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.

천마의 GABA-benzodiazepine 수용체 복합체에 대한 조절작용

하정희,이동웅,어경윤,하정상,김현주,용철순,허근 영남대학교 약품개발연구소 1998 영남대학교 약품개발연구소 연구업적집 Vol.8 No.-

Methanol extract of G. elata inhibited the binding of [³H]Ro15-1788, a selective benzodiazepine receptor antagonist, to benzodiazepine receptor of rat cortices. Saturation experiments followed by Scatchard analysis of the results showed that the inhibition of [³H]Ro15-1788 binding by G. elata. appeared to be competitive. These competitive inhibiton of the butanol fraction was observed to be higher than the methanol extract. Methanol extract of G. elata inhibited a [³H]flunitrazepam, a selective benzodiazepine receptor agonist, binding to benzodiazepine receptor. GABA significantly enhanced the inhibition of [³H]flunitrazepam binding by G. elata, and these "positive GABA shift" supported the strong possibility of agonistic activity to benzodiazepine receptor. Butanol fraction was observed to be higher than crude extract by methanol in an agonistic activity to benzodiazepine receptor, furthermore enhanced the binding of [³H]SR95531 to GABA_(A) receptor. Butanol fraction of G. elata significantly diminished the pentylenetetrazole-induced lethality of mice. From these results, it can be concluded that substance or substances with neurochemical properties characteristic of a benzodiazepine receptor agonist may be important components, and contribute to the anticonvulsant property of G. elata.

Digitized QT dispersion by the Valsalva Maneuver in Hypertensive Patients

( Hee Jeoung Yoon ),( Seung Won Jin ),( Jong Min Lee ),( Woo Seung Shin ),( Yong Suk Oh ),( Man Young Lee ),( Ki Bae Seung ),( Tai Ho Rho ),( Jae Hyung Kim ),( Soon Jo Hong ),( Kyu Bo Choi ) 대한내과학회 2005 The Korean Journal of Internal Medicine Vol.20 No.2

항염증 활성이 증진된 민들레 잎의 열수 추출물 제조조건 설정

고윤정(Yoon Jeoung Koh),박용곤(Yong Kon Park),김윤숙(Yoon Sook Kim),차동수(Dong Soo Cha),최희돈(Hee Don Choi) 한국식품영양과학회 2009 한국식품영양과학회지 Vol.38 No.3

민들레 잎으로부터 항염증 활성 물질을 분리하여 기능성식품 소재로 개발하기 위해 민들레 잎의 적정 열수추출 및 항염증 활성물질의 농축조건을 조사하였다. 60~90℃의 추출온도에서의 추출물의 특성을 조사한 결과, 60℃ 추출물의 수율이 가장 높았고, flavonoid의 함량은 온도가 증가함에 따라 증가하였지만 항염증 활성은 감소하는 경향을 나타내었다. 가장 높은 항염증 활성을 나타낸 60℃ 추출물의 유용성분의 추출을 증가시키기 위해 세포벽 분해 효소를 처리한 결과 민들레 잎에서 추출된 flavonoid 함량과 추출수율이 1.5배 증가하고 항염증 활성도 감소하지 않는 것으로 나타나 세포벽 분해효소 처리가 항염증 활성물질의 추출증가에 상당한 영향을 미치는 것으로 나타났다. 또한 효소 처리에 의한 민들레 잎 추출물로부터 추출한 항염증 활성물질을 농축시키기 위해 column chromatography를 실시한 결과, Amberlite XAD-2와 Sepabeads SP-850에 흡착된 물질 모두 항염증 활성이 매우 높은 것으로 나타났지만 Sepabeads SP-850에 흡착된 물질의 수율이 2배 이상 높았기 때문에 민들레 잎의 항염증 활성물질을 농축하는데 Sepabeads SP-850 resin이 훨씬 효과적임을 알 수 있었다. To materialize anti-inflammatory compounds from dandelion leaves, we studied optimal conditions of hot water extraction and concentration. We investigated the properties of extracts on various temperatures between 60 and 90℃. Extraction yields at 60℃ were the highest at 39.2±1.3% and flavonoid contents were increased by heating. However, anti-inflammatory activities were remarkably decreased by increasing temperature. According to the results that the highest anti-inflammatory activities of water extract were demonstrated at 60℃, cell wall degrading enzyme treatment was carried out to increase extraction yield of anti-inflammatory compounds. The enzyme treatment resulted in increased yields and flavonoids from dandelion leaves of 1.5-fold and anti-inflammatory activities were not decreased. Also, column chromatography was used for concentration of anti-inflammatory compounds from extract of dandelion leaves treated with enzyme. Anti-inflammatory activities of adsorbed compounds on Amberlite XAD-2 and Sepabeads SP-850 were significantly increased. However, yields of adsorbed compounds were increased over two-folds on Sepabeads SP-850 compared to Amberlite XAD-2. Thus Sepabeads SP-850 was more effective than Amberlite XAD-2 to concentrate the anti-inflammatory compounds of dandelion leaves.

피부생검으로 확진한 관동맥 조영술 후의 중증 콜레스테롤 색전증 2예

김종진,박준철,채장성,김재형,홍순조,최규보,장성희,진승원,박희철,장이선,윤희정,김희열,이혜경 대한내과학회 2002 대한내과학회지 Vol.63 No.1

Cholesterol embolism is due to dislodgment of cholesterol crystals from the atheromatous aorta resulting in an occlusion of small arteries. Cholesterol emboli may occur spontaneously but usually develops as a complication of vascular procedures. The organs most frequently involved are the skin and the kidneys but any organ can be affected. Cutaneous manifestations include livedo reticularis, indurated firm violaceous painful plaques and noduli tending to show central necrosis and tender blue toes. We report two cases of cutaneous cholesterol embolization of lower extremities with the impairment of renal function after coronary angiography, proven by skin biopsy.

발작성야간혈색소뇨증(PNH)의 진단을 위한 CD55/CDig 검사의 유용성

강윤희,박찬정,지현숙 대한임상병리학회 1998 대한임상병리학회지 Vol.18 No.1

급성전골수성백혈병의 치죠 후 골수소견과 치료반응지표

강윤희,박찬정,지현숙,이규형,이정신,김우건,김상희 大韓血液學會 1998 大韓血液學會誌 Vol.33 No.3

Biological Functions of the COOH-Terminal Amino Acids of the $\alpha$-Subunit of Tethered Equine Chorionic Gonadotropin

Jeoung, Youn-Hee,Yoon, Jong-Taek,Min, Kwan-Sik The Korean Society of Animal Reproduction 2010 Reproductive & developmental biology Vol.34 No.1

Glycoprotein hormones have a common $\alpha$-subunit that is involved in the signaling pathway together with G protein, adenylcyclase and cAMP induction; however, it is an unclear how this common structure is related to hormonal action. To determine the biological functions of the COOH-terminal amino acids in the $\alpha$-subunit of these glycoprotein hormones, a tethered-molecule was constructed by fusing the $NH_2$-terminus of the $\alpha$-subunit to the COOH-terminus of the $\beta$-subunit of equine chorionic gonadotropin (eCG). The following deletion mutants were created by PCR; Ile was inserted at position 96 to form ${\Delta}96$, Lys was substituted at position 95 to form ${\Delta}95$, His was inserted at position 93 to form ${\Delta}93$ and Tyr was substituted at position 87 to form ${\Delta}87$. Each mutant was transfected into CHO-K1 cells. Tethered-wt eCG, and ${\Delta}96$, ${\Delta}95$, and ${\Delta}93$ mutants were efficiently secreted into the medium but the ${\Delta}87$ mutant was not secreted. Interestingly, the RT-PCR, real-time PCR, and northern blot analyses confirmed that the RNA was transcribed in the ${\Delta}87$ mutant. However, the ${\Delta}87$ mutant protein was not detected in the medium or the intracellular fraction of the cell lysates. The LH- and FSH-like activities of the recombinant proteins were assayed in terms of cAMP production using rat LH/CG and rat FSH receptors. The metabolic clearance rate (MCR) was determined by injecting rec-eCG (2 IU) into the tail vein. The ${\Delta}95$ and ${\Delta}93$ mutants were completely inactive in both the LH- and FSH-like activity assays. The ${\Delta}96$ mutant showed slight activity in the LH-like activity assay. In comparison to the wild type, the activity of the ${\Delta}96$ mutant in the FSH-like activity assay was the highest among all the mutants. The MCR assay in which rec-eCG was injected showed a peak at 10 min in all the treatment groups, which disappeared 4 h after injection. These results imply a direct interaction between the receptor and the COOH-terminal region of the a-subunit. The data also reveal a significant difference in the mechanism by which the eCG hormone interacts with the rLH and rFSH receptors. The COOH-terminal region of the $\alpha$-subunit is very important for the secretion and functioning of this hormone.

Anti-Inflammatory Effect of Taraxacum officinale Leaves on Lipopolysaccharide-Induced Inflammatory Responses in RAW 264.7 Cells

Yoon-Jeoung Koh,Dong-Soo Cha,고제상,박현진,Hee-Don Choi 한국식품영양과학회 2010 Journal of medicinal food Vol.13 No.4

To investigate the efficacy and the mechanism of the anti-inflammatory effect of Taraxacum officinale leaves (TOLs), the effect of a methanol extract and its fractions recovered from TOLs on lipopolysaccharide (LPS)-induced responses was studied in the mouse macrophage cell line, RAW 264.7. Cells were pretreated with various concentrations of the methanol extract and its fractions and subsequently incubated with LPS (1μg/mL). The levels of nitric oxide (NO), prostaglandin (PG) E2, and pro-inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 were determined using enzyme-linked immunosorbent assays. Expressions of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 and activation of mitogen-activated protein (MAP) kinases were analyzed using western blotting. The methanol extract and its fractions inhibited LPS-induced production of NO, pro-inflammatory cytokines, and PGE2 in a dose-dependent manner. The chloroform fraction significantly suppressed production of NO, PGE2, and two pro-inflammatory cytokines (TNF-α and IL-1β) in a dose-dependent manner with 50% inhibitory concentration values of 66.51, 90.96, 114.76, and 171.06μg/mL, respectively. The ethyl acetate fraction also inhibited production of the inflammatory molecules. The chloroform and ethyl acetate fractions reduced LPS-induced expressions of iNOS and COX-2 and activation of MAP kinases in a dose-dependent manner. Among the fractions of the methanol extract, the chloroform and ethyl acetate fractions exhibited the most effective anti-inflammatory activities. These results show that the anti-inflammatory effects of TOLs are probably due to down-regulation of NO, PGE2, and pro-inflammatory cytokines and reduced expressions of iNOS and COX-2 via inactivation of the MAP kinase signal pathway.

Postoperative Results of Kyphoplasty for Osteoporotic Vertebral Compression Fractures

Yoon, Won-Ki,Roh, Sung-Woo,Rhim, Seung-Chul,Lee, Chun-Sung,Kwon, Soon-Chan,Kim, Jeoung-Hee The Korean Neurosurgical Society 2005 Journal of Korean neurosurgical society Vol.37 No.4

Objective: We analyze pain relief, deformity correction and complication rate after percutaneous kyphoplasty for osteoporotic vertebral compression fractures. Methods: The authors retrospectively reviewed medical records and radiological findings of 32 patients who underwent percutaneous kyphoplasty for osteoporotic vertebral compression fractures. Results: The patients had significant pain improvement with the procedure. The visual analogue scale score reduced from 8.6 to 3.4 significantly after the procedure. The midline vertebral body height significantly increased postoperatively, but mean kyphotic angle did not. There was no serious complication except one case of epidural cement leakage without neurological impairment. Conclusion: Balloon kyphoplasty safely can reduce severe back pain and returned geriatric patients to higher activity levels. The midline vertebral height is restored significantly. However kyphotic deformity correction is not significant as contrary to what we expected from the present study before it was carried out.