著者

竹内 裕紀 岩本 整 中村 有紀 河地 茂行 島津 元秀 畝崎 榮 平野 俊彦

出版者

一般社団法人 日本臓器保存生物医学会

雑誌

Organ Biology (ISSN:13405152)

巻号頁・発行日

vol.22, no.1, pp.7-22, 2015 (Released:2015-09-10)

参考文献数

59

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Corticosteroids or steroids are useful drug in clinical renal transplantation because of multiple effects in immunosuppression. There are not a few renal transplant recipients who need steroid therapy, although various new immunosuppressive drugs have developed. However, steroid dosage should be kept as low as possible and preferably withdrawn, because adverse effects of steroids are the most problematical in immunosuppressive drugs. The individual difference of efficacy and adverse effects of steroids depends on pharmacodynamics factor. We have been tried to resolve the dual nature of steroid therapy by steroid sensitivities test using peripheral blood mononuclear cell(PBMC). We clarified significant relationship in steroid sensitivity and clinical outcome, relative immunosuppressive efficacy of steroid, availability of methylprednisolone as immunosuppressive drug, utility for selecting patients who can sustain steroid withdrawal, and pharmacodynamic interaction of calcineurin inhibitors and steroids. We describe here not only results of pharmacodynamic research of steroid sensitivity test, but also comprehensive issues, i. e., history of steroid therapy in renal transplantation, action mechanism of steroid and factor of individual difference of steroid sensitivity, pharmacokinetics of steroid, suppression of hypothalamic-pituitary-adrenal system and immune system, adverse effects of steroid, and practice toward optimal steroid therapy for individual renal recipients.

著者

矢野 育子

出版者

一般社団法人 日本臓器保存生物医学会

雑誌

Organ Biology (ISSN:13405152)

巻号頁・発行日

vol.26, no.2, pp.131-137, 2019 (Released:2019-09-26)

参考文献数

14

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A physiologically based pharmacokinetic model adapted to the clinical data was constructed in order to evaluate the contribution of liver regeneration as well as hepatic and intestine CYP3A5 genotypes on tacrolimus pharmacokinetics in adult patients after living-donor liver transplantation. As a result, the oral clearance of tacrolimus was affected by the CYP3A5 genotypes in both the liver and intestine to the same extent. Population pharmacokinetic and pharmacodynamic analysis of mycophenolate was performed in 49 patients undergoing hematopoietic stem cell transplantation. Simulations based on the final parameters show that the dosage adjustment based on plasma concentrations of mycophenolate is required especially for patients with renal dysfunction and/or diarrhea. In conclusion, pharmacometrics is a useful methodology for individualized and optimized therapy of immunosuppressants.

著者

石川 洋一

出版者

一般社団法人 日本臓器保存生物医学会

雑誌

Organ Biology (ISSN:13405152)

巻号頁・発行日

vol.25, no.1, pp.51-55, 2018 (Released:2018-03-14)

参考文献数

6

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Children needs the dosage forms suitable for pediatric use. A surface body area and weight change rapidly by the age. Therefore the dosage flexibility for pediatric formulation is needed. Moreover, oral medication has to be good taste. Development of age-appropriate medicine is important, because it usually influences children’s treatment adherence. Recently, improved technology of the orally disintegrating tablet (ODT) in Japan and the active development of mini-tablets formulation in foreign countries is attracting attention. The pediatric medicine manufacturing laboratory started by our center facilitates support the promotion of development of pediatric formulation.

著者

岩本 整 杉本 昌弘 沖原 正章 赤司 勲 木原 優 今野 理

出版者

一般社団法人 日本臓器保存生物医学会

雑誌

Organ Biology (ISSN:13405152)

巻号頁・発行日

vol.27, no.2, pp.125-131, 2020 (Released:2020-08-19)

参考文献数

38

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The early and accurate diagnosis of rejection after renal transplantation is required for the well-being of recipients. To develop minimally invasive diagnosis the wide variety of novel biomarkers has been evaluated in biofluids such as blood and urea, using metabolomics that performs simultaneous identification and quantification of hundreds of metabolites. Here, we reviewed the recent researches to explore the biomarkers applicable for the diagnosis of rejection after renal transplantation.

著者

林 昌洋

出版者

一般社団法人 日本臓器保存生物医学会

雑誌

Organ Biology (ISSN:13405152)

巻号頁・発行日

vol.18, no.3, pp.279-286, 2011-12-10 (Released:2014-11-26)

参考文献数

17

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While careful consideration to avoid a second scourge like thalidomide is required, disadvantages for mothers and fetuses by restraint of necessary drug prescription because of too much concern about the effects on fetuses must be avoided. Information sources to evaluate teratogenicity of drugs themselves include epidemiological investigations, case reports, and animal reproduction studies and are considered more reliable in this order. And breast milk is the best source of nutrition and it also serves as a source of substances providing immunity for a newborn infant. However, there are times when nursing mothers may have to take some kind of medication, so it is necessary to evaluate the effect of drugs that are transferred to infants through breast milk, and to select medications with minimal adverse effects.

著者

井家 益和 畠 賢一郎

出版者

一般社団法人 日本臓器保存生物医学会

雑誌

Organ Biology (ISSN:13405152)

巻号頁・発行日

vol.22, no.1, pp.57-65, 2015 (Released:2015-09-10)

参考文献数

21

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The various types of cells exist in three-layer structure, i. e., epidermis, dermis and subcutaneous tissue of human skin. Keratinocytes, melanocytes, Langerhans cells and Merkel cells are in the epidermis, fibroblasts, mast cells, histiocyte, plasma cells and dermal dendrocytes in the dermis, and adipocytes in the subcutaneous tissue. The dermal fibroblasts are isolated by outgrowth derived from dermis tissue for primary culture and can be repeatedly passaged with serum-containing medium. The epidermal keratinocytes are obtained from trypsinization of fullthickness skin biopsy. The serum-containing medium with some growth factors and feeder layer of 3T3 cells, so called Greenʼs method, can offer an environment for the preferable proliferation of keratinocytes. The keratinocytes cultured with serum-free medium become differentiated under increased calcium concentration. The melanocytes are easily cultured in the commercial medium without serum. But the melanocytes cultured with keratinocyte by the Greenʼs method can only reconstruct an intercellular function. Cells obtained from human skin are useful tools in various cell therapies.

著者

栁 佑典

出版者

一般社団法人 日本臓器保存生物医学会

雑誌

Organ Biology (ISSN:13405152)

巻号頁・発行日

vol.25, no.2, pp.183-187, 2018 (Released:2018-07-24)

著者

大段 秀樹

出版者

一般社団法人 日本臓器保存生物医学会

雑誌

Organ Biology (ISSN:13405152)

巻号頁・発行日

vol.24, no.2, pp.227, 2017 (Released:2017-08-31)

著者

陳 豊史 本山 秀樹 土屋 恭子 高萩 亮宏 齊藤 正男 田中 里奈 宮本 英 大畑 恵資 高橋 守 近藤 健 青山 晃博 伊達 洋至

出版者

一般社団法人 日本臓器保存生物医学会

雑誌

Organ Biology (ISSN:13405152)

巻号頁・発行日

vol.23, no.2, pp.164-167, 2016 (Released:2016-08-31)

参考文献数

15

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To overcome the severe donor shortage in lung transplantation, it is crucial to use the marginal donor lungs and lungs from cardiac-death donors, which are supposed to be actually or potentially damaged. To utilize these damaged donor lungs safely, it is important to evaluate such donor lungs objectively before lung transplantation. Recently, ex vivo lung perfusion (EVLP) was developed and has been introduced internationally. Several clinical trials are also ongoing in Europe and North America. In this situation, we also established EVLP in small and large animals. Then, we have investigated the quality of donor lungs using EVLP and tried to treat the donor lungs during EVLP before lung transplantation. We also established several injured lung models and performed various experiments using EVLP, proving that damaged donor lungs could be treated with several drugs using EVLP. Furthermore, we investigated the detection of the regional lung damage using thermography. Herein, we demonstrated our findings and discussed the future of EVLP.

著者

高橋 将文

出版者

一般社団法人 日本臓器保存生物医学会

雑誌

Organ Biology (ISSN:13405152)

巻号頁・発行日

vol.25, no.2, pp.205-206, 2018 (Released:2018-07-24)

著者

小林 英司

出版者

一般社団法人 日本臓器保存生物医学会

雑誌

Organ Biology (ISSN:13405152)

巻号頁・発行日

vol.19, no.1, pp.107-108, 2012-07-10 (Released:2014-11-26)

参考文献数

3

著者

村田 聡一郎 大河内 信弘

出版者

一般社団法人 日本臓器保存生物医学会

雑誌

Organ Biology (ISSN:13405152)

巻号頁・発行日

vol.21, no.2, pp.271-273, 2014-07-10 (Released:2014-11-10)

参考文献数

12

著者

深井 原 島田 慎吾 若山 顕治 嶋村 剛 山下 健一郎 藤堂 省 武冨 紹信

出版者

一般社団法人 日本臓器保存生物医学会

雑誌

Organ Biology (ISSN:13405152)

巻号頁・発行日

vol.20, no.2, pp.176-180, 2013-07-10 (Released:2014-11-26)

参考文献数

17

被引用文献数

1

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Extended criteria donor(ECD)グラフトの安全な利用のために,新しい臓器修復,保存法の実用化が求められている.単純冷保存に対する臓器灌流の優位性は腎移植,肝移植で示された.心停止グラフトは,摘出後ただちに酸素化灌流すれば灌流温度によらず修復されるが,灌流前に冷保存が加わると修復されがたい.本稿では,腎臓,肝臓の単純冷保存と臓器灌流の知見を整理し,実用性の高い方法論を確立するために克服しなければならない課題を明らかにすることを目的とする.

著者

圷 尚武 丸山 通広 大月 和宣 石田 健倫 齋藤 友永 西郷 健一 長谷川 正行 青山 博道 剣持 敬 野口 洋文

出版者

一般社団法人 日本臓器保存生物医学会

雑誌

Organ Biology

巻号頁・発行日

vol.24, no.2, pp.175-179, 2017

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1型糖尿病に対する膵島移植が国内で始まったものの,依然として大きな問題はドナー不足である.その解決手段のひとつとして,心停止下ドナーのような,条件の悪いいわゆるマージナルドナーより採取された膵臓の有効な利用である.LifePort^TM(LP)はOrgan Recovery Systems社により開発された臓器搬送用の持続冷却灌流装置であり,現在欧米において障害を伴った腎臓の搬送に臨床応用され,その有効性が確認されている.本装置はマージナルドナーから採取された臓器移植,特に虚血再潅流障害を受けやすい膵臓の保存に有用で,膵島移植の安全性や成績の向上に有効であると考えられる.本研究では,ビーグル犬を使用し,障害膵モデルより膵臓を摘出し,LPにより持続冷却灌流保存することにより,膵臓の障害が最小限に抑えられ,従来法であるUW液や2層法による浸漬保存に比べて分離膵島の収量や機能が改善でき,臨床膵島移植に応用し,成績向上に寄与することを目的とした.[方法]ビーグル犬から30分の温阻血時間をおいて全膵を摘出し,LPにて24時間持続冷却灌流保存(LP群),UW液にて24時間冷却浸漬保存(UW群),2層法にて24時間冷却浸漬保存(2層法群)し,膵島分離を行い,その形態・機能を比較検討した.[結果]形態的には,LP群でより大きく,形の良い膵島が分離できた.また,膵島収量については,純化前後でLP群においてUW群や2層法群に比べて良好であった.また,分離膵島のインスリン分泌能を評価するStatic Incubationの結果でも,LP群でUW群や2層法群に比べて良好な結果であった.[結論]心停止下ドナーよりの膵島移植を想定したモデルにおいて,LPによる障害膵の持続冷却灌流保存は,UW液や2層法による冷却浸漬保存に比べて,分離膵島の収量や機能保持に優れていることが示唆された.しかし,臨床応用のためには,さらなる保存条件や膵島分離法の改善が必要であると考えられた.

著者

絵野沢 伸

出版者

一般社団法人 日本臓器保存生物医学会

雑誌

Organ Biology

巻号頁・発行日

vol.24, no.1, pp.91-92, 2017

著者

本間 真人

出版者

一般社団法人 日本臓器保存生物医学会

雑誌

Organ Biology (ISSN:13405152)

巻号頁・発行日

vol.19, no.1, pp.91-97, 2012-07-10 (Released:2014-11-26)

参考文献数

15

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Pharmacogenetic information in the package insert was reviewed. Most of the information was gene polymorphisms for the drug metabolizing enzymes such as cytochrome-P450 (CYP) and UDP-glucuronyl transferase(UGT), which alter the pharmacokinetics for substrate drugs resulting in individual variation of drug response including efficacy and adverse effects. In the typical substrates for these enzymes (proton pump inhibitors, clopidogrel, irinotecan and warfarin), difference in the pharmacological efficacy and side effects are discussed among the patients groups carrying different genotypes. HLA types identified for drug-induced serious dermatitis and hypersensitivity for abacavir, carbanazepine and alloprinol are also included in this review.

著者

山本 景子 嶋本 隆司

出版者

一般社団法人 日本臓器保存生物医学会

雑誌

Organ Biology (ISSN:13405152)

巻号頁・発行日

vol.21, no.1, pp.49-59, 2014-01-10 (Released:2014-04-10)

参考文献数

34

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It takes long time and huge cost to develop new drugs. However, average successrate from first-in human to registration in all therapeutic areas is approximately 11%. Notably,success rate in oncology area is 5% or less. Development of new drugs carries out under generalconsideration for clinical trials(ICH E8)and therapeutic guidelines. The treatment landscape ofoncology is rapidly changing. Antineoplastic drugs have been developed from non-specificcytotoxic drugs to specific molecular targeted agents sometimes with companion diagnostics. Theantineoplastic drug should be developed in each type of cancer and this article shows how to developantineoplastic drugs and current treatment landscape in lung cancer, colorectal cancer, and breastcancer as representative cancer types. In addition, development of immunotherapy is emerging inmalignant melanoma and probably beyond this indication.Recently, Ipilimumab (an antibody against cytotoxic T-lymphocyte-associated antigen 4[CTLA-4]) and Vemurafenib (BRAF kinase inhibitor) were approved by US Food and DrugAdministration(FDA). New treatment of immunotherapies incorporates in this article, including theanti-PD-1 antibody which can inhibit newly identified immune check point.

著者

家入 一郎

出版者

一般社団法人 日本臓器保存生物医学会

雑誌

Organ Biology (ISSN:13405152)

巻号頁・発行日

vol.21, no.2, pp.247-253, 2014-07-10 (Released:2014-11-10)

参考文献数

7

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Genetic information, which is useful for understanding and describing large interindividual differences in the pharmacokinetics and pharmacodynamics of clinically useful drugs, is continuously increasing. Genetic polymorphism in drug metabolizing enzymes and drug transporters has been focused on currently, especially for cytochrome P-450s (CYPs, such as CYP2C9, CYP2C19, and CYP2D6), and organic anion transporting polypeptides 1B1(OATP1B1)and pglycoprotein, respectively, are available in various clinical situations. Currently in Japan, pharmacogenomic(PGx)observations are incorporated into drug labels(for various types of drugs such as proton pump inhibitors(PPIs), anti-cancer drugs and NSAIDs), highly advanced medical technology(e. g., CYP2C19 genotyping for eradication of H. pylori by PPIs), and national healthcare insurance for the genotyping test(e. g., UGT1A1 genotyping in irinotecan therapy). Nevertheless, the clinical uptake of PGx knowledge has been limited. Concise and reproducible evidences, the genotyping cost, and education of PGx utility for medical staffs should be considered for the future medicine.

著者

松野 直徒

出版者

一般社団法人 日本臓器保存生物医学会

雑誌

Organ Biology (ISSN:13405152)

巻号頁・発行日

vol.22, no.1, pp.66-68, 2015 (Released:2015-09-10)