• 대한한의학회지
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• 제33권3호
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• pp.184-199
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• 2012

Objectives: There is a steady increase in the prevalence of obesity worldwide and obesity is often accompanied by inflammation. Although much emphasis has been placed on the adipose tissue inflammation in obesity, a study with herbal medicine is few. This study aimed to investigate the antidiabetic and anti-inflammatory effect of a complex herbal medicine (CHM) composed of Cornus officinalis, Dioscorea rhizoma, Aurantii fructus, and Mori Foliumon on obese type 2 diabetes mice. Methods: Type 2 diabetes mellitus and obesity were induced by Surwit's high fat, high sucrose diet for 8 weeks. Mice were divided into ND (normal diet, n=10), HFD (high fat and high sucrose diet, n=10), CHM (high fat and high sucrose diet with complex herbal medicine, n=10) and Met (high fat and high sucrose diet with metformin, n=10) groups. The body weight, fructosamine and OGTT (oral glucose tolerance test) were measured. After 8 weeks the blood samples of all mice were taken from the heart, and lipid profiles were measured. Epididymal fat pad, histological size of the adipocyte tissue and liver weights were measured. Inflammatory markers such as leptin and adipocyte tissue macrophage were measured to evaluate the effect of CHM on adipocyte tissue inflammation. Results: Compared with the HFD group, there was an improvement in OGTT and epididymal fat decreased in the CHM group. White adipocyte size and adipocyte tissue macrophage decreased in CHM group. Conclusions: These results suggest that CHM has antidiabetic and anti-inflammatory effects in high fat, high sucrose diet induced obese mice.

• Genomics & Informatics
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• 제16권3호
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• pp.52-58
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• 2018

In this report, we present a case study of how pharmacogenomics and pharmacometabolomics can be useful to characterize safety and pharmacokinetic profiles in early phase new drug development clinical trials. During conducting a first-in-human trial for a new molecular entity, we were able to determine the mechanism of dichotomized variability in plasma drug concentrations, which appeared closely related to adverse drug reactions (ADRs) through integrated omics analysis. The pharmacogenomics screening was performed from whole blood samples using the Affymetrix DMET (Drug-Metabolizing Enzymes and Transporters) Plus microarray, and confirmation of genetic variants was performed using real-time polymerase chain reaction. Metabolomics profiling was performed from plasma samples using liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. A GSTM1 null polymorphism was identified in pharmacogenomics test and the drug concentrations was higher in GSTM1 null subjects than GSTM1 functional subjects. The apparent drug clearance was 13-fold lower in GSTM1 null subjects than GSTM1 functional subjects (p < 0.001). By metabolomics analysis, we identified that the study drug was metabolized by cysteinylglycine conjugation in GSTM functional subjects but those not in GSTM1 null subjects. The incidence rate and the severity of ADRs were higher in the GSTM1 null subjects than the GSTM1 functional subjects. Through the integrated omics analysis, we could understand the mechanism of inter-individual variability in drug exposure and in adverse response. In conclusion, integrated multi-omics analysis can be useful for elucidating the various characteristics of new drug candidates in early phase clinical trials.

• 한국식품저장유통학회지
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• 제7권3호
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• pp.308-312
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• 2000

산초유 전지질 분획에서 주요 구성지방산 조성은 eicosenoic acid 30.88%, linoleic acid 23.4%, oleic acid 19.94%, palmitic acid 10.52% 순으로 나타났으며, n-9계열 일가불포화지방산이 약 60% 이상을 차지하였다. 또한 산초유의 각 지질 분획의 구성지방산 조성에서는, triglyceride 분획에서 eicosenoic acid가 41.16%로 가장 높았고, 나머지 분획들에서는 oleic acid가 34.32~53.58%로 높게 나타났다. 마우스를 24시간 절식시킨 상태에서 산초유를 마리당 500 mg씩 강제 경구투여 한 후 혈청 및 간장 전지질의 지방산 조성을 투여전, 투여 3시간 및 6시간 후의 경시적인 변화를 관찰한 결과, 혈청 전지질 중의 eicosenoic acid가 투여 전에는 존재가 확인되지 않았으나, 투여 3시간 및 6시간 후에는 경시적으로 유의적인 증가를 보였다. 간장에서도 산초유 투여 6시간 후에 eicosenoic acid의 유의적인 증가가 나타났다. 따라서, 혈청 및 간장 전지질 중의 eicosenoic acid의 증가는 산초 원료유의 섭취 영향과 지방질 대사과정에서 oleic acid로부터의 전환이 시사되어진다. 이상의 결과로부터, 산초유에는 일반 종실유와는 달리 n-9 계열 일가불포화지방산인 eicosenoic acid와 oleic acid가 많이 함유되어 있으며, 마우스의 혈청 및 간장 전지질 중의 지방산 조성의 변화는 경구투여한 원료유 지방산 섭취의 영향을 받는 것으로 시사되어졌다.

• Journal of Chest Surgery
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• 제30권11호
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• pp.1092-1096
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• 1997

혈전 탄성 묘사도는 일회의 채혈로 지혈기능의 전반적인 평가를 가능하게 하는데, 혈소판 응집과 응괴 강 도와 섬유소 교차결합을 통한 초기의 혈소판-섬유소 상호작용 시간부터 궁극적인 응괴 용해 까지의 단백질 응고 폭포와 혈소판의 상호반응을 기록하는 것이다. 1996년 4월 1일부터 1996년 8월 31일까지 개심술을 받은 35명의 환자를 대상으로(평균 연령 34$\pm$12) 혈전 탄성 묘사도를 수술전, 수술직후, 수술1시간후, 수술 24시간 후에 조사하였다. 전통적인 혈액학적인 지표들과 혈전탄성 묘사도 자료를 통계 분석으로 비교하였다. 체외 순환전의 혈전 탄성 묘사도의 최대 진측과 혈소판 수와, 체외 순환 24시간 후에는 혈전 탄성 묘사도의 R값 및 K값 그리고 알파 앵글이 활성 응고 시간과 통계학적인 의미있는 상관관계가 있었다. 그리고 체외 순환후 24시간 동안의 술후 출혈의 예측 정확도는 혈전 탄성 묘사도가 100%(P=0.0043)로 활성 응고 시간(57%)와 기존의 응고 검사(43%)와 비교해서 더 좋은 방법임을 알 수 있었다. 결론적으로 혈전 탄성 묘사도는 사용이 쉽 고 임상적으로 정확하고 비용면에서 유용하여 지혈문제를 가진 환자에게 효과적으로 처치\ulcorner 수 있는 자료를 제시할 수 있다 하겠다.

• 한국임상수의학회지
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• 제27권5호
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• pp.614-617
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• 2010

3년령, 암컷 점박이 하이에나가 분만의 증상을 나타내나 분만이 이루어지지 않아 이를 교정하기 위해 충북대학교 동물의료센터에 의뢰되었다. 분만 징후가 관찰된 후 5일이 경과되었고, 스스로 분만이 불가능하였기 때문에 제왕절개를 계획하였다. 수술 전 혈액화학검사 결과 심각한 질소혈증이 관찰되었으며, 수술 중 골반입구를 폐쇄하고 있는 태아의 두부가 요도를 압박하여 배뇨가 불가능하였음을 확인하였다. 또한 확장된 자궁내의 태아는 견관절굴절위를 나타내고 있었으며, 태아의 두부가 골반입구로 진입할 수 없을 정도의 크기를 나타내고 있었다. 태아의 상태는 폐사 후 부패가 진행된 상태였으며, 과다 체중(모체의 약 5%)을 나타냈다. 이 증례는 점박이 하이에나에서 과대태아 및 견관절굴절위로 인한 난산이 신후성 질소혈증을 일으킨 최초의 보고이다.

• Journal of Pharmaceutical Investigation
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• 제34권3호
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• pp.215-222
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• 2004

The purpose of the present study was designed to evaluate the bioequivalence of two oxiracetam tablets, Neuromed tablet (Korea Drug Co., reference drug) and Neuracetam tablet (Sam Jin Pharmaceutical Co., test drug), according to the guidelines of Korea Food and Drug Administration (KFDA). Release of oxiracetam from the tablet in vitro was tested using KP VIII Apparatus II method with various dissolution media (pH 1.2, 4.0, 6.8 buffer solution and water). Twenty-four healthy volunteers, $23.7\;{\pm}\;2.4$ year in age and $68.9\;{\pm}\;6.2$ kg in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was performed. After oral administration of a tablet containing 800 mg of oxiracetam, blood samples were taken at predetermined time intervals and concentrations of oxiracetam in plasma were determined using HPLC-MS-MS. The dissolution profiles of two formulations were very similar at all dissolution media. In addition, pharmacokinetic parameters such as $AUC_t$, $C_{max}$ and $T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_t$ and $C_{max}$ untransformed $T_{max}$. The results showed that the differences between two formulations based on the reference drug were 0.42%, 0.45% and -12.58% for $AUC_t$, $C_{max}$ and $T_{max}$, respectively. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals for the log transformed data were within the acceptance range of log 0.8 to log 1.25 (e.g., $log0.94{\sim}log1.06$ and $log0.90{\sim}log1.07$ for $AUC_t$, and $C_{max}$, respectively), indicating that Neuracetam tablet is bioequivalent to Neuromed tablet. The major pharmacokinetic parameters, $AUC_t$, and $C_{max}$ met the criteria set by KFDA for bioequivalence indicating that Neuracetam tablet is bioequivalent to Neuromed tablet.

• Journal of Pharmaceutical Investigation
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• 제38권6호
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• pp.413-419
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• 2008

Carvedilol, is a nonselective $\beta$-blocking agent and it also has vasodilating properties that are attributed mainly to its blocking activity at ${\alpha}_1$-receptors. The purpose of the present study was to evaluate the bioequivalence of two carvedilol tablets, $Dilatrend^{(R)}$ tablet 12.5 mg (Chong Kun Dang Pharmaceutical Co., Ltd.) and Cadilan tablet 12.5 mg (KyungDong Pharmaceutical. Co., Ltd.), according to the guidelines of the Korea Food and Drug Administration (KFDA). The release of carvedilol from the two carvedilol formulations in vitro was tested using KP VIII Apparatus II method with pH 4.5 dissolution medium. Thirty two healthy male subjects, $25.00{\pm}3.09$ years in age and $70.71{\pm}11.35\;kg$ in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After a single tablet containing 12.5 mg as carvedilol was orally administered, blood samples were taken at predetermined time intervals and the concentrations of carvedilol in serum were determined using HPLC with fluorescence detector. The dissolution profiles of two formulations were similar in the tested dissolution medium. The pharmacokinetic parameters such as $AUC_t$, $C_{max}$ and $T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_t$, $C_{max}$ and untransformed $T_{max}$. The results showed that the differences between two formulations based on the reference drug, $Dilatrend^{(R)}$ tablet 12.5 mg, were 4.66%, 8.33% and -7.45% for $AUC_t$, $C_{max}$ and $T_{max}$, respectively. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log 0.8 to log 1.25 (e.g., $\log\;0.9823{\sim}\log\;1.1042$ and $\log\;1.0132{\sim}\log\;1.1875$ for $AUC_t$ and $C_{max}$, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating Cadilan tablet 12.5 mg was bioequivalent to $Dilatrend^{(R)}$ tablet 12.5 mg.

• Fisheries and Aquatic Sciences
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• 제7권1호
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• pp.1-9
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• 2004

Sweet smelt (Plecoglossus altivelis) were fed four different diets supplemented with either perilla oil $(2.0\%)$ rich in 18:3n-3 (CP), and perilla oil and Enteromorpha compressa meal $(2.0\%)$ (CPA), soybean oil rich in 18:2n-6 (CO), or soybean oil and algal meal (CA) for 4 weeks. The growth performance, fatty acid composition of muscle, plasma lipid peroxidation and blood components of the sweet smelt were then determined. The specific growth rate and feed efficiency in the fish fed the CPA diet were the highest, while the other groups showed similar results. The fatty acid composition of muscle in sweet smelt reflected the dietary lipids; 18:3n-3 was higher in the fish fed the CP and CPA diets, and 18:2n-6 was higher in the fish fed the CO and CA diets. The other fatty acid profiles presented almost no differences with respect to the diet composition. The fish fed the CA, CP and CPA diets contained significantly lower levels of triglyceride, thiobarbituric acid-reactive substances and hydroxyl radical in their plasma than that fed the CO diet. Phagocytic activity was the highest in the fish fed the CPA diet and higher in those of the fish fed the CP and CA diets compared to the CO diet group. The results from this study suggest that a dietary supplement of $2.0\%$ perilla oil together with $2.0\%$ E. compressa meal may improve the growth and health of cultured sweet smelt.

• 한국임상약학회지
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• 제18권1호
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• pp.38-44
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• 2008

Rebamipide, ($\pm$)-2-(4-chlorobenzoylamino)-3-[2(1H)-quinolinon-4-yl] propionic acid, is used for mucosal protection, healing of gastroduodenal ulcers, and treatment of gastritis. It works by enhancing mucosal defense, scavenging free radicals and temporarily activating genes encoding cyclooxygenase-2. The purpose of the present study was to evaluate the bioequivalence of two rebamipide tablets, $Mucosta^{(R)}$ (Korea Otsuca Pharmaceuticals Co., Ltd.) and Mustar (Korean Drug Co., Ltd.), according to the guidelines of the Korea Food and Drug Administration (KFDA). The release of rebamipide from the two rebamipide formulations in vitro was tested using KP VIII Apparatus II method with pH 6.8 dissolution medium. Twenty six healthy male subjects, $23.46{\pm}2.63$ years in age and $66.62{\pm}8.97\;kg$ in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After a single tablet containing 100 mg as rebamipide was orally administered, blood samples were taken at predetermined time intervals and the concentrations of rebamipide in serum were determined using HPLC with fluorescence detector. The dissolution profiles of two formulations were similar in the tested dissolution medium. The pharmacokinetic parameters such as $AUC_t$, $C_{max}$ and $T_{max}$ were calculated, and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_t$, $C_{max}$ and untransformed $T_{max}$. The results showed that the differences between two formulations based on the reference drug, $Mucosta^{(R)}$ were -5.08, 3.52 and -9.71 % for $AUC_t$, $C_{max}$ and $T_{max}$, respectively. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log 0.8 to log 1.25 (e.g., log 0.84$\sim$log 1.07 and log 0.90$\sim$log 1.17 for $AUC_t$ and $C_{max}$, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating Mustar tablet was bioequivalent to $Mucosta^{(R)}$ tablet.

• 약학회지
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• 제47권5호
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• pp.339-344
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• 2003

Atenolol is a water soluble, ${\beta}_1$ selective adrenoceptor antagonist used in the treatment of angina and hypertension. It is primarily eliminated renally with minimal hepatic metabolism. The purpose of the present study was to evaluate the bioequivalence of Samchundang Atenolol (Samchundang Pharmaceutical Co., Korea.) to Tenolmin(Hyundai Pharmaceutical Ind. Co., Korea). The atenolol release from the two atenolol tablets in vitro was tested using KP VII Apparatus II method with various different kinds of dissolution media (pH 1.2, 4.0, 6.8 buffer solution and water). Twenty four normal male volunteers, 22.83$\pm$1.99 years in age and 65.82$\pm$7.15 kg in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After one tablet containing 50 mg of atenolol was orally administered, blood was taken at predetermined time intervals and the concentrations of atenolol in serum were determined using HPLC method with fluorescence detector. The dissolution profiles of two atenolol tablets were very similar at all dissolution media. Besides, the pharmacokinetic parameters such as $AUC_{t}$, $C_{max}$ and $T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_{t}$ and $C_{max}$ and untransformed $T_{max}$. The results showed that the differences in $AUC_{t}$, $C_{max}$ and $T_{max}$ between two tablets based on the Tenolmin were 3.74％, 4.38％ and 17.77％, respectively. There were no sequence effects between two tablets in these parameters. The 90％ confidence intervals using logarithmically transformed data were within the acceptance range of log(0.8) to log(1.25) (e.g., log(0.98)∼log(1.l1) and log(0.95)∼log(1.l5) for $AUC_{t}$ and $C_{max}$ respectively), indicating that Samchundang Atenolol tablet is bioequivalent to Tenolmin tablet.