• 대한임상독성학회지
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• 제17권2호
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• pp.118-125
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• 2019

Purpose: Non-benzodiazepine hypnotic drugs (including zolpidem) are associated with an increased risk of suicide and suicidal ideation. Considering the wide usage of zolpidem, this drug should be considered a possible etiology for stupor or coma in any patient exposed to this drug. However, there are no reports on zolpidem blood levels in emergency department patients in Korea. We therefore reviewed the analyzed data of a toxicology laboratory at one university affiliated hospital. Methods: The sex, age, chief symptoms, suspiciousness of poisoning, and presumption of poison were analyzed from January 2018 to June 2019. The detection frequency and level of zolpidem in the patient blood were compared to the mental changes presented, which is the main consequence of zolpidem. Results: A total of 229 toxicological analyses, requested to a toxicological laboratory at one university affiliated hospital, were reviewed. Among 229 patients, the mean age was 54.3±20.7 years old with 113 women and 116 men. 8.7% of patients have psychiatric illness and 39.7% were poisoned intentionally. The chief symptoms detected were: mental change 55.0%, gastrointestinal 14.4%, cardiovascular 10.5%, focal neurological 7.4%, respiratory 3.5%, none 8.7%, and unknown 0.4%. A request for detailed reports revealed that causative poisons were specified only in 20.1% cases. Zolpidem was detected in 22.3% cases (51/229), with median blood level 1.26 mg/L (interquartile 0.1, 5.06 mg/L) and urine 0.90 mg/L (interquartile 0.11, 5.6 mg/L). Furthermore, zolpidem was more frequently detected in toxicology analysis of patients where mental change was the primary symptom, as compared to other symptoms (32.5% vs. 9.7%, p<0.01). Conclusion: This study reported the blood level of zolpidem in suspected poisoning patients admitted to the emergency department.

• Archives of Pharmacal Research
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• 제24권6호
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• pp.584-589
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• 2001

Isopropryl 2-(1-3-dithiethane-2-ylidene)-2 [N-(4-methyl-thiazole-2-yl) carbamoyl] acetate (YH439) is currently under phase ll clinical trials by the Yuhan Research Center for use as a hepatoprotective agent. Unfortunately, the oral bioavailbility of YH439, which is sparingly soluble in water (i.e., $0.3{\;}\mu\textrm{g}/ml{\;}or{\;}0.91{$\mu}M$ at room temperature), reportedly, is negligibleregardless of the dose administered to rats in the 10-300 mg/kg range. The bioavailability of the compound increased up to 24%, when administered in the form of a micellar solution ($700{\;}\mu\textrm{g}/ml$or 2.1 mM for YH439) at a dose of 10 mg/kg, suggesting that its limited solubility is associated with its negligible bioavailability. In order to obtain additional informmation concerning the bioavailability of YH439, the mechanism(s) involved in gastrointestinal (Gl) absorption were investigated in the present study. For this purpose, the transport of YH430 across a Caco-2 cell monolayer was measured in a $Transwell^{\circledR}$. A permeability of $4.07{\times}10^{-5}{\;}cm/s$ was obtained for the absorptive (i.e., apical to basolateral direction) transport of $0.42{\mu}M$ YH439, implicating that the in vivo Cl absorption is nearly complete. The absorptive transport exhibited a slight concentration-dependency with an intrinsic clearance ($CL_{i}$) of $0.38{\mu}L/{\textrm{cm}^2}/sec$, which accounted for 28.1% of the total intrinsic clearance (i.e., $CL_i$ plus the intrinsic clearance for the linear component) of the transport. Thus, saturation of the absorption process appears to be a minor factor in limiting the bioavailability of the compound. The apparent permeability of YH439 from the basolateral to the apical direction (i.e., efflux, $6.67{\times}10^{-5}{\;}cm/s$) was comparable to that for absorptive transport, but, interestingly, a more distinct concentration-dependency was observed for this transport. However, the efflux does not appear to influence the bioavailability of the compound, as evidenced by the sufficiently high permeability in the absorption direction. Rather, a reportedly extensive first-pass hepatic metabolism appears to be a principal factor in limiting the bioavailability. In this respect, reducing the first-pass metabolism by some means would lead to a higher bioavailability of the compound. Thus, elevation of the absorption rate of YH439 becomes a necessity. From a practical point of view, increasing the concentration of YH439 in the Cl fluid appears to be a feasible way to increase the absorption rate, because the compound is primarily absorbed via a linear mechanism. In summary, the solubilization of YH439, as previously demonstrated for a micellar solution of the compound, appears to be a practical way to increase the oral bioavailability of YH439.

• Journal of Dental Anesthesia and Pain Medicine
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• 제19권1호
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• pp.55-66
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• 2019

Background: Postoperative nausea and vomiting (PONV) frequently occurs following bimaxillary orthognathic surgeries. Compared to opioids, Nefopam is associated with lower incidences of PONV, and does not induce gastrointestinal tract injury, coagulopathy, nephrotoxicity, or fracture healing dysfunction, which are common side effects of Nonsteroidal anti-inflammatory drugs. We compared nefopam- and fentanyl-induced incidence of PONV in patients with access to patient-controlled analgesia (PCA) following bimaxillary orthognathic surgeries. Methods: Patients undergoing bimaxillary orthognathic surgeries were randomly divided into nefopam and fentanyl groups. Nefopam 120 mg or fentanyl $700{\mu}g$ was mixed with normal saline to a final volume of 120 mL. Patients were given access to nefopam or fentanyl via PCA. Postoperative pain intensity and PONV were measured at 30 minutes and 1 hour after surgery in the recovery room and at 8, 24, 48, and 72 hours after surgery in the ward. The frequency of bolus delivery was compared at each time point. Results: Eighty-nine patients were enrolled in this study, with 48 in the nefopam (N) group and 41 in the fentanyl (F) group. PONV occurred in 13 patients (27.7%) in the N group and 7 patients (17.1%) in the F group at 8 hours post-surgery (P = 0.568), and there were no significant differences between the two groups at any of the time points. VAS scores were $4.4{\pm}2.0$ and $3.7{\pm}1.9$ in the N and F groups, respectively, at 8 hours after surgery (P = 0.122), and cumulative bolus delivery was $10.7{\pm}13.7$ and $8.6{\pm}8.5$, respectively (P = 0.408). There were no significant differences in pain or bolus delivery at any of the remaining time points. Conclusion: Patients who underwent bimaxillary orthognathic surgery and were given nefopam via PCA did not experience a lower rate of PONV compared to those that received fentanyl via PCA. Furthermore, nefopam and fentanyl did not provide significantly different postoperative pain control.

• 생명과학회지
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• 제29권6호
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• pp.735-739
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• 2019

용담(Gentiana scabra)의 근경 및 뿌리를 말린 한약재는 우리나라, 중국, 일본을 포함하는 동아시아 지역에서 아주 오래 전부터 각종 염증성 피부 질환, 소화불량, 식욕부진, 위염, 당뇨병 등의 치료를 목적으로 한의학에서 널리 처방되어 왔다. 본 연구에서는 용담이 위장관 운동 기능에 미치는 영향을 검정하기 위해 용담의 열수 및 에탄올 추출물을 각각 제조하였으며, 마우스에서 in vivo 위 배출 속도 및 위장관 이송률을 측정하는 실험을 수행하였다. 위 배출 속도는 용담 열수 추출물 1 g/kg 투여 시 유의적으로 증가하였다. 위장관 이송률은 용담 열수 추출물 0.1 및 1 g/kg 투여 시, 그리고 용담 에탄올 추출물 1 g/kg 투여 시 유의적으로 증가하였으며, 두 추출물 모두 용량 의존적 증가 양상을 보였다. 더욱이, 용담 열수 추출물 1 g/kg 투여 시의 위장관 이송률은, 1990년대까지 임상에서 가장 강력한 위장관 운동 촉진제로 쓰였으나 2000년 이후 부작용으로 시장에서 철수된 약물인 cisapride 투여 시보다 그 수치가 높았다. 이러한 결과들은 용담 열수 추출물이 잠재적으로 cisapride를 대체할 수 있는 위장관 운동 촉진제로 개발 가능한 후보 물질임을 시사한다.

• Journal of Korean Neurosurgical Society
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• 제62권1호
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• pp.106-113
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• 2019

Objective : The efficacy of preoperative embolization for hypervascular metastatic spine disease (MSD) such as renal cell and thyroid cancers has been reported. However, the debate on the efficacy of preoperative embolization for non-hypervascular MSD still remains unsettled. The purpose of this study is to determine whether preoperative embolization for non-hypervascular MSD decreases perioperative blood loss. Methods : A total of 79 patients (36 cases of preoperative embolization and 43 cases of non-embolization) who underwent surgery for metastatic spine lesions were included. Representative hypervascular tumors such as renal cell and thyroid cancers were excluded. Intraoperative and perioperative estimated blood losses (EBL), total number of transfusion and calibrated EBL were recorded in the embolization and non-embolization groups. The differences in EBL were also compared along with the type of surgery. In addition, the incidence of Adamkiewicz artery and complications of embolization were assessed. Results : The average age of 50 males and 29 females was $57.6{\pm}13.5$ years. Lung (30), hepatocellular (14), gastrointestinal (nine) and others (26) were the primary cancers. The demographic data was not significantly different between the embolization and the non-embolization groups. There were no significant differences in intraoperative EBL, perioperative EBL, total transfusion and calibrated EBL between two groups. However, intraoperative EBL and total transfusion in patients with preoperative embolization were significantly lower than in non-embolization in the corpectomy group (1645.5 vs. 892.6 mL, p=0.017 for intraoperative EBL and 6.1 vs. 3.9, p=0.018 for number of transfusion). In addition, the presence of Adamkiewicz artery at the index level was noted in two patients. Disruption of this major feeder artery resulted in significant changes in intraoperative neuromonitoring. Conclusion : Preoperative embolization for non-hypervascular MSD did not reduce perioperative blood loss. However, the embolization significantly reduced intraoperative bleeding and total transfusion in corpectomy group. Moreover, the procedure provided insights into the anatomy of tumor and spinal cord vasculature.

• 생명과학회지
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• 제31권1호
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• pp.28-36
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• 2021

Edwardsiella piscicida는 어류의 출혈성 패혈증 및 사람의 위장 감염의 중요한 원인균이다. 세균이 생존을 하기 위해서는 환경변화에 적응하기 위한 특수한 메커니즘이 필요하다. 따라서 E. piscicida가 삼투압 변화 환경을 감지하고 이에 반응하는 메커니즘을 이해하기 위하여 본 연구에서는 다양한 염도 조건에서 단백질 발현 형태와 세균의 생리적 특성을 분석하였다. EnvZ-OmpR의 two-component 조절 시스템의 일부인 OmpR 단백질은 세균의 염분 스트레스 감지와 관련이 있다. 이 단백질이 E. piscicida에서 어떤 생리적 역할을 하는지는 밝혀지지 않고 있다. 이 연구에서는 염분 스트레스에 대한 OmpR 단백질의 기능을 조사 하였다. OmpR을 발현하지 못하는 돌연변이체를 분석한 결과 구연산염 이용, H2S 생성 및 인돌 생산의 능력이 야생형과 비교했을 때 차이가 나는 것으로 확인되었다. 전체 ompR 유전자를 가지는 플라스미드를 돌연변이 균주에 도입하여 분석한 결과 위의 세가지 표현형은 야생형과 같아졌다. 지연된 성장률도 부분적으로 회복되었음을 볼 수 있었다. 이 연구에서 OmpR이 세포 운동성과의 관련성을 찾아볼 수 없었다. 이 연구의 결과들을 종합하면, 돌연변이 분석, 성장 분석, MALDI-TOF MS, qRT-PCR 및 표현형 연구 결과는 E. piscicida의 OmpR이 삼투압 조절, 생육, 포린 발현, 독성 관련 유전자(eseC, eseD 및 evpC) (ETAE_1826) 및 기능을 알 수 없는 특정 유전자(ETAE_1540 및 ETAE_2706)와 관련이 있다고 사료된다.

• Journal of Microbiology and Biotechnology
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• 제30권12호
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• pp.1819-1826
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• 2020

Increasing evidence suggests a potential role of microbial colonization in the inception of chronic airway diseases. However, it is not clear whether the lung and gut microbiome dysbiosis is coincidental or a result of mutual interaction. In this study, we investigated the airway microbiome in interleukin 13 (IL-13)-rich lung environment and related alterations of the gut microbiome. IL-13-overexpressing transgenic (TG) mice presented enhanced eosinophilic inflammatory responses and mucus production, together with airway hyperresponsiveness and subepithelial fibrosis. While bronchoalveolar lavage fluid and cecum samples obtained from 10-week-old IL-13 TG mice and their C57BL/6 wild-type (WT) littermates showed no significant differences in alpha diversity of lung and gut microbiome, they presented altered beta diversity in both lung and gut microbiota in the IL-13 TG mice compared to the WT mice. Lung-specific IL-13 overexpression also altered the composition of the gut as well as the lung microbiome. In particular, IL-13 TG mice showed an increased proportion of Proteobacteria and Cyanobacteria and a decreased amount of Bacteroidetes in the lungs, and depletion of Firmicutes and Proteobacteria in the gut. The patterns of polymicrobial interaction within the lung microbiota were different between WT and IL-13 TG mice. For instance, in IL-13 TG mice, lung Mesorhizobium significantly affected the alpha diversity of both lung and gut microbiomes. In summary, chronic asthma-like pathologic changes can alter the lung microbiota and affect the gut microbiome. These findings suggest that the lung-gut microbial axis might actually work in asthma.

• 병원약사회지
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• 제35권4호
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• pp.453-462
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• 2018

Background : The prevalence of chronic hepatitis C virus (HCV) tends to be higher in the elderly. Pegylated interferon and ribavirin therapy (Peg-IFN/RBV) was recommended as the first-line treatment in the past decades, but this regimen showed unsatisfactory results in terms of safety and efficacy especially in elderly patients. Recently, it was demonstrated that dual therapy with daclatasvir and asunaprevir was well tolerated and led to high sustained virological response (SVR) rates, irrespective of age. We conducted a study to evaluate the efficacy and safety of daclatasvir plus asunaprevir by involving elderly patients aged above 65 years. Methods : We retrospectively analyzed clinical data from chronic hepatitis C virus (HCV) genotype 1b patients treated with daclatasvir plus asunaprevir from September 2015 to December 2016 at Seoul St. Mary's hospital. The patients were divided into two groups as elderly patients (older than 65 years) and non-elderly patients (younger than 65 years) and compared the efficacy and safety. Results : A total of 112 patients were treated with daclatasvir plus asunaprevir for chronic hepatitis C. Among them, 101 patients completed the whole treatment, and in 88 patients the amount of HCV RNA was measured after 12 weeks of treatment. There was no significant difference in SVR at 12 weeks between both the groups (p=0.68). Typically, 91.4%(32/35) of elderly patients and 94.3%(50/53) of non-elderly patients achieved SVR12. Common adverse events included elevation in transaminase level, headache, and gastrointestinal disorders. There was no statistical difference in the symptoms between the two groups. Conclusions : The combination therapy with daclatasvir plus asunaprevir exhibited similar rates of SVR12 in HCV elderly patients without leading to further adverse events compared to non-elderly patients. Therefore, it is proposed that daclatasvir plus asunaprevir therapy could be considered as an effective and safe treatment, even in patients aged over 65 years.

• 생명과학회지
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• 제32권3호
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• pp.263-269
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• 2022

암 악액질은 암으로 인한 다기관 대사성 질환으로 식욕부진과 체중 감소가 주요 증상이다. 일반적으로 암 환자의 식욕부진과 체중감소는 항암화학요법 치료와 암 환자의 생존율에 악영향을 미치는 심각한 문제이다. 암 악액질은 일반적으로 췌장암, 폐암, 결장암 등 소화기관 암 환자의 약 80%에서 동반되는 것으로 알려져 있으며, 림프종이나 유방암 환자에서는 비교적 드물다. 암 악액질에 의한 식욕부진은 화학요법에 의해서도 일어나지만, 화학요법과는 독립적으로 발생하는 것으로 알려져 있다. 암 악액질의 발병기전으로는 종양 조직에 의해 과도하게 증가되는 염증성 사이토카인에 의한 정상 조직 기능의 저하가 주요 원인이다. 암 악액질의 메커니즘은 아직 완전히 이해되지 않았기 때문에 현재 악액질을 치료할 치료제나 진단 바이오마커가 없는 실정이다. 최근 발표된 연구에서는 암세포에서 분비되는 물질이 악액질에 의한 식욕억제를 일으키는 것이 확인되었고 그 분자생물학적 기전이 밝혀졌다. 이 물질의 발현 및 분비 증가는 암 환자의 악액질 증상과 통계적으로 상관관계가 있는 것으로 밝혀져 암악액질 진단 및 치료제 개발에 활용될 것으로 기대된다. 이 논문에서는 암 악액질의 주요증상인 섭식장애와 체중감소의 이해를 돕고자 알려진 원인과 분자 기전들의 내용을 소개하겠다.

• 한국임상수의학회지
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• 제39권5호
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• pp.207-216
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• 2022

Canine babesiosis has been scarcely investigated in the Republic of Korea (ROK). Although it is known that Babesia gibsoni is its primary causative agent, its clinical presentation has not been completely clarified in the ROK. Consequently, the aim of this study was to evaluate the clinical appearance of this parasitic infection based on the anamnesis of the patient and compare of hematological and biochemical test results. Four hundred whole blood samples from patients with a presumptive diagnosis of tick-borne disease were analyzed by polymerase chain reaction (PCR) to amplify the Babesia spp. 18S rRNA gene and by a rapid diagnostic test kit (VetAll Laboratories^®) to detect B. gibsoni seroreactive animals. Thirty-six (9.0%) dogs were PCR-positive but only 24 (6.0%) were seropositive. The investigation revealed that all the courses of the disease are present in the ROK, with the acute course being predominant. The acute course tends to consist of inappetence, lethargy, pyrexia, gastrointestinal symptoms, and occasionally hematuria. It also occurs with common hematological abnormalities, such as thrombocytopenia and anemia, and to a lesser extent biochemical abnormalities, such as hyperbilirubinemia, hypoalbuminemia, and elevated liver enzymes. This research shows that B. gibsoni is an endemic hemoparasite capable of producing a variety of clinical manifestations in dogs. For its accurate diagnosis, a descriptive history of the clinical signs, hematology, and biochemical profile of the patient, along with a well-performing PCR assay, are essential. These findings will help in planning pragmatic preventive strategies against this potent threat in the ROK.