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.

Donepezil, Tacrine and α-Phenyl-n-tert-Butyl Nitrone (PBN) Inhibit Choline Transport by Conditionally Immortalized Rat Brain Capillary Endothelial Cell Lines (TR-BBB)

Young-Sook Kang,Kyeong-Eun Lee,Na-Young Lee,Tetsuya Terasaki 대한약학회 2005 Archives of Pharmacal Research Vol.28 No.4

In the present study, we have characterized the choline transport system and examined the influence of various amine drugs on the choline transporter using a conditionally immortalized rat brain capillary endothelial cell line (TR-BBB) in vitro. The cell-to-medium (C/M) ratio of [3H]choline in TR-BBB cells increased time-dependently. The initial uptake rate of [3H]choline was concentration-dependent with a Michaelis-Menten value, Km, of 26.2 ± 2.7 µM. The [3H]choline uptake into TR-BBB was Na+-independent, but was membrane potential-dependent. The [3H]choline uptake was susceptible to inhibition by hemicholinium-3, and tetraethylammonium (TEA), which are organic cation transporter substrates. Also, the uptake of [3H]choline was competitively inhibited with Ki values of 274 µM, 251 µM and 180 µM in the presence of donepezil hydrochloride, tacrine and α-phenyl-n-tert-butyl nitrone (PBN), respectively. These characteristics of choline transport are consistent with those of the organic cation transporter (OCT). OCT2 mRNA was expressed in TR-BBB cells, while the expression of OCT3 or choline transporter (CHT) was not detected. Accordingly, these results suggest that OCT2 is a candidate for choline transport at the BBB and may influence the BBB permeability of amine drugs.

성인의 급성 설사에 대한 로페라미드 옥사이드의 효과: 위약과의 무작위 이중 맹검 비교 다시설 시험

박영태,정희진,박중원,이계희,김나영,임선희,윤병철,한동수,이오영 大韓消化器病學會 1998 大韓消化器病學會誌 Vol.31 No.5

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

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.

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.

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.

범법정신장애자의 정신의학적 특성분석

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

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

The alteration of serine transporter activity in a cell line model of amyotrophic lateral sclerosis (ALS)

Lee, Na-Young,Kim, Yunha,Ryu, Hoon,Kang, Young-Sook Academic Press 2017 Biochemical and biophysical research communication Vol. No.

<P><B>Abstract</B></P> <P>The alteration of <SMALL>D</SMALL>-serine levels is associated with the pathogenesis of sporadic ALS and mutant SOD1 (G93A) animal model of ALS. However, the exact mechanism of <SMALL>D</SMALL>-serine transport is not known in ALS. To better understand the distribution of <SMALL>D</SMALL>-serine in ALS, we determined the activity and the expression of serine transporter in a motor neuronal cell line model of ALS (NSC-34/hSOD1<SUP>G93A</SUP> cells). The uptake of [<SUP>3</SUP>H]<SMALL>D</SMALL>-serine was significantly lower in NSC-34/hSOD1<SUP>G93A</SUP> cells than in control NSC-34 and NSC-34/hSOD1<SUP>wt</SUP> cells. In contrast, the uptake of [<SUP>3</SUP>H]<SMALL>L</SMALL>-serine, precursor of <SMALL>D</SMALL>-serine, was markedly increased in NSC-34/hSOD1<SUP>G93A</SUP> cells compared to control NSC-34 and NSC-34/hSOD1<SUP>wt</SUP> cells. Both [<SUP>3</SUP>H]<SMALL>D</SMALL>-serine and [<SUP>3</SUP>H]<SMALL>L</SMALL>-serine uptake were saturable in these cells. The estimated Michaelis-Menten constant, <I>K</I> <SUB>m</SUB>, for <SMALL>D</SMALL>-serine uptakes was higher in NSC-34/hSOD1<SUP>G93A</SUP> cells than in NSC-34/hSOD1<SUP>wt</SUP> cells while the <I>K</I> <SUB>m</SUB> for <SMALL>L</SMALL>-serine uptake was 2 fold lower in NSC-34/hSOD1<SUP>G93A</SUP> cells than in control cells. [<SUP>3</SUP>H]<SMALL>D</SMALL>-serine and [<SUP>3</SUP>H]<SMALL>L</SMALL>-serine uptakes took place in a Na<SUP>+</SUP>-dependent manner, and both uptakes were significantly inhibited by system ASC (alanine-serine-cysteine) substrates. As a result of small interfering RNA experiments, we found that ASCT2 (SLC1A5) and ASCT1 (SLC1A4) are involved in [<SUP>3</SUP>H]<SMALL>D</SMALL>-serine and [<SUP>3</SUP>H]<SMALL>L</SMALL>-serine uptake in NSC-34/hSOD1<SUP>G93A</SUP> cells, respectively. The level of SLC1A4 mRNA was significantly increased in NSC-34/hSOD1<SUP>G93A</SUP> compared to NSC-34 and NSC-34/hSOD1<SUP>wt</SUP> cells. In contrast, the level of SLC7A10 mRNA was relatively lower in NSC-34/hSOD1<SUP>G93A</SUP> cells than the control cells. Together, these data suggest that the pathological alteration of <SMALL>D</SMALL>- and <SMALL>L</SMALL>-serine uptakes in ALS is driven by the affinity change of <SMALL>D</SMALL>-and <SMALL>L</SMALL>-serine uptake system.</P> <P><B>Highlights</B></P> <P> <UL> <LI> The alteration of <SMALL>D</SMALL>-serine levels is associated with the pathogenesis of ALS. </LI> <LI> The uptake of <SMALL>D</SMALL>-serine is reduced in a motor neuronal cell line model of ALS. </LI> <LI> In contrast, the uptake of <SMALL>L</SMALL>-serine, precursor of <SMALL>D</SMALL>-serine, was markedly increased in a motor neuronal cell model of ALS. </LI> <LI> The alteration of <SMALL>D</SMALL>- and <SMALL>L</SMALL>-serine uptakes in ALS is driven by the affinity change of <SMALL>D</SMALL>- and <SMALL>L</SMALL>-serine uptake system. </LI> </UL> </P>