• Title/Summary/Keyword: Trial Mass

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Utility of Integrated Analysis of Pharmacogenomics and Pharmacometabolomics in Early Phase Clinical Trial: A Case Study of a New Molecular Entity

  • Oh, Jaeseong;Yi, Sojeong;Gu, Namyi;Shin, Dongseong;Yu, Kyung-Sang;Yoon, Seo Hyun;Cho, Joo-Youn;Jang, In-Jin
    • Genomics & Informatics
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    • v.16 no.3
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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.

Effects of Whey Protein-rich Meal Substitute in 4-Week Diet Trial on Body Weight, Body Fat, and Body Composition of Overweight or Obese Females (유청단백 함유 체중조절용 식사대체제를 이용한 4주 다이어트 프로그램이 과체중 및 비만 여성의 체중, 체지방 및 체성분에 미치는 영향)

  • Xi, Mei-Zhu;Zhang, Yi-Lin;Choi, Young-Bin;Jeong, Gi-Hee;Kim, Gun-Woo;Park, Yong-Woo;Lee, Bog-Hieu
    • Journal of the East Asian Society of Dietary Life
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    • v.26 no.1
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    • pp.25-33
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    • 2016
  • The study was performed to investigate the effects of whey protein-rich meal substitute added with vitamins, minerals, and lactobacillus powder probiotics on weight loss, body fat, and body composition in 24 female volunteers for 4 weeks. Whey protein-rich meal substitute was consumed with low-fat, high calcium milk (1% fat, 260 mg/200 mL) twice a day. Subjects submitted 3-day diet records and a life-style questionnaire before the study. During the study, subjects were required to turn in a diet record every day and consume the meal substitute formula in the metabolic ward at C university for 4 weeks. Anthropometric measurements were carried out weekly by Inbody 7.0. The dietary intake and anthropometric data were analyzed to compare changes before and after the study by paired t-test with SPSS version 23.0. The subjects were mostly early 20's and either overweight or obese and highly motivated to lose weight. Most of the subjects consumed three meals per day regularly and spent mostly 10~15 minutes for a meal. Their caloric intake was relatively low and decreased from 1,360 kcal at week 0 to 1,100 kcal after 4 weeks. However, total protein intake increased while carbohydrate and fat intakes decreased (p<0.05) after the trial. Nine vitamin intakes after the study improved compared to those before the study (p<0.05). After the study, subjects showed lower body weight (-1.8 kg), body fat (-0.94 kg), percent body fat (-0.86%), as well as waist circumference (-4.52 cm), hip circumference (-0.44 cm), waist hip ratio (-0.05), and triceps skinfold thickness (-2.39 mm) compared to those at week 0 (p<0.05). Muscle mass tended to be less compared to week 0, although there was no significant differences between weeks 0 and 4. In conclusion, diet trial with whey protein-rich meal substitute induced weight loss and positively changed body fat parameters and body composition.

The Anti-obesity Effects of Bangpungtongseong-san and Daesiho-tang: A Study Protocol of Randomized, Double-blinded Clinical Trial (방풍통성산 및 대시호탕의 항비만효과 분석: 단일기관 무작위배정 이중맹검 임상시험 프로토콜)

  • Oh, Jihong;Shim, Hyeyoon;Cha, Jiyun;Kim, Ho Seok;Kim, Min Ji;Ahn, Eun Kyung;Lee, Myeong-Jong;Lee, Jun-Hwan;Kim, Hojun
    • Journal of Korean Medicine for Obesity Research
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    • v.20 no.2
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    • pp.138-148
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    • 2020
  • Objectives: The aim of this study is to evaluate the effects of Bangpungtongseong-san (Fangfengtongsheng-san, BTS) and Daesiho-tang (Dachaihu-tang, DST) on weight loss and improvement in lipid metabolism and glucose metabolism. Furthermore, we intend to develop a prediction model for drug effects through the analysis of the single nucleotide polymorphism (SNP), gut-microbiota, and the expression of immune-related biomarkers. Methods: This study is a single-center, randomized, double-blind, parallel-design clinical trial. One hundred twenty-eight participants will be assigned to the BTS group (n=64) and DST group (n=64). Both groups will be administered 4 g medication three times a day for up to 2 weeks. The primary outcomes is weight loss. The secondary outcomes include bioelectrical impedance analysis, waist circumstance, body mass index, total cholesterol, high-density lipoprotein, triglyceride, insulin resistance. The exploratory outcomes include 3-day dietary recall, food frequency questionnaire, quality of life questionnaire, gut microbiota analysis, immune biomarkers analysis, and SNP analysis. Assessment will be made at baseline and at week 4, 8, and 12. Conclusions: This protocol will be implemented by approval of the Institutional Review Board of Dongguk University. The results of this trial will provide a systematic evidence for the treatment of obesity and enable more precise herbal medicine prescriptions.

Study on the Recognition and Behavioral Intention for Alcohol-reduction Programs (절주프로그램의 인지도 및 이용의도에 영향을 미치는 요인 연구)

  • 장혜정;심재선;박종애
    • Korean Journal of Health Education and Promotion
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    • v.21 no.1
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    • pp.243-257
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    • 2004
  • Alcohol consumption is a major source of health problems, for example, alchol consumption is related to liver diseases. In addition, the social and economic costs related to alcohol consumption are enormous. This study was conducted to evaluate the current status and influencing factors related to the recognition and behavioral intention for both drinking and alcohol-reduction programs. Three effective alcohol-reduction programs of clinic program, mass education, and alliance were considered. To explain the health behavior for drinking and alcohol-reduction programs, a five-stage behavioral intention model was built and 500 questionnaires were completed through a telephone survey. Stages of the model composed of recognition of the programs, past experiences, present drinking status, intention for drinking, and behavioral intention for alcohol-reduction programs. As a result, recognition rates of the programs were low in general, therefore the strategies of education, public relations, and advertisement need to be pursued. The alcohol dependency resulted in the fact that success rate was 30% although trial rate of alcohol-reducing was 23%. The necessity of alcohol-reduction programs were suggested. In addition, significant factors related to the intention for alcohol-reducing were individual attitude and reluctancy to pay their time and money. An insignificant factor was the attitude to their alcohol-reduction by other people. Behavioral intention rates for alcohol-reducing clinics were 4%, and those for mass education were 8%. There were very low purchase rates for clinic program, mass education, and alliance. In conclusion, evidenced-based and effective alcohol-reduction programs need to be encouraged to drinkers by medical doctors, and the strategies of education, public relations, and advertisement are also recommended. In addition, continuing legal and systematic support for alcohol-reducing would lower the drinking rate and ultimately contribute to the nation's health promotion.

Sparganosis in the Lumbar Spine : Report of Two Cases and Review of the Literature

  • Park, Jin-Hoon;Park, Young-Soo;Kim, Jong-Sung;Roh, Sung-Woo
    • Journal of Korean Neurosurgical Society
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    • v.49 no.4
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    • pp.241-244
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    • 2011
  • Sparganosis is a rare parasitic infection affecting various organs, including the central nervous system, especially the lumbar epidural space. This report describes the identification of disease and different strategies of treatments with preoperative information. A 42-year-old man presented with a 2-year history of urinary incontinence and impotence. He had a history of ingesting raw frogs 40 years ago. Magnetic resonance (MR) imaging showed an intramedullary nodular mass at conus medullaris and severe inflammation in the cauda equina. A 51-year-old woman was admitted with acute pain in the left inguinal area. We observed a lesion which seemed to be a tumor of the lumbar epidural space on MR imaging. She also had a history of ingesting inadequately cooked snakes 10 years ago. In the first patient, mass removal was attempted through laminectomy and parasite infection was identified during intra-operative frozen biopsy. Total removal could not be performed because of severe arachnoiditis and adhesion. We therefore decided to terminate the operation and final histology confirmed dead sparganum infection. We also concluded further surgical trial for total removal of the dead worm and inflammatory grannulation totally. However, after seeing another physician at different hospital, he was operated again which resulted in worsening of pain and neurological deficit. In the second patient, we totally removed dorsal epidural mass. Final histology and enzyme-linked immunosorbent assay (ELISA) confirmed living sparganum infection and her pain disappeared. Although the treatment of choice is surgical resection of living sparganum with inflammation, the attempt to remove dead worm and adhesive granulation tissue may cause unwanted complications to the patients. Therefore, the result of preoperative ELISA, as well as the information from image and history, must be considered as important factors to decide whether a surgery is necessary or not.

The development of UV falme detector (UV 화재감지장치 개발)

  • Gwon, O-Seung;Jeong, Chang-Gi;Lee, Bok-Yeong
    • Fire Protection Technology
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    • s.28
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    • pp.48-54
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    • 2000
  • The technique detects radiant energy form a flaming fire of fuels contained carbonaceous material can be applied to fast growing fires. This technique applied detectors are ultimately effective when early detecting fire alarm system is required or the smoke and heat detectors can not applied. In Korea Fire regulation, a flame detector should be install in case that the installation height is higher than 20[m], chemical plant, hangar refinery. Therefore it is really necessary that a flame detector has to be developed as soon as possible. With foundation technique of flame detector, ideal sensing element and stable circuit design, a trial UV flame detector is manufactured. The stable and reliable technique of flame detector is established through the repeateed perfomance test and modification. An early detecting fire alarm device is developed through the modification, supplement of the structure and circuit. Results of the R & D for the manufacture of an excellent flame detecting device is carried out with the establishment of technique for the mass production and the qualified manufacturing process.

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Bacterial Soft Rot of Cauliflower by Erwinia carotovora subsp. carotovora (Erwinia carotovora subsp. carotovora에 의한 흰색꽃양배추 세균성 무름병)

  • 박덕환;류경렬;김점순;임춘근
    • Korean Journal Plant Pathology
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    • v.14 no.4
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    • pp.364-366
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    • 1998
  • Bacterial soft rot was occurrenced on stems of cauliflower at a trial field of Alpine Agricultural Experiment Station, Kangwon-Do, Korea. the symptoms began as a small water-soaked lesion, which enlarged rapidly in diameter. The tissue within the affected region became slimy, disintegrating into a mushy mass of disorganized cells. The causal organism was isolated from the diseases lesions and was identified as Erwinia carotovora subsp. carotovora based on the morphological, physiological and chemical characteristics , and on the results of the Biolog program (Biolog Inc., U. S. A.). E. carotovora subsp. carotovora is the first described bacterium which causes bacterial soft rot on cauliflower in Korea.

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The Relationship between Epicardial Fat Thickness and Dampness-Phlegm Pattern in the Patients with ischemic stroke

  • Woo, Ji Myung
    • The Journal of Korean Medicine
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    • v.38 no.4
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    • pp.104-109
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    • 2017
  • Objectives: Epicardial fat is true visceral fat that is known to be associated with metabolic syndrome, high abdominal fat, insulin resistance, coronary artery diseases, low coronary flow reserve and subclinical atherosclerosis. Dampness-Phlegm pattern is one of the pattern diagnosis of traditional Korean medicine. Previous studies showed that Dampness-Phlegm pattern is associated with hypertension, dyslipidemia, metabolic syndrome. This study is intended to find association between Dampness-Phlegm pattern and epicardial fat thickness. Methods: This study was a community-based single center trial. Ischemic stroke patients within 30 days after their ictus were enrolled. Epicardial fat thickness was measured using transthoracic echocardiography. Other measured and obtained variables are medical history, weight, height, body mass index, fasting blood glucose, cholesterol, triglycerol, high density lipoprotein, lipid and low density lipoprotein. Results: Three hundred sixty six were enlisted, and one hundred forty were diagnosed with the Dampness-Phlegm pattern. Dampness-Phlegm pattern group had significantly thicker epicardial fat. Binary logistic regression also showed statistically significant result. Conclusions: This study showed close association between epicardial fat and Dampness-Phlegm pattern. This result suggests a clue to standardization of pattern identification.

Dielectric Classification and Addition of New Ferroelectric Members by Synthesis for Perovskite Titanate Family

  • Nakamura, Testsuro;Shan, Yue Jin;Miyata, Mayuko;Kobashi, Kazuhisa;Inaguma, Yoshiyuki;Itoh, Mitsuru
    • The Korean Journal of Ceramics
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    • v.5 no.1
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    • pp.82-86
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    • 1999
  • For nonconducting perovskite titanates ATiO3 and A'1/2A"1/2TiO3, 5 ferroelectric members were discriminated from 17 quantum paraelectric members via average mass of A ions m(A): ferroelectric for m(A)〉110 a.u. and quantum paraelectric for m(A)<100 a.u. An intuitive explanation of the origin of the discrimination is given concenrned with the ferroelectric soft modes in perovskite ATiO3. Based on the above discrimination, trial synthesis of ferroelectric candiate substances are presented.

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The design and evaluation of automatic balancing equipment for the grinding machine (연삭기용 자동 밸런싱 장치의 설계 및 평가)

  • 장홍석;최대봉;황주호;홍준희
    • Proceedings of the Korean Society of Machine Tool Engineers Conference
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    • 2001.04a
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    • pp.309-314
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    • 2001
  • The balance of high speed spindle system with high precision rotation like grinding machine is very important. Traditionally, we use trial and error method to balance the spindle. It takes much time. So we are developing the automatic balancing equipment being used in the grinding machine. The balancing head we develop is wireless. It will be used high-speed grinding machine. We use influence coefficient method to control the automatic balancer. Experiments are based on automatic and manual balancing. We perform test of the vibration filter. It helps to remove noise. The filter and experiments with automatic balancing controller show that automatic balancing control can be successfully achieved with the quick response and good stability characteristics.

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