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대량의 황산동 투여가 백서의 부신 및 뇌하수체에 미치는 영향에 관한 형태학적 연구

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 Morphological effect of excess copper sulfate on the adrenal gland anterior hypophysis of the rat 
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[영문] [한글] Merphological Effect of Excess Copper Sulfate on the Adrenal Gland and Anterior Hypophysis of the Rat Sang Ho Cho, M.D. Department of Medical Science, The Graduate School, Yonsei University (Directed by Prof. Dong Sik Kim, M.D. and Prof. Yoo Bock Lee, M.D.) The mechanism by which copper exerts its toxic effect on the hepatic cells in Wilson's disease is not known yet. Attempts to produce hepatic dysfunction and morphological lesions equivalent to Wilson's disease in experimental animals have been unsuccessful. Experimentally induced deposits of copper in hepatic cell generally do not produce necrosis or cirrhosis (Howell, 1959 ; McNary, 1963; Barka et al., 1964). Recently, results of many experiments on this subject suggested that sequestration of copper by lysosomes may protect hepatocytes from toxic effects of this metal (Goldfischer and Moskal, 1966; Goldfischer, 1967; Goldfischer and Sternlieb, 1968; Goldfischer et al., 1970). The corticosteroid is known to stabilize lysosome in vivo (Weissmann, 1965). According to the results of many experiments, one of the consequences of adrenalectomy or hypophysectomy in rats is an increased ceruloplasmin with a restoration of normal levels when the animals are given corticosterone (Evans and Wiederanders, 1968; Gregoriades and Sources, 1969: Evans et al., 1970). On the basis of these results, Evans and Cornatzer (1971) have considered that following adrenalectomy or hypophysectomy, bile flow was significantly decreased suggesting that adrenal steroids regulate biliary copper excretion by choleretic action. But studies of the role of the adrenals in the metabolism of copper have been concerned mainly with effect of adrenalectomy and of certain corticosteroids on the activity of plasma ceruloplasmin (El-Mofty et al., 1959; Evans and Wiederanders, 1967, 1968). Attempting to gain a better understanding of the role of the adrenals in copper metabolism, the influence of administration of excess copper on both adrenals and anterior hypophysis is examined. Materials and Methods Adult female albino rats were divided into two groups and treated as follows: Group Ⅰ: Normal control 24 rats Group Ⅱ: CuSO^^4 treated 84 rats In experimental group, 0.3 c.c. of 0.5% copper sulfate solution was given intraperitoneally per animal daily and 0.3 c.c. of distilled water was given by same method in control group. At 1st, 3rd, 5th, 7th, l0th, 15th, and 30th days, 12 rats were killed in experimental group and 6 rats in control group by exanguination. The unfixed adrenals and pituitary glands were weighed on the chemical balance in order to verify enlargement. For light microscopic examination, adrenals and liver were fixed in 10% neutral formalin and pituitary glands were fixed in Zenker's solution. They were embedded in paraffin and stained with hematoxyli-eosin. Additionally, liver sections stained with diethyldithiocarbamate stain (Howell, 1959) and pituitary sections stained with P.A.S. reaction. Sudan stain with the adrenal sections were performed. Specimens for Schultz reaction were obtained from the adrenal gland. The specimens were fixed in formol-calcium for 2 to 3 days and cut 10μ frozen sections. And then they were washed for 24 hours in several changes of distilled water, placed he sections into ferric ammonium sulfate solution for one week at 37℃ washed sections in 3 changes of acetate buffer one hour in each, rinsed quickly in distilled water, placed in 5% formalin for 10 minutes, mounted on slides, applied a drop of acetic-sulfuric acid mixture (1:1) to a cover slip and examine immediately under the microscope. Results and Summary 1) The intracellular deposition of copper was increased gradually, but neither hepatic cell necrosis nor cirrhosis were noted throughout the whole experimental period. 2) The excess amount of copper sulfate loading caused increased weight and hyperplastic changes of zona fasciculata and zona reticularis combined with increased accmulation of lipids in adrenal gland of adult rat after the administration as early as the first day. And also increased functional activity was induced. However, these hyperplastic changes and increased functional activity in adrenal gland did not progressively increase as copper loading increased. 3) In anterior hypophysis, increased weight and hyperplastic changes of beta cells were caused after the administration of the first day. But these changes did not progressively increase as copper loading increased. On the basis of the above results it is speculated that an increased amount of adrenocortical hormones as a result of adrenocortical hyperfunction, mediated by the pituitary, in excess copper loaded rats may protect the hepatic cells from the toxic effects of excess copper.
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2. Thesis / Dissertation (학위논문) > 1. College of Medicine (의과대학) > Ph.D. (박사)
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