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Effect of Dietary Selenium on the Colon Carcinogenesis in Male ICR Mice

  • Cho, Min-Haeng;Kim, Jun-Hyeong;Hue, Jin-Joo;Kang, Bong-Su;Park, Hyun-Ji;Nam, Sang-Yoon;Yun, Young-Won;Kim, Jong-Soo;Jeong, Jae-Hwang;Lee, Beom-Jun
    • Journal of Food Hygiene and Safety
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    • v.25 no.3
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    • pp.269-277
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    • 2010
  • Selenium is an essential micronutrient for normal body function and functions as an essential constituent of selenoproteins. This study was carried out to investigate effect of selenium on the formation of colonic aberrant crypt foci (ACF) and tumor formation in a mouse model. Five-week old ICR mice were acclimated for one week and fed different selenium diet (0.02, 0.1, and 0.5 ppm) for 12 weeks. Animals received three intraperitoneal injections of azoxymethane (10 mg/kg B.W. in saline for 3 weeks), followed by 2% dextran sodium sulfate in the drinking water for a week. There were four experimental groups, including a normal control group and three different selenium levels groups. After sacrifice, the total numbers of aberrant crypt (AC) and ACF were measured in the colonic mucosa after methylene blue staining. The number of tumors was noted for tumor incidence. Liver selenium concentration was measured using ICP-AES method. Gutathione peroxidase (GPx) activity was determined using a GPx assay kit in the liver and colon. TUNEL assay and proliferating cell nuclear antigen (PCNA) staining were performed to examine the cell apoptosis and cell proliferation, respectively. Immunohistochemistry of $\beta$-catenin was also performed on the mucous membrane tissue of colon. The activity of GPx in the liver and colon was decreased in the selenium-deficient diet group while it was increased in the selenium-overloaded diet group. Apoptotic positive cells were increased in the selenium-overloaded diet group but decreased in the selenium-deficient diet group. PCNA staining area was decreased in the selenium-overloaded diet group. In addition, the $\beta$-catenin protein level in the selenium-deficient diet group was increased but decreased in the selenium-overloaded diet group. These results indicate that dietary selenium might exert a modulating effect on colon cancer by inhibiting the development of ACF and colon tumor formation in this mouse model.

Evaluation of Embolization Effect of Hepatocellular Carcinoma by Hepatic Arterial Flow Study with $^{99m}Tc$-MAA SPECT (간암에서 색전술의 효과를 평가하는데 있어서 $^{99m}Tc$-MAA SPECT를 이용한 간동맥 혈류 검사의 의의)

  • Lee, Byung-Hee;Yoo, Hyung-Sik;Lee, Jong-Doo;Chung, Jin-Ill;Park, Chang-Yun;Lee, Jong-Tae
    • The Korean Journal of Nuclear Medicine
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    • v.28 no.1
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    • pp.62-68
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    • 1994
  • This study was aimed to compare the density of the functional microcirculation of hepatocellular carcinoma (HCC) with normal liver and to investigate the effect of hepatic-arterial oily chemoembolization (HAE) by radionuclide examination. Methods : Eight patients with HCC proven by biopsy in five, and clinically and radiologically in three were included. The mixture of 2 cc normal saline with three to four mCi of $^{99m}Tc$-MAA was infused through a hepatic-arterial catheter for a minute. Dynamic images were obtained at a rate of 4 sec per frame for a minute, and static images and SPECT were followed. Results : In three patients who underwent hepatic arterial angiography (HAA) alone, radioactivity was markedly increased in tumors compared to the adjacent liver immediately after infusion of $^{99m}Tc$-MAA. The ratios of tumoral and extratumoral up-take (T/E ratio) were above 6.5 (range; $6.5{\sim}l9$, mean; 12.5). In four of the five patients who under-went superselective HAE, T/E ratio were remark-ably decreased ($0.5{\sim}1.3$). The areas of embolization were better delineated in radionuclide study than in postembolization HAA. In the other one who was considered to be embolized completely on HAA, strong radiouptake in the tumor was disclosed (T/E ratio; 7.0). Conclusions : Therefore hepatic-arterial flow study with radionuclide imaging using $^{99m}Tc$-MAA can be a valuable method to assess the accurate embolization effect in HCC.

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The Comparison of Efficacy of Glutathione S-transeferase Placental Form Positive and Iron-Resistant Lesions in the Detection of Hepatocarcinogens (간발암성 물질 검색에 있어서 Glutathione S-transeferase Placental Form 양성 병소와 철 저항 병소의 유효성 비교 연구)

  • 강경선;김형진;이영순
    • Journal of Food Hygiene and Safety
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    • v.6 no.1
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    • pp.1-12
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    • 1991
  • Fischer 344 rats aged six weeks were diYided into four groups and group 1, 2, and 3 of rats were given an intraperitoneal injection of diethylnitrosamine at 200 mg/kg body weight and group 4 was given saline alone. Two weeks after beginning of the experiment, group 1 and 2 of rats were begun to feed on diets containing 0.02% 2-acetylaminofluorene as a promoter for four weeks. Three weeks after beginning of the experiment, all groups were performed partial hepatectomy. During the last two weeks, group 1 and 3 of rats were received subcutaneously 3 consecutive weekly doses of iron dextran at 0.125 ml/100 g body weight. Subcutaneous injection of iron dextran resulted in hepatic siderosis in group 1 and 3 of rats. Pre neoplastic nodules were identified histopathologically by two markers, resistance to exogenous iron accumulation and glutathione S-transeferase placental form (GST-P) activity, while early carcinogen induced foci were hardly resistant to iron accumulation and though a few lesions were identified, it could hardly be distincted from normal hepatocytes of surroundings. However, GST-P positive nodules as well as foci were clearly distincted from normal hepatic cells of surroundings. In the quantitative analysis of carcinogen-induced nodules and foci, more lesions were detected by immunohistochemical method for GST-P than by prussian blue staining for resistant to iron accumulation. It is concluded that immunohistochemical marker for GST-P is more sensitive and reliable than iron-resistance marker, and that iron-resistance is not useful marker for early detection of carcinogen-induced hepatic lesions.

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Changes of Arachidonic Acid Metabolites in Silica-Exposed Alveolar Macrophage of Rats (유리규산분진에 폭로된 흰쥐의 폐포대식세포에 있어 아라키돈산 대사산물의 변화)

  • Lim, Young;Yun, Im-Goung
    • Tuberculosis and Respiratory Diseases
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    • v.39 no.4
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    • pp.304-309
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    • 1992
  • Background: The alveolar macrophage may metabolize arachidonic acid through cyclooxygenase- and lipoxygenase- catalyzed pathways to produce a variety of metabolites of arachidonic acid. The production of these metabolites of arachidonic acid may enhance the defensive ability of the challenged lung. However, continued stimulation with the consequent production of proinflammtory metabolites of arachidonic acid, may ultimately enhance the disease process by contributing to chronic bronchoconstriction, fibrosis, and the persistent release of toxic oxygen species. Silicosis is an example of a disease process resulting from chronic exposure of the lung to foreign particles. This study was carried out to evaluate the changes of arachidonic acid metabolites from macrophages in experimental silicosis. Methods: We measured $PGE_2$, and $LTB_4$ in cultured macrophages taken from rats by radioimmunoassay at 24 and 48 hours after stimulation by silica dust, natural carbon dust, lipopolysaccharide, calcium ionophore (A23187) and medium (RPMI) as a control. For the experimental silicosis, 50 mg silica in 0.5 ml saline was administered intratracheally into the rat and grown to 20 weeks and measured $PGE_2$, and $LTB_4$ in the cultured macrophages lavaged from that rat. The used stimulants were the same as above. Results: 1) The amount of $PGE_2$ in the cultred macrophages from normal rat was significantly decreased in the group which was stimulated with silica dust for 48 hours compare with control non-stimulated group. 2) In the experimental silicosis group, $PGE_2$, release in cultured macrophages after 48 hours incubation with silica and natural carbon dust tended to be lower than those of non-stimulated group. 3) There were marked changes of $LTB_4$ in the groups of normal rats which were incubated with silica for 24, 48 hours and natural carbon for 48 hours compared with non-stimulated group. 4) In the experimental silicosis group, the release of $LTB_4$ was significantly increased macrophages cultured with silica and natural carbon dust after 24 and 48 hours incubation compared with non-stimulated group. Conclusion: The results of these studies suggest that the in vitro exposure of rat alveolar macrophge to silica and coal dust results in an alteration in alveolar macrophage metabolism of arachidonic acid that may promote an inflammatory reaction in lung tissue.

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A Study of the Capsuloligamentous Anatomy of the Glenohumeral Joint Using Magnetic Resonance Imaging and Three-Dimensional Imaging. Dynamic In Vivo Study (자기공명 영상 및 3차원 영상을 이용한 견관절 관절낭-인대의 해부학적 연구. 역동학적 생체연구)

  • Park Tae-Soo;Choi Il-Yong;Joo Kyung-Bin;Kim Sun-Il;Kim Jun-Sic;Paik Doo-Jin
    • Journal of the Korean Arthroscopy Society
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    • v.4 no.2
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    • pp.154-158
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    • 2000
  • Purpose : The purpose of this study is to demonstrate changes in the orientation ortho glenohumeral ligaments(GHL) in different degrees of abduction and rotation of the normal healthy individuals. Materials and Methods : Saline Magnetic Resonance(MR) arthrography of nine consecutive shoulders of normal healthy adults were checked. At that time, MR images were obtained in three different positions of abduction and external rotation($0^{\circ}C\;and\;0^{\circ},\;45^{\circ}C\;and\;25^{\circ}C,\;90^{\circ}$ and maximum, respectively). From a series of consecutive MRI, three-dimensional images were reconstructed after detecting the location of the middle glenohumeral ligament(MGHL) and the inferior glenohumeral ligament(IGHL) using workstation computer. Results : The shape of the MGHL was taken in double curved, and straight, and finally curved again in three different positions of the shoulder in sequence. On the other hand, the shape of the IGHL was obliquely positioned, and curvilinear, and finally straight and extended at lower part of the anterior surface of the humeral head. Conclusions : At $45^{\circ}$ of abduction and $25^{\circ}$ of external rotation, and at $90^{\circ}$ of abduction and maximal external rotation of the shoulder, the MGHL and the IGHL had the role of the most important static stabilizer of the glenohumeral joint repectively.

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Radiation Protection Effect of Blueberries in the Hematopoietic Cells of White Rats (흰쥐의 조혈세포에서 블루베리의 방사선 방호효과)

  • Lee, Jun-Haeng
    • Journal of the Korean Society of Radiology
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    • v.16 no.3
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    • pp.335-341
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    • 2022
  • The purpose of this study was to investigate the radiation protection effect of blueberries. The experimental animals used in this study were 8-week-old 21 SD male rats weighed 280-300 g. The animals were set to a normal group (A), a 5 Gy control group (B), and a 5 Gy experimental group (C) of seven rats each, and (50 mg/kg/day) of physiological saline solution of blueberries were orally administered twice a day with an oral dose of (200 mg/kg/day) for seven days and 5 Gy of radiation was irradiated in the case of groups B and C. As a result, it was identified that there was significance in white blood cells in this study (p<0.000). There was no significant difference in red blood cells or platelets. When examined in detail, among white blood cells (WBC), neutrocytes were found to be significantly different among the three groups: normal, control, and experimental groups (p<0.004). Lymphocytes were also found to be statistically significantly different among the three groups (p<0.000). Monocytes were not found to be statistically significantly different (p<0.483). When red blood cells (RBC) were examined, hemoglobin (HGB) was not found to be statistically significant different among the three groups (p<0.291). Hematocrit (HCT) was not found to be statistically significantly different among the three groups, either (p<0.564). Mean corpuscular volume (MCV) was found to be statistically significantly different among the three groups (p<0.001). Mean corpuscular hemoglobin (MCH) was also found to be statistically significantly among the three groups (p<0.028). Mean corpuscular hemoglobin concentration (MCHC) was found to be statistically significantly different among the three groups(p<0.020). Red blood cell distribution width (RDW) was not found to be statistically significantly different among the three groups (p<0.09). When platelets (PLT) were examined in detail, mean platelet volume (MpV) was found to be statistically significantly different among the three groups (MpV) (p<0.04). In conclusion, based on this study, blueberries are considered to have radiation protection effects.

The Lung Expression of Proinflammatory Cytokines, TNF-$\alpha$ and Interleukin 6, in Early Periods of Endotoxemia (내독소혈증 유발 급성폐손상에서 폐장내 Proinflammatory Cytokines 발현에 관한 고찰)

  • Moon, Seung-Hyug;Kim, Yong-Hoon;Park, Choon-Sik;Lee, Shin-Je
    • Tuberculosis and Respiratory Diseases
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    • v.45 no.3
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    • pp.553-564
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    • 1998
  • Background: The immediate hoot response to LPS is the production of proinflammatory cytokines that act as intercellular mediators in inflammatory reactions, including acute lung injury. These "early response" cytokines transmit signals from recognition cells to target or effector cells. This host response is further amplified by the expression of leukocyte chemoattractants, growth factors, and adhesion molecules, resulting in an array of proinflammatory events. This experiment was performed to define the lung origin of proinflammatory cytokines, such as TNF-$\alpha$, IL 6 in early periods of endotoxin induced acute lung injury (ALI). Method: The healthy male Sprague-Dawley, weighted 150 - 250g, were divided into saline control (NC) and endotoxemia-induced ALI (ETX-), and leukopenic endotoxemia-induced ALI (CPA-ETX-Group) which was induced by cyclophosphamide, 70 mg/kg i.p. injection. Acute lung injury was evoked by LPS, 5 mg/kg, intravenously administered. Bronchoalveolar lavage was performed at 0, 3, 6 h after LPS-treated to estimate the influx of phagocytes and concentration of total protein, and cytokines as TNF-$\alpha$ and IL 6 by a bioassy using MIT method. We also examined the localization of TNF-$\alpha$ and IL 6 protein in endotoxemia-challenged lung tissue by immunohistochemical stain (IH). Results: The total cell, macrophage and PMN count in BALF were elavated in ETX group compared to NC(p<0.05). In CPA-ETX group, total cell and macrophage count in BALF were not changed compared to NC. but PMN count was markedly reduced and it took part in less than 0.1 % of total BAL cells (p<0.01). The protein concentration in BALF were significantly increased in ETX and CPA-ETX group Compared to NC (p<0.05), but there was significant difference between ETX- and CPA-ETX group only at 6 h (p<0.05). This observation suggested that even if PMNs are involved in the pathogenesis of acute lung injury, their role cannot be viewed as essential The concentration of TNF-$\alpha$ and IL 6 in BALF was significantly increased in the ETX- and CPA-ETX group compared to NC. There was no difference between ETX- and CPA-ETX group. In IH, anti-TNF-$\alpha$- and anti-IL 6 antibody was strongly localized at interstitial monocytes and alveolar macrophages in endotoxemia-challenged lung tissue. From above point of view, activated alveolar macrophage/monocyte considered as a prominent source of proinflammatory cytokines in endotoxemia-challenged lung injury. Conclusion: The prominent source of proinflammatory cytokines in early periods of endotoxemia-induced lung injury will be the activated resident macrophages like an alveolar macrophage and interstitial monocytes. The pulmonary macrophage/monocyte will impact the initiation and continuance of lung injury without PMNs's certain inflammatory role, particularly in endotoxemia-induced acute lung injury.

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Effect of Acutely Increased Glucose Uptake on Insulin Sensitivity in Rats (단기간의 당섭취 증가가 인슐린 감수성에 미치는 영향)

  • Kim, Yong-Woon;Ma, In-Youl;Lee, Suck-Kang
    • Journal of Yeungnam Medical Science
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    • v.14 no.1
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    • pp.53-66
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    • 1997
  • Insulin resistance is a prominent feature of diabetic state and has heterogeneous nature. However, the pathogenetic sequence of events leading to the emergence of the defect in insulin action remains controversial. It is well-known that prolonged hyperglycemia and hyperinsulinemia are one of the causes of development of insulin resistance, but both hyperglycemia and hyperinsulinemia stimulate glucose uptake in peripheral tissue. Therefore, it is hypothesized that insulin resistance may be generated by a kind of protective mechanism preventing cellular hypertrophy. In this study, to evaluate whether the acutely increased glucose uptake inhibits further glucose transport stimulated by insulin, insulin sensitivity was measured after preloaded glucose infusion for 2 hours at various conditions in rats. And also, to evaluate the mechanism of decreased insulin sensitivity, insulin receptor binding affinity and glucose transporter 4 (GLUT4) protein of plasma membrane of gastrocnemius muscle were assayed after hyperinsulinemic euglycemic clamp studies. Experimental animals were divided into five groups according to conditions of preloaded glucose infusion: group I, basal insulin ($14{\pm}1.9{\mu}U/ml$) and basal glucose ($75{\pm}0.7mg/dl$), by normal saline infusion; group II, normal insulin ($33{\pm}3.8{\mu}U/ml$) and hyperglycemia ($207{\pm}6.3mg/dl$), by somatostatin and glucose infusion; group III, hyperinsulinemia ($134{\pm}34.8{\mu}U/ml$) and hyperglycemia ($204{\pm}4.6mg/dl$), by glucose infusion; group IV, supramaximal insulin ($5006{\pm}396.1{\mu}U/ml$) and euglycemia ($l00{\pm}2.2mg/dl$), by insulin and glucose infusion; group V, supramaximal insulin ($4813{\pm}687.9{\mu}U/ml$) and hyperglycemia ($233{\pm}3.1mg/dl$), by insulin and glucose infusion. Insulin sensitivity was assessed with hyperinsulinemic euglycemic clamp technique. The amounts of preloaded glucose infusion(gm/kg) were $1.88{\pm}0.151$ in group II, $2.69{\pm}0.239$ in group III, $3.54{\pm}0.198$ in group IV, and $4.32{\pm}0.621$ in group V. Disappearance rates of glucose (Rd, mg/kg/min) at steady state of hyperinsulinemic euglycemic clamp studies were $16.9{\pm}3.88$ in group I, $13.5{\pm}1.05$ in group II, $11.2{\pm}1.17$ in group III, $13.2{\pm}2.05$ in group IV, and $10.4{\pm}1.01$ in group V. A negative correlation was observed between amount of preloaded glucose and Rd (r=-0.701, p<0.001) when all studies were combined. Insulin receptor binding affinity and content of GLUT4 were not significantly different in all experimental groups. These results suggest that increased glucose uptake may inhibit further glucose transport and lead to decreased insulin sensitivity.

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Role of Growth Factors and Cytokines on Bleomycin Induced Pulmonary Fibrosis (Bleomycin 유도 폐 섬유화에 있어서 성장인자 및 Cytokine의 역할)

  • Lee, Yong-Hee;Jung, Soon-Hee;Ahn, Chul-Min;Kim, Sung-Kyu;Cho, Sang-Ho
    • Tuberculosis and Respiratory Diseases
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    • v.44 no.4
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    • pp.871-888
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    • 1997
  • Background : It is now thought that the earliest manifestation of idiopathic pulmonary fibrosis is alveolitis, that is, an accumulation of inflammatory and immune effector cells within alveolar walls and spaces. Inflammatory cells including alveolar macrophages and resident normal pulmonary tissue cells participate through the release of many variable mediators such as inflammatory growth factors and cytokines, which contribute to tissue damage and finally cause chronic pulmonary inflammation and fibrosis. This study was performed to investigate the source and distribution pattern of transforming growth factor-${\beta}_1$(TGF-${\beta}_1$), platelet derived growth factor(PDGF), basic fibroblast growth factor(bFGF), interleukin 1(IL-1), interleukin 6(IL-6), tumor necrosis factor-$\alpha$ (TNF-$\alpha$) and the role of these mediators on bleomycin(BLM)-induced pulmonary injury and fibrosis in rats. Method : Wistar rats were divided into three groups(control group, BLM treated group, BLM and vitamine E treated group). Animals were sacrificed periodically at 1, 2, 3, 4, 5, 7, 14, 21, 28 days after saline or BLM administration. The effects were compared to the results of bronchoalveolar lavage fluid analysis, light microscopic findings, immunohistochemical stains for six different mediators(TGF-${\beta}_1$, PDGF, bFGF, IL-1, IL-6 and TNF-$\alpha$) and mRNA in situ hybridization for TGF-${\beta}_1$. Results : IL-1 and IL-6 are maximally expressed at postbleomycin 1~7th day which are mainly produced by neutrophils and bronchiolar epithelium. It is thought that they induce recruitment of inflammatory cells at the injury site. The expression of IL-1 and IL-6 at the bronchiolar epithelium within 7th day is an indirect evidence of contribution of bronchiolar epithelial cells to promote and maintain the inflammatory and immune responses adjacent to the airways. TNF-$\alpha$ is mainly produced by neutrophils and bronchiolar epithelial cells during 1~5th day, alveolar macrophages during 7~28th day. At the earlier period, TNF-$\alpha$ causes recruitment of inflammatory cells at the injury site and later stimulates pulmonary fibrosis. The main secreting cells of TGF-${\beta}_1$ are alveolar macrophages and bronchiolar epithelium and the target is pulmonary fibroblasts and extracellular matrix. TGF-${\beta}_1$ and PDGF stimulate proliferation of pulmonary fibroblasts and TGF-${\beta}_1$ and bFGF incite the fibroblasts to produce extracellular matrix. The vitamine E and BLM treated group shows few positive cells(p<0.05). Conclusion : After endothelial and epithelial injury, the neutrophils and bronchiolar epithelium secrete IL-1, IL-6, TNF-$\alpha$ which induce infiltration of many neutrophils. It is thought that variable enzymes and $O_2$ radicals released by these neutrophils cause destruction of normal lung architecture and progression of pulmonary fibrosis. At the 7~28th day, TGF-${\beta}_1$, PDGF, bFGF, TNF-$\alpha$ secreted by alveolar macrophages sting pulmonary fibroblasts into proliferating with increased production of extracellular matrix and finally, they make progression of pulmonary fibrosis. TNF-$\alpha$ compares quite important with TGF-${\beta}_1$ to cause pulmonary fibrosis. Vitamine E seems to decrease the extent of BLM induced pulmonary fibrosis.

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Effect of Green Tea Extract on Healing of Contaminated Wound in Dogs (개의 피부 감염창 치유에 대한 녹차 추출물의 국소도포 효과)

  • Kim, Bo-Ram;Cheong, Jong-Tae;Park, Hyun-Jeong;Yun, Young-Min;Lee, Kyoung-Kap;Kang, Tae-Young;Kim, Jae-Hoon;Bae, Jong-Hee;Lee, Joo-Myoung
    • Journal of Veterinary Clinics
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    • v.24 no.4
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    • pp.550-556
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    • 2007
  • The purpose of this study is to assess healing effect of the green tea on Staphylococcus contaminated wound. On the back of 7 dogs, 6 full-thickness skin wounds($2cm{\times}2cm$) were made and Staphylococcus intermedius was inoculated. Each wound was applied with the 2%(experimental group I), 1%(experimental group II) extract of green tea and normal saline(control group I) after inoculation. The wound contraction rate of the experimental group I and II was higher than that of the control group in entire period. And from the $6^{th}\;to\;22^{nd}$ day, the wound contraction rate of the experimental group I and II was significantly higher than that of the control group(p<0.05). The occupation rate of wound healing in the experimental group I was higher than that of the control group from $0\;to\;9^{th}$ day except from $1^{st}\;to\;2^{nd}$ day and also higher than that of the experimental group II from $0\;to\;3^{rd}$ day except from $1^{st}\;to\;2^{nd}$ day. And the occupation rate of wound healing in the experimental group II was higher than that of the control group from $1^{st}\;to\;8^{th}$ day except from $2^{nd}\;to\;3^{rd}$ day. According to concentration of green tea extract increased, the wound contracted more vigorously in earlier period. The tensile strength of the experimental group I and II was significantly higher than that of the control group(p<0.05). And that of the experimental group I was also higher than in the experimental group II(p<0.05). The number of S. intermedius in the experimental group I and II was decreased more rapidly than that of the control group. From the $4^{th}$ to the $11^{th}$ day, the number of S. intermedius in the experimental group I was significantly lower than that of the experimental group II and the control group. And from the $4^{th}$ to the $7^{th}$ day, the number of S. intermedius in the experimental group was significantly lower than that of the control group. The histopathological findings of the experimental group I and II were similar to those of the control group on the $1^{st}\;and\;4^{th}$ day. On $14^{th}$ day, reepithelialization was completed in the experimental group I and II except the control group. Higher wound contraction rate, better bacteriocidal action, higher tensile strength and better histopathological findings were observed in the experimental group I and II than in the control group. These results suggest that the topical application of green tea extract can promote contaminated wound healing in dogs.