• 약학회지
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• 제52권5호
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• pp.331-344
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• 2008

Recently, the FDA (Food and Drug Administration) of the United States and many advanced countries remark biomarkers and surrogate endpoints as a critical path tool on model based drug development. Economic, technical and social profit on model based drug development like a reduction of the length of research and development have been achieved. Therefore we summarize previous studies about biomarkers and surrogate endpoints and suggest a development direction of therapeutic agents. In diabetes mellitus (DM) and osteoporosis, there are remarkable increases in number of patients and most of patients take medicine during their whole lifetime. For this reason, many patients with DM and osteoporosis have a tolerance on their medicine. We expect that research and development on biomarkers and surrogate endpoints will contribute to new drug development on DM and osteoporosis. Biomarkers for DM are blood levels of glucose, insulin, ${HbA}_{1c}$, CRP, alpha-glucosidase, adiponectin and DPP-4. Among these, validated surrogate endpoints for DM are blood levels of glucose, insulin and ${HbA}_{1c}$ Biomarkers for osteoporosis are BMD, BMC, trabecular volume, ICTP, DPD, osteocalcin, the activity of osteoclast and production of osteoblast. The validated surrogate endpoints for osteoporosis are BMD only. This review summarizes all suggested biomarkers and surrogate endpoints in DM and osteoporosis. The biomarkers are classified by drugs, and the method of validation for surrogate endpoints is suggested. This information would contribute to suggest a direction of DM and osteoporosis therapeutic agent development.

• 한국식품저장유통학회지
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• 제19권3호
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• pp.400-405
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• 2012

포도 3종(Campbell early, MBA, 거봉)의 과피와 씨를 물과 ethanol을 이용하여 추출하였다. ${\alpha}$-Glucosidase 저해 활성은 대부분의 추출물에서 저해 활성을 보였으며, 물 추출물이 가장 높은 저해 활성을 보였다. 그에 따라 물 추출물을 이용하여 streptozotocin (STZ)에 의해 유도된 당뇨 마우스모델의 고혈당에 미치는 영향을 조사한 결과 캠벨(씨)의 물 추출물을 처리한 당뇨 유발 마우스의 혈당은 시간이 지날수록 그 수치가 떨어져 3시간이 지난 후에는 정상 수치까지 떨어지는 것을 확인할 수 있었고, 거봉(씨) 물 추출물을 처리한 마우스에서는 혈당 상승이 1/3 수준으로 완화되었다. 이러한 결과를 통하여 포도의 과피와 씨 추출물은 고혈당 개선에 효과를 지닐 것으로 판단되었으며 향후 혈당에 관련된 기타분자표적의 추적이 필요하다고 판단된다.

• Animal cells and systems
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• 제16권4호
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• pp.329-336
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• 2012

This study evaluated ecological health, using various biomarkers and bioindicators, of pale chub (Zacco platypus) as a sentinel species, in Daejeon Stream, South Korea, during AprilMay 2011. The biomarkers and bioindicators were compared among three sites of control: Reference ($C_z$), transition ($T_z$), and the urban zones ($U_z$); and the 7-Ethoxyresorufin-O-deethylase (EROD) activity, DNA damage, acetylcholinesterase (AChE) activity, and vitellogenin (VTG) concentrations were more significantly increased in the $U_z$ than in the $C_z$. Also, physiological markers such as condition factor, liver somatic index, visceral somatic index, and gonad somatic index were significantly increased in the $U_z$ than in the $C_z$. For the health assessments, three categorized parameters of blood chemistry, molecular biomarkers, and physiological bioindicators were standardized and calculated as a star-plot, representing values of Integrated Health Response (IHR). Values of IHR had more significant (P<0.05) increases in the $U_z$ than any other zones, indicating an impairment of ecological health by organic matter, nutrients (N, P), and toxic chemicals. This study is based on low levels of biological organization approach of molecular and physiological biomarkers and bioindicators, so further study of high-levels of biological organization approach such as community and population is required for overall range of health assessments. The approach of IHR values, however, may be useful in providing early warning of future impacts on ecological health.

• Safety and Health at Work
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• 제2권2호
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• pp.169-175
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• 2011

Objectives: The questionnaire of occupational stress index (OSI) has been popular in the workplace, and it has been tailored for bus drivers in Taiwan. Nevertheless, its outcomes for participants are based on self-evaluations, thus validation by their physiological stress biomarker is warranted and this is the main goal of this study. Methods: A cross-sectional study of sixty-three city bus drivers and fifty-four supporting staffs for comparison was conducted. Questionnaire surveys, 24-hour urine cortisol testing, and blood draws for dehydroepiandrosterone-sulfate (DHEA-S) testing were performed. The measured concentrations of these biological measures were logarithmically transformed before the statistical analysis where various scores of stressor factors, moderators, and stress effects of each OSI domain were analyzed by applying multiple linear regression models. Results: For drivers, the elevated 24-hour urine cortisol level was associated with a worker's relationship with their supervisor and any life change events in the most recent 3 months. The DHEA-S level was higher in drivers of younger age as well as drivers with more concerns relating to their salary and bonuses. Non-drivers showed no association between any stressor or satisfaction and urine cortisol and blood DHEA-S levels. Conclusion: Measurements of biomarkers may offer additional stress evaluations with OSI questionnaires for bus drivers. Increased DHEA-S and cortisol levels may result from stressors like income security. Prevention efforts towards occupational stress and life events and health promotional efforts for aged driver were important anti-stress remedies.

• Journal of Gastric Cancer
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• 제19권2호
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• pp.183-192
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• 2019

Purpose: Due to adverse events, dose reduction or withdrawal of adjuvant chemotherapy is required for some patients. To identify the predictive factors for tolerability to postoperative adjuvant S-1 monotherapy in gastric cancer (GC) patients, we evaluated the predictive values of blood indicators. Materials and Methods: We analyzed 98 patients with pStage II/III GC who underwent postoperative adjuvant S-1 monotherapy. We retrospectively analyzed correlations between 14 parameters obtained from perioperative routine blood tests to assess their influence on the withdrawal of postoperative adjuvant S-1 monotherapy, within 6 months after discontinuation. Results: Postoperative adjuvant chemotherapy was discontinued in 21 patients (21.4%) within 6 months. Univariable analysis revealed that high preoperative albumin-bilirubin (ALBI) scores had the highest odds ratio (OR) for predicting the failure of adjuvant S-1 chemotherapy (OR, 6.47; 95% confidence interval [CI], 2.08-20.1; cutoff value, -2.696). The high ALBI group had a significantly shorter time to failure of postoperative adjuvant S-1monotherapy (hazard ratio, 3.48; 95% CI, 1.69-7.25; P=0.001). Multivariable analysis identified high preoperative ALBI score as an independent prognostic factor for tolerability (OR, 10.3; 95% CI, 2.33-45.8; P=0.002). Conclusions: Preoperative ALBI shows promise as an indicator associated with the tolerability of adjuvant S-1 monotherapy in patients with pStage II/III GC.

• Journal of Animal Science and Technology
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• 제63권2호
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• pp.453-460
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• 2021

Oxytocin (OXT) and serotonin (5-HT) are essential neurotransmitters associated with the behavior of animals. Recently, we found that the plasma concentration of OXT is positively correlated with horse docility and friendliness toward humans. However, the relationships between the neurotransmitters and other temperaments such as fearfulness, dominance, and trainability are unknown. This study aimed to identify whether the plasma concentration of OXT or 5-HT is correlated with fearfulness, dominance, and trainability of horses. Blood samples of 34 horses were collected at the Horse Industry Complex Center of Jeonju Kijeon College. The concentration of OXT and 5-HT was measured in the plasma samples using enzyme-linked immunosorbent assays. The fearfulness, dominance, and trainability of horses were scored by three professors who were very familiar with the horses. One-way analysis of variance with the least significant difference post-hoc analysis was used to compare the scores for fearfulness and dominance among groups. The trainability of horses was compared using the student t-test. The 5-HT was negatively correlated with dominance, but it had no relation with fearfulness. The OXT appeared to be negatively correlated with fearfulness and dominance in horses. Furthermore, OXT was positively correlated with the trainability of horses. Additionally, 5-HT appeared to enhance trainability. In conclusion, the concentration of OXT or 5-HT in horse blood plasma can be used as a biomarker to monitor the fearfulness, dominance, or trainability of horses.

• 대한인간공학회지
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• 제26권1호
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• pp.11-18
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• 2007

The physiological and biochemical responses of healthy men and women to life stress were measured in order to temperature, blood pressure (BP), heart rate (HR) and galvanic skin response (GSR) were selected as physiological stress indices and salivary cortisol level was used as a biochemical stres biomarker. Twenty six (male 14 and female 13) colege students were participated in the experiment. Female showed the significant higher value of salivary cortisol level (p<0.01), diastolic BP (p<0.01), and HR (p<0.01) than male. The difference of skin temperature between forehead and fingertip correlated significantly with salivary cortisol level (p<0.01). The LF(low frequency)/HF(high frequency) ratio of HRV also correlated significantly with salivary cortisol level (p<0.01). However, BP, HR and GSR corelated insignificantly with salivary cortisol level. We suggest that LF/HF ratio of HRV and skin temperature may be good indices for the assessment of life stress, and may apply to measure the stress level of individual in real time.

• IMMUNE NETWORK
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• 제15권4호
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• pp.177-185
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• 2015

Although rheumatoid arthritis (RA) is the most common chronic inflammatory autoimmune disease, diagnosis of RA is currently based on clinical manifestations, and there is no simple, practical assessment tool in the clinical field to assess disease activity and severity. Recently, there has been increasing interest in the discovery of new diagnostic RA biomarkers that can assist in evaluating disease activity, severity, and treatment response. Proteomics, the large-scale study of the proteome, has emerged as a powerful technique for protein identification and characterization. For the past 10 years, proteomic techniques have been applied to different biological samples (synovial tissue/fluid, blood, and urine) from RA patients and experimental animal models. In this review, we summarize the current state of the application of proteomics in RA and its importance in identifying biomarkers and treatment targets.

• Childhood Kidney Diseases
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• 제19권2호
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• pp.71-78
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• 2015

The incidence of acute kidney injury (AKI) in critically ill pediatric patients has been reported as increasing to 25 %, depending on population characteristics. The etiology of AKI has changed over the last 10-20 years from primary renal disease to the renal conditions associated with systemic illness. The AKI in pediatric population is associated with increased mortality and morbidity, and prevention is needed to reduce the consequence of AKI. It is known that the most important risk factors for AKI in critically ill pediatric patients are clinical conditions to be associated with decreased renal blood flow, direct renal injury, and illness severity. Renal hypoperfusion leads to neurohormonal activation including renin-angiotensin-aldosterone system, sympathetic nervous system, antidiuretic hormone, and prostaglandins. Prolonged renal hypoperfusion can result in acute tubular necrosis. The direct renal injury can be predisposed under the condition of renal hypoperfusion, and appropriate treatment of volume depletion is important to prevent AKI. The preventable causes of AKI include contrast-induced nephropathy, hemodynamic instability, inappropriate mediation use, and multiple nephrotoxic insults. Given the evidence of preventable factors for AKI, several actions such as the use of protocol for prevention of contrast-induced nephropathy, appropriate treatment of volume depletion, vigorous treatment of sepsis, avoidance of combinations of nephrotoxic medications, and monitoring of levels of drugs should be recommended.

• Molecular & Cellular Toxicology
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• 제5권2호
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• pp.165-171
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• 2009

Biomarkers indicating past exposure to radiation have not yet been entirely satisfactory. In this study, we validated several genes reported as radiation response genes, as biomarkers to detect past exposure to radiation in occupationally exposed workers, especially workers in the medical field. A total of 54 radiation workers in hospital were investigated for radiation exposure dose. Their average radiation dose of recent one year was 1.09 mSv ($\pm$1.63) with a 10.63 mSv ($\pm$12.91) cumulative dose. The results of the multiple regression analysis for the various variables indicate that the Hsc70 (P=0.0292) and ORAL (P=0.0045) may be candidate biomarkers for the recent 1 year radiation exposure in radiation workers, whereas AEN (P=0.0334) and PGAMI (P=0.0003) might be for cumulative exposure.