• The Korean Journal of Physiology and Pharmacology
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• 제4권3호
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• pp.185-195
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• 2000

Vascular diseases are significant complications of diabetes mellitus (DM), and the endothelial cells may play a pivotal role in the development of vascular disease in DM. Endothelin-1 (ET-1) released from endothelium is a potent vasoconstrictor peptide and circulating level of ET-1 is increased in a variety of disease states. The purpose of this study was to determine the changes of responsiveness to ET-1 in DM, and we experimented on the changes in the ET-1-induced contraction, levels of nitrite and lipid peroxidation, and ET-1 immunoreactivity in aorta from streptozotocin-induced DM rats. DM was induced by single injection of streptozotocin (55 mg/kg, i.p.). The immunoreactive ET-1 levels in endothelial layer of thoracic aorta were much higher in DM rats than control rats. Nitrite in tissue homogenate was decreased and plasma nitrite was increased in DM rats. Malondialdehyde (MDA) was significantly increased in DM rats and cGMP was not significantly different between control and DM rats. ET-1 produced concentration- dependent contractile responses that are significantly attenuated in DM rats compared to controls. In the presence of selective $ET_A$ receptor antagonist BQ610, the maximum contraction was decreased and the concentration ratios for BQ610 yielded $pA_2$ values of 7.3 (slope, 0.65) in control rats, whereas BQ610 had no antagonistic effect on ET-1-induced contraction in DM rats. However, pretreatment with BQ788, an $ET_B$ receptor antagonist, maximum response was decreased and the dose-response curves for ET-1 were shifted to the right in both groups and $pA_2$ values were 7.9 and 7.7 (slope, 1.05 in control and DM rats), respectively. IRL 1620 and sarafotoxin S6c, $ET_B$ agonists, induced relaxation in control rats but not in DM rats. These results indicate that endothelial cell dysfunction and enhanced immunoreactivity of ET-1 have been found in DM rat and ET-1-induced contraction was attenuated in DM rat. These attenuated responses might be at least in part caused by the alteration of $ET_A$ receptor properties (e.g. desensitization), and partly related with an alteration in intracellular mechanism for contraction to ET-1.

• 한국발생생물학회지:발생과생식
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• 제21권2호
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• pp.111-120
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• 2017

Equine chorionic gonadotropin (eCG) is a unique molecule that elicits the response characteristics of both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in other species. Previous studies from this laboratory had demonstrated that recombinant eCG (rec-eCG) from Chinese hamster ovary (CHO-K1) cells exhibited both FSH- and LH-like activity in rat granulosa and Leydig cells. In this study, we analyzed receptor internalization through rec-eCGs, wild type eCG ($eCG{\beta}/{\alpha}$) and mutant eCG ($eCG{\beta}/{\alpha}{\Delta}56$) with an N-linked oligosaccharide at $Asn^{56}$ of the ${\alpha}-subunit$. Both the rec-eCGs were obtained from CHO-K1 cells. The agonist activation of receptors was analyzed by measuring stimulation time and concentrations of rec-eCGs. Internalization values in the stably selected rat follicle-stimulating hormone receptor (rFSHR) and rat luteinizing/chorionic gonadotropin receptor (rLH/CGR) were highest at 50 min after stimulation with 10 ng of $rec-eCG{\beta}/{\alpha}$. The dose-dependent response was highest when 10 ng of $rec-eCG{\beta}/{\alpha}$ was used. The deglycosylated $eCG{\beta}/{\alpha}{\Delta}56$ mutant did not enhance the agonist-stimulated internalization. We concluded that the state of activation of rFSHR and rLH/CGR could be modulated through agonist-stimulated internalization. Our results suggested that the eLH/CGRs are mostly internalized within 60 min by agonist-stimulation by rec-eCG. We also suggested that the lack of responsiveness of the deglycosylated $eCG{\beta}/{\alpha}{\Delta}56$ was likely because the site of glycosylation played a pivotal role in agonist-stimulated internalization in cells expressing rFSHR and rLH/CGR.

• Clinical and Experimental Reproductive Medicine
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• 제25권2호
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• pp.115-122
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• 1998

The maintenance of a viable pregnancy has long been viewed as an immunological paradox. The deveolping embryo and trophoblast are immunologically foreign to the maternal immune system due to their maternally inherited genes products and tissue-specific differentiation antigens (Hill & Anderson, 1988). Therefore, speculation has arisen that spontaneous abortion may be caused by impaired maternal immune tolerance to the semiallogenic conceptus (Hill, 1990). Loss of recall antigen has been reported in immunosuppressed transplant recipients and is associated with graft survival (Muluk et al., 1991; Schulik et al., 1994). Progesterone $(10^{-5}M)$ has immunosuppressive capabilities (Szekeres-Bartho et al., 1985). Previous study showed that fertile women, but not women with unexplained recurrent abortion (URA), lose their immune response to recall antigens when pregnant (Bermas & Hill, 1997). Therefore, we hypothesized that immunosuppressive doses of progesterone may affect proliferative response of lymphocytes to trophoblast antigen and alloantigen. Proliferative responses using $^3H$-thymidine ($^3H$-TdR) incorporation of peripheral blood mononuclear cells (PBMCs) to the irradiated allogeneic periperal blood mononuclear cells as alloantigen, trophoblast extract and Flu as recall antigen, and PHA as mitogen were serially checked in 9 women who had experienced unexplained recurrent miscarriage. Progesterone vaginal suppositories (100mg b.i.d; Utrogestan, Organon) beginning 3 days after ovulation were given to 9 women with unexplained RSA who had prior evidence of Th1 immunity to trophoblast. We checked proliferation responses to conception cycle before and after progesterone supplementation once a week through the first 7 weeks of pregnancy. All patients of alloantigen and PHA had a positive proliferation response that occmed in the baseline phase. But 4 out of 9 patients (44.4%) of trophoblast antigen and Flu antigen had a positive proliferative response. The suppression of proliferation response to each antigen were started after proliferative phase and during pregnancy cycles. Our data demonstrated that since in vivo progesterone treated PBMCs suppressed more T-lymphocyte activation and $^3H$-TdR incorporation compare to PBMCs, which are not influenced by progesterone. This data suggested that it might be influenced by immunosuppressive effect of progesterone. In conclusion, progesterone may play an important immunological role in regulating local immune response in the fetal-placental unit. Furthermore, in the 9 women given progesterone during a conception cycle, Only two (22%) repeat pregnancy losses occured in these 9 women despite loss of antigen responsiveness (one chemical pregnancy loss and one loss at 8 weeks of growth which was karyotyped as a Trisomy 4). These finding suggested that pregnancy loss due to fetal aneuploidy is not associated with immunological phenomena.

• Radiation Oncology Journal
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• 제12권1호
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• pp.81-90
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• 1994

Purpose : The aim of this study is to analyze the clinical results of thermo-irradiation treatment for surgically unresectable advanced hepatoma with or without hepatic arterial chemo-embolization (HACE), chemotherapy (CT) and interferon (IFN) therapy. Materials and Methods : Between February 1990 and December 1992, 45 Patients with surgically unresectable advanced hepatomas were treated by thermo-irradiation with or without hepatic arterial chemo-embolization and other treatment modalities. Among them, We analyzed retrospectively 25 patients who received more than three times of hyperthermias. Mean age was 50 years (range : 18-71 years) and male to female ratio was 20 : 5. In the study, treatment was administered as follows : 3 patients received radiation therapy(RT) and hyperthermia (HT). 3 received RT+HT+CT. 3 received RT+HT+HACE. 1 received RT+HT+CT+HACE. 2 received RT+HT+CT+IFN. 10 received RT+HT+HACE+IFN. 3 received RT+HT+CT+HACE+IFN. Radiation therapy was done by a 6 MV linear accelerator Patients were treated with daily fractions of 180 cGy to doses of 11Gy-50Gy (median 30Gy). Local hyperthermia was done by HEH-500C(Omron Co. Japan), 30-45 min/session, 2 sessions/wk and the number of HT sessions ranged from 3 to 17 (median 7 times). 15 patients of 25 were followed by abdominal CT scan or abdominal ultra-sonogram. The following factors were analyzed :Age, histologic grade, sex. number of hyperthermia, total RT dose, hepatic arterial chemo-embolization. Results : Of 25 patients. there were observed tumor regression (partial response and minimal response) in 6 (24$ \% $), no response in 8 (32$ \% $), progression in 1 (4$ \% $) and not evaluable ones in 10 (40$ \% $) radiographically. The over all 1-year survival was 25$ \% $, with a mean survival of 33 weeks. The treatment modes of partial and minimal responsive patients (PR+MR)were as follows : Two were treated with RT+HT+HACE, 2 were done with RT+HT+HACE+IFN Remaining 2 were treated with RT+HT+CT+HACE+IFN. The significant factor affecting the survival rate were RT dose (more than 25 Gy), HACE, number of HT (above 6 times), responsiveness after treatment (PR + MR). Age, sex, histologic differentiation, chemotherapy, interferon therapy were not statistically significant factors affecting the survival rate. Conclusion : Although follow-up duration was short, the thermo-irr3diBtion with/without hepatic arterial chemo-embolization was well tolerated and there were no serious complicatons. In future, it is considered the longer follow up and prospective, well controlled trials should be followed to evaluate the efficacies of survival advantage.

• Neonatal Medicine
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• 제16권2호
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• pp.146-153
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• 2009

목 적: 고식적인 치료에 반응하지 않는 기관지폐 이형성증에 대한 치료로서 덱사메타손 구제 치료의 사용현황을 조사하기 위해 본 연구를 시행하였다. 방 법: 2004년 3월부터 2008년 8월까지 서울대학교 어린이병원 및 분당서울대학교병원 신생아 중환자실에 입원하여 기관지폐 이형성증으로 치료를 받은 251례의 미숙아를 대상으로 후향적으로 연구하였다. 산모와 신생아들의 인구학적, 임상적 특성을 살펴보았으며, 덱사메타손 구제 치료의 반응성에 따라 반응군 및 비반응군간의 차이점을 비교 분석하였다. 또한 덱사메타손 구제 치료에 따른 합병증을 조사하였다. 결 과: 93례(37.1%)가 중증도의 기관지폐 이형성증으로 분류되었으며, 모든 덱사메타손 구제 치료는 중증도의 기관지폐 이형성증을 가진 사례에서 시행되었다. 덱사메타손은 고식적인 치료가 실패하여 기관 발관이 불가능한 호흡 곤란을 가진 24례(9.6%)에서 투여되었다. 투여된 사례 중 14례(58.3%)에서 덱사메타손 구제 치료에 반응을 나타냈다. 비반응군은 보다 많은 산소 공급을 요구하였으며 폐동맥 고혈압이 동반되는 경우가 많았다. 반응군은 입원 기간의 단축과 사망률의 감소 소견을 보였다. 고용량의 덱사메타손을 투여하는 것이 저용량에 비하여 보다 효과적으로 기계 환기에서 이탈을 유도한다는 근거는 도출되지 않았다. 패혈증은 덱사메타손 구제 치료 이후에 가장 빈번하게 발생하는 합병증이다. 결 론: 중증의 기관지폐 이형성증에서 폐동맥 고혈압이 발생하기 전에 덱사메타손 구제 치료를 시행하는 것이 치료 효과 측면에서 도움이 될 수 있다. 폐동맥 고혈압이 동반된 경우에는 합병증의 발생 가능성으로 인해 덱사메타손 구제 치료를 하지 않는 것이 바람직하다.

• Journal of Yeungnam Medical Science
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• 제18권2호
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• pp.226-238
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• 2001

본 연구는 만성 신부전 환자의 빈혈 치료로 사용되는 EPO의 효과를 감소시키는 여러 원인을 조사하고 각각의 원인에 대한 적절한 치료를 함으로써 EPO의 치료 효과를 향상시키고자 2001년 4월 현재까지 영남대학교 의과대학 부속병원 인공 신장실에서 6개월 이상 혈액 투석중인 72명을 대상으로 전향적 연구를 시행하였다. 전체 대상군(n=72) 에서 IVAA 12주 치료와 철분 상태에 따른 IVAA 효과를 판정하여 가장 효과적인 기능성 철 결핍 군에게는 IVAA 치료를 8주 연장하였다. 혈중 알루미늄이 4 ${\mu}g/l$ 이상군과 저장철이 500 ${\mu}g/l$ 이상인 군에게는 DFO를 8주간 투여하였다. Tsat 20% 미만 군에서는 경구 철 투여를 증가시키면서 IVAA 12주간 투여하였고, i-PTH가 120 pg/ml 이상 군에게는 비타민 $D_3$를 투여하였다. 성적은 다음과 같다. 1. 전체 대상군(n=72) 에게 IVAA 12주 치료 후 혈색소는 투여 전에 비해 투여 후 2, 4, 6주에 유의한 증가를 보였으나, 이후 지속적인 효과를 보이지는 않았다. 2. 철분 상태에 따른 분류 군중 IVAA 12주 치료에 가장 효과적인 반응을 보인 군은 혈중 ferritin이 100-500 ${\mu}g/l$이고 Tsat이 30% 이하 군이었다. IVAA 20주간 투여 결과, 혈색소는 초기 $9.01{\pm}0.73$에서 2, 4주에 각각 $9.56{\pm}1.01$ g/dl, $9.45{\pm}0.93$ g/dl로 유의한 증가를 보였고, EPO는 초기 $116.4{\pm}50.8$ IU/kg/week에서 2, 4, 6, 10, 12, 16, 20주에 각각 $85.4{\pm}74.4$ IU/kg/week, $86.8{\pm}69.8$ IU/kg/week, $95.3{\pm}63.4$ IU/kg/week, $92.4{\pm}63.9$ IU/kg/week, $94.8{\pm}68.2$ IU/kg/week, $93.4{\pm}50.2$ IU/kg/week로 유의한 감소를 보였다. 또한, 초기 Tsat $20.3{\pm}5.4%$에서 2, 6, 16, 20주에 각각 $27.5{\pm}12.8%$, $28.2{\pm}15.2%$, $32.1{\pm}17.3%$, $29.2{\pm}12.9%$로 유의한 상승을 보였다. 3. 혈중 알루미늄이 4 ${\mu}g/l$ 이상 군(n=12)에서 IVAA 12주간 투여 후 DFO 8주간 치료 결과, IVAA 12주간 투여시 혈색소의 유의한 변화는 없었으나, DFO 투여사 투여 전 EPO $145.8{\pm}72.2$ IU/kg/week에서 투여후 2, 4, 6, 8 주에 각각 $104.5{\pm}95.7$ IU/kg/week, $88.2{\pm}99.9$ IU/kg/week, $90.9{\pm}67.1$ IU/kg/week. $99.1{\pm}58.9$ IU/kg/week로 EPO의 유의한 감소를 보였다. 그러나 혈중 알루미늄은 DFO 전후에 유의한 차이를 보이지 않았다. 4. 혈중 ferritin이 500 ${\mu}g/l$ 이상 군 (n=25)에서 IVAA 12주간 투여 후 DFO 8주간 치료 결과, 혈색소와 EPO 용량의 유의한 차이는 없었다. 5. Tsat 20% 미만 군(n=7) 에서 경구 철 투여를 증가시키면서 IVAA 12주간 투여 결과, 투여 10주에 Tsat의 유의한 상승을 동반한 EPO 용량의 감소를 보였으나, 혈색소의 유의한 변화는 없었다. 6. I-PTH 200 pg/rnl 이상 군(n=10)에서 비타민 $D_3$ 치료 결과, 비타민 $D_3$ 치료 후 2주부터 지속적으로 유의한 i-PTH의 억제에도 불구하고 혈색소와 EPO 용량의 유의한 차이는 없었다. 결론적으로 만성 신부전 환자의 빈혈 치료로 사용되는 EPO의 효과를 감소시키는 원인 중 기능성 철 결핍성 빈혈 환자에서의 IVAA 치료는 Tsat의 증가 및 혈색소의 증가와 EPO의 감량 효과가 있었고, 혈중 알루미늄이 증가된 경우, 저용량의 DFO 사용으로 EPO의 감량 효과를 나타내었다. 이러한 결론을 확인하려면 향후 대규모의 전향적 연구가 필요하리라 생각된다.