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Preclinical Study of DA-5018, a Non-narcotic Analgesic Agent

  • Kim, Soon-Hoe
    • Proceedings of the PSK Conference
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    • 2000.04a
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    • pp.70-81
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    • 2000
  • DA-5018 is a synthetic capsaicin derivative under development as a non-narcotic a analgesic ag$\varepsilon$nt. DA-50 18 showed a potent analgesic activity against acute and chronic pain m model(Tablel, 2.), but it had a narrow margin of safety. DA-5018 did not bind to opioid(${\kappa}, {\delta}, {\mu}$), NKl, CGRP receptors in vitro and its analgesic effect was not antagonized by naloxone, a and it did not develop analgesic tolerance. In addition DA-5018 had no inhibitory effects against c cyclooxygenase and 5-lipooxygenase activities. DA-5018 significantly increased the relcase of substance P from the slices of the rat spinal cord. These results suggest that DA-50 18 is not a narcotic nor aspirin-like analgesic and the release of substance P is one of analgesic mechanism of action of DA-5018. We found that DA-5018 was almost ten times more potent and was at l least IOO-times less irritable compared to capsaicin. Accordingly development of topical formula was adopted. Topical formula was desiged and screened by flux test of DA-5018 using hairless mouse skin and several formulas were selected. With these topical formulas we a assessed the analgesic efficacy and carried out the toxicity, skin irritation and pharmacokinetic studies. In streptozotocin-induced hyperalgesic rat and 50 % galactose-fed hyperalgesic rat as diabetic pain models, DA-5018 cream increased the pain thresh이ds up to 77.0% and 24.4% respectively, while Zostrix-HP(capsaicin cream) incr$\varepsilon$as cd by 65.9% and 21.0%. DA-5018 c cream showed a good analgesic effect as welI in FCA-induced arthritic rat. DA-5018 cream did not show any toxicological signs in acute and chronic toxicity test and had little skin irritation in car swclIing and scratching t$\varepsilon$st. Pharmacokinetics of DA-50 18 were studied after topical application of ${14}^C$-Iabelled or unlabelIed DA-5018 cream. Plasma and skin concentrations c except applied skin wcre below the dctection limit and after 7-day cummulative application, plasma concentrations were also below detection limit DA-50 18 may have an advantag$\varepsilon$ ov$\varepsilon$r c capsaicin and is now being developed as a topical agent for the treatment of pains. DA-50 18 cream was approved for Korean IND and is now under a Phase II clinical study for arthritic pain a after finising Phase I study. DA-50 18 was also liscensed out to Stiefel Company in America in

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The Prognostic Significance of Tumor Angiogenesis and Expression of Vascular Endothelial Growth Factor in Papillary Carcinomas of the Thyroid Gland (갑상선 유두상 암종에서 종양혈관형성 및 혈관내피성장인자 발현의 예후인자적 의의)

  • Kang Hun-Dae;Kim Seong-Bae;Kim Tae-Hyun;Oh Sang-Hoon;Yoon Hye-Kyong;Kim Sang-Hyo
    • Korean Journal of Head & Neck Oncology
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    • v.20 no.2
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    • pp.135-142
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    • 2004
  • Objectives: The purpose of this study was to evaluate for prognostic significance of VEGF expression and tumor angiogenesis in papillary carcinomas of the thyroid. Materials and Methods: The materials were 79 cases of papillary thyroid carcinomas, and age, sex, tumor size, multiplicity of tumor, capsular invasion, lymph node metastasis, recurrence, TNM stage, DeGroot stage and AMES scale were evaluated. An immunohistochemical stains for CD 34 to estimate microvessel density (MVD), and VEGF were done. MVD was defined as an average count of vessels per ${\times}400$ power field in the most vascularized area. VEGF expression was interpreted as 1+ and 2+ according to staining intensity and percentages of positive cells. Results: Mean score of MVD was $39.7{\pm}16.9.$ MVD were significantly higher in cases with capsular invasion (p=0.0001), lymph node metastasis (p=0.0001), TNM stage III (p=0.0022), DeGroot stage III (p=0.0163) and high risk group by AMES scale (p=0.0001). VEGF 2+ expression rate was significantly increased in cases with capsular invasion and lymph node metastasis (p=0.0006, p=0.0013), and in cases with TNM stage III, DeGroot stage III and high risk group by AMES scale (p=0.0236, p=0.0003, p=0.0293). In VEGF 2 + expression group, MVD was significantly higher than in VEGF 1 + group (p=0.0008), and MVD showed positive relation to VEGF 2 + expression (r=0.4616). Conclusion: VEGF expression and high MVD were significantly correlated to capsular invasion, lymph node metastasis, TNM stage III, DeGroot stage III and high risk group by AMES scale. The expression of VEGF and high MVD could be considered to be one of prognostic factor in papillary thyroid carcinomas.

Effects of the Combined-administration of Ginseng Radix Rubra and Vitis Fructus on Immune Response (홍삼(紅蔘).포도(葡萄) 병용투여가 면역반응에 미치는 영향)

  • Park, Hun;Lee, Kyung-A;Jeon, Yong-Keun;Leem, Jae-Yoon;Shin, Tae-Yong;So, June-No;Ahn, Mun-Saeng;Kwon, Jin;Eun, Jae-Soon
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.20 no.2
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    • pp.420-427
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    • 2006
  • Immunological activities of the combined-administration of Ginseng Radix Rubra and Vitis Fructus were examined in C57BL/6 mice. Ginseng Radix Rubra and Vitis Fructus were extracted with distilled water or 40% ethyl alcohol. Ginseng Radix Rubra water extracts (GW), the mixture (1:1) of Ginseng Radix Rubra and Vitis Fructus water extracts [GVW(1:1)], the mixture (1:3) of Ginseng Radix Rubra and Vitis Fructus water extracts [GVW(1:3)], 40% ethyl alcohol extracts of Ginseng Radix Rubra (GE), the mixture (1:1) of Ginseng Radix Rubra and Vitis Fructus 40% ethyl alcohol extracts [GVE(1:1)] and the mixture (1:3) of Ginseng Radix Rubra and Vitis Fructus 40% ethyl alcohol extracts [GVE(1:3)] were administered p.o. once a day for 7 days, respectively. GVW(1:1) and GVW(1:3) decreased the viability of thymocytes increased by GW, but GVE(1:1) and GVE(1:3) increased the viability of thymocytes decreased by GE. GVW(1:1) and GVW(1:3) increased the viability of splenocytes decreased by GW or GE. Also, GVW(1:1) and GVE(1:1) enhanced the population of helper T cell in thymocytes, and GVE(1:1) and GVE(1:3) decreased the population of cytotoxic T cells increased by GE. Furthermore, GVW(1:1), GVW(1:3), GVE(1:1) and GVE(1:3) enhanced the population of $B220^+$ cells decreased by GW or GE, and decreased the population of $Thyl^+$ cells increased by GW or GE, and decreased the population of splenic $CD4^+$ cells increased by GW or GE. In addition, GVW(1:1) and GVW(1:3) decreased the phagocytic activity and the production of nitric oxide in peritoneal macrophages increased by GW, but GVE(1:1) and GVE(1:3) enhanced the phagocytic activity and the production of nitric oxide in peritoneal macrophages decreased by GE. These results suggest that Vitis Fructus has an regulative action on immune response of Ginseng Radix Rubra.

A case of fused thoracic vertebrae, and lumbar vertebrae, sacrum and ilium of African elephant (Loxodonta africana) were fused one another partially (아프리카코끼리(Loxodonta africana)의 흉추골유합과 요추골, 천골 및 장골이 유합된 1례)

  • Kim, Chong-sup;Won, Chung-kil;Cho, Gyu-hen;Cho, Kyu-woan;Park, Joong-suk;Rho, Gyu-jin
    • Korean Journal of Veterinary Research
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    • v.42 no.2
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    • pp.131-136
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    • 2002
  • The vertebrae of female African elephant (Loxodonta africana) of twenty-eight years old were observed macroscopically. The result was summarized as follows; the vertebral formula of African elephant was $C_7$ $T_{21}$ $L_3$ $S_4$ $Cd_{21}$. The total length of the vertebral column removed intervertebreal disks was 353 cm. The length of each segment of vertebral column was 44 cm in cervical, 142 cm in thoracic, 21 cm in lumbar, 27 cm in sacral and 119 cm in caudal vertebrae. The 17th and 18th thoracic vertebrae (T) were partially fused each other in four parts: the transverse processes of 17th and 18th T, caudal articular process of 17th T and cranial articular process of 18th T, left mammilary process of 18th T and left transverse process of 17th T, and vertebral arch of 17th and 18th T, respectively. Others partial fusions also observed among the third luwbar, sacrum and ilium. These were in between transverse process of third lumbar vertebra and cranial parts of wing of sacrum, lateral part of sacrum and tuber sacrale, respectively. The sternum was consisted of three pieces; one is a part of anterior prestemum, two is the part from caudal demifacet at second facet to cranial demifacet at third facet in middle mesosternum, which is divided vertically into an half at second and third facets, respectively, and the last is the part between caudal demifacet of third facet in middle mesosternum and the posterior xiphisternum. There are 21 pairs of ribs, six sternal, ten asternal ribs and the last five being floating ribs.

혐기성 슬러지를 이용한 디젤오염토양의 분해

  • 박현철;이태호;박태주
    • Proceedings of the Korean Society of Soil and Groundwater Environment Conference
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    • 2003.09a
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    • pp.298-301
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    • 2003
  • 생물학적 토양오염 복원기술은 산소와 영양염류를 오염토양에 공급하여 호기성 미생물의 대사작용을 자극함으로써 유류를 생분해 하는 방법으로 널리 사용되고 있다. 유류에 오염된 토양은 혐기성 상태인 경우가 대부분이기 때문에, 호기성 미생물을 이용하기 위해서는 충분한 산소를 공급하여야 하므로 운전비가 많이 드는 단점이 있다. 최근에는 혐기성 미생물을 이용하여 유류오염 토양을 정화하는 방법이 보고되고 있다. 혐기성 생분해 방법은 다소 분해 속도는 느리지만 산소를 공급하지 않기 때문에 경제적인 유류오염토양 복원 방법으로 주목받고 있다. 본 연구에서는 디젤을 사용하여 인위적으로 10000 mg/kg.TPH soil의 농도로 오염시킨 토양 50g을 100$m\ell$ 용적의 vial에 주입하고 하수처리장의 혐기성 소화조 슬러지를 15$m\ell$, 30$m\ell$을 주입하여 배양하였으며 TPH의 분해량과 CH$_4$$CO_2$ 발생량을 측정하였다. vial의 기상을 $N_2$가스로 치환함으로써 혐기성 상태가 되도록 하였으며, 35$^{\circ}C$에서 90일간 배양하였다. 그 결과, 슬러지를 주입하지 않은 대조군의 경우에는 TPH의 분해가 거의 없었지만, 슬러지를 주입한 경우에는 TPH(Total Petroleum Hydrocarbon)농도가 55% 제거된 것으로 나타났다. TPH의 분해는 CH$_4$$CO_2$ 발생량과 밀접한 상관관계를 보였다. 본 연구의 결과로부터 하수처리장의 혐기성 소화조 슬러지를 이용한 유류오염 토양의 복원 가능성을 확인할 수 있었다.양에서 유동 가능성이 있는 중금속만을 추출하였다. 분석실험은 토양의 Cd2+ 와 Pb2+를 대상으로 행하여졌으며, 여러 토양에서 추출 분석한 결과를 EDTA분석결과와 비교하였다. 실험결과, 중금속은 매우 신속하게 고분자 자성체와 결합하였고, 그 후 자성체를 외부 자장으로 모은 후 산으로 용해시키고, 결합된 중금속은 Graphite furnace AAS로 분석함으로써 빠르고 효율적으로 분석실험을 수행할 수 있음을 알 수 있었다. 한편, 실험에서 나타난 수치들을 비교 검토한 결과 토양 분석시 sandy soil에서는 자성체를 이용한 분석이 EDTA에 의한 방법보다 더 높은 추출도를 보인 반면, silt 함량이 많은 토양의 경우에서 EDTA분석에서 더 높은 중금속 추출도를 보였다.s 중에서 490nm와 555nm의 복합밴드를 포함하는 OC2 알고리즘(ocean color chlorophyll 2 algorithm)을 사용하는 것이 OC2 series 및 OC4 알고리즘보다 좋은 추정 값을 도출할 수 있을 것으로 기대된다.환경에서는 5일에서 7월에 주로 이 충체의 유충이 발육되고 전파되는 것으로 추측되었다.러 가지 방법들을 적극 적용하여 금후 검토해볼 필요가 있을 것이다.잡은 전혀 삭과가 형성되지 않았다. 이 결과는 종간 교잡종을 자방친으로 하고 그 자방친의 화분친을 사용할 때만 교잡이 이루어지고 있음을 나타내고 있다. 따라서 여교잡을 통한 종간잡종 품종육성 활용방안을 금후 적극 확대 검토해야 할 것이다하였다.함을 보이고 있다.X> , ZnCl$_{3}$$^{-}$같은 이온과 MgCl$^{+}$, MgCl$_{2}$같은 이온종을 형성하기 때문인것 같다. 한편 어떠한 용리액에서

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Correlation between Magnifying Narrow-band Imaging Endoscopy Results and Organoid Differentiation Indicated by Cancer Cell Differentiation and its Distribution in Depressed-Type Early Gastric Carcinoma

  • Tatematsu, Hidezumi;Miyahara, Ryoji;Shimoyama, Yoshie;Funasaka, Kohei;Ohno, Eizaburou;Nakamura, Masanao;Kawashima, Hiroki;Itoh, Akihiro;Ohmiya, Naoki;Hirooka, Yoshiki;Watanabe, Osamu;Maeda, Osamu;Ando, Takafumi;Goto, Hidemi
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.5
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    • pp.2765-2769
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    • 2013
  • Background: A close association between patterns identified by magnifying narrow-band imaging (M-NBI) and histological type has been described. M-NBI patterns were also recently reported to be related to the mucin phenotype; however, detials remain unclear. Materials and Methods: We investigated the cellular differentiation of gastric cancer lesions, along with their mucosal distribution observed by M-NBI. Ninety-seven depressed-type early gastric cancer lesions (74 differentiated and 23 undifferentiated adenocarcinomas) were visualized by M-NBI. Findings were divided into 4 patterns based on abnormal microvascular architecture: a chain loop pattern (CLP), a fine network pattern (FNP), a corkscrew pattern (CSP), and an unclassified pattern. Mucin phenotypes were judged as gastric (G-type), intestinal (I-type), mixed gastric and intestinal (M-type), and null (N-type) based on 4 markers (MAC5AC, MUC6, MUC2, and CD10). The relationship of each pattern of microvascular architecture with organoid differentiation indicated by cancer cell differentiation and its distribution in each histological type of early gastric cancer was investigated. Results: All CLP and FNP lesions were differentiated. The cancer cell distribution showed organoid differentiation in 84.2% (16/19) and 61.1% (22/36) of the two types of lesions, respectively, and there was a significant difference from the unclassified pattern with organoid differentiation (p<0.001). Almost all (94.7%; 18/19) CSP lesions were undifferentiated, and organoid differentiation was observed in 72.2% (13/18). There was a significant difference from the unclassified pattern with organoid differentiation (p<0.05). Conclusions: Cellular differentiation and distribution are associated with microvascular architecture observed by M-NBI.

Butyrate and taurine exert a mitigating effect on the inflamed distal intestine of European sea bass fed with a high percentage of soybean meal

  • Rimoldi, Simona;Finzi, Giovanna;Ceccotti, Chiara;Girardello, Rossana;Grimaldi, Annalisa;Ascione, Chiara;Terova, Genciana
    • Fisheries and Aquatic Sciences
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    • v.19 no.10
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    • pp.40.1-40.14
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    • 2016
  • Background: Due to the paucity of oceanic resources utilized in the preparation of diets for cultured fish, commercial feed producers have been trying to replace fishmeal (FM) using alternative protein sources such as vegetable protein meals (VMs). One of the main drawbacks of using VMs in fish feed is related to the presence of a variety of anti-nutritional factors, which could trigger an inflammation process in the distal intestine. This reduces the capacity of the enterocytes to absorb nutrients leading to reduced fish growth performances. Methods: We evaluated the mitigating effects of butyrate and taurine used as feed additives on the morphological abnormalities caused by a soybean meal (SBM)-based diet in the distal intestine of sea bass (Dicentrarchus labrax). We used three experimental diets, containing the same low percentage of FM and high percentage of SBM; two diets were supplemented with either 0.2% sodium butyrate or taurine. Histological changes in the intestine of fish were determined by light and transmission electron microscopy. Infiltration of $CD45^+$ leucocytes in the lamina propria and in the submucosa was assessed by immunohistochemistry. We also quantified by One-Step Taqman$^{(R)}$ real-time RT-PCR the messenger RNA (mRNA) abundance of a panel of genes involved in the intestinal mucosa inflammatory response such as $TNF{\alpha}$ (tumor necrosis factor alpha) and interleukins: IL-8, IL-$1{\beta}$, IL-10, and IL-6. Results: Fish that received for 2 months the diet with 30% soy protein (16.7% SBM and 12.8% full-fat soy) developed an inflammation in the distal intestine, as confirmed by histological and immunohistochemistry data. The expression of target genes in the intestine was deeply influenced by the type of fish diet. Fish fed with taurine-supplemented diet displayed the lowest number of mRNA copies of IL-$1{\beta}$, IL-8, and IL-10 genes in comparison to fish fed with control or butyrate-supplemented diets. Dietary butyrate caused an upregulation of the $TNF{\alpha}$ gene transcription. Among the quantified interleukins, IL-6 was the only one to be not influenced by the diet. Conclusions: Histological and gene expression data suggest that butyrate and taurine could have a role in normalizing the intestinal abnormalities caused by the SBM, but the underling mechanisms of action seem different.

Characteristics of InGaAs/GaAs/AlGaAs Double Barrier Quantum Well Infrared Photodetectors

  • Park, Min-Su;Kim, Ho-Seong;Yang, Hyeon-Deok;Song, Jin-Dong;Kim, Sang-Hyeok;Yun, Ye-Seul;Choe, Won-Jun
    • Proceedings of the Korean Vacuum Society Conference
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    • 2014.02a
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    • pp.324-325
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    • 2014
  • Quantum wells infrared photodetectors (QWIPs) have been used to detect infrared radiations through the principle based on the localized stated in quantum wells (QWs) [1]. The mature III-V compound semiconductor technology used to fabricate these devices results in much lower costs, larger array sizes, higher pixel operability, and better uniformity than those achievable with competing technologies such as HgCdTe. Especially, GaAs/AlGaAs QWIPs have been extensively used for large focal plane arrays (FPAs) of infrared imaging system. However, the research efforts for increasing sensitivity and operating temperature of the QWIPs still have pursued. The modification of heterostructures [2] and the various fabrications for preventing polarization selection rule [3] were suggested. In order to enhance optical performances of the QWIPs, double barrier quantum well (DBQW) structures will be introduced as the absorption layers for the suggested QWIPs. The DBWQ structure is an adequate solution for photodetectors working in the mid-wavelength infrared (MWIR) region and broadens the responsivity spectrum [4]. In this study, InGaAs/GaAs/AlGaAs double barrier quantum well infrared photodetectors (DB-QWIPs) are successfully fabricated and characterized. The heterostructures of the InGaAs/GaAs/AlGaAs DB-QWIPs are grown by molecular beam epitaxy (MBE) system. Photoluminescence (PL) spectroscopy is used to examine the heterostructures of the InGaAs/GaAs/AlGaAs DB-QWIP. The mesa-type DB-QWIPs (Area : $2mm{\times}2mm$) are fabricated by conventional optical lithography and wet etching process and Ni/Ge/Au ohmic contacts were evaporated onto the top and bottom layers. The dark current are measured at different temperatures and the temperature and applied bias dependence of the intersubband photocurrents are studied by using Fourier transform infrared spectrometer (FTIR) system equipped with cryostat. The photovoltaic behavior of the DB-QWIPs can be observed up to 120 K due to the generated built-in electric field caused from the asymmetric heterostructures of the DB-QWIPs. The fabricated DB-QWIPs exhibit spectral photoresponses at wavelengths range from 3 to $7{\mu}m$. Grating structure formed on the window surface of the DB-QWIP will induce the enhancement of optical responses.

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Combined Trial of Fish Oil and Exercise Training Prevents Impairment in Insulin Action on Glucose Transport of Skeletal Muscle Induced by High-Fat Diet in Rats

  • Lee, Ji-Hyun;Kim, Jong-Yeon;Kim, Yong-Woon;Park, So-Young;Youn, Woon-Ki;Jang, Eung-Chan;Park, Deok-Il;Kim, Suck-Jun;Kim, Eun-Jung;Lee, Suck-Kang
    • The Korean Journal of Physiology and Pharmacology
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    • v.4 no.2
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    • pp.91-97
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    • 2000
  • The purpose of the present study was to determine the preventive effects of combined interventional trial of fish oil treatment and exercise training on insulin resistance of skeletal muscle in high-fat fed rats. Male Wistar rats were randomly divided into chow diet (CD), high-fat diet (HF), high-fat diet with fish oil (FO), high-fat diet with exercise training (EX), and FO+EX groups. The rats in control group were fed chow diet containing, as percents of calories, 58.9% carbohydrate, 12.4% fat, and 28.7% protein. High-fat diet provided 32% energy as lard, 18% as corn oil, 27% as carbohydrate and 23% as casein. The fish oil diet had the same composition as the high fat diet except that 100 g menhaden oil was substituted for corn oil. Insulin sensitivity was assessed by in vitro glucose transport in the soleus muscle after diet treatment and treadmill running for 4 weeks. While the FO or EX only partially prevented insulin resistance on glucose transport and visceral obesity induced by high-fat diet, these interventions completely corrected hyperinsulinemia and hyperglycemia from the high-fat diet. The rats in the FO+EX showed normalized insulin action on glucose transport, plasma chemicals and visceral fat mass. Insulin-mediated glucose transport was negatively associated with total visceral fat mass (r=-0.734; p<0.000), plasma triglyceride (r=-0.403; p<0.05) and lepin (r=-0.583; p<0.001) concentrations with significance. Multiple stepwise regression analysis showed that only total visceral fat mass was independently associated with insulin-mediated glucose transport (r=-0.668; p<0.000). In conclusion, combined interventional trial of FO+EX recovered insulin resistance on glucose transport of skeletal muscle induced by high-fat diet. Visceral fat mass might be more important factor than plasma TG and leptin to induce insulin resistance on glucose transport of skeletal muscle in high-fat fed rats.

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Medico-Legal Consideration of Hemopneumothorax - Closing Claim Study- (${\cdot}$기흉과 관련된 의료법학적 문제에 대한 고찰 -종결된 사건을 중심으로-)

  • Bae, Hyu-Na;Cheon, Young-Jin
    • Journal of Chest Surgery
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    • v.39 no.2 s.259
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    • pp.117-126
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    • 2006
  • Background: The purpose of this study is to describe the characteristics of malpractice claims related to hemopneumothorax and to identify the causes and potential preventability of such claims. Material and Method: A retrospective study was performed by reviewing the records in the Lawnb website and Lx CD-rom: the records on closed malpractice claims involving hemopneumothorax were abstracted from the files available for analysis. The records were reviewed and were analysed to determine the etiology of hemopneumothorax, patient age, results of lawsuit and indemnity payment, underlying diseases, cause of death or complications, and the factors associated with a successful defense. Result: Seven closed claim involving hemopneumothorax were founded in the data for malpractice. Three claims were supreme court decision, one was a high court decision and three claims were district court decision. The most common cause of death was tension pneumothorax. Four of which resulted in indemnity payments. Conclusion: While malpractice claims involving hemopneumothorax were uncommon, they resulted in a high rate and amount of indemnity payments. Claims are more common in pediatric patients. In case of iatrogenic hemopneumothorax, post-procedural X-ray can improve patient outcome and is also associated with decreased indemnity risks. Informed consent is also important.