Kim, Kyung Eun;Kim, Hwajin;Heo, Rok Won;Shi, Hyun Joo;Yi, Chin-ok;Lee, Dong Hoon;Kim, Hyun Joon;Kang, Sang Soo;Cho, Gyeong Jae;Choi, Wan Sung;Roh, Gu Seob
The Korean Journal of Physiology and Pharmacology
/
v.19
no.5
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pp.451-460
/
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.
Objects: $^{99m}-lactosylated$ human serum albumin (LSA) is a newly synthesized radiopharmaceutical that binds to asialoglycoprotein receptors, which are specifically presented on the hepatocyte membrane. Hepatic uptake and blood clearance of LSA were evaluated in rat with acute hepatic injury induced by dimethylnitrosamine (DMN) and results were compared with corresponding findings of liver enzyme profile and these of histologic changes. Materials and Methods: DMN (27 mg/kg) was injected intraperitoneally in Sprague-Dawley rat to induce acute hepatic injury. At 3(DMN-3), 8(DMN-8), and 21 (DMN-21) days after injection of DMN, LSA injected intravenously, and dynamic images of the liver and heart were recorded for 30 minutes. Time-activity curves of the heart and liver were generated from regions of interest drawn over liver and heart area. Degree of hepatic uptake and blood clearance of LSA were evaluated with visual interpretation and semiquantitative analysis using parameters (receptor index : LHL3 and index of blood clearance : HH3), analysis of time-activity curve was also performed with curve fitting using Prism program. Results: Visual assessment of LSA images revealed decreased hepatic uptake in DMN treated rat, compared to control group. In semiquantitative analysis, LHL3 was significantly lower in DMN treated rat group than control rat group (DMN-3: 0.842, DMN-8: 0.898, DMN-21: 0.91, Control: 0.96, p<0.05), whereas HH3 was significantly higher than control rat group (DMN-3: 0.731,.DMN-8: 0.654, DMN-21: 0.604, Control: 0.473, p<0.05). AST and ALT were significantly higher in DMN-3 group than those of control group. Centrilobular necrosis and infiltration of inflammatory cells were most prominent in DMN-3 group, and were decreased over time. Conclusion: The degree of hepatic uptake of LSA was inversely correlated with liver transaminase and degree of histologic liver injury in rat with acute hepatic injury.
Park, Hae-Jin;Kim, Mi-Hwa;Chun, Mi-Son;Oh, Yeong-Teak;Suh, Tae-Suk
Progress in Medical Physics
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v.21
no.2
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pp.165-173
/
2010
In this paper, we evaluated the performance of 3D CRT, IMRT and three kind of RA plannings to investigate the clinical effect of RA with liver cancer case. The patient undergoing liver cancer of small volume and somewhat constant motion were selected. We performed 3D CRT, IMRT and RA plannings such as 2RA, limited triple arcs (3RA) and 3MRA with Eclipse version 8.6.15. The same dose volume objectives were defined for only CTV, PTV and body except heart, liver and partial body in IMRT and RA plannings. The steepness of dose gradient around tumor was determined by the Normal Tissue Objective function with the same parameters in place of respective definitions of dose volume objectives for the normal organs. The approach between the defined dose constraints and the practical DVH of CTV, PTV and Body was the best in 3MRA and the worst in IMRT. The DVHs were almost the same among RAs. Plans were evaluated using Conformity Index (CI), Homogeneity Index (HI) and Quality of coverage (QoC) by RTOG after prescription with dose level surrounding 98% of PTV in the respective plans. As a result, 3MRA planning showed the better favorable indices than that of the others and achieved the lowest MUs. In this study, RA planning is a technique that is possible to obtain the faster and better dose distribution than 3D CRT or IMRT techniques. Our result suggest that 3MRA planning is able to reduce the MUs further, keeping a similar or better targer dose homogeneity, conformity and sparing normal tissue than 2RA or 3RA.
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.
Kim, Jung-Shin;Kim, Hye-Young;Park, Yoo-Kyoung;Kim, Tae-Seok;Kang, Myung-Hee
Journal of Nutrition and Health
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v.36
no.9
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pp.933-941
/
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.
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.
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.
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.
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.
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.
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