptake and fluorescent intensity of fluorescent liposome containing DT-NBD was higher than NBD PE. Therefore, the novel NBD-labeled DOTAP analog seems to be effectively used for investigation of the cellular interaction and transfection mechanism of DOTAP liposome.