• Title/Summary/Keyword: 면역억제제

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The Effects of Tacrolimus versus Cyclosporine on Acute Graft Rejection Episode and Acute Renal Dysfunction Following Pancreas Transplantation (췌장이식환자에서 Tacrolimus와 Cyclosporine이 급성거부반응과 신장장애에 미치는 영향)

  • Oh, Jung Mi;Klassen, David
    • Korean Journal of Clinical Pharmacy
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    • v.9 no.2
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    • pp.81-87
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    • 1999
  • 췌장이식의 성공률은 지난 10년 동안 상당히 상승되었다. International Pancreas Transplant Registry에 따르면 1995년 이래 미국에서만 매년 1,000건 이상의 췌장이식이 실시되고 있다. 장기이식후 나타나는 급성 거부반응은 이식 후 6개월 이내에 가장 높은 빈도수로 나타난다. 췌장이식환자에서는 신장을 이식한 것보다 두배나 높은 거부반응을 나타나며 이로 인한 입원율의 증가 항림프제(antilyinphocyte) 사용과 감염의 증가로 이환율이 높다. 더구나 Cyclosporine (CsA)을 기초로 한 면역억제제요법의 사용은 높은 급성 거부반응률(acute graft rejection)을 초래하여 이식한 장기의 조직손실이 문제가 되고 있다. 새로운 면역억제제인 Tacrolimus (FK506)의 사용은 이식환자에서의 거부반응을 감소시켜 생존율을 증가시키는 것으로 알려져 있다. Tacrolimus는 neutral macrolide로 cyclic peptide인 CsA과는 화학 구조는 매우 다르나 비슷한 면역억제 효과를 보인다. 하지만 Tacrolimus의 사용시 신경독성, 신독성, 특히 고혈당증의 발생률이 높아 일부 이식센터에서는 장기 이식 후에 사용하기를 꺼리기도 한다. 하지만 여러 연구논문에서 간과 신장 이식 후 급성 거부반응 예방에 Tacrolimus는 CsA에 비해 이점이 있는 결과를 발표하였다. 결과적으로, 현재 췌장이식 후 Tacrolimus를 기초로 한 면역억제의 효과에 대한 연구가 활발히 진행중이다. 따라서 본 연구에서는 1994-1996년 사이에 Tacrolimus 또는 CsA를 기초로 한 면역억제요법을 투여 받은 췌장이식환자 101명을 후향적으로 조사하여 Tacrolimus (n=54)와 CsA(n=57)의 급성 거부반응 예방 효과와 신부전 발생률을 비교하였다. 모든 환자는 항림프구 약물, Azathioprine, Prednisone을 이식 후 면역억제제로 투여 받았다 기준선으로부터 $20\%$ 이상의 혈청 creatinine의 상승이 있는 환자에서는 급성 신부전으로 정의하였고 신장생검법으로 거부반응을 진단하였다 Matched-pair analysis에 따르면 췌장이식환자의 6개월 생존율은 CsA군에서 $97\%$, Tacrolimus군에서 $96\%$로 별다른 차이가 없었으며 (p=0.57), 6개월간의 이식한 췌장의 보존율은 CsA군에서는 $88\%, Tacrolimus에서 $91\%$. 유의한 차이는 없었다(p=0.29). 췌장이식 후 6개월 동안 Tacrolimus의 사용은 생검으로 증명되는(biopsy-proven) 급성 거부반응의 발생빈도는 CsA보다 유의하게 낮았을 뿐만 아니라 (p<0.05) 거부반응 증상의 심각도 또한 감소시켰다 (p=0.03). 급성거부반응 발생빈도의 감소로 Tacrolimus군에서 antilymphocyte 치료가 유의하게 줄어들었다(p=0.01). CsA군에서 Tacrolimus보다 신부전의 발생률이 높았으나 통계학적 차이는 없었다. 췌장이식후의 최적의 면역억제요법의 결정하기 위해서는 향후 Tacrolimus와 CsA을 비교하는 전향적 무작위 연구가 필요하다.

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The Use of Gui-Pi-Tang in Small Animals with Immune-Mediated Blood Disorders (면역매계성 혈액장애를 가진 소동물에서 귀비탕의 사용)

  • Busta, Isabelle;Xie, Huisheng;Kim, Min-Su
    • Journal of Veterinary Clinics
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    • v.26 no.2
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    • pp.181-184
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    • 2009
  • Immune-mediated hemolytic anemia(IMHA) is one of the most common causes of anemia in small animals and immune-mediate thrombocytopenia(IMT) is also an immune mediated disease that affects small animals. The initial treatment for IMHA and IMT is medical suppression of the immune system with glucocorticoids and other immunosuppressive drugs. However, even with appropriate treatments, some animals are not responsive to the treatment and may need further immunosuppressive therapies or some alternative medicines. An eight-year-old spayed female Siamese cat with IMHA and an eight-year-old castrated male King Charles Spaniel dog with IMT were referred to the traditional medical service of the veterinary medical center. Both animals were unresponsive to steroids or other immunosuppressive treatments. Gui-Pi-Tang, one of the traditional herbal medicines, was administered to the animals. After 1-month of Gui-Pi-Tang administration, the packed cell volume(PCV) of the cat and platelets count of the dog had showed remarkable improvement. After four months of follow up in the cat, and 18 months of follow up in the dog, the improved PCV and platelet counts of the animals were maintained normally. Therefore, Gui-Pi-Tang might be considered as an alternative treatment in small animals with immune-mediated blood disorders.

The Morphologic Changes by Immunosuppression after Heterotopic Transplantation of the Murine Cryopreserved Trachea: An Animal Model for Obliterative Bronchiolitis (이소 이식된 쥐 기관의 면역억제 및 초냉동 보관에 의한 형태학적 변화: 폐색성 모세기관지염의 연구를 위한 동물 실험 모델)

  • 이창하;성숙환;오미혜
    • Journal of Chest Surgery
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    • v.32 no.3
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    • pp.215-223
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    • 1999
  • Background: The replacement of the narrowed long-segment trachea with various prosthetic materials or tissue grafts remains a difficult and unsolved surgical problem. Homologous cryopreserved tracheal transplantation has been considered to treat the irreversibly-damaged organs, such as in the lung or heart transplantation and also to overcome the limited supply of donor organs. We examined the morphological changes and the immunosuppressive effects of the cryopreserved trachea after the heterotopic transplantation in the rats. Material and Method: Sixty tracheal segments harvested from 30 donor Wistar rats were heterotopically implanted into the peritoneal cavity of 20 recipient Wistar rats and 40 Sprague Dawley rats. The 60 recipient rats were divided into 6 groups(10 rats/ group). In groups I, II, and III, 30 tracheal segments were implanted immediately after the harvesting and in groups IV, V, and VI, the segments were implanted 28 days after the cryopreservation. Groups I and IV were Wistar syngeneic controls. Groups II and V were Sprague Dawley recipients receiving no immunosuppression and Groups III and VI, were Sprague Dawley recipients receiving immunosuppressive agents. At 28 days all rats were sacrificed and the tracheal segments were evaluated grossly and histologically. Result: Immunosuppression of the tracheal segments had a significant influence on the changes of the tracheal lumen and tracheal epithelial cells, irrespective of the cryopreservation of the trachea(p<0.001). In groups III and VI receiving immunosuppressive agents, the tracheal lumen was patent and the normal epithelial cells were observed, however in the other groups not receiving the immunosuppressive agents, there were almost luminal obliteration by the proliferation of the fibrous tissues and a loss of the epithelial cells, the findings were similar to those in the case of obliterative bronchiolitis after a lung and a heart-lung transplantation. Conclusion: With the appropriate immunosuppressive agents, the lumen and the respiratory epithelium of the transplanted tracheal segment were well preserved, even after the cryopreservation of the tracheal segment, which shows the possibility of the long-term preservation and homologous transplantation of the trachea. But fibroproliferative obliteration of the tracheal lumen and the loss of the normal respiratory epithelial cells, characteristic findings of obliterative bronchiolitis, were observed in the groups without the immunosuppression. This experiment using the rat trachea may be useful in studying the pathogenesis, treatment, and prevention of obliterative bronchiolitis after a lung and a heart-lung transplantation.

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Immunomodulatory Effects of Polysaccharides Derived from Persimmon Leaves on Cyclophosphamide-induced Immunosuppressed Mice (감잎 유래 다당체가 면역억제 마우스의 면역조절에 미치는 영향)

  • Cho, Chang-Won;Rhee, Young Kyoung;Kim, Young-Chan;Han, Chun-Ji;Shin, Kwang-Soon;Hong, Hee-Do
    • Korean Journal of Food Science and Technology
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    • v.45 no.5
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    • pp.636-641
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    • 2013
  • We prepared 2 different crude polysaccharides from persimmon leaves, by hot water (PLW-0) and pectinase digestion (PLE-0), respectively. PLW-0 and PLE-0 showed similar sugar compositions and contained 11 different sugars, including rarely observed sugars such as 2-methyl-fucose, 2-methyl-xylose, apiose, and aceric acid. However, the uronic acid content of PLE-0 was lower than that of PLW-0, because of pectinase treatment. In normal mice, administration of PLW-0 and PLE-0 increased the spleen index and splenocyte proliferation. The effect of PLE-0 on the spleen index and splenocyte proliferation was greater than that of PLW-0. We subsequently assessed the immunomodulatory activities of PLW-0 and PLE-0 on cyclophosphamide (CY)-induced immunosuppressed mice. We revealed that mice treated with PLW- 0 or PLE-0 showed increased splenocyte proliferation, NK cell activity, and white blood cell numbers. Taken together, our results indicate that PLW-0 and PLE-0 can enhance immune function in normal mice and modulate CY-induced immune suppression.

Experimental Model of Cardiac Xenograft, Mouse Heart to Rat. (이종이형의 심장이식의 실험적 모델)

  • Kim, Byung-Il;Sohn, Sang-Tae;Shin, Sung-Ho;Chung, Won-Sang;Kim, Hyuk;Kim, Young-Hak;Kang, Jung-Ho;Jee, Heng-Ok;Lee, Chul-Burm;Seo, Jung-Kuk
    • Journal of Chest Surgery
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    • v.32 no.1
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    • pp.1-4
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    • 1999
  • Background: The transplantation of organs between phylogenetically disparate or harmonious species has invariably failed due to the occurrence of hyperacute rejection or accerelated acute rejection. But, concordant cardiac xenograft offer us an opportunity to study xenotransplantation in the absence of hyperacute rejection. Current therapeutics for the prolongation of survival of rodent concordant xenotransplantation are not ideal with many regimens having a high mortality rate. Cyclosporine A & Mycophenolate Mofetil are new immunosuppresive agent which has been shown to be effective at prolonging survival of allograft, as purine synthesis inhibitor. Material and Method: We used white mongrel rats as recipient and mice as donor, divided 4 groups(n=6), control group(Group 1) has no medication or pretreatment, Group 2 has splenectomy as pretreatment 7∼10 days before transplantation, Group 3 has Cyclosporine A treatment group, Group 4 has combined treatment of Cyclosporine A & Mycophenolate Mofetil(RS 61443). We compared survival time. Reuslt: We can't find significant difference of survival time between each groups. Conclusion: We concluded that rejection of cardiac xenograft was different from rejection of allograft, and new immunossuppresive Agent(Mycophenolate Mofetil, Cyclosporine A) was not effective for prolongation of survival time after cardiac xenograft.

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Immunosuppressive Effects of Herbal Plant Extracts on Alloantigen Reactive Cell Proliferation and Cytotoxicity (일부 한약재의 동종항원에 대한 세포증식 및 살세포반응 억제효과)

  • 정영란;하미혜;김성호;조성기;변명우;조현욱;서권일;이성태
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.29 no.6
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    • pp.1133-1138
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    • 2000
  • 본 실험에서는 동양에서 예로부터 민간요법이나 한방에서 주로 많이 쓰여지고 있는 8가지 종류의 한약재에 대해서 면역억제제로써 사용 가능성을 실험하였다. 그 결과, 당귀, 산사, 어성초, 오가피, 황기의 추출물은 동종항원에 반응하는 순수분리 T 세포의 증식을 농도 의존적으로 억제 시켰다. 또한 이들 T 세포의증식에 있어써 필수적인 IL-2를 포함한 cytokine 즉, IL-2, IL-4, IL-10, IFN-${\gamma}$ 의 생산량은 대조군에 비해 실험군에서 유의한 차이가 없었고 특히 T 세포 증식에 필수적인 IL-2의 생산량의 변화가 거의 없었다. 이는 한약재에 의한 T 세포증식에 필수적인 IL-2의 생산량을 억제하기 때문에 일어나는 결과가 아님을 알 수 있었다. 그리고 T 세포의 살세포작용 억제를 직접적으로 측정하기 위하여 세포내 LDH의 양을 조사한 결과 모든 대조군에서 50%이상의 살세포작용 억제가 일어났고, 그 중 특히 오가피와 황기에서는 100% 살세포작용 억제가 일어났다. 따라서 본 실험에서 사용되 당귀, 산사, 어성초, 오가피, 황기 등의 5가기 약재가 부작용 없는 면역억제로써 사용 가능성이 높은 것으로 생각된다.

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Clonorchis sinensis: Analysis Characterization of Somatic and Metabolic Antigen (II) Profile of the Worm, Excretory-secretory and Billis Antigen in C. sinensis Infected Rabbit (간흡충 : 충체 및 대사성 항원의 특성분석 (II) 간흡충 감염 가토에서 간흡충, 분비배설액 및 담즙 항원의 분획 양상)

  • Yong-Suk Ryang;Yoon-Kyung Cho;Ji-Sook Lee
    • Biomedical Science Letters
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    • v.3 no.2
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    • pp.89-94
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    • 1997
  • The authors characterized the proteins of the crude antigen obtained from Clonorchis sinensis worm and excretory-secretory and billis from rabbits, experimentally infected for 3 months. Protein composition was observed after adding a cysteine proteinase inhibitor E-64 and a serine proteinase inhibitor PMSF, respectively. SDS-PAGE of the crude antigen from C. sinensis recovered from the infected rabbits, the crude antigen from the adult worm excretory-secretory, and the crude antigen from billis of the rabbits resolved 26, 27 and 19 profiles between 200-9 kDa, respectively. When E-64 supplemented 29, and 22 bands, respectively. More study should be carried out in the future on the immunological characteristics and the monoclonal antibody of the each antigen.

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Hepatitis E Virus Inhibits Activation of Signaling Molecules Involved in Induction of Type I Interferon (E형 간염 바이러스에 의한 제 1형 인터페론 신호전달분자 활성 억제)

  • Myoung, Jinjong
    • Microbiology and Biotechnology Letters
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    • v.46 no.4
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    • pp.320-325
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    • 2018
  • Hepatitis E virus (HEV) infection accounts for 20 million annual infections worldwide. HEV can be fatal in approximately 20-30% of pregnant women. HEV infections are normally self-limiting and mostly asymptomatic. However, in patients with insufficient immunity, such as acquired immunodeficiency syndrome patients, chronic and often fatal infections may ensue. Therefore, it is likely that host immune responses, especially interferon responses, play a critical role in HEV infection control. Here, we report that an HEV-encoded non-structural protein down-regulates type I interferon response. In addition, some other immune genes involved in the induction of type I interferon may be regulated as well. Detailed molecular mechanisms are currently being studied.

연구실탐방-한미약품(주)중앙연구소 제제연구팀

  • Korean Federation of Science and Technology Societies
    • The Science & Technology
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    • v.31 no.4 s.347
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    • pp.70-71
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    • 1998
  • 면역 억제제인 「마이크로 에멀션 제제기술 」을 개발한 한미약품 중앙연구는 다국적기업인 노바티스사로부터 향후 20년 총 2천억원 규모의 로열티를 받게 되었다. 장기의식 후에 따르는 조직이식거부반응을 막아 환자의 생존율을 늘려주는 획기적인 면역억제제의 신기술 개발은 "세계최고의 위업"이라는 평을 받고 있다. 외환에 시달리는 요즘 막대한 달러의 로열티는 시민들의 주름살을 펴주는 낭보가 아닐 수가 없다.

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Experimental activation of cryptosporidiosis in mice by immunosuppression (면역억제에 의한 마우스의 Cryptosporidium 발현 실험)

  • 채종일;신손문
    • Parasites, Hosts and Diseases
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    • v.28 no.1
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    • pp.31-38
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    • 1990
  • Cryptosporidium, a coccidian parasite first described by Tyzzer (1907) from a laboratory mouse, has become an important human enteric pathogen causing overwhelming diarrhea especially in immunocompromised patients such as AIDS. This parasite has been reported from over 20 countries and is recognized as a cosmopolitan species. In Korea, however, thEre has been no report on human as well as animal cryptosporidiosis. This study was performed so as to verify the presence of Cryptosporidium in Korea by activating the parasite from laboratory mice by immunosuppression. Total 65 conventionally.bred ICR mice including a control (5 mice) and 3 experimental groups (20 each) were used for this study. Group I was immunosuppressed with Prednisolone injection (1 mg IM, every other day) for 7 weeks. Group II (prednisolone injection and tetracycline administration) and Group III. (prednisolone injection and trimethoprim-sulfamethoxazole administration) were prepared to observe the effect of antibacterial agents on the activation of cryptosporidiosis. In fecal examinations of mice Cryptosporidium oocysts($4-6{\mu\textrm{m}}$ in size) were detected from 1 week after the start of immunosuppression and the mice began to die. In H-E stained tissue sections of the lower jejunum, numerous very small ($2~4{\;}{\mu\textrm{m}}$), dense, ovoid or spherical, slightly basophilic bodies were seen attached on the free border of mucosal epithelial cells. In scanning and transmission electron microscopic observations, these organisms were identified as various developmental stages of Cryptosperidium. The species is considered to be C. parvum. Cryptosporidiosis was activated not only in Group I but also in Group II and III, indicating no protective effects of the antibacterial agents used, although the mice in Group II and III lived longer than those in Group I. The present study confirmed that Cryptosporidium exists in laboratory mice bred in Korea, and predicts possible occurrence of human cryptosporidiosis in Korea.

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