• Journal of Pharmaceutical Investigation
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• 제28권2호
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• pp.73-80
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• 1998

In order to elucidate the effect of N-demethylation on the in vivo metabolite kinetics, especially hepatic first-pass effect of trimebutine(TMB), the N-demethylation of TMB to N-monodesmethyl trimebutine(N-TMB) was studied in rats. TMB(10 mg/kg) and N-TMB(10 mg/kg) were injected into the femoral and the portal vein, respectively. And the pharmacokinetic parameters were obtained from the plasma concentration-time profiles of TMB and N-TMB determined by the simultaneous analysis using high-performance liquid chromatography. It was supposed that these drugs were almost metabolized in vivo because the urinary and biliary excreated amounts of TMB and N-TMB were lower than 0.1% of the administered dose. According to the hepatic biotransformation model and metabolic pathways of TMB proposed, it was found that the fraction of systemic clearance of TMB which formed N-TMB in liver$(G_{mi})$ was 0.826, that of TMB which furnishes the available N-TMB to the systemic circulation$(F_{mi})$ was 0.083, and the absolute hepatic bioavailability of N-TMB formed trom TMB$(F_{mi.p})$ was 0.1. These results showed that TMB was suspected of the sequential hepatic first-pass metabolism and N-demethylated by 82.6%. Therefore, the residue would be hydrolyzed by the esterase in the liver. That is, the ability of N-demethylation of TMB was 4.75-fold larger than that of hydrolysis by the esterase in rats.

• 한국임상수의학회지
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• 제25권5호
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• pp.363-369
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• 2008

The aim of this study was to establish an experiment animal model for easy diagnosis and monitoring effect of treatment of cholelithiasis by cholesterol and mixed gall stone. In 12 adult beagle dogs, five dogs there were in the control group and seven dogs in the experiment group with ligated cystic duct. General clinical signs were recorded, CBC and blood chemistry were examined. Control group and experiment group were evaluated every 2 weeks for a period of 20 weeks. The results were (1) Total blirubin, cholesterol, alanine aminotransferase (ALT), aspartate aminotransferase (AST) activity were significantly higher in the experiment group with ligated cystic duct than control group during 2-8 weeks. (2) Total alkaline phosphatase (TALP) activity was significantly higher when compare with control group during 2-8 weeks. Bone alkaline phosphatase(BALP) activity was increased slightly between 2 and 8 weeks but was decreased between 10 and 20 weeks. (3) Blood urea nitrogen (BUN) was decreased between 2 and 8 weeks. After 10 weeks, this was in normal range. (4) On complate blood count (CBC), $Ca^{2+}$ and P were not changed until 20 weeks. (5) On clinical signs in experimental group, they observed a depression, yellow color of mucus membrane and conjunctiva, xanthinuria and xanthochromic. The present study showed that the experimental animal model with ligated cystic duct was a useful model to study biliary tract disease.

• Archives of Pharmacal Research
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• 제28권2호
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• pp.203-208
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• 2005

Scoparone is a major component of the shoot of Artemisia capillaris (Compositae), which has been used for the treatment of hepatitis and biliary tract infection in oriental countries. In the present study we observed that, scorparone exhibited no cytotoxic effect in unstimulated macrophages, but reduced the release of nitric oxide (NO) and prostaglandin $E_2\;(PGE_2)$ upon stimulation by IFN-${\gamma}$/LPS or LPS. The inhibitory effects were found to be in conjuction with the suppression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in IFN-${\gamma}$/LPS stimulated RAW 264.7 cells. Moreover, scoparone also attenuated the production of tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-$1{\beta}$ and IL-6 in LPS-stimulated RAW264.7 cells. These results suggest that scoparone decreases the production of the inflammatory mediators such as NO and $PGE_2$ in macrophages by inhibiting iNOS and COX-2 expression.

• Archives of Pharmacal Research
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• 제26권1호
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• pp.83-88
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• 2003

KR-984055 is a new oral cephalosporin antibiotic with activity against both gram-positive and gram-negative bacteria. Lipophilic ester-type prodrugs of KR-984055, i.e., KR-999001 and KR-999002, have been synthesized in an attempt to increase the oral bioavailability of this broad-spectrum antibiotic agent. In this study we determined the oral bioavailability of KR-984055 and its prodrugs in the rat, and evaluated the pharmacokinetic model that best describes the plasma concentration behavior following single intravenous (IV) and oral single dose. In addition, concentrations in plasma as well as biliary and urinary recovery of KR-984055 were determined. Also, protein binding of KR-984055 in plasma was examined in vitro. The degree of protein binding of KR-984055 was in the range of 92.09~94.77%. KR-984055 exhibited poor oral bioavailability (7.02$\pm$1.58%). The observed oral bioavailabilities of KR-984055 from KR-999001 and KR-999002 were 38.77$\pm$2.81 % and 39.81$\pm$5.25%, respectively. These data were calculated from the levels of free KR-984055 in plasma. Oral KR-999001 and KR-999002 were not recovered from plasma, suggesting that it was readily cleaved to free KR-984055. KR-999001 and KR-999002 appear to be an efficient oral prod rug of KR-984055 that deserved further clinical evaluation in human.

• Archives of Pharmacal Research
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• 제19권5호
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• pp.359-367
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• 1996

The pharmacokinetics of LB20304 was investigated following intravenous (IV) and oral administration to rats and dogs. Additionally, in vitro metabolism and serum protein binding studies were also conducted. The total body clearance, apparent volume of distribution, terminal half-life, and extent of bioavailability were 21.8 ml/min/kg, 2265 ml/kg, 93.6 min, and 30.8% for rats; and 7.95 ml/min/kg, 4144 ml/kg, 363 min, and 81.1% for dogs, respectively. LB20304 was stable in the liver microsome containing NADPH generating system and its serum protein binding was 58.5-65.8% for rats, 19.1-29.6% for dogs, and 56.9-59.6% for humans. Its tissue concentration levels in lever, stomach, small intestine, and kidney were 9.5 to 26.1 times greater than plasma level, but the concentration in testis was quite low and that in brain was negligible in rats. The 48 hr urinary recovery of the dose was 44% for IV dosing and 14% for oral dosing, shereas the 48 hr biliary recovery of the dose was 6.4% for IV dosing and 4.5% for oral dosing in rats. In summary, the pharmacokinetic properties of LB20304 were characterized by its good oral absorption, long plasma half-life, and good tissue distribution.

• 기본간호학회지
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• 제5권1호
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• pp.47-64
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• 1998

This study was conducted to collect the baseline data of physical health status and nursing needs of the elderly for developing an educational program for nursing professionals. The data was collected from 287 people who were 65 years old or older belonging to a selected 8 out of the 39 welfare centers in Pusan during the period from February 25 to November 30, 1996. Socio-demographic characteristics, frequency of hospitalization, and the prevalence of chronic illnesses were measured to assess the physical health status of the center's elderly admitted to the hospital during the period of data collection. The 5-point Likert-type scale composed of 20 items was used. The data was analyzed with the Statistical Package for the Social Sciences Program (SPSS PC+). The results were summarized as follows : 1. The proportion of elderly subjects with chronic illnesses was 73.6%. Among 6 types of chronic illnesses, hypertension was the most prevalent(23.7%), cardiovascular disease was the second(18.1%), gastrointestinal disease the third(17.1%), musculosskeletal disease the fourth(12.9%), liver and biliary disease the fifth(12.5%), and diabetes the sixth. 2. The average score of the subjects' health status was 3.649 on the 5-point Likert scale. Among the 6 factors related to physical health, personal hygiene was the strongest factor(4.612) ; elimination was the second(4.491) ; sensation the third(4.369), outside activity the fourth(3.675), digestion the fifth(3.331), and sexual life the sixth. 3. Gender, marital status, religion, educational level, family structure, living arrangements, and perceived health status were significantly related to the elderly's physical health status. 4. Among the nursing needs of the elderly, emotional support and care was the strongest need(74.2%) ; physical therapy was the second(73.2%) ; education about diease control the third(64.8%) ; medication the fourth(63.8%) ; and the range of motion exercise the fourth(61.0%).

• Journal of the Korean Data and Information Science Society
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• 제27권5호
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• pp.1253-1262
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• 2016

위험률에 변화점이 존재할 경우 위험률 변화점에 대한 추정 정확한 모수 추정을 위해 매우 필요하다. 본 연구에서는 한 개 위험률 변화점이 존재하는 경우 위험률의 변화점 추정량에 대한 비교 연구를 수행하였다. 우도함수에 기반한 모수적 방법인 Matthews와 Farewell (1982) 위험률 변화점 추정량과 Nelson-Aalen 누적 위험률에 기반한 비모수적 방법의 Zhang 등 (2014) 위험률 변화점 통계량을 고찰하여 특성을 파악하였다. 모의실험에서 지수분포를 따르는 생존데이터에 대해 위험률 변화점이 한 개 있는 경우 중도절단이 없는 경우와 중도절단이 있는 경위험률 추정량의 능력을 평균제곱오차를 계산하여 비교하였다. 실제 데이터에 대한 적용으로 백혈병 생존데이터와 원발성 담백증 경화 생존데이터에 대해 위험률 변화점을 추정하고 비교해 보았다.

• 보건교육건강증진학회지
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• 제30권5호
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• pp.201-210
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• 2013

Objectives: The public relies on the news media to understand health risks. To examine the surveillance function of Korean health journalism, this study compared the rank-order of the 10 most frequently diagnosed cancers with that of the 10 cancers most frequently covered by three major Korean newspapers. Methods: News stories published between 1999 and 2010 by the Chosun-Ilbo, Joong-Ang-Ilbo, and Dong-A-Ilbo were examined. Data on cancer incidence were collected using the epidemiological data published by a governmental public health institution. To compare the level of the crude rates and the amount of news coverage, rank-order correlation tests and regression analyses were employed. Results: A reduction in the rank-ordered correlation coefficient was observed despite an increase in the overall number of cancer news stories released. The significance of the correlation disappeared after 2006. The big difference of the rank order between the crude rate and the amount of news coverage was observed in the cancer of breast, uteri, thyroid, and gallbladder/biliary. Finally, the three newspapers did not follow the amount change in stomach, lung, liver, and uterine cervix cancer. The four cancers' rank orders of crude rate were lowering, signifying a reduction of the comparative dangerousness of the four cancers. Conclusions: The news media's customization of news content and the negative bias in journalism are suggested as possible influences on the news media's inaccurate representation of cancer risk.

• Advances in pediatric surgery
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• 제18권1호
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• pp.12-17
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• 2012

The purpose of this study is to analyse clinical impact of specific MRI findings in liver in patients of long-term survivors after Kasai portoenterostomy (KPE). Twenty-eight patients who were underwent KPE were followed up more than 5 years. Macro-regenerative nodule (MRN) and beaded-duct dilatation (BDD) were considered as important findings in liver MRI. The association between these findings in MRI and clinical indicator, serum bilirubin level and history of cholangitis were evaluated. Sixteen patients (57.1%) were shown MRN in liver MRI. Therewere 14 patients(50%) whose MRI showed BDD. Serum total and direct bilirubin were 3.6 mg/dL and 1.8 mg/dL respectively in positive MRN group whereas 1.4 mg/dL and 0.7 mg/dL in negative MRN group (p = 0.427). Serum total and direct bilirubin level were 4.2 mg/dL and 2.1 mg/dL in patients with BDD negative group compare to 1.1 mg/dL and 0.5 mg/dL in BDD positive group (p = 0.281). The odds ratio to have cholangitis in the patient with MRN was 2.3 and 0.53 in patient with BDD in their MRI findings. MRN in liver MRI may suggest high bilirubin level and more chance to have cholangitis, but the findings of BDD may related to low bilirubin level and less change to have cholangitis.

• 약학회지
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• 제37권4호
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• pp.383-388
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• 1993

Pharmacokinetics of aucubin, an irdoid glucoside, was compared in rats of experimental hepatic failure(EHF). EHF was induced by CCI$_{4}$ or D-galactosamine pretreatment. This work was designed to find out any differences in the pharmacokinetics of aucubin that may explain the different protective effect of aucubin on CCI$_{4}$- and galactosamine-induced EHF : aucubin reportedly protected CCI$_{4}$-inducing hepatotoxicity effectively, but did not for galactosamine-hepatotoxicity. EHF was induced by intraperitoneal injection Of CCI$_{4}$(0.9ml/kg) or galactosamine(250 mg/kg) to Wistar rats 24 hr before the pharmacokinetic study. The rats were fasted during the 24 hr. Aucubin was iv injected at a dose of 15 mg/kg and the plasma aucubin was assayed by HPLC. There were no significant differences in the pathophysiologies(body weight, liver weight, GTP, hematocrit, blood cell distrbution and plasma protein binding of aucubin) between the two EHF models except GOP which was significantly (p<0.05) higher in CCI$_{4}$-than in galactosamine-EHF. On the other hand, pharmacokinetics of aucubin such as total cleatance(CL$_{t}$), distribution volume at steady-state(Vd$_{ss}$), and mean residence time(MRT) differed significantly(p<0.05) between the models : for example, CL$_{t}$ was increased two fold by CCI$_{4}$, but not by galaclosamine ; Vd$_{ss}$, in galactosamine-EHF was higher than that in CCI$_{4}$-EHF ; MRT was decreased by CCI$_{4}$, but increased conversely by galactosamine. The increase of CL$_{t}$(and decrease of MRT) in rats of CCI$_{4}$-EHF was contrary to the general expectation for the hepatic failure : most of the hepatic failures have been known to decrease CL$_{t}$ of the administered drugs. Whether the difference in the pharmacokinetics is responsible for the different protective effect of aucubin against the two EHF models is of interest. However, much more studies on biliary excretion, urinary excretion, and hepatic uptake in cellular level should be preceded before any conclusions are made on the role of different pharmacokinetics on the different pharmacology of aucubin.