• The Korean Journal of Physiology and Pharmacology
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• 제19권5호
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• pp.451-460
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• 2015

Sirtuin 1 (SIRT1) is a mammalian $NAD^+$-dependent protein deacetylase that regulates cellular metabolism and inflammatory response. The organ-specific deletion of SIRT1 induces local inflammation and insulin resistance in dietary and genetic obesity. Macrophage-mediated inflammation contributes to insulin resistance and metabolic syndrome, however, the macrophage-specific SIRT1 function in the context of obesity is largely unknown. C57/BL6 wild type (WT) or myeloid-specific SIRT1 knockout (KO) mice were fed a high-fat diet (HFD) or normal diet (ND) for 12 weeks. Metabolic parameters and markers of hepatic steatosis and inflammation in liver were compared in WT and KO mice. SIRT1 deletion enhanced HFD-induced changes on body and liver weight gain, and increased glucose and insulin resistance. In liver, SIRT1 deletion increased the acetylation, and enhanced HFD-induced nuclear translocation of nuclear factor kappa B (NF-${\kappa}B$), hepatic inflammation and macrophage infiltration. HFD-fed KO mice showed severe hepatic steatosis by activating lipogenic pathway through sterol regulatory element-binding protein 1 (SREBP-1), and hepatic fibrogenesis, as indicated by induction of connective tissue growth factor (CTGF), alpha-smooth muscle actin (${\alpha}$-SMA), and collagen secretion. Myeloid-specific deletion of SIRT1 stimulates obesity-induced inflammation and increases the risk of hepatic fibrosis. Targeted induction of macrophage SIRT1 may be a good therapy for alleviating inflammation-associated metabolic syndrome.

• 대한핵의학회지
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• 제37권6호
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• pp.418-427
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• 2003

목적: $^{99m}-lactosylated$ serum albumin ($^{99m}Tc-LSA$)은 간세포에 특이적으로 결합하는 간수용체 영상용 방사성의약품으로 새로이 합성되었다. 간섬유화를 유발하는 dimethylnitrosamine (DMN)을 투여한 간 손상 흰쥐 모델에서 $^{99m}Tc-LSA$의 역동학적인 간섭취를 조사하고 간효소치의 변화와 조직학적 소견을 비교하여, LSA의 간섭취가 간기능의 변화를 반영하는지를 연구하였다. 대상 및 방법: SD계 흰쥐에 DMN를 27 mg/kg으로 복강 내 주사하여 급성 간손상을 유도하고 대조군과 비교하였다. DMN을 주사한 흰쥐를 3일(DMN-3), 8일(DMN-8), 21일(DMN-21)에 $^{99m}Tc-LSA$ (1,665 mg/kg) 29 MBq를 정맥 주사하여, 30분 동안 동적 영상을 획득하고 간과 심장부위에 관심영역을 설정하여 간과 심장부위의 시간방사능 곡선을 얻었다. 간기능 평가를 위해 시간방사능 곡선을 이용하여 간섭취지수와 혈중제거지수를 구하였고 곡선 최적화를 시행하였다. DMN 투여군과 대조군의 간효소치의 변화와 간조직의 광학현미경 소견을 비교하였다. 결과: 대조군에서는 $^{99m}Tc-LSA$가 빠르게 간에 섭취되고 혈중에서 제거되었으나 DMN을 처리한 군에서는 간섭취가 낮았다. 간섭취지수의 비교에서 대조군에 비해 DMN 처리군에서 유의하게 간섭취지수가 낮았다(DMN-3: 0.842, BMN-8: 0.898, DMN-21: 0.91, 대조군: 0.96, p<0.05). 혈중제거지수의 비교에서도 대조군에 비해 DMN 처리군에서 혈중제거지수가 유의하게 높았다(DMN-3: 0.731, DMN-8: 0.654, DMN-21: 0.604, 대조군: 0.473, p<0.05). 비선형 회귀분석에서 $R_2$값은 0.9이상으로 좋은 일치를 보였고, 대조군에서 K값이 DMN처리군에 비해 크고 (DMN-3: 0.28, DMN-8: 0.41, DMN-21: 0.46, 대조군: 0.97, p<0.05), $T_{1/2}$값은 작았다(DMN-3: 2.5, DMN-8: 1.7, DMN-21: 1.5, 대조군: 0.7, p<0.05). 간효소치의 변화는 DMN-3군에서는 대조군에 비해 상승하였으나 DMN-8, DMN-21군에서는 간효소치의 상승이 관찰되지 않았다. 간조직 소견의 경우 DMN-3군에서 중심정맥 주위에 괴사가 관찰되었으나 DMN-8군, DMN-21군에서는 미약한 정도의 염증세포 침윤만이 관찰되었다. 결론: $^{99m}Tc-LSA$ 간신티그래피의 간섭취 정도는 간손상과 반비례하였으며 간섭취의 변화는 조직학적 손상이 심한 정도와 간손상후 회복되는 과정을 반영하여 주었다. $^{99m}Tc-LSA$ 간신티그래피가 간손상을 평가하고 간손상후 회복되는 과정을 추적하는 간수용체 영상용 방사성 의약품으로 사용될 수 있을 것으로 생각된다.

• 한국의학물리학회지:의학물리
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• 제21권2호
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• pp.165-173
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• 2010

본 논문에서는 간암 환자를 대상으로 3차원입체조형치료와 세기조절방사선치료와 3종류의 래피드아크 치료를 위한 치료계획을 수행하여 각각의 선량분포와 선량 체적 히스토그램(Dose Volume Histogram, DVH)의 특성을 비교, 평가하고 이를 통해 래피드아크 치료 환자에 대한 적절한 갠트리 회전수의 범위를 제시하고자 하였다. 치료계획은 작은 종양의 용적을 가지며 내부 장기 및 종양의 움직임이 비교적 작은 간암환자를 대상으로 3차원입체조형치료와 세기조절방사선치료와 더블아크(double arcs)와 제한적인 트리플아크(limited triple arcs)와 멀티플아크(multiple arcs)치료에 대해 Eclipse 8.6 버전에서 시행하였다. 또한 치료계획 시 임상표적용적(Clinical Target Volume, CTV)과 치료표적용적(Planning Target Volume, PTV)에 동일한 최적화 조건을 적용하였고, 각각의 정상조직에는 개별적인 선량 제한치 적용대신 종양 주변 정상조직에서의 선량 감소율을 일괄적으로 적용하였다. 임상표적용적과 치료표적용적의 전체 몸에 적용한 치료계획 선량 제한치에 대한 실제 계산결과의 만족도는 래피드아크가 세기조절방사선치료보다 높았으며 래피드아크에서 더블아크와 제한적인 트리플아크와 멀티플아크는 만족도가 거의 동일하였다. 또한 각 치료계획에서 치료표적용적에 계획한 선량 제한치에 따라 SALT group이 제안한 Conformity Index (CI)가 0.98인 선량 분포범위에 처방선량을 결정하였다. 이때 RTOG에서 제안한 CI, Homogeneity Index (HI), Quality of Coverage (QOC)와 Lomax and Scheib에서 제안한 Healthy tissue conformity index (HTCI) 등을 평가하였다. 항목별로 차이는 있지만 총체적인 평가 결과는 멀티플아크가 전체적으로 좋았으며 모니터 단위 값의 비교에서도 멀티플아크가 가장 작았다. 본 연구를 통하여 래피드아크 치료는 기존에 시행하고 있는 3차원입체조형치료 또는 세기조절방사선치료 기법보다 더욱 최적의 선량 분포를 구현한다는 것을 알 수 있었다. 또한 래피드아크 치료계획에서 멀티플아크 치료계획은 더블 또는 제한된 트리플아크 치료계획보다 모니터 단위 값이 작고, 선량의 균질성 및 종양내의 최소선량은 비슷하거나 좋아지는 동시에 주변 정상조직에는 선량이 감소되는 것을 알 수 있었다.

• Toxicological Research
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• 제32권3호
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• pp.231-237
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• 2016

Eryngium foetidum Linn. leaves (EF) are widely used in Thailand and many countries throughout Asia as a culinary seasoning and a traditional medicine. However, adverse effect of high dose consumption in long duration has not been evaluated. The aim of this study was to investigate chronic toxicity of EF in mice. Thirty-two ICR male mice were divided into 4 groups of 8 mice each. The mice were fed AIN-76 rodent diet, or AIN-76 rodent diet supplemented with ground freeze-dried EF at 0.8%, 1.6% and 3.2% that is equivalent to approximately 35, 73 and 155 times that of human consumption, respectively, at 97.5 percentile for a period of 24 weeks. At the end of experiment, the mice were euthanized and blood samples were collected for hematological and biochemical evaluations. Necropsy was performed while visceral organs such as lung, liver, kidneys, spleen etc. were collected, weighed and histopathologically examined. Blood urea nitrogen (BUN) results of mice in 1.6% and 3.2% EF diet groups were significantly higher than the BUN of control group. No significant difference was noted in other biochemical and hematological properties between the treatment groups and control; all results were within normal range. Histopathology of almost all visceral organs showed no significant changes. However, tubulonephrosis and chronic interstitial nephritis were observed in the groups treated with 1.6% and 3.2% EF diet. Body weight was reduced significantly at week 12 to week 20 when compared to the control group while relative kidney weights were significantly increased. In conclusion, the consumption of EF in diet at high doses illustrated the adverse effect on some biochemical parameters and histopathology in mice. Our findings suggested that EF daily consumption for 24 weeks, at higher doses than the 0.8% EF diet (35 times of human consumption), might cause adverse effect on kidney function in mice.

• Journal of Nutrition and Health
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• 제36권9호
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• pp.933-941
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• 2003

It has been suggested that green juice supplementation may have some health promoting benefits. We evaluated the effects of green juice (Angelica keiskei) consumption on parameters of lipid profiles and plasma antioxidant status in healthy male smokers. Fifty-four smokers were supplemented with 300 ml of green juice for 6 weeks while maintaining their normal diet. Blood samples were collected on week 0 and week 6 in order to evaluate plasma lipid profiles (total cholesterol, triglyceride, LDL-cholesterol, HDL-cholesterol) , plasma antioxidant vitamin levels (ascorbic acid, $\alpha$ -tocopherol, ${\gamma}$ -tocopherol, $\alpha$ -carotene, $\beta$ -carotene, cryptoxanthin and lycopene) , the degree of LDL oxidation and GOT, GPT levels for liver function. Plasma ascorbic acid level remained at the same level. However, $\alpha$ -tocopherol and ${\gamma}$ -tocopherol normalized by total cholesterol (p <0.05) and $\beta$ -carotene (p <0.001) level were all significantly increased after green juice supplementation. Plasma cholesterol was reduced for 12%, LDL-cholesterol was reduced for 9.3% after green juice consumption, while plasma triglyceride and HDL-cholesterol was not changed. Oxidized LDL assessed by conjugated diene (CD) , was decreased (p < 0.0001) after green juice consumption. These results further support a role for green juice supplementation in the improvement of lipid status, prevention of lipid peroxidation, and thereby reducing risk factors of numerous diseases associated with elevated oxidative stress in smokers.

• Asian-Australasian Journal of Animal Sciences
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• 제21권10호
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• pp.1479-1485
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• 2008

Two completely randomized block design experiments were conducted to evaluate the effect of gamma irradiation processing of canola meal on performance parameters of broiler chicks (Ross 308) and protein quality of canola meal. Protein efficiency ratio (PER) and net protein ratio (NPR) were measured as indices of canola meal protein quality. Samples of canola meal were tested for nutritional value after being irradiated at dose levels 10, 20 and 30 kGy. Glucosinolate content was reduced 40, 70 and 89 percent at irradiation dose levels of 10, 20 and 30 kGy respectively (p<0.01). Percent of erucic acid in total fatty acid content increased 44, 58 and 48% as a function of radiation dose (p<0.01). Dose levels did not affect feed conversion ratio (FCR) and body weight gain of chicks (p>0.05). Liver weight was decreased by irradiation dose (p<0.05). The same trend was observed for kidney weights, but this trend was not significant (p>0.05). Gamma irradiation processing of canola meal had no significant effect on $T_3$ level in blood of chickens that consumed canola meal, but $T_4$ level of chicken blood at the 30 kGy dose decreased significantly (p<0.05). PER and NPR were not affected by radiation dose level (p>0.05). Gamma irradiation seems to be a good procedure to improve the nutritional quality of canola meal.

• Toxicological Research
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• 제18권4호
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• pp.401-409
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• 2002

Phthalate esters have possible effects on the endocrine system. Di-n-butyl phthalate (DBP) is one of the most commonly wed phthalic acid esters (PAEs). It is extensively wed as a plasticizer in elastomers, as a solvent for printing inks and resins, and as a textile lubricating agent. It is also present in the formulations of various cosmetic products. DBP has been identified as a reproductive toxicant in several animal species and also know as a endocrine disruptor. The objective of this study was to investigate the effect of DBP on developmental immune Junction wing rat pups as experimental animals. Timed-bred pregnant SD rats were orally dosed with 0, 250, 500, or 750 mg DBP/kg body weight once a day from gestational day (GD) 5 to 18 and postpartum day (PD) 3 to 18. On PD22, the dams and their pups were euthanized and examined for alteration in parameters associated to immune function. The results showed no significant changes in body weight, thymus weight, thymus and spleen cellularities, the polyclonal activation respones of splenocyte with ConA and LPS, and also the distribution of arterial blood cells and thymocyto subsets in both rat dam and pups. However DBP exposure on rat dam resulted in increases of liver weights of dam and their pups except 750 mg DBP/kg, and body and spleen weights in pups except 750 mg DBP/kg. On the other hands, distribution rates of CD8+ T cells at 500 mg DBP/kg and B cells at 750 mg DBP/kg among splenocyte subsets were significantly increased in rat pups, unlike dams. Reasons of these distribution alterations of CD8+ T cells and B cells in rat pups are under study.

• Journal of Nutrition and Health
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• 제27권1호
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• pp.79-89
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• 1994

The purpose of this study was to investigate the relationship between body fat and risk factors of chronic diseases in obese children and eventually to contribute to the prevention and treatment of childhood obesity. Anthropometric parameters such as height, weight, skinfold thickness, circumferences, body fat content were measured in 55 obese subjects of age 5-20. Blood pressure, serum components, daily food intakes were also considered. The average age of the subjects was 12.5$\pm$3.3yrs and the mean obesity index was 64.7$\pm$21.3%. The average percentage of body fat was 35.6$\pm$5.4% and the mean weight of lean body mass was 45.3$\pm$13.9kg. Mean total muscle weight of the subjects was estimated to be 34.11$\pm$1.3kg. The mean systolic and diastolic blood pressures of the obese were 134.8$\pm$15.8mmHg and 69.6$\pm$11.6mgHg respectively. The concentrations fo serum triglyceride, total cholersterol, HDL-cholesterol, LDL-cholesterol were estimated to be 246.0$\pm$136.4mg/dl, 257.0$\pm$54.3mg/dl, 48.2$\pm$13.1mg/dl and 158.9$\pm$53.5mg/이 respectively. The concentrations of serum GOT and GPT were 34.6$\pm$17.1U/L and 24.7$\pm$15.3U/L. The mean content of uric acid is serum was 6.2$\pm$1.9mg/dl. Of these 55 children, 82% has hyperlipidemia, 26% was abnormal liver function and 24% was hyperuricemia. One patient was diabetic. Eighty seven% of them have developed more than one complications.

• Asian Pacific Journal of Cancer Prevention
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• 제15권14호
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• pp.5617-5620
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• 2014

Objective: To evaluate the prognosis of different ways of drainage for patients with obstructive jaundice caused by hilar cholangiocarcinoma. Materials and Methods: During the period of January 2006- March 2012, percutaneous transhepatic catheter drainage (PTCD)/ percutaneous transhepatic biliary stenting (PTBS) were performed for 89 patients. According to percutaneous transhepatic cholangiography (PTC), external drainage was selected if the region of obstruction could not be passed by guide wire or a metallic stent was inserted if it could. External drainage was the first choice if infection was diagnosed before the procedure, and a metallic stent was inserted in one week after the infection was under control. Selection by new infections, the degree of bilirubin decrease, the change of ALT, the time of recurrence of obstruction, and the survival time of patients as the parameters was conducted to evaluate the methods of different interventional treatments regarding prognosis of patients with hilar obstruction caused by hilar cholangiocarcinoma. Results: PTCD was conducted in 6 patients and PTBS in 7 (p<0.05). Reduction of bilirubin levels and ALT levels was obvious after the procedures (p<0.05). The average survival time with PTCD was 161 days and with PTBS was 243 days (p<0.05). Conclusions: With both drainage procedures for obstructive jaundice caused by hilar cholangiocarcinoma improvement in liver function was obvious. PTBS was found to be better than PTCD for prolonging the patient survival.

• Asian Pacific Journal of Cancer Prevention
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• 제14권9호
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• pp.5473-5476
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• 2013

Background: In our study, the LDH, albumin, hemoglobin, neutrophile, thrombocyte, lymphocyte counts and prognostic significance of neutrophile-lymphocyte and thrombocyte-lymphocyte ratios in NSCLC derived from these counts obtained during regular examinations of patients were examined. Materials and Methods: Histopathologically diagnosed non-small-cell-lung cancer patients between 2008 and 2010 were included in the study. Before the treatment, full blood count including routine lymphocyte count, blood biochemistry examinations including liver (AST, ALT, total protein, Albumin), LDH and kidney (BUN, Cre) function tests were performed. Results: A total of 156 patients, 76 of whom (48.7%) were female and 80 of whom (51.3%) were male were included. Mean hemoglobin level was determined as 12. Overall survival was found to be significantly dependent on whether patients were anemic or not (p: 0.005). Mean LDH level was determined as 233.4. There was nosurvival difference between patients with and without high LDH (p: 0.532). In patients where NLR showed systemic inflammatory response, overall survival was 10.8 months whereas this duration was 19.6 months in patients where the systemic inflammatory response was negative (p: 0.012). In patients where TLR showed systemic inflammatory response, overall survival was 13.6 months whereas this duration was 21.9 months in patients where the systemic inflammatory response was negative (p: 0.04). Conclusions: Molecular methods have been changing rapidly in today's world and they manage the treatment besides defining the prognosis of patients. However, easily accessible and cheap laboratory parameters should be considered in the prognosis of patients besides these new methods.