• 한국환경성돌연변이발암원학회지
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• 제23권4호
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• pp.131-134
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• 2003

There are significant differences in the extent of drug interactions between subjects. The influence of the genetic make up of drug metabolizing enzyme activities (CYP3A5, CYP2C19 and UDP-glucuronosyl transferase) on the pharmacokinetic drug interaction potential were studied in vivo. Nineteen healthy volunteers were grouped with regard to the $CYP3A5^{*}3$ allele, into homozygous wild-type (CYP3A5^{*}1/1^{*}1$, n=6), heterozygous $(CYP3A5^{*}1/^{*}3$, n=6), and homozygous variant-type $(CYP3A5^{*}3/^{*}3$, n=7) subject groups. The pharmacokinetic profile of intravenous midazolam was characterized before and after itraconazole administration (200 mg once daily for 4 days), and also following rifampin pretreatment (600 mg once daily for 10 days), with a washout period of 2 weeks in between. For omeprazole and moclobemide pharmacokinetic interaction study 16 healthy volunteers were recruited. The volunteer group comprised 8 extensive metabolizers and 8 poor metabolizers of CYP2C19, which was confirmed by genotyping. Subjects were randomly allocated into two sequence groups, and a single-blind, placebo-controlled, two-period crossover study was performed. In study I, a placebo was orally administered for 7 days. On the eighth morning, 300 mg of moclobemide and 40 mg of placebo were coadministered with 200 mL of water, and a pharmacokinetic study was performed. During study n, 40 mg of omeprazole was given each morning instead of placebo, and pharmacokinetic studies were performed on the first and eighth day with 300 mg of moclobemide coadministration. In the UGT study pharmacokinetics and dynamics of 2 mg intravenous lorazepam were evaluated before and after rifampin pretreatment (600 mg once daily for 10 days), with a washout period of 2 weeks in between. The subjective and objective pharmacodynamic tests were done before and 1, 2, 4, 6, 8, and 12 hrs after lorazepam administration. The pharmacokinetic profiles of midazolam and of its hydroxy metabolites did not show differences between the genotype groups under basal and induced metabolic conditions. However, during the inhibited metabolic state, the $CYP3A5^{*}3/^{*}3$ group showed a greater decrease in systemic clearance than the $CYP3A5^{*}1/^{*}1$ group $(8.5\pm3.8$ L/h/70 kg vs. $13.5\pm2.7$ L/h/70 kg, P=0.027). The 1'-hydroxymidazolam to midazolam AUC ratio was also significantly lower in the $CYP3A5^{*}3/^{*}3$,/TEX> group $(0.58\pm0.35,$ vs. $1.09\pm0.37$ for the homozygous wild-type group, P=0.026). The inhibition of moclo-bemide metabolism was significant in extensive metabolizers even after a single dose of omeprazole. After daily administration of omeprazole for 1 week, the pharmacokinetic parameters of moclobemide and its metabolites in extensive metabolizers changed to values similar to those in poor metabolizers. In poor meta-bolizers, no remarkable changes in the pharmacokinetic parameters were observed. The area under the time-effect curves of visual analog scale(VAS), choice reaction time, and continuous line tracking test results of lorazepam was reduced by 20%, 7%, 23% respectively in induced state, and in spite of large interindividual variablity, significant statistical difference was shown in VAS(repeated measures ANOVA, p=0.0027).

• 한국식품영양과학회지
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• 제37권12호
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• pp.1554-1559
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• 2008

STZ를 이용한 당뇨유발은 독성물질에 의한 췌장 세포의 파괴를 인위적으로 유도시킴으로써 일정하게 고혈당을 유지 시켜주는 방법이다. 장기적인 고혈당은 인슐린의 민감도를 감소시키고 췌장기능을 저하시키며 잠재적으로는 당뇨병의 악화 및 심혈관 합병증을 유도한다(28,29). 이에 본 연구에서는 STZ로 당뇨를 유발한 흰쥐에 AD복합물을 단회 및 반복 투여한 후 혈당변화에 미치는 영향을 조사한 결과 AD복합물의 단회 투여에서 시간별($0{\sim}4$시간)로 혈당변화가 관찰되었다. DC군의 공복혈당은 $437.3{\pm}28mg/dL$에서 3시간 후의 혈당이 $443.3{\pm}28mg/dL$로 거의 변화가 없었던 반면 AD1군은 $414.0{\pm}19mg/dL$에서 $358{\pm}35mg/dL$로 AD2군은 $401.0{\pm}28mg/dL$에서 $351{\pm}16mg/dL$로 혈당이 낮춰졌다. 또한 경구당부하 실험에서는 DC군에 비해 AD복합물 투여군이 포도당 투여 1시간 후의 혈당상승을 억제하고 빠른 속도로 원래의 혈당으로 회복시키는 역할을 하는 것으로 확인되었다. 이러한 결과들이 AD복합물의 장기투여에서도 나타나는지 확인하기 위하여 STZ로 당뇨를 유발시킨 흰쥐에 4주 동안 AD복합물을 투여하고 1주마다 혈당변화를 측정한 결과 DC군은 4주 동안 투여 전(0주) 혈당인 $385{\pm}9mg/dL$를 마지막 주인 4주까지 $365{\pm}6mg/dL$로 꾸준히 비슷하게 유지한 반면, AD1군은 투여 전 혈당인 $349{\pm}9mg/dL$에서 $260{\pm}8mg/dL$로 감소한 것으로 나타났고 AD2군은 투여 전 혈당인 $430{\pm}10mg/dL$에서 $267{\pm}38mg/dL$로 공복 시 혈당저하 효능을 갖는 것으로 나타났다. 또한 AD복합물의 투여는 당뇨로 인한 체중감소를 억제하는 효과가 나타났다. 이러한 결과는 체내의 당대사를 촉진시켜 공복혈당감소와 체중감소억제 효과가 나타난 것으로 사료된다.

• 한국가축번식학회지
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• 제21권3호
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• pp.255-264
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• 1997

The purpose of this study was attempted to investigate the number changes of the growing and mature follicles in ovary following repeats of pregnant mare serum gonadotropin(PMSG) treatments for superovulation in nulliparous rats. Thirty two rats(Sprague-Dawely, about 200~250 gm) were randomized into 4 groups. Control group rats were sacrified at estrus phase confirmed by vaginal smear. PMSG-treated group 1 rats, PMSG-treated group 2 rats and PMSG-treated group 3 rats were sacrified at 48 hrs after injection once with PMSG 25 IU, after 2 repeated injection by a week interval, and 3 repeated injection, respectively. The uteri and ovaries of rats were removed and weighed and then were observed grossly and serial sections of all ovaries and some sections of uteri by paraffin embedding were stained with H-E. Number of ovarian follicles about 3 grades of small, middle and large follicles from seondary and follicles were investigated by LM photographies of ovary preparations. The criteria of the small, middle, and large follicles were based as small follicle with preantral follicles with 2~4 layers of granulosa cells surrounding the oocyte, as secondary follicles with more than 5 layers of granulosa cells and early signs of antral cavity or with small clefts on either side of the oocytes, and as tirtiary follicles with a single medium sized antral cavity or large well-formed antral cavity, respectively. In gross findings, the wall of the uteri in control group were thin, and those in 3 PMS-treated group were markedly thickened and some uterine lumen of those filled with fluid. In histological findings, the walls of the uteri from 3 PMSG-treated groups were hypertrophied and their blood and lymph vessels were dilated than those of control group. The ovaries fo 3 PMSG-treated groups were more increased in size and the cortexes were more developed and increased in width but there are no difference of development and changes in 3 PMSG-treated groups. The weight of the uteri and ovaries per rat in PMSG -treated group 1, 2 and 3 were a, pp.ared to be significantly increased 171.4$\pm$47.6%, 162.3$\pm$43.9%, 206.9$\pm$30.4%, respectively than those of control groups. The mean number of follicle per ovary in control group were a, pp.ared to be 17.1$\pm$3.5, 46.2$\pm$14.5, and 74.3$\pm$22.7 at large, middle and small follicles, respectively and total number of these 3 grade follicles per ovary were a, pp.ared to be 137.7$\pm$31.7. The mean number of follicle per ovary in PMSG-treated group 1 were a, pp.ared to be 25.6$\pm$7.3, 78.1$\pm$29.9, and 83.2$\pm$34.0, at large, middle and small follicles, respectively and total number of these 3 grade follicles were a, pp.ared to be 187.5$\pm$58.8. The mean number of follicle per ovary in PMS-treated group 2 were a, pp.ared to be 21.9$\pm$5.2, 67.8$\pm$16.8, and 68.0$\pm$14.9 at large, middle and small follicles, respectively and total number of these 3 grade follicles were a, pp.ared to be 157.7$\pm$26.2. The mean number of follicle per ovary in PMS-treated group 3 were a, pp.ared to be 21.7$\pm$4.8, 61.5$\pm$17.0, and 59.7$\pm$16.2 at large, middle and small follicles, respectively and total number of these 3 grade follicles were a, pp.ared to be 143.5$\pm$29.6. The number of follicles in PMSG-treated group 1 a, pp.ared to be more number than other 2 PMSG-treated gruops and tended to be decreased by frequency of PMSG-treatment.

• 대한핵의학회지
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• 제3권1호
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• pp.51-58
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• 1969

To clarify the hematologic effects of the radioiodine ($^{131}I$) in therapeutic doses ($5{\sim}10$ mCi) on the various thyroid patients, authors studied the peripheral blood pictures of 396 goitrous patients before and after radioiodine ($^{131}I$) administrations in the Isotope Clinic of Seoul National University Hospital. Among these 396 cases of goiters, we gave 5 to 10 mCi of radioiodine ($^{131}I$) with single or fractionated administrations. The blood pictures of peripheral blood were repeated after 3 months in 40 cases of 65 cases who had been treated with $^{131}I$. The blood pictures of non-treated thyroid patients were compared with that of normal Korean values to clarify any difference between normal and goiter. The blood pictures of hyperthyroid patients treated with $^{131}I$ therapy were compared with the blood pictures of non-treated thyroid patients. The results were as following: 1) The incidence according to type: Toxic diffuse goiter: 35.4% Nontoxic nodular goiter: 29.7% Euthyroid: 13.8% Nontoxic diffuse goiter: 12.6% Hypothyroidism: 4.3% Thyroiditis($\bar{s}$ subacute form): 1.8% Toxic nodular goiter: 1.4% Malignancy: 1.0% 2) Age incidence: The range of distribution was 11 to 71 years. The peak incidence was found in the 4th decade of life. $80.6{\sim}82.6%$ of those 396 cases were found among the 3rd, 4th and the 5th decades of life. 3) Sex incidence: Sex ratio of male:female was 1:7.8. 4) The most outstanding findings in peripheral blood before treatment were decreased erythrocyte count and hemoglobin value in all types of thyroid diseases, especially in. the cases of hypothyroidism and thyroiditis. Hook worm-infested patients showed no significant difference in erythrocytes and hemoglobin values from those of other hook worm free patients. 5) Total leukocytes count was within normal range. Differential count of W.B.C. showed increased percentile of lymphocyte in diffuse toxic goiter and thyroiditis. 6) 39 cases of diffuse goiter treated with $^{131}I$ toxic showed amelioration in the anemia and restoration to normal range of lymphocyte count in association with increased percentile of neutrophiles 3 months after administration, except a case of toxic nodular goiter. One can observe anemia in slight degree, and increased lymphocytes count in hypothyroidism. Therapeutic dose of radioiodine ($^{131}I$) does not result any residual effect on the hematopoietic function. Radioiodine ($^{131}I$) therapy resulted in improvement of thyroid function in association of amelioration of pevious abnormal blood pictures. 7) Authors did not observe any myxedema resulted from radioiodine therapy during the 3 months period in this study.