• Childhood Kidney Diseases
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• v.3 no.2
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• pp.130-144
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• 1999

Purpose : Long-term use of Cyclosporine(CsA) reduce renal blood flow by afferent arteriolar vasoconstriction and lead to chronic pathologic changes of CsA nephrotoxicity - 1) interstitial nephritis(IN); tubular atrophy (TA) and/or interstitial fibrosis(IF),2) arteriolopathy(AP). The Object of this study is to estimate the incidence of chronic pathologic CsA nephrotoxicity by duration of treatment and type of renal disease, relationship between histologic and clinical nephrotoxicity, and optimal duration of CsA therapy. Methods : 102 children with steroid resistant or dependent nephrotic syndrome confirmed by renal biopsy and treated with CsA from 1986 to 1997 were enrolled in this study(58 MCNS, 10 FSGS, 10 MGN, 15 $Henoch-Sch\"{o}nlein$ purpura nephritis with nephrotic syndrome (HSPN) and 9 IgA nephropathy with nephrotic syndrome(IgAN)). CsA was administered for 1yr, 1.5yr, 2yr in 24, 12, 22 MCNS patients and 2, 2, 6 FSGS patients respectively, 1yr, 2yr in MGN and 1yr in HSPN and IgAN. Sequential biopsies were done in all 102 patients after CsA treatment for evaluation of pathologic nephrotoxicity. Results : Complete remission rate was 92.2% (100% in MCNS and MGN, 80% in FSGS, 86.6% in HSPN and 55.5% in IgAN). Incidence of relapse during 6months after CsA treatment was significantly decreased compaed with relapsing spisodes during 6months before CsA treatment in MCNS(P<0.0001) and FSGS(P<0.0001). According to pathologic changes, 71 patients(69.6%) showed no pathological change, 24 patients(23.5%) showed IN and 7 patients(6.8%) showed AP. IN was 16.6%, 33.3%, 27.2% in 1, 1.5, 2 year of CsA treatment group in MCNS. AP was 0%, 16.6%, 9% in 1, 1.5, 2 year of CsA treatment group in MCNS. 14 out of 58 MCNS(24.1%) showed IN and 4 out of 58 MCNS(6.8%) showed AP. Incidence of pathologic change was significantly lower in CsA therapy of <1yr than >1yr(P=0.03). There were no significant difference of incidence of pathologic change in original renal disease, age and sex. Conclusion : Duration of CsA treatment was significant risk factor for nephrotoxicity and optimal duration seemed to be 1 year. Pathologic change due to nephrotoxicity did not correlate with deterioration of renal function and only detectable by renal biopsy.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.1 no.1
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• pp.45-55
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• 1998

Purpose: To make objective standards of small intestinal mucosal changes in cow's milk-sensitive enteropathy (CMSE) we analyzed histological changes of endoscopic duodenal mucosa biopsy specimens from normal children and patients of CMSE. Methods: We review the medical records of patients who had been admitted and diagnosed as CMSE by means of gastrofiberscopic duodenal mucosal biopsy following cow's milk challenge and withdrawal. Thirteen babies with CMSE, ranging from 14 days to 56 days of age, were studied. Five non-CMSE patients were used as control, ranging from 22 days to 72 days of age. The morphometric parameters under study were villous height, crypt zone depth, ratio of villous height to crypt zone depth, total mucosal thickness and length of surface epithelium by using H & E stained specimens under the drawing apparatus attached microscope. In addition, the numbers of lymphocytes in the epithelium and eosinophil cells in the lamina propria and epithelium were measured. Results: In the duodenal mucosal biopsy specimens in CMSE we found partial and subtotal villous atrophy with an increased number of interepithelial lymphocytes. The mean villous height($135{\pm}59\;{\mu}m$), ratio of villous height to crypt zone depth ($0.46{\pm}0.28$), total mucosal thickness ($499{\pm}56\;{\mu}m$), length of surface epithelium of small intestinal mucosa ($889{\pm}231\;{\mu}m$) in CMSE was significantly decreased compared with the control (p<0.05). The mean crypt zone depth ($311{\pm}65\;{\mu}m$) was significantly greater than the control ($188{\pm}24\;{\mu}m$)(p<0.05). Infiltration of interepithelial lymphocytes ($34.1{\pm}10.5$) were significantly greater than the control ($13.6{\pm}3.6$)(p<0.05). The number of eosinophil cells in both lamina propria and epithelium was no significant differences between groups (p>0.05). The small intestinal mucosa in treated CMSE showed much improved enteropathy of villous height, crypt zone depth, interepithelial lymphocytes compared with the control as well as untreated CMSE. Conclusion: Quantitation of mucosal dimensions confirmed the presence of CMSE. It seems to be a limitation in the capacity of crypt cells to compensate for the loss of villous epithelium in CMSE. Specimens obtained by gastrofiberscopic duodenal mucosal biopsy were suitable for morphometric diagnosis of CMSE. Improvement of CMSE also can be confirmed histologically after the therapy of protein hydrolysate.

• Korean Journal of Agricultural Science
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• v.17 no.1
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• pp.34-44
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• 1990

The study was carried out to elucidate the effects of ovarian function on the thyroid gland, adrenal gland and uterus in female rats. One hundred and forty-four mature female rats were allotted into the three groups ; ovariectomized group, estradiol treated group and intact control group. The ovaries of 48 heads of rats were completely removed. Forty eight heads of rats were administered with $200{\mu}g$ of estradiol benzoate every 48 hours. Serum estradiol-$17{\beta}$ and progesterone levels were determined with radioimmunoassay method at 3, 6, 12, 24 hours and 5, 10, 15 days after treatment. The rats were necropsied to measure weights of thyroid gland, adrenal gland and uterus and to examine the histological changes in the organs. The results obtained were as follows ; 1. Serum estradiol-$17{\beta}$ levels were rapidly decreased below 27.20pg/ml 18 hours after ovariectomy. In estradiol treated rats the levels were rapidly increased 18 hours after treatment, but thereafter slowly decreased. The significant differences in the estradiol level were found between the group at every observation time. 2. Serum progesterone levels were significantly decreased after ovariectomy and estradiol injection. The lowest level was found in the group of ovariectomized rats. 3. The weights of thyroid glands decreased in ovariectomized rats rather than in intact rats 5 days after treatment. The weights tended to increase after estradiol injection but significant differences between the groups were seen on 10th and 15th days. 4. In the histological findings of thyroid glands, follicular epithelial cells were changed to be squamous 5 days after ovariectomy and accompanied pyknosis 10 days and karyorrhexis 15 days after ovariectomy. On the contrary follicular epithelial cells were changed to be columnar with hypertrophy 10 days after estradiol injection. 5. The significant differences in adrenal gland weights were recognized between all the groups 5 and 15 days after treatment in ovariectomized rats were lighter than intact rats and the adrenal gland weights were rather heavier in estradiol treated rats. 6. The days after ovariectomy the adrenal glands were atrophied accompanying with pyknosis in the cortical cells of zona fasciculata. The cells in zona fasciculata and zona reticularis started to hypertrophy 5 days after estradiol injection, but no changes were found in the zona glomerulosa of adrenal cortex and in the adrenal medulla. 7. The significant differences in uterus weights were recognized between the groups at each observation time. After ovariectomy the uterus weights decreased rapidly but after estradiol injection they increased rapidly. 8. Through histological examination of uterus, the atrophy and degeneration started to occur in endometrium and lamina propria 12 hours after ovariectomy, and in myometrium one day after ovariectomy, and the changes progressed rapidly after that. On the contrary, the myometrium was proliferated and hypertrophied from 12 hours after estradiol-$17{\beta}$ injection.

• Korean Journal of Agricultural Science
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• v.19 no.1
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• pp.51-64
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• 1992

This experiment was carried out to elucidate the effects of the thyroid function on lactation in female rats. One hundred and five female rats, whose body weight was approximately 250g with normal parturition, were divided into 3.5 THY, 35 PTU, and 35 CON. The $30{\mu}g$ L-thyroxine per rat was administered subcutaneously for the THY group with 3-days intervals arid 0.03% propylthiouracil solution was drunk for the PTU group. After the treatments body weight, thyroid weights and prolactin levels in serum, and histological changes in thyroid and mammary gland were investigated for 3 weeks with 3-days interval. The results obtained were as follows 1. The body weights of PTU group were lower than those of CON arid THY groups. The changes in body weights were significant between 3 and 6 days and between 15 and 18 days. 2. Differences in thyroid weight among the groups were significant after 9 days, The thyroid weights of PTU group were much higher than those of CON and THY group. 3. The follicular epithelia of PTU group after 6 days showed cuboidal phenomena which were accompanied by hypertrophy and hyperplasia, and this phenomena continued until post weaning period. Those of THY group after 9 days showed a squamous degeneration together with pyknosis. 4. The prolactin concentrations of THY group were higher than the other groups after 12 days. and those of CON group were higher than the others after 18 days. However, those of PTU group were lower all through the period. 5. The secretary epithelial cells of THY and CON groups became cuboidal after 12 days, but after 15 days the differentiation of mammary tissue was progressing in THY group faster than CON group. The degeneration of mammary tissue were observed in PTU group as time lapses, so after 15 days the exfoliation of secretory epithelium and atrophy of alveolus were recognized. 6. The body weights of offspring for all experimental groups were increasing as time lapses, but the values for PTU group were markedly lower than the others.

• The Journal of Korean Obstetrics and Gynecology
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• v.30 no.4
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• pp.18-44
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• 2017

Purpose: The object of this study was to observe the anti-climacterium activity of Gagamguibiondam-tang (GGOT) on ovariectomized (OVX) rats, a well-documented rodent models resembles with women postmenopausal climacterium symptoms, as including cardiovascular diseases, obesity, hyperlipidemia, osteoporosis, organ steatosis and mental disorders. Methods: In this study, anti-climacteric effects were evaluated separated into three categories; 1) anti-obese, 2) anti-uterine atrophy and 3) anti-osteoporotic effects. Five groups were used (8 rats in each group); sham control, OVX control, GGOT 500, 250 and 125 mg/kg administered groups. Twenty-eight days after bilateral OVX surgery, GGOT were orally administered, once a day for 84 days, and then the changes on the body weight and gain during experimental periods, serum estradiol levels, abdominal fat pad and uterus weights with histopathology of abdominal fat pads (total thickness and mean adipocyte diameters) and uterus (total, epithelial and mucosal thickness, percentages of uterine gland regions) for anti-obese and estrogenic effects. In addition, femur, tibia and fourth or fifth lumbar vertebrae (L4 or L5) wet, dry and ash weights, mineral density (BMD), bone strength (failure load), serum osteocalcin and bone specific alkaline phosphatase (bALP) contents, histological and histomorphometrical analyses - bone mass and structure with bone resorption, were monitored for anti-osteoporosis activity. Results: As a result of OVX, noticeable increases of body weight and gains, food and water consumption, weights of abdominal fat pad deposited in dorsal abdominal cavity, serum osteocalcin levels were demonstrated in this experiment with decrease of uterus, femur, tibia and L5 weights, serum bALP and estradiol levels. In addition, marked hypertrophic changes of adipocytes located in deposited abdominal fat pads, uterine disused atrophic changes, decreases of bone mass and structures of femur, tibia and L4 were also observed in OVX control rats with dramatic increases of bone resorption markers, the Ocn and OS/BS at histopathological and histomorphometrical analysis in this study as compared with sham-operated control rats, suggesting the estrogen-deficient climacterium symptoms - obese and osteoporosis were induced by OVX, respectively. However, these estrogen-deficient climacterium symptoms induced by bilateral OVX in rats were significantly inhibited by 84 days of continuous oral treatment of GGOT 500, 250 and 125 mg/kg, respectively. Especially, GGOT 500, 250 and 125 mg/kg showed clear dose-dependent inhibitory activities on the OVX-induced climacterium signs. Conclusion: The results suggest that oral administration of GGOT 500, 250 and 125 mg/kg has clear dose-dependent favorable anti-climacterium effects - estrogenic, anti-obese and anti-osteoporotic activities in OVX rats in this experiment.