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      • 마약길항제의 방출 제어형 제제 (제2보) : 나록손 이식제제의 생체적합성 및 약물속도론적 평가 Biocompatibility and Pharmacokinetics of Naloxone Implant

        문미란,박주애,이승진,김형국,김길수 梨花女子大學校 藥學硏究所 1995 藥學硏究論文集 Vol.- No.5

        For the effective administration of narcotic antagonist, the application of sustained release implantable systems with biodegradable polyphosphazene was examined. Using poly[(diethyl glutamate)-co-(ethyl glycinate) phosphazene]. the implantable devices containing naloxone hydrochloride were prepared and in vivo implantation studies were carried out subcutaneously in rat and rabbit with this preparation for the biocompatibility and pharmacokinetics. The histological finding in rats at initial time period was the inflammation that occurred focally around the implants, but they were showed subsequent mild and limited chronic inflammations and the irreversible changes such as necrosis and degeneration of the muscle or connective tissues were not observed. Therefore the placebo and naloxone implants are considered to be biocompatible formulations histologically. In pharmacokinetic studies, the release of naloxone from the naloxone implants into blood plasma was maintained in 192 hours, but the initial burst effect was observed. If this problem was solved, the application for the narcotic antagonist sustained release systems can be expected.

      • KCI등재

        정신분열병 환자의 우울증에서 Paroxetine과 삼환계 항우울제 병용치료

        심주철,공보금,박정환,윤영란,신재국,김정익,안동성,김용관,차인준,김영훈 大韓神經精神醫學會 1997 신경정신의학 Vol.36 No.4

        저자들은 마산동서병원에 입원중인 우울증이 동반된 정신분열증 환자 10명을 대상으로 사용중인 항정신병약물에 paroxetine과 저용량의 삼환계 항우울제를 6주간 병용투여한 후 우울증상에 대한 효과와 치료의 안전성 및 약물상호작용을 알아보았다. Paroxetine은 고정량의 항정신병약물과 삼환계 항우울제에 부가하여 일일 20㎎을 6주간 병용하게 하였으며, 임상상태는 HDRS, HARS, UKU Side Effect Rating Scale등의 평가척도를 사용하여 평가하였다. 또한 약동학적 약물상호작용은 삼환계 항우울제들의 혈장농도를 HPLC로 측정하여 분석하였다. 결과는 다음과 같다. 1) 10명의 전체 대상환자에서의 HDRS 평균점수는 TCA와 paroxetine 병용투여 6주후에 통계적으로 유의하게 감소되었다. 이중 40%의 환자에서는 병용투여 6주후에 HDRS 점수상 50% 이상의 감소를 보여, 일부의 환자들에서는 정신분열병에 동반된 우울증상의 치료에 소량의 삼환계 항우울제와 paroxetine의 병용치료가 효과가 있음을 확인하였다. 2) 두 명의 환자에게서 심각한 약물독성이 발생하였다. 이중 한 명은 삼환계 항우울제의 높은 혈중농도로 인한 항콜린성 위기(anticholinergic crisis) 소견을 보였으며, 다른 한 명은 인지기능 및 의식수준은 명료하였으나 망상과 환각증상이 약화되는 소견을 보였다. 따라서 본 연구에서 시도된 복합적 약물치료의 경우, 삼환계 항우울제의 혈중농도의 측정을 포함한 세심한 임상적 추적이 필요하다고 생각된다. 3) 기저치의 amitriptyline과 그 대사물인 nortriptyline의 농도합. imipramine과 대사물인 desipramine의 농도합은 각각 47.8-226.5ng/㎖. 80.5-395.6ng/㎖였으며 일반적으로 이들 약물들의 단독사용시에 문헌에 보고된 혈중농도를 훨씬 상회하고 있었다. 이는 병용투여된 항정신병 약물 약시 강력한 CYP2D6 효소억제제로서 기저치의 삼환계 항우울제들의 혈장농도를 이미 상당히 증가시켰던 것으로 판단되며, 그러한 결과로 인해 본 연구에서는 paroxetine이 이전의 문헌보고들과는 달리 뚜렷하게 삼환계 항우울제들의 혈장농도를 증가시키지 못하였다. 본 연구는 SSRI와 삼환계 항우울제의 병합 투여가 우울증의 개선 효과를 빠르게 하고, 치료역을 넓히고, 약물상호작용의 결과 paroxetine이 삼환계 항우울제의 혈중농도를 증가시킨다는 기존의 연구결과를 이용하여 정신분열병 우울증상의 치료에 parotextine과 소량의 삼환계 항우울제를 병용하는 방법을 시도해 본 연구이다. 저자들은 이러한 약물치료가 일부의 환자들에게서 효과가 있음을 관찰하였으나, 항정신병약물과 삼환계 항우울제를 병용투여 할 경우는 물론 이에 paroxetine과 같은 선택적 세로토닌 재흡수 억제제를 병용할 경우 복합약물상호작용의 결과로 약물독성의 위험성이 크며 세심한 주의가 필요함을 경험하였다. Depression is well-known to comorbid with several psychiatric disorders. Many schizophrenics also suffer from depression in the course of their illness. Combined therapy of SSRI and tricyclic antidepressants were reported to have benefits in some depressed patients. Paroxetine, a potent CYP2D6 inhibitor, increases the blood levels of tricyclic antidepressant markedly. Using paroxetine, we tried this combined therapy in the treatment of depressive symptoms in 10 chronic schizophrenic inpatients and evaluated its efficacy and drug interactions between paroxetine and tricyclic antidepressants. The following results were obtained : 1) The mean score of Hamilton's Depression Rating Scale(HDRS) was reduced significantly after 6 weeks-trials of this combined therapy for the mild depressive symptoms in 10 chronic schizophrenics. In four patients, 50% or more reductions in the scores of HDRS were noticed at final evaluation. 2) Two among our 10 subjects experienced severe toxic behavioral problems. Anticholinergic crisis with toxic confusion due to high blood levels of tricyclics was found in one patient and the other showed rapid clinical deterioration in his psychotic symptoms such as delusion and hallucination without any consciousness alternation. 3) Baseline plasma levels of tricyclics before adding paroxetine were higher than expected in our chronic schizophrenic subjects maintained with their antipsychotic medications. Several antipsychotics were also known as a potent CYP2D6 inhibitors and to increase the blood levels of tricyclics. Because the blood levels of tricyclics had already increased significantly by the use of antipsychotics, adding paroxetine to antipsychotics and tricyclic antidepressant in our subjects could increase the blood levels of tricyclics not so much as previously reported in the literatures.

      • KCI등재후보

        전공의들의 직업적 유해인자 및 직업만족도

        송혜란,김진하,변주현,이광영,이덕희,김호찬 大韓産業醫學會 2003 대한직업환경의학회지 Vol.15 No.3

        목적: 전공의는 여러 유해인자에 노출되어지고 있으며 과중한 업무로 인한 수면 부족에 시달리고 있다. 본 연구는 전공의의 건강상태의 기초 자료를 제공하고 향후개선 방안을 도출하기 위하여 시행하였다. 방법: 연구대상은 2000년 3사관학교와 국군군의학교에 입소한 전체 1,316명 중 전공의 수련과정 없이 입대한 의사와 치과의사, 한의사를 제외한 881명을 대상으로 설문지를 배포하여 784부(회수율: 89.0%)를 회수하고 이중 분석이 가능한 704(79.9%)명의 자료를 최종 분석하였다. 결과: 월평균 당진횟수는 레지던트 1년차에서 19회 정도이었다. 당직 시 평균 수면시간은 레지던트 1년차에서 4시간미만 이었다. 수련기간 동안 전공의의 20%이상에서 방사선, 레이저, 살균소독제, 마취가스, 항암제에 노출되었으며 예방대책은 방사선과 레이저의 노출의 경우 35%정도를 제외하고는 10%내외로 조사되었다. 연구대상자중 91.1%에서 수련기간 동안 주사침이나 시술에 의해 손상을 입었으며 그 중 본인이 감염된 경우는 HBV 2.3%(4명), HCV 0.6%(1명)으로 조사되었다. 응답자의 28.4%에서 자신의 직업에 불만족 하였으며 96.5%가 과중한 업무부담을 느꼈고 69.5%가 동일한 임금수준에서 직업을 바꾸고자 한다고 응답하였다. 결론: 전공의는 수련기간 동안 물리적, 화학적, 생물학적 유해인자에 노출되고 있었으나 이에 대한 보호나 예방대책은 거의이루어지지 않고 있었으며 과중한 업무부담으로 수면부족을 초래하여 가장 중요한 환자 진료에 지장을 받고 있었다. 수련기간 동안 대다수가 의사로서 직업에 대한 흥미를 가지고 있었으나 업무부담과 진료이외의 업무 등으로 소득과 조건이 비슷하다면 다른 직업을 선택하고자 하였다. 이상의 결과를 토대로 전공의들을 위한 유해인자의 보호대책 및 예방대책을 마련하며 과중예방대책이 마련되어야 하고 업무환경개선 및 업무로 인한 건강장해에 대한 정당한 보상이 향후에 마련되어야 할 것이다. Objects: Residents are exposed to various hazards and harassed by sleep dificiency due to overwork. This study was performed to outline the health condition of residents and develop the ways of improving it. Mehtods: A questionnaire was distributed to 881 army doctors who enrolled at the Korea Third Military Academy and The Armed force Health Service School in 2000 with the exception of medical doctors who joined the armed service without going through intern and resident periods, dental and oriental medical doctors. 784(89.0%) of the 881 questionnaires were resident of which 704 cases (79.9%). This should actually be 89.0% were regarded for analyses as being reliable data. Results: More than 20% of residents were exposed to radiation, laser, disinfectants, anesthetic gas, and anticancer drugs during their training periods with preventive neasures for each of these hazards taken in about 10% of the cases of the lesser hazards but in about 35% for the hazards from radiation and laser. 91.1% of residents had experience of needlestick injuries during theirtraining periods with over 36.3% being exposed to patients with infection during that time. The cases contracting HBV and HCV diseases due to pricking are 2.3% and 0.6% respectively. The average number of night duties per month during a one-year resident's period was about 10. The average sleeping time on duty during a one-year residents was less than 4 hours. 28.4% of respondents were not satisfied with their occupation, 96.5% delt tired from overwork and 69.5% wanted to change their occupation to another that would pay the same salary. Conclusion: Residents are exposed to harmful physical, chemical and biological factors, but the preventive care seldom undertaken. In addition, their overwork brings about lack of sleep which causes them problems when giving medical treatment to patients during their training periods. Despite the resident's interest in an occupation as a doctor, many intend to select other occupations if they can receive the same salary. According to the above results, preventative systems and measures should be prepared with environmental improvements for residents, and proper rewards for their overwork should be accomplished

      • 논에 殺蟲劑 처리가 天敵昆蟲과 거미群集에 미치는 영향

        李海浜,金胄弼,全正蘭 동국대학교 산업기술대학원 1993 산업기술논문집 Vol.1 No.-

        An arthropod community structure in a rice peddy field ecocystem was investigated. Sampling was conducted using D-vac sucker at the Experimental Station of Dongguk University in Namyangju-Gun, Kyonggi province during the periods from August to October in 1992. During the period of investigation, 112 species, 34 families and 6 orders were represented for the insect cummunity in untreated plots, while 104 species, 41 families and 5 orders in treated plots. And among them, 45 and 31 species of entomophagous insect were listed from the untreated and treated plots with 17.5% vs 5.2% in the occupancy rate, respectively, suggesting that pesticide usage lead the reduced number of immigrating and emigrating natural enemies. The other hand, 25 species in 13 families of the spider were represented in the untreated plots whereas 15 species in 8 families in treated plots. Spiders which collected in untreated plots were twice as high in abundance as those in treated plots. Tetragnatha sp. (Tetragnathidae) was the most abundance species in treated plots. Dominant species of untreated plots, Piratasubpiraticus (Lycosidae), occurred in very low number in treated plots. During the growing season, the temporal pattern of species diversity are measured using species diversity (H'), species richness (S) and species evenness index (J'). The tendency of communities to return to its predisturbed state were observed in treated plots. The positive correlation was obtained for spider species diversity and prey abundance in untreated plots but in treated plots.

      • SCOPUSKCI등재

        위, 소장, 대장을 침범한 Peripheral T-cell Lymphoma 1예

        김영범,이소현,신용운,김치열,우재순,임형은,최혜란,박찬섭,주영채,김진주 대한소화기내시경학회 1991 Clinical Endoscopy Vol.11 No.2

        This article is the case report of the peripheral T-cell lymphoma which involove the stomach, small bowel, and colon. A 40-year-old male was admitted to Inha University hospital because of epigastric pain, diarrhea, and weight loss. He was taken by gastrofiberscopy with biopsy, upper G-I series, colonscopy with biopsy, lower G-I series, ultrasonogram, and abdominal computerized tomogram. Endoscopic picture demonstrated the malignant ulcer in the posterior wall of angle. Sigmoidoscopic picture demonstrated the polipoid hyperemic mucosal edema. In the X-ray & endoscopic findings, the lesion was suspected as lymphoma. Histologically, the lesion was diagnosed as peripheral T-cell lymphoma. Immunohistochemical staining using UCHL-1(pan-T-cell maker) demonstrated the lymphoma as T-cell origin. The patient was treated with the multiagent chemotherapy(Bleomycin + Vincristin + Cyclophosphamide + PDS).

      • KCI등재

        Relative Effectiveness of COVID-19 Vaccination in Healthcare Workers: 3-Dose Versus 2-Dose Vaccination

        Kim Sung Ran,Kang Hyeon Jeong,Jeong Hye Rin,Jang Su Yeon,Lee Jae Eun,Kim Da Eun,Lee Hae Ry,Cho Min Hee,Noh Ji Yun,Cheong Hee Jin,Kim Woo Joo,Song Joon Young 대한의학회 2022 Journal of Korean medical science Vol.37 No.35

        The omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is known to have high infectivity and is more likely to evade vaccine immunity. However, booster vaccination is expected to strengthen cross-reactive immunity, thereby increasing the vaccine effectiveness (VE). This study aimed to evaluate the relative VE of the 3-dose (booster) vaccination compared with the 2-dose primary series vaccination in healthcare workers during omicron variant-dominant periods. During the omicron-dominant period from February 1, 2022 to February 28, 2022, a 1:1 matched case-control study was conducted. Healthcare workers with positive SARS-CoV-2 test results were classified as positive cases, whereas those with negative results served as controls. Compared with the 2-dose primary series vaccination, booster vaccination with mRNA vaccine showed moderate VE (53.1%). However, in multivariate analysis including the time elapsed after vaccination, the significant VE disappeared, reflecting the impact of recent vaccination rather than the third dose itself.

      • SCIESCOPUS
      • Prediction of drug-induced immune-mediated hepatotoxicity using hepatocyte-like cells derived from human embryonic stem cells

        Kim, Dong Eon,Jang, Mi-Jin,Kim, Young Ran,Lee, Joo-Young,Cho, Eun Byul,Kim, Eunha,Kim, Yeji,Kim, Mi Young,Jeong, Won-il,Kim, Seyun,Han, Yong-Mahn,Lee, Seung-Hyo Elsevier 2017 Toxicology Vol.387 No.-

        <P><B>Abstract</B></P> <P>Drug-induced liver injury (DILI) is a leading cause of liver disease and a key safety factor during drug development. In addition to the initiation events of drug-specific hepatotoxicity, dysregulated immune responses have been proposed as major pathological events of DILI. Thus, there is a need for a reliable cell culture model with which to assess drug-induced immune reactions to predict hepatotoxicity for drug development. To this end, stem cell-derived hepatocytes have shown great potentials. Here we report that hepatocyte-like cells derived from human embryonic stem cells (hES-HLCs) can be used to evaluate drug-induced hepatotoxic immunological events. Treatment with acetaminophen significantly elevated the levels of inflammatory cytokines by hES-HLCs. Moreover, three human immune cell lines, Jurkat, THP-1, and NK92MI, were activated when cultured in conditioned medium obtained from acetaminophen-treated hES-HLCs. To further validate, we tested thiazolidinedione (TZD) class, antidiabetic drugs, including troglitazone withdrawn from the market because of severe idiosyncratic drug hepatotoxicity. We found that TZD drug treatment to hES-HLCs resulted in the production of pro-inflammatory cytokines and eventually associated immune cell activation. In summary, our study demonstrates for the first time the potential of hES-HLCs as an <I>in vitro</I> model system for assessment of drug-induced as well as immune-mediated hepatotoxicity.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Generation and characterization of hES-HLCs for evaluation of drug-induced immune cell-mediated hepatotoxicity. </LI> <LI> The secretion of inflammatory cytokines is highly enhanced from APAP-treated hES-HLCs. </LI> <LI> Immune cells are activated and produce pro-inflammatory cytokines by conditioned medium from hES-HLCs cultured with APAP. </LI> <LI> Hepatotoxic results in hES-HLCs are consistent with those of primary human hepatocytes. </LI> <LI> Hepatotoxic drugs such as TZD, and non-hepatotoxic drugs such as aspirin and metformin, are also validated with our drug screening system. </LI> </UL> </P>

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