Les copolymères à blocs contenant une partie souple et une partie dure constituent aujourd'hui une classe de matériaux très attractifs en raison de leurs propriétés résultant de la combinaison de deux homopolymères de nature différente. Dans le cadre des copolymères à blocs à forte teneur en polydiméthylsiloxane (PDMS), une méthode de synthèse originale en deux étapes, compatibilisation puis extension, a été développée. Respectueuse de l'environnement grâce à l'utilisation du procédé d'extrusion réactive, cette approche ouvre une nouvelle voie vers le développement d'élastomères thermoplastiques. L'objectif de cette thèse est d'élaborer à l'état fondu des copolymères à blocs à base de PDMS silicone à partir de la réaction époxy-amine puis, par une réaction d'allongement d'obtenir un matériau avec une forte proportion en PDMS. Dans un premier temps, une étude de la réaction époxy-amine sur molécules modèles a été réalisée à partir d'oligodiméthylsiloxanes α,ω- fonctionnalisés époxy et d'une alkylamine. Indépendamment de la température et du ratio molaire, la réaction a permis d'obtenir des copolymères greffés de type (A2B2)n. Dans un deuxième temps, cette stratégie a ensuite été appliquée à des systèmes polymères tels que le polyéthylène et le polyamide. A cette échelle, la réaction s'est produite et conduit à des produits de type (A2B2)n. Dans un troisième temps, l'ensemble des copolymères synthétisés ont été étudiés lors de la réaction d'allongement, basée sur l'insertion de siloxanes cycliques à l'aide d'une superbase. Dépendante de la température et de la quantité de catalyseur, cette réaction a été étudiée sur molécules modèles et sur des systèmes polymères / Nowadays hard-soft block copolymers consist of a very attractive material class because of their properties resulting of the combination of two different homopolymers. In the case of block copolymers with on a high polydiméthylsiloxane (PDMS) content, an innovative 2-step synthesis method, compatibilization and extension, has been developed. Using an environmental friendly route such as a reactive extrusion process, this approach opens a new synthesis pathway towards the development of thermoplastic elastomers. The goal of this thesis is to develop mass block copolymers based on PDMS using the epoxy-amine reaction, followed by an extension reaction to reach a material with a high percent of silicone. Firstly, a study of the epoxy-amine reaction on model molecules was carried out between a low molecular weight PDMS and an alkylamine. Independently of the temperature and the molar ratio, the reaction allowed to obtain graft copolymers with an (A2B2)n type structures. Secondly, this strategy has then been applied in polymer systems such as polyethylene and polyamide. At this scale, the reaction occurred and lead to products with (A2B2)n type structures. Thirdly, all synthesized copolymers were studied during the extension reaction, based on the insertion of cyclic siloxanes using a catalysis system. Depending of the temperature and the catalyst quantity, this reaction was investigated on model molecules and polymer systems

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第20225号 / 医博第4184号 / 新制||医||1019(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 伊達 洋至, 教授 Shohab YOUSSEFIAN, 教授 川村 孝 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第21018号 / 医博第4364号 / 新制||医||1028(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 小川 誠司, 教授 柳田 素子, 教授 江藤 浩之 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

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Objectives: Adequate organ perfusion, as well as appropriate blood pressure levels at the time of unclamping, is crucial for early and long-term graft function and outcome in simultaneous pancreas–kidney transplantation (SPKT). However, the optimal intraoperative mean arterial pressure (MAP) level has not well been defined. Methods: From a prospectively collected database, the medical data of 105 patients undergoing SPKT at our center were retrospectively analyzed. A receiver operating characteristic (ROC) analysis was preliminarily performed for optimal cut-off value for MAP at reperfusion, to predict early pancreatic graft function. Due to these results, we divided the patients according to their MAP values at reperfusion into <91 mmHg (n = 47 patients) and >91 mmHg (n = 58 patients) groups. Clinicopathological characteristics and outcomes, as well as early graft function and long-term survival, were retrospectively analyzed. Results: Donor and recipient characteristics were comparable between both groups. Rates of postoperative complications were significantly higher in the <91 mmHg group than those in the >91 mmHg group (vascular thrombosis of the pancreas: 7 (14%) versus 2 (3%); p = 0.03; pancreatitis/intraabdominal abscess: 10 (21%) versus 4 (7%); p = 0.03; renal delayed graft function (DGF): 11 (23%) versus 5 (9%); p = 0.03; postreperfusion urine output: 106 ± 50 mL versus 195 ± 45 mL; p = 0.04). There were no significant differences in intraoperative volume repletion, central venous pressure (CVP), use of vasoactive inotropic agents, and the metabolic outcome. Five-year pancreas graft survival was significantly higher in the >91 mmHg group (>91 mmHg: 82% versus <91 mmHg: 61%; p < 0.01). No significant differences were observed in patient and kidney graft survival at 5 years between both groups. Multivariate Cox regression analysis affirmed MAP < 91 mmHg as an independent prognostic predictor for renal DGF (HR 3.49, 1.1–10.8, p = 0.03) and pancreas allograft failure (HR 2.26, 1.0–4.8, p = 0.01). Conclusions: A MAP > 91 mmHg at the time point of reperfusion was associated with a reduced rate of postoperative complications, enhancing and recovering long-term graft function and outcome and thus increasing long-term survival in SPKT recipients.

Mesenchymal stem cells and their regenerative and immunomodulatory potential Abstract Mesenchymal stem cells (MSCs) possess multidirectional regenerative ability, which, together with their immunomodulatory potential, makes them promising cell type for therapy of wide variety of diseases. Despite ongoing research, which proved MSCs application to be safe, reported effect of MSCs administration on patients is not convincingly beneficial yet. In our work we focused on elucidation of MSCs role in regeneration of vital organs, heart and liver, where a large damage is life threatening for patients and any improvement in therapy would save many lives. Similar situation is in Graft versus host disease (GVHD), where MSCs immunomodulatory properties could be beneficial. Role of MSCs in heart regeneration was examined in vitro. Primary adult swine cardiomyocytes (CMCs) were co-cultured with or without swine MSCs for 3 days and morphological and functional parameters (contractions, current, respiration) of CMCs were measured. MSCs showed supportive effect on CMCs survival, especially at day 3 of the experiment, where in co-culture was significantly higher number of viable CMCs with physiological morphology and maintained function. Effect of MSCs on liver regeneration was observed in swine model of chronic liver...

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No description available.

Background: Patients with steroid-refractory intestinal acute graft-versus-host disease (aGvHD) and bronchiolitis obliterans syndrome (BOS) represent a population with a high need for alternative and effective treatment options. Methods: We report real-life data from 18 patients treated with extracorporeal photopheresis (ECP). This cohort consisted of nine patients with steroid-refractory intestinal aGvHD and nine patients with BOS. Results: We document partial or complete clinical response and reduction of symptoms in half of the patients with intestinal acute GvHD and patients with BOS treated ECP. Responding patients tended to stay on treatment longer. In patients with BOS, stabilization of lung function and forced expiratory volume was observed, whereas, less abdominal pain, less diarrhea, and a reduction of systemic corticosteroids were seen in patients with intestinal acute GvHD. Conclusions: ECP might not only abrogate symptoms but also reduce mortality caused by complications from high-dose steroid treatment. Taken together, ECP offers a serious treatment avenue for patients with steroid-refractory intestinal acute GvHD and BOS.

Background/Objectives: The sequence of graft implantation in simultaneous pancreas-kidney transplantation (SPKT) warrants additional study and more targeted focus, since little is known about the short- and long-term effects on the outcome and graft survival after transplantation. Material and methods: 103 patients receiving SPKT in our department between 1999 and 2015 were included in the study. Patients were divided according to the sequence of graft implantation into pancreas-first (PF, n = 61) and kidney-first (KF, n = 42) groups. Clinicopathological characteristics, outcome and survival were reviewed retrospectively. Results: Donor and recipient characteristics were similar. Rates of post-operative complications and graft dysfunction were significantly higher in the PF group compared with the KF group (episodes of acute rejection within the first year after SPKT: 11 (18%) versus 2 (4.8%); graft pancreatitis: 18 (18%) versus 2 (4.8%), p = 0.04; vascular thrombosis of the pancreas: 9 (14.8%) versus 1 (2.4%), p = 0.03; and delayed graft function of the kidney: 12 (19.6%) versus 2 (4.8%), p = 0.019). The three-month pancreas graft survival was significantly higher in the KF group (PF: 77% versus KF: 92.1%; p = 0.037). No significant difference was observed in pancreas graft survival five years after transplantation (PF: 71.6% versus KF: 84.8%; p = 0.104). Kidney graft survival was similar between the two groups. Multivariate analysis revealed order of graft implantation as an independent prognostic factor for graft survival three months after SPKT (HR 2.6, 1.3–17.1, p = 0.026) and five years (HR 3.7, 2.1–23.4, p = 0.040). Conclusion: Our data indicates that implantation of the pancreas prior to the kidney during SPKT has an influence especially on the early-post-operative outcome and survival rate of pancreas grafts.