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.

Efficacy of Long-Term Tenofovir-Based Therapy in Chronic Hepatitis B Patients with Previous Nucleos(t)ide Analogues Treatment Experience

( Na Eun Lee ),( Hong Seon Son ),( Sung Hoon Choi ),( Chang Hun Lee ),( Seung Young Seo ),( Seong Hun Kim ),( Sang Wook Kim ),( Seung Ok Lee ),( Soo Teik Lee ),( Dae Ghon Kim ),( In Hee Kim ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: Tenofovir disoproxil fumarate (TDF) is considered as the preferred treatment option for chronic hepatitis B (CHB) patients with treatment failure or resistance to prior nucleos(t)ide analogues (NAs) treatment. We investigated the efficacy of long-term TDF-based therapy in CHB patients with previous NAs-experience. Methods: This study included total 251 patients who had previous history of NAs therapy and were treated with TDF mono (n=173) or TDF combined with other NA (n=78) from August 2012 to March 2017. Virologic response (VR) was defined as undetectable serum HBV DNA by PCR (<20 IU/mL). Results: Mean age of patients was 49.3 years, median duration of TDF therapy was 27.2 months, 75.7% were HBeAg-positive, and median HBV DNA was 3.7 log10IU/mL. The cumulative rates of VR were 188/244 (77.0%), 180/211 (85.3%), and 146/161 (90.7%) at 12, 24, and 36 months, respectively. Multivariate analysis showed that body mass index (OR 0.77, 95% CI 0.61-0.95, p=0.0189) and duration of TDF therapy (OR 1.09, 95% CI 1.02-1.18, p=0.0221) was significantly associated with VR. TDF monotherapy, HBeAg-positivity, platelet count, serum albumin was associated with VR in the univariate analysis, but not significant in the multivariate analysis. In relation to renal safety, patients showed renal impairment (7, 3.0%), mild hypophosphatemia (15, 7.2%), severe hypophosphatemia (1, 0.4%). Conclusions: Long-term TDF-based therapy demonstrated highly effective in viral suppression and relatively favorable renal safety in CHB patients with previous NA-experience. The body mass index and duration of TDF therapy was independent factors associated with VR.

페미니스트 정의론의 관점에서 본 일본군 성노예제 문제의 의미와 과제

이나영(Lee, Na-Young) 계명대학교 여성학연구소 2018 젠더와 문화 Vol.11 No.2

이 글은 일본군 ‘위안부’ 운동에 대한 폄훼와 왜곡이 심각하고 피해당사자들이 돌아가시고 있는 현실에 착목한다. 일본의 아베 정권이 과거 사실을 부인하고 ‘도덕적 책임’이라는 수사로 법적 책임을 회피하며 당사자들이 비존재할 순간을 기다리는 시점에 우리에게 남겨진 과제는 무엇인가. 기존의 법적/도덕적 책임이라는 이분법을 넘어 피해당사자들의 정신을 계승하고 우리에게 남겨진 책임을 강조할 수 있는 방법은 무엇인가. 필자는 아이리스 영의 정의론을 검토함으로써 이러한 난국을 돌파하려 한다. 먼저 영의 정치적 책임론의 의미를 파악하고 책임에 관한 연결모델을 통해 일본군 성노예제 문제를 이해하고자 했다. 그러나 법적인 죄가 추궁당하지 않을 때 정치적 책임의 영역이 오히려 확장되어 왔기에, 법적-도덕적 책임과 연결된 정치적 책임의 층위론적 모델을 대안으로 제시하고자 한다. This article focuses on the fact that while the controversy over the Japanese military "comfort women" is still under way and the victims are passing away, there is still serious disagreement and distortion of the situation. It is therefore important to ask what tasks remain for sympathizers and advocates of the victims, when the Abe administration in Japan denies the past and avoids legal responsibility by arguing for ‘moral responsibility,’ as it waits for the relevant parties to die out. How are we to transcend the dichotomy of traditional legal/moral responsibility while upholding the spirit of the victims and emphasizing our own responsibilities? This paper aims to address these difficulties through a critical examination of Iris Young’s justice theory. First, the meaning of Young’s ‘political responsibility’ is explored and the issue of sexual slavery in Japan is investigated through a connection model of responsibility. However, since the domain of political responsibility has been enlarged in the absence of legal criminal action, an alternative stratigraphic model of political responsibility linked to legal-moral responsibility is suggested.

Furosemide에 의한 소디움 운반체 발현의 변화

오윤규 ( Yoon Kyu Oh ),나기영 ( Ki Young Na ),이재욱 ( Jay Wook Lee ),장혜련 ( Hye Ryun Chang ),박영선 ( Young Sun Park ),박정환 ( Jung Hwan Park ),주권욱 ( Kwon Wook Joo ),김근호 ( Gheun Ho Kim ),이정상 ( Jung Sang Lee ),한진석 ( 대한신장학회 2003 Kidney Research and Clinical Practice Vol.22 No.2

배경 : 임상에서 흔히 사용하는 이뇨제 furosemide는 비후상행각에서 Na+-K+-2CI- cotranspoter (NKCC2)를 억제하여 NaCl 재흡수를 차단하여 이뇨작용을 나타낸다. Furosemide를 장기간 투여하면 내성과 대사성 알카리증의 부작용이 발생할 수 있는데, 이는 집합관에 도달하는 소디움 증가와 관련 있을 가능성이 있다. 방법 : 저자들은 furosemide의 내성이나 부작용이 집합관 상피 소디움 통로 (ENaC) 단백발현의 변화와 관련이 있는지를 확인하고자, Sprague-Dawley rat에서 farosemide (12 mg/day)을 7일간 지속적 피하 주입한 후 반정량적 immunoblotting과 면역조직화학법을 이용하여 NKCC2, Na +-CL- cotransporter (NCC), ENaC 단백의 발현을 관찰하였다. 실험기간 동안 수분과 전해질 용액 (0.8% NaCl & 0.1% KCl)을 자유롭게 섭취하도록 하여 체액 감소를 방지하였다. 결과 : 부형약 (vehicle)을 투여한 대조군에 비하여, furosemide를 투여한 군에서 각각 요량과 요 소디움 배설이 증가하였으나, 체중, 혈청 알도스테론치 및 크레아티닌 청소율은 차이가 없었다. Furosemid 투여 후 NKCC2 단백은 피질 (151±10 vs. 100±10%, p<0.05)과 외수질 (122±5 vs. 100±3%, p<0.01)에서 증가해 있었다. ENaC 단백은 세 가지 subunit 모두 furosemide 투여 후 대조군에 비하여 피질 (α:187±25 vs. 100±22%, p<0.05; β:155±8 vs. 100±15%, p<0.05; γ:168±16 vs. 100±9%, p<0.05)과 외수질 (α:171±27 vs. 100±17%, p<0.05; β :986±91 vs. 100±33%, p<0.01; γ :242±24 vs. 100±22%, p<0.01)에서 증 가하였다. 면역조직화학법에서도 furosemide를 투여한 군의 집합관 주세포에서 ENaC β-subunit가 더 강하게 염색되었다. 결론 : 이상에서 장기간 furosemide 투여시 집합관 ENaC 발현이 증가하며, 이러한 원위부네프론의 적응 반응이 이뇨제 내성을 유발하는데 기여할 것으로 생각한다. Background : Furosemide inhibit NaCl absorption in the thick ascending limb and produce an increase in distal delivery of Na+. We carried out semiquantitative immunoblotting and immunohistochemistry of rat kidneys to investigate whether chronic furosemide infusion is associated with compensatory increases in the abundance of Na+ transporters in distal nephron. Methods : Osmotic minipumps were implanted into Sprague-Dawley rats to deliver 12 mg/day of furosemide(n=6) with simultaneous administration of 0.8% NaCl and 0.1% KCl in drinking water for 7days. Results : Compared with vehicle infused controls, urine volume and urine sodium amount were increased. However, there were no differences in body weight, serum aldosterone, and creatinine clearance. The abundance of Na+-K+-2CI - cotransporter after furosemide infusion was increased in cortex (151±10 vs. 100±10%, p<0.05) and outer medulla (122±5 vs. 100±3%, p<0.01). In furosemide infusion group, the abundance of all three subunits of epithelial sodium channel (ENaC) was increased both in cortex (α:187±25 vs. 100±17%, p<0.05; β:155±8 vs. 100±15%, p<0.05; γ :168±16 vs. 100±9%, p<0.05) and outer medulla (α:171±27 vs. 100±17%, p<0.05; β :986±91 vs. 100±33%, p<0.01; γ :242±24 vs. 100±22%, p<0.01). Consistent with these results, ENaC β-subunit immunohistochemistry showed a remarkable increase in immunoreactivity in the principal cells of collecting ducts with furosemide treatment. Conclusion : These increases in the abundance of ENaC protein may account for the generation of diuretic tolerance.

Glyoxal-induced exacerbation of pruritus and dermatitis is associated with <i>staphylococcus aureus</i> colonization in the skin of a rat model of atopic dermatitis

Han, Rafael Taeho,Kim, Hye Young,Ryu, Hyun,Jang, Wooyoung,Cha, Seung Ha,Kim, Hyo Young,Lee, JaeHee,Back, Seung Keun,Kim, Hee Jin,Na, Heung Sik Elsevier 2018 Journal of dermatological science Vol.90 No.3

<P><B>Abstract</B></P> <P><B>Background</B></P> <P>Atopic dermatitis (AD) is a highly pruritic, chronic inflammatory skin disease associated with hyperreactivity to environmental triggers. Among those, outdoor air pollutants such as particulate matter (PM) have been reported to aggravate pre-existing AD. However, underlying mechanisms of air pollution-induced aggravation of AD have hardly been studied.</P> <P><B>Objective</B></P> <P>To investigate the molecular mechanisms by which glyoxal, a PM-forming organic compound, exacerbates the symptoms of AD induced by neonatal capsaicin treatment.</P> <P><B>Methods</B></P> <P>Naïve and AD rats had been exposed to either fresh air or vaporized glyoxal for 5 weeks (2 h/day and 5 days/week) since one week of age. Pruritus and dermatitis were measured every week. The skin and blood were collected and immunological traits such as Staphylococcus aureus skin colonization, production of antimicrobial peptides and immunoglobulin, and mRNA expression of inflammatory cytokines were analyzed.</P> <P><B>Results</B></P> <P>Exposure to glyoxal aggravated pruritus and dermatitis in AD rats, but did not induce any symptoms in naïve rats. Staphylococcus aureus skin colonization was increased in the skin of both naïve and AD rats. Expression of antimicrobial peptides such as LL-37 and β-defensin-2 was also increased by exposure to glyoxal in the skin of both naïve and AD rats. The mRNA expression of Th1-related cytokines was elevated on exposure to glyoxal. However, serum immunoglobulin production was not significantly changed by exposure to glyoxal.</P> <P><B>Conclusion</B></P> <P>In AD rats, exposure to glyoxal exacerbated pruritus and cutaneous inflammation, which was associated with increased colonization of <I>S. aureus</I> and subsequent immunological alterations in the skin.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Exposure to glyoxal aggravated the symptoms in AD rats, but did not induce AD in naïve rats. </LI> <LI> <I>S. aureus</I> skin colonization and subsequent expression of antimicrobial peptides were increased after exposure to glyoxal. </LI> <LI> Exposure to glyoxal elevated the production of Th1-related cytokines such as TNF-α and IFN-γ in the AD lesional skin. </LI> </UL> </P>

Comparison of Virologic Response and Renal Safety of Long-Term Antiviral Therapy with Tenofovir and Entecavir in Naive Patient with Chronic Hepatitis B

( Hong Seon Son ),( Sung Hoon Choi ),( Na Eun Lee ),( Chang Hun Lee ),( Seung Young Seo ),( Seong Hun Kim ),( Sang Wook Kim ),( Seung Ok Lee ),( Soo Teik Lee ),( Dae Ghon Kim ),( In Hee Kim ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: Tenofovir (TDF) entecavir (ETV) are considered as the preferred treatment options for treatment-naïve chronic hepatitis B (CHB) patients. We compared the virologic response and renal safety of long-term TDF versus ETV therapy in naïve CHB patients. Methods: This retrospective study included total 432 patients who were treated with TDF (n=205) or ETV (n=227) from August 2012 to March 2017. Virologic response (VR) was defined as undetectable serum HBV DNA by PCR (<20 IU/mL). Results: Mean age of patients, sex, baseline serum levels of AST, ALT, creatinine, and HBV DNA were not significantly different between TDF and ETV groups. The cumulative rates of VR between TDF and ETV groups were 71.6% vs. 61.8% (p=0.477), 88.1% vs. 79.6% (p=0.058), and 84.8% vs. 83.7% (p=0.966) at 1, 2, and 3 years, respectively. The cumulative rates of genotypic resistance between TDF and ETV groups were 0% vs. 0%, 0% vs. 1.5% (p=0.404), and 0% vs. 2.2% (p=0.447) at 1, 2, and 3 years, respectively. Incidences of renal impairment and hypophosphatemia during treatment up to 3 years were not significantly different between two groups. Multivariate analysis showed that HBeAg-positivity (OR 0.27, 95% CI 0.12-0.58, p=0.0012) and serum HBV DNA at 1 year 2000 IU/mL (OR 0.09, 95% CI 0.03-0.25, p<0.0001) were significantly associated with VR. Conclusions: Long-term TDF and ETV treatments appear to have similar virologic response and renal safety in naïve CHB patient. However, long-term ETV therapy might to be associated with genotypic resistance in 2.2% up to 3 years, while none of patients on TDF therapy did.

국가예방접종전산등록체계 개발을 위한 민간의료 기관 하부구조 및 환경 조사연구

이무식,김은영,이건세,이석구,홍지영,김건엽,김대경,신의철,이연경,기몽서,나백주,김영택 한국모자보건학회 2003 한국모자보건학회지 Vol.7 No.2

대한약전 수재 의약품의 기기분석법에 관한 연구(ⅩⅡ) : 고속액체크로마토그래프를 이용한 아크리놀 및 그 제제의 분석법에 관한 연구 Studies on analytical Methods of actinol and its preparations by HPLC

이석호,옥치석,최보경,김영옥,최리나,박상애,최명신,김길수,이강춘 식품의약품안전청 1997 식품의약품안전청 연보 Vol.1 No.-

아크리놀은 살균,소독에 쓰이는 약물로서 연로제 및 지사제용도의 경구투여제제등게 이용되고 있다. 공정서에 수재된 아크리놀의 분석법은 적정법이고 제제에서늬 분석법은 확립되지 않았고 원료의 적정법을 제제에 적용시 다른 주성분이나 부형제 또는 안정제 드으이 영향으로 분석오차가 생길 우려가 있다. 따라서 아크리놀을 보다 신속·정확하게 확인 및 정량분씬을 할 수 있고 강도와 분리능이 우수한 HPLC를 이용하여 아크리놀을 분석하고자 하였다. MPLC 분석조건은 이동상 :아세료니트릴 · 1% 인산일수소나트륨혼합액(40:60)(p템 5.2), 칼랏 :옥타데실실릴화한 실리카칼럼,검출기 :자외부흡광광도계(측정파장 : 254nm)을 사용하여 양호한 결과를 얻었다. 틴PLC법의 분석 결과, 검량선의 상관계수는 0.9999, 재현성(aSD(%))은 0.5234. 정균회수율은 100.28%(RSD=0.89%)로 정량성 및 재현성이 높온 분석 결과를·얻었다. 또한 시판품에 대하여 려PLC분석법과 공정서에 수재된 적정법의 시칩결과를 비교하였을 때 핀Plf법인 더욱 정확한 결과를 얻을 수 있었으므로, 조작이 간편하고 재현성이 높은 딘PLC분석법을 약전차정의 기초자료로 활용하고자 한다. We describe a method for the determination of acrino1 and its preparations by HPLC. The optimum analrtical coriditions were as follows;column : u-Bondapak C_(18) mobile phase : acetonitrile 1% Na_(2)HPO_(4), buffer (40:60)(pH 5.2), detector : 254nm, flow rate 1.OmL/min, injection volumn : 5uL, The calibration curve at 254nm was linear within the range of 10 ~ 140㎍/mL. This HPLC method has been validated to be precise, accurate and linear. This method has also been found to be applicable to other formulations containing acrinol.

범법 정신 장애자와 일반 정신 장애자의 약물 사용 양상에 관한 비교 분석

이길홍,박두병,나철,이재광,기백석,이재우,유영식,이영식,이헌재 중앙대부설한국의과학연구소 1991 한국의과학 Vol.23 No.1

톡소포자충 배양시 약제투여에 따른 Toxoplasma P30 유전자의 발현

이상걸,이영하,김계영,나영언,신대환 충남대학교 의과대학 지역사회의학연구소 1996 충남의대잡지 Vol.23 No.2

To know the drugs effect on gene expression and its regulating mechanism by RT-PCR and southern blot hybridization assay based on detection of the P30 gene encoding the major surface antigen, P30 of Toxoplasma gondii and the DNA synthesis in T. gondii infected HeLa cells. The experiment was performed and the results were as follows. 1. The thymidine incooperation in DNA of HeLa cell and T. gondii infected HeLa cell reached peak level at 36 hours and suddenly decreased at 48 hours. The uracil incooperation in DNA of T. gondii reached peak level at 48 hours. 2. The decrease of P30 gene expression began from 24 hours after pyrimethamine treated and 36 hours after methotrexate treated in T. gondii. The results were some what different. Pyrimethamine was more sensitive and acted earlier to T. gondii than Methotrexate did. The decrease of P30 gene expression of T. gondii was regulated these drugs in dose dependent manner. 3. The effects of dibutyryl cyclic AMP on P30 gene expression increased peak at 24 hours and on contrary decreased at 60 hours after treatment in dose dependent manner, but at 10mM high concentration of dibutyryl cAMP, P30 gene expression was supressed. 4. Actinomycine D supressed the P30 gene expression of T. gondii in HeLa cell. As the results, we presume pyrimethamine acts more powerful and earlier to supresses P30 gene expression than methotrexate, and it is regulated at transcription level. The results of RT-PCR were in agreement with that of southern blot hybridization.