• Parasites, Hosts and Diseases
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• v.61 no.1
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• pp.33-41
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• 2023

The discovery of new antimalarial drugs can be developed using asynchronized Plasmodium berghei malaria parasites in vivo in mice. Studies on a particular stage are also required to assess the effectiveness and mode of action of drugs. In this report, we used endoperoxide 6-(1,2,6,7-tetraoxaspiro [7.11] nonadec-4-yl) hexan-1-ol (N-251) as a model antimalarial compound on P. chabaudi parasites. We examined the antimalarial effect of N-251 against ring-stage- and trophozoite-stage-rich P. chabaudi parasites and asynchronized P. berghei parasites using the 4-day suppressive test. The ED₅₀ values were 27, 22, and 22 mg/kg, respectively, and the antimalarial activity of N-251 was verified in both rodent malaria parasites. To assess the stage-specific effect of N-251 in vivo, we evaluated the change of parasitemia and distribution of parasite stages using ring-stage- and trophozoite-stage-rich P. chabaudi parasites with one-day drug administration for one life cycle. We discovered that the parasitemias decreased after 13 and 9 hours post-treatment in the ring-stage- and trophozoite-stage-rich groups, respectively. Additionally, in the ring-stage-rich N-251 treated group, the ring-stage parasites hindered trophozoite parasite development. For the trophozoite-stage-rich N-251 treated group, the distribution of the trophozoite stage was maintained without a change in parasitemia until 9 hours. Because of these findings, it can be concluded that N-251 suppressed the trophozoite stage but not the ring stage. We report for the first time that N-251 specifically suppresses the trophozoite stage using P. chabaudi in mice. The results show that P. chabaudi is a reliable model for the characterization of stage-specific antimalarial effects.

• Korean Journal of Clinical Pharmacy
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• v.25 no.2
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• pp.74-79
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• 2015

Objective: Treatment with sulfonylureas in combination with metformin improves glycemic control in type 2 diabetes mellitus (T2DM), but is associated with hypoglycemia and weight gain. This retrospective study aims to compare the effectiveness of dipeptidylpeptidase-4 (DPP-4) inhibitors and sulfonylureas as an add-on therapy to metformin in patients with T2DM. Methods: Data from medical records of 355 T2DM patients received therapy either DPP-4 inhibitors (DPP-4 inhibitor group) or sulfonylurea (SU group) in combination with metformin from 1 March 2009 to 30 September 2011 were retrospectively reviewed. Of total 355 patients, 231 patients were in DPP-4 inhibitor group and 124 patients were in SU group. Baseline Hemoglobin $A_{1c}$ ($HbA_{1c}$) level in SU group was higher than DPP-4 inhibitor group with a statistically significant difference (8.6% vs. 7.8%). Comparative analysis between DPP-4 inhibitor group and SU group was performed for $HbA_{1c}$ values, amounts of $HbA_{1c}$ changes, and rates of $HbA_{1c}$ changes from baseline at 6-month intervals and incidence rates of major cardiocerebral events. Results: SU group showed larger $HbA_{1c}$ changes in both amounts and rates compared to DPP-4 inhibitor group, although statistical significance was not found in all study periods. Proportions of patients with stable $HbA_{1c}$ <6.5% or 7% were significantly higher in DPP-4 inhibitor group than SU group (<6.5%: 30.4% vs. 13.4%, <7%: 72.3% vs. 41.2%). Time to achieve stable $HbA_{1c}$ <6.5% was not significantly different, but time to achieve stable $HbA_{1c}$ <7% was shorter in DPP4 inhibitor group than SU group with a significant difference. The incidence rate of cardiocerebral events in group of patients with or without previous events was 1.7%, not significantly lower than that in DPP-4 inhibitor group (4.0%). For newly encountered cardiocerebral events during the treatment, incidence rates of two groups did not differ significantly. Conclusion: DPP-4 inhibitors were as effective as sulfonylureas in achieving the $HbA_{1c}$ goal of less than 6.5% or 7% and cardiocerebral event rates did not differ between the two drugs.

• Korean Journal of Clinical Pharmacy
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• v.20 no.2
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• pp.107-113
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• 2010

서 론: 중환자실에서 집중적 인슐린 요법에 의한 평균혈당강하는 사망률을 감소시키는 것으로 나타났으나 이로 인한 저혈당 및 혈당변동은 새로운 문제로 대두되고 있다. 본 연구에서는 혈당과 관련한 여러 요인들이 사망에 미치는 영향을 규명하고 적정 혈당치를 확인하고자 하였다. 연구방법: 2008년 2월부터 7월 사이인 6개월 동안 서울아산병원 외과계 중환자실에서 4일 이상 재실한 18세 이상의 성인 환자를 대상으로 전자 의무기록 조사를 통해 후향적으로 연구가 진행되었다. 연구를 위해 환자의 인구학적 특성, 수술의 종류, 중환자실에서의 재실기간, 사망여부, 스테로이드 사용 유무, 기계적 인공호흡기의 사용유무, 신대체요법의 사용유무, 혈당치, 재실기간 중 스테로이드 사용유무와 인슐린 양, 입원 후 첫 24시간 동안의 포도당 주입속도, 입원 후 2일 이내와 그 이후에 발생한 균혈증 감염, APACH II와 SOFA 점수를 조사하였다. 혈당수치는 각각의 환자에서 중환자실 입실 후 가장 처음 측정된 혈당, 재실기간 중 가장 높은 혈당과 가장 낮은 혈당수치를 조사하였고 중환자실 전체 재실기간 동안 혈당수치의 평균과 변동계수를 계산하였다. 이상의 혈당관련지표를 포함한 인자들이 일차 종속변수인 사망에 어떠한 영향을 주는지를 환자를 생존군과 사망군으로 나누어 분석하였고 ROC (receiver operator characteristic) 곡선을 사용하여 혈당지표와 APACH 및 SOFA 점수의 cut-off치를 구하여 이로부터 단변량 및 다변량 분석을 시행하였다. 결 과: 연구에 포함된 환자는 170명 이었고 그 중 23명이 연구 기간 중 중환자실에서 사망하였다. 생존자에 비해 사망자의 최대혈당은 유의적으로 높았고 최소혈당치는 유의적으로 낮아 높은 변동계수를 보였다. ROC곡선으로부터 산출된 혈당치들의 cut-off 수치는 최소혈당치 70 mg/dL, 변동계수 25%, 최대혈당치 250 mg/dL, 평균혈당치 150 mg/dL이었다. 다변량분석에서 최소혈당이 70 mg/dL 보다 큰 경우가 낮은 경우에 비해 오즈비가 0.922(95% 신뢰구간 0.881-0.965)로 유의성 있게 낮았으며 변동계수가 25% 보다 높은 집단의 경우 그보다 낮은 집단에 비해 오즈비가 1.121(95% 신뢰구간 1.017-1.236)로 유의성 있게 높았다. Kaplan-Meier 생존분석 결과 최소혈당치 70 mg/dL와 변동계수 25%에 따라 생존기간에 유의성 있는 차이가 나타났다.(각각 P < 0.001, P < 0.05) 결 론: 고혈당 발생의 감소뿐 아니라 최소혈당치를 70 mg/dL 이상으로 유지하면서 변동을 최소화하는 것이 외과계 중환자실에서의 사망률감소를 위한 중요한 요인임을 알 수 있었다.

• Journal of Microbiology and Biotechnology
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• v.17 no.6
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• pp.1024-1030
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• 2007

We investigated the human apolipoprotein E2 (apoE2) transgenic mouse as an animal model system for age-related macular degeneration (AMD). Transgenic mice expressing human apoE2 and C57BL/6J mice were fed normal chow or a high-fat diet for 4 weeks. Eyes were collected from the mice and lipid deposits in retinal pigment epithelium (RPE) were assessed using electron microscopy. The expressions of apoE, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and pigment-epithelium derived factor (PEDF), which are molecular markers for angiogenesis, were assessed with immunohistochemistry. Eyes from apoE2 mice, regardless of diet, contained lipid accumulation in RPE under electron microscopy, whereas control C57BL/6J eyes did not. Lipid accumulation was found predominantly in the RPE and the Bruch's membrane and increased in the eyes of apoE2 mice after one month of a high-fat diet ($8{\pm}2\;per\;50{\mu}m^2$ for normal chow and $11{\pm}2\;per\;50\;{\mu}m^2,\;p<0.05)$. ApoE expression was similar in the apoE2 and control mice; however, VEGF and bFGF were overexpressed in the retinal pigment epithelium of apoE2 eyes compared with control eyes, and PEDF expression was slightly decreased. These expression patterns of VEGF, bFGF, and PEDF suggest angiogenesis is progressing in apoE2 eyes. In conclusion, the eyes of apoE2 mice develop typical lipid accumulations, a common characteristic of AMD, making them a suitable animal model for AMD. The expression profile of VEGF and bFGF on the retinal pigment epithelium suggests that apoE2 may induce neovascularization by altering angiogenic cytokines.

• Clinical and Experimental Pediatrics
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• v.55 no.9
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• pp.309-315
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• 2012

Human respiratory syncytial virus (HRSV) is a major cause of severe respiratory tract illnesses in infants and young children worldwide. Despite its importance as a respiratory pathogen, there is currently no licensed vaccine for HRSV. Following failure of the initial trial of formalin-inactivated virus particle vaccine, continuous efforts have been made for the development of safe and efficacious vaccines against HRSV. However, several obstacles persist that delay the development of HRSV vaccine, such as the immature immune system of newborn infants and the possible Th2-biased immune responses leading to subsequent vaccine-enhanced diseases. Many HRSV vaccine strategies are currently being developed and evaluated, including live-attenuated viruses, subunit-based, and vector-based candidates. In this review, the current HRSV vaccines are overviewed and the safety issues regarding asthma and vaccine-induced pathology are discussed.

• IMMUNE NETWORK
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• v.3 no.3
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• pp.169-175
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• 2003

The intestinal immune system can discriminate between harmful and unharmful antigens and do not provoke productive immunity to unharmful antigen. Thus oral administration of antigen is one of classical methods for inducing antigen-specific immune tolerance in the periphery. Furthermore, oral tolerance has been investigated for the treatment of autoimmune disorders in human clinical trials. However, the detail mechanism of oral tolerance and contributing factors are not defined clearly at this time. Recent studies demonstrate unique types of immune cell that suppressing immune response, such as regulatory T cell and tolerogenic dendritic cell. This article reviews the factors involved in oral tolerance and discusses our current understanding base on the recent literatures and our works.

• Clinical and Experimental Pediatrics
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• v.64 no.12
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• pp.642-651
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• 2021

Background: Infantile colic (IC) is excessive crying in otherwise healthy children. Despite vast research efforts, its etiology remains unknown. Purpose: Most treatments for IC carry various side effects. The collection of evidence may inform researchers of new strategies for the management and treatment of IC as well as new clues for understanding its pathogenesis. This review and meta-analysis aimed to evaluate the efficacy and possible mechanisms of probiotics for mananaging IC. Methods: Ten papers met the study inclusion and exclusion criteria, and the meta-analysis was conducted using Review Manager (RevMan) software and a random-effects model. Results: This meta-analysis revealed that probiotics are effective for treating infantile colic, while the review showed that this efficacy may be due to their anti-inflammatory effects. Conclusion: Probiotics may be an important treatment option for managing infantile colic due to their anti-inflammatory properties.

• Journal of Pharmaceutical Investigation
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• v.39 no.1
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• pp.13-18
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• 2009

Docetaxel is an anticancer agent with low aqueous solubility. More extensive clinical use of this drug is somewhat delayed due to lack of appropriate delivery vehicles. An attempt was made to adopt an o/w emulsion as the drug carrier which incorporated docetaxel in the propyleneglycerol stabilized by a mixed-emulsifier system. A suitable formulation was found in this study: 10 mg/mL docetaxel, 10% (w/v) oil blend, 4% (w/v) PG, 3% (w/v) Solutol HS 15 in 2.25% (w/v) glycerol solution. The formulated emulsion has very good stability when stored at $40^{\cird}C$, and the docetaxel containment efficiency can be maintained above 95% and the mean emulsion diameter around $10{\mu}m$ for at least 3 months. The formulated emulsion is a promising carrier for docetaxel and other lipophilic drugs.

• The Journal of Korean Medicine
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• v.28 no.1 s.69
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• pp.117-125
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• 2007

Objectives : This study was to assess the Traditional chinese medicine forecast subjects that had been expected to be accomplished over 20 year (1990-2010). The result will help Korea medical society to compare the status of Korean Medicine with that of Traditional Chinese Medicine and to plan for polices and studies on Korean Traditional Medicine. Methods : Assessed targets were the subjects selected by the China Academy of Chinese Medical Sciences, which are classified into 6 fields. These were assigned by the quantity of related theses. Reference source is CAJ（China academic Journal) of CNKI (China National Knowledge infrastructure). Results : 1) Forecast subject ratio by field was basic theory 31% / clinical research 17% / Chinese herbal drug 17% / acupuncture and moxa 17% / Tui-na(推拿) and Qi-gong(氣功) 9% / medical information, literature history 6%. 2) Accomplishment percentage (full accomplishment) by field was medical information, literature, history 60% / basic theory 50% / acupuncture and moxa 46% Tui-na(推拿) and Qi-gong(氣功) 38% / chinese herbal drug 25% / clinical research 23%. Conclusions : 78% of all forecast subjects were accomplished or partially accomplished. According to 'accomplishment percentage by field', while those in the medical information, literature, history field were most realized of all, those in the clinical research field were least realized.

• Journal of Pharmaceutical Investigation
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• v.25 no.3
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• pp.43-51
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• 1995

The in vitro skin permeability of 16 drugs with a wide span of lipophilicity (log P ranging from -0,95 to 4.40) was evaluated with an ethanol/panasate 800 (tricaprylin, P-800) (40/60) lipophilic binary vehicle and an ethanol/water (60/40) hydrophilic binary vehicle with lauric acid, The skin permeability of the drugs was enhanced by the use of the ethanol/P-800 (40/60) binary vehicle or the ethanol/water (60/40) binary vehicle with lauric acid; permeation rate was increased and lag time' was decreased. The relationship between lipophilicity and skin permeation rate of the drugs showed parabolic shapes with their peaks at much greater hydrophilic range compared with other past references. In the in vivo skin absorption of theophylline using abdominal rat skin, the ethanol/P-800 (40/60)-7% (w/w) ethycellulose gel produced a good feature as a sustained-release preparation, and the ethanol/water (60/40)-3 % (w/w) HPMC gel with lauric acid showed the highest BA value. The results suggest that the lipophilicity of a drug is a main factor for prediction of the skin permeability of the drug and that the ethanol/P-800 (40/60) binary vehicle and ethanol/water (60/40) binary vehicle with lauric acid would be good candidates for clinical transdermal application of hydrophilic drugs.