mouse-model-for-pancreas-transplantation-using-modified-cuff

Mouse Model for Pancreas Transplantation Using a Modified Cuff Technique

Mouse models have several advantages in transplantation research, including easy handling, a variety of genetically well-defined strains, and the ...

Medical University Innsbruck

&#x957F;&#x671F;&#x751F;&#x5B58;&#x540E;&#x56FA;&#x4F53;&#x5668;&#x5B98;&#x79FB;&#x690D;&#x800C;&#x53D7;&#x5230;&#x4E86;&#x52A8;&#x8109;&#x8840;&#x7BA1;&#x79FB;&#x690D;&#x672F;&#x540E;&#x3001; &#x6162;&#x6027;&#x53D8;&#x5316;&#x79F0;&#x4E3A;&#x6162;&#x6027;&#x79FB;&#x690D;&#x80BE;&#x8840;&#x7BA1;&#x75C5;&#x53D8; (&#x7EA4;)&#x3002;&#x75C5;&#x53D8;&#x4E3B;&#x8981;&#x5305;&#x62EC;&#x589E;&#x6B96;&#x5BFC;&#x81F4;&#x8239;&#x53EA; &#xFF1B; &#x6536;&#x7A84;&#x7684;&#x8840;&#x7BA1;&#x5E73;&#x6ED1;&#x808C;&#x7EC6;&#x80DE;&#x8FD9;&#x4E9B;&#x75C5;&#x53D8;&#x53EF;&#x5728;&#x51E0;&#x4E2A;&#x6708;&#x5185;&#x5236;&#x5B9A;&#x3002;&#x6CA1;&#x6709;&#x6709;&#x6548;&#x7684;&#x6CBB;&#x7597;&#xFF0C;&#x4EE5;&#x9632;&#x6B62;&#x7A74;&#x6211;&#x4EEC;&#x4EE5;&#x524D;&#x6307;&#x51FA;&#x7684; p38 &#x4E1D;&#x88C2;&#x7D20;&#x6D3B;&#x5316;&#x86CB;&#x767D;&#x6FC0;&#x9176; (MAPK) &#x6291;&#x5236;&#x836F;&#x7406;&#x4F5C;&#x7528;&#x6291;&#x5236;&#x8840;&#x7BA1;&#x5E73;&#x6ED1;&#x808C;&#x7EC6;&#x80DE;&#x7684;&#x589E;&#x6B96;&#x3002;&#x6211;&#x4EEC;&#x5047;&#x8BBE;&#xFF0C;&#x4F53;&#x5185;&#x6291;&#x5236; p38 MAPK &#x5728;&#x5C0F;&#x9F20;&#x540C;&#x79CD;&#x5F02;&#x4F53;&#x52A8;&#x8109;&#x79FB;&#x690D;&#x5C06;&#x9632;&#x6B62;&#x7A74;&#x6211;&#x4EEC;&#x5728;&#x8FD9;&#x91CC;&#x62A5;&#x544A;&#x8FD9;&#x79CD;&#x5C01;&#x9501;&#x7684; p38 MAPK&#xFF0C;&#x4E00;&#x4E2A;&#x4FE1;&#x53F7;&#x5206;&#x5B50;&#x53C2;&#x4E0E;&#x7EC6;&#x80DE;&#x51CB;&#x4EA1;&#x3001; &#x7EC6;&#x80DE;&#x5206;&#x88C2;&#x548C;&#x7EC6;&#x80DE;&#x6B7B;&#x4EA1;&#xFF0C;&#x663E;&#x8457;&#x6291;&#x5236;&#x7A74;&#x9274;&#x4E8E;&#x6700;&#x8FD1;&#x7684;&#x6570;&#x636E;&#x8868;&#x660E;&#x6291;&#x5236; p38 MAPK &#x6709;&#x5E0C;&#x671B;&#x7684;&#x65B9;&#x6CD5;&#x6CBB;&#x7597;&#x81EA;&#x8EAB;&#x514D;&#x75AB;&#x6027;&#x75BE;&#x75C5;&#xFF0C;&#x52A0;&#x4E0A;&#x6211;&#x4EEC;&#x76EE;&#x524D;&#x7684;&#x7814;&#x7A76;&#x7ED3;&#x679C;&#xFF0C;&#x7EA4;&#x7684; p38 MAPK &#x5C01;&#x9501;&#x4F3C;&#x4E4E;&#x662F;&#x4E00;&#x4E2A;&#x5408;&#x7406;&#x7684;&#x65B9;&#x6CD5;&#x5E94;&#x8003;&#x8651;&#x7684;&#x4E34;&#x5E8A;&#x5E94;&#x7528;&#x3002;

&#x5C01;&#x9501;&#x7684; p38 MAPK &#x6291;&#x5236;&#x6162;&#x6027;&#x79FB;&#x690D;&#x80BE;&#x8840;&#x7BA1;&#x75C5;&#x53D8;&#x3002;

Long-term survival after solid-organ transplantation is hampered by chronic changes in the arteries of the grafts, called chronic allograft vasculopathy (CAV). The lesions consist mainly of proliferating vascular smooth muscle cells that cause narrowing of the vessels; these lesions can develop within a few months. There is no effective treatment to prevent CAV. We previously noted that the pharmacological inhibition of p38 mitogen-activated protein kinase (MAPK) suppresses the proliferation of vascular smooth muscle cells. We hypothesized that in vivo inhibition of p38 MAPK in mice bearing allogeneic aortic allografts would prevent CAV. We here report that blockade of p38 MAPK, a signaling molecule involved in cell division, apoptosis, and cell death, markedly suppresses CAV. Given recent data indicating that inhibition of p38 MAPK is a promising approach for the treatment of autoimmune diseases plus our present findings, p38 MAPK blockade for CAV seems a reasonable approach to consider for clinical application.

Blockade of p38 MAPK inhibits chronic allograft vasculopathy.

La survie &agrave; long terme apr&egrave;s que la transplantation d&#39;organes solides est entrav&eacute;e par des changements dans les art&egrave;res des greffons, chroniques appel&eacute;e vasculopathie chronique allogreffe (CAV). Les l&eacute;sions consistent principalement en des cellules musculaires lisses vasculaires prolif&egrave;rent qui causent le r&eacute;tr&eacute;cissement des vaisseaux ; ces l&eacute;sions peuvent se d&eacute;velopper dans les prochains mois. Il n&#39;y a aucun traitement efficace pour pr&eacute;venir la CAV. Nous avons remarqu&eacute; pr&eacute;c&eacute;demment que l&#39;inhibition pharmacologique de p38 mitogen-activated protein kinase (MAPK) supprime la prolif&eacute;ration des cellules musculaires lisses vasculaires. Nous avons suppos&eacute; que, in vivo, l&#39;inhibition de p38 MAPK dans des souris porteuses d&#39;une allogreffe aortique allog&eacute;nique emp&ecirc;cherait CAV. Nous rapportons ici que le blocage de p38 MAPK, une mol&eacute;cule de signalisation impliqu&eacute;e dans la division cellulaire, l&#39;apoptose et la mort des cellules, supprime nettement CAV. Compte tenu des donn&eacute;es r&eacute;centes indiquant que l&#39;inhibition de p38 MAPK est une approche prometteuse pour le traitement de maladies auto-immunes ainsi que nos r&eacute;sultats, blocus MAPK p38 pour CAV semble une approche raisonnable pour prendre en compte pour l&#39;application clinique.

Blocus de p38 MAPK inhibe la vasculopathie chronique d&#39;allogreffe.

Langfristiges &Uuml;berleben nach Solid-Organtransplantation durch chronische Ver&auml;nderungen in den Arterien des die Grafts behindert wird genannt chronische Allograft Vaskulopathie (CAV). Die Hautver&auml;nderungen bestehen haupts&auml;chlich aus proliferierenden Zellen vaskul&auml;rer Glatter Muskelzellen, die Verengung der Gef&auml;&szlig;e verursachen; Diese L&auml;sionen entwickeln sich innerhalb weniger Monate. Es gibt keine wirksamer Behandlung zur Verhinderung von CAV. Wir erw&auml;hnt, dass die pharmakologische Hemmung der p38 Mitogen-aktivierte Proteinkinase (MAPK) die Verbreitung von vaskul&auml;ren glatten Muskelzellen unterdr&uuml;ckt. Wir die Hypothese auf, dass in Vivo Hemmung der p38 MAPK bei M&auml;usen mit allogener aortalen Herztransplanate CAV verhindern w&uuml;rde Wir hier Berichten die Blockade der p38 MAPK, eine signalisierende Molek&uuml;l Zellteilung, Apoptosis, beteiligt und Zelle Tod, deutlich unterdr&uuml;ckt Cav. Aktuelle Daten, dass die Hemmung der p38 MAPK ist ein vielversprechender Ansatz f&uuml;r die Behandlung von Autoimmunerkrankungen sowie unsere derzeitigen Erkenntnisse gegeben, scheint p38 MAPK Blockade f&uuml;r CAV ein vern&uuml;nftiger Ansatz f&uuml;r die klinische Anwendung zu pr&uuml;fen.

Blockade der p38 MAPK hemmt chronischen Allograft Vaskulopathie.

Sopravvivenza a lungo termine dopo trapianto di organo solido &egrave; ostacolato dalla croniche cambiamenti nelle arterie degli innesti, chiamata vasculopatia cronica allotrapianto (CAV). Le lesioni consistono principalmente di cellule muscolari lisce vascolari proliferanti che causano il restringimento dei vasi; Queste lesioni possono sviluppare entro pochi mesi. Non non c&#39;&egrave; alcun trattamento efficace per evitare che il CAV. Abbiamo notato in precedenza che l&#39;inibizione farmacologica della chinasi di proteina mitogene-attivata p38 (MAPK) sopprime la proliferazione delle cellule muscolari lisce vascolari. Abbiamo ipotizzato che in vivo, inibizione di p38 MAPK nei topi cuscinetto allogenici allograft aortica impedirebbe Cav. Abbiamo qui segnalare quel blocco di p38 MAPK, una molecola di segnalazione coinvolta nella divisione cellulare, apoptosi e morte delle cellule, marcatamente sopprime Cav. Dato recenti dati indicano che l&#39;inibizione di p38 MAPK &egrave; un approccio promettente per il trattamento di malattie autoimmuni pi&ugrave; i nostri risultati presenti, blocco di p38 MAPK per CAV sembra un approccio ragionevole considerare per l&#39;applicazione clinica.

Blocco di p38 MAPK inibisce la vasculopatia cronica allotrapianto.

&#x56FA;&#x5F62;&#x81D3;&#x5668;&#x79FB;&#x690D;&#x52D5;&#x8108;&#x30B0;&#x30E9;&#x30D5;&#x30C8;&#x3001;&#x6162;&#x6027;&#x7684;&#x306A;&#x5909;&#x5316;&#x306B;&#x3088;&#x3063;&#x3066;&#x59A8;&#x3052;&#x3089;&#x308C;&#x3066;&#x3044;&#x308B;&#x5F8C;&#x306E;&#x9577;&#x671F;&#x751F;&#x5B58;&#x306F;&#x6162;&#x6027;&#x540C;&#x7A2E;&#x8840;&#x7BA1;&#x75C7; (CAV) &#x3068;&#x547C;&#x3070;&#x308C;&#x307E;&#x3059;&#x3002;&#x75C5;&#x5909;&#x306F;&#x8840;&#x7BA1;&#x306E;&#x72ED;&#x7A84;&#x3092;&#x5F15;&#x304D;&#x8D77;&#x3053;&#x3059;&#x4E3B;&#x306B;&#x8840;&#x7BA1;&#x5E73;&#x6ED1;&#x7B4B;&#x306E;&#x7D30;&#x80DE;&#x5897;&#x6B96;&#x3067;&#x3042;&#x308A;&#x307E;&#x3059;&#x3002;&#x3053;&#x308C;&#x3089;&#x306E;&#x75C5;&#x5909;&#x306F;&#x6570;&#x30F6;&#x6708;&#x4EE5;&#x5185;&#x306B;&#x958B;&#x767A;&#x3067;&#x304D;&#x307E;&#x3059;&#x3002;&#x305A;&#x308A;&#x3053;&#x307F;&#x3092;&#x9632;&#x3050;&#x305F;&#x3081;&#x306B;&#x52B9;&#x679C;&#x7684;&#x306A;&#x6CBB;&#x7642;&#x6CD5;&#x306F;&#x306A;&#x3044;&#x3067;&#x3059;&#x3002;&#x6211;&#x3005; &#x306F;&#x4EE5;&#x524D; p38 &#x30DE;&#x30A4;&#x30C8;&#x30B8;&#x30A7;&#x30F3;&#x6D3B;&#x6027;&#x5316;&#x30D7;&#x30ED;&#x30C6;&#x30A4;&#x30F3;&#x30AD;&#x30CA;&#x30FC;&#x30BC; &#xFF08;MAPK&#xFF09; &#x306E;&#x85AC;&#x7406;&#x4F5C;&#x7528;&#x306E;&#x963B;&#x5BB3;&#x304C;&#x8840;&#x7BA1;&#x5E73;&#x6ED1;&#x7B4B;&#x7D30;&#x80DE;&#x306E;&#x5897;&#x6B96;&#x3092;&#x6291;&#x5236;&#x3059;&#x308B;&#x3053;&#x3068;&#x3092;&#x6307;&#x6458;&#x3057;&#x307E;&#x3057;&#x305F;&#x3002;&#x751F;&#x4F53;&#x5185;&#x306E;&#x305A;&#x308A;&#x3053;&#x307F;&#x30DE;&#x30A6;&#x30B9;&#x540C;&#x7A2E;&#x5927;&#x52D5;&#x8108;&#x79FB;&#x690D;&#x30E2;&#x30C7;&#x30EB;&#x3092;&#x8EF8;&#x53D7;&#x306B;&#x304A;&#x3051;&#x308B; p38 MAPK &#x306E;&#x963B;&#x5BB3;&#x3092;&#x9632;&#x3050;&#x3060;&#x308D;&#x3046;&#x3001;&#x6211;&#x3005; &#x3068;&#x4EEE;&#x5B9A;&#x6211;&#x3005; &#x306F;&#x3001;p38 MAPK &#x30B7;&#x30B0;&#x30CA;&#x30EB;&#x5206;&#x5B50;&#x306E;&#x7D30;&#x80DE;&#x5206;&#x88C2;&#x3001;&#x30A2;&#x30DD;&#x30C8;&#x30FC;&#x30B7;&#x30B9;&#x3001;&#x95A2;&#x4E0E;&#x306E;&#x5C01;&#x9396;&#x3092;&#x3053;&#x3053;&#x3067;&#x5831;&#x544A;&#x3057;&#x7D30;&#x80DE;&#x6B7B;&#x3001;&#x8457;&#x3057;&#x304F;&#x305A;&#x308A;&#x3053;&#x307F;&#x3092;&#x6291;&#x5236;&#x3057;&#x307E;&#x3059;&#x3002;P38 MAPK &#x306E;&#x963B;&#x5BB3;&#x304C;&#x81EA;&#x5DF1;&#x514D;&#x75AB;&#x75BE;&#x60A3;&#x306B;&#x52A0;&#x3048;&#x3066;&#x79C1;&#x9054;&#x306E;&#x5B58;&#x5728;&#x306E;&#x8ABF;&#x67FB;&#x7D50;&#x679C;&#x306E;&#x6CBB;&#x7642;&#x306E;&#x305F;&#x3081;&#x306E;&#x6709;&#x671B;&#x306A;&#x30A2;&#x30D7;&#x30ED;&#x30FC;&#x30C1;&#x3067;&#x3042;&#x308B;&#x3053;&#x3068;&#x3092;&#x793A;&#x3059;&#x6700;&#x8FD1;&#x306E;&#x30C7;&#x30FC;&#x30BF;&#x3092;&#x4E0E;&#x3048;&#x3001;p38 MAPK &#x5C01;&#x9396; CAV &#x306E;&#x5408;&#x7406;&#x7684;&#x306A;&#x30A2;&#x30D7;&#x30ED;&#x30FC;&#x30C1;&#x3078;&#x306E;&#x81E8;&#x5E8A;&#x5FDC;&#x7528;&#x3092;&#x691C;&#x8A0E;&#x3059;&#x308B;&#x3088;&#x3046;&#x3067;&#x3059;&#x3002;

P38 MAPK &#x306E;&#x5C01;&#x9396;&#x6162;&#x6027;&#x540C;&#x7A2E;&#x8840;&#x7BA1;&#x75C7;&#x3092;&#x6291;&#x5236;&#x3057;&#x307E;&#x3059;&#x3002;

&#xC194;&#xB9AC;&#xB4DC;-&#xC7A5;&#xAE30; &#xC774;&#xC2DD;, &#xC774;&#xC2DD;&#xC758; &#xB3D9;&#xB9E5;&#xC758; &#xB9CC;&#xC131; &#xBCC0;&#xD654;&#xC5D0; &#xC758;&#xD574; &#xBC29;&#xD574; &#xD6C4; &#xC7A5;&#xAE30; &#xC0DD;&#xC874; &#xB9CC;&#xC131; allograft vasculopathy (&#xAE30;&#xAC11; &#xBD80; &#xB300;) &#xB77C;&#xACE0; &#xD569;&#xB2C8;&#xB2E4;. &#xBCD1; &#xBCC0;&#xC774; &#xC8FC;&#xB85C;; &#xD608;&#xAD00;&#xC774; &#xC881;&#xC544;&#xC9C0;&#xB294; &#xC6D0;&#xC778; &#xBC29;&#xC9C0;&#xD560; &#xD608;&#xAD00; &#xD3C9;&#xD65C; &#xADFC; &#xC138;&#xD3EC;&#xB97C; &#xAD6C;&#xC131; &#xC774;&#xB7EC;&#xD55C; &#xBCD1; &#xBCC0;&#xC740; &#xBA87; &#xAC1C;&#xC6D4; &#xC774;&#xB0B4;&#xC5D0; &#xAC1C;&#xBC1C;&#xD560; &#xC218; &#xC788;&#xC2B5;&#xB2C8;&#xB2E4;. CAV.&#xB97C; &#xBC29;&#xC9C0; &#xD558;&#xAE30; &#xC704;&#xD574; &#xD6A8;&#xACFC;&#xC801;&#xC778; &#xCE58;&#xB8CC;&#xAC00;&#xC785;&#xB2C8;&#xB2E4;. &#xC6B0;&#xB9AC;&#xB294; &#xC774;&#xC804;&#xC5D0; &#xC57D;&#xB9AC; &#xC5B5;&#xC81C; p38 &#xBB3C;&#xC9C8; &#xD65C;&#xC131;&#xD654; &#xD55C; &#xB2E8;&#xBC31;&#xC9C8; &#xD0A4; &#xB2C8; &#xC544; &#xC81C; (MAPK)&#xC758; &#xD608;&#xAD00; &#xD3C9;&#xD65C; &#xADFC; &#xC138;&#xD3EC;&#xC758; &#xC99D;&#xC2DD; &#xC5B5;&#xC81C;&#xB97C; &#xC9C0;&#xC801; &#xD588;&#xB2E4;. &#xC6B0;&#xB9AC;&#xB294; &#xBE44;&#xBCF4; &#xC5B5;&#xC81C; &#xC0DD;&#xC950; allogeneic &#xB300;&#xB3D9;&#xB9E5; allografts &#xBCA0;&#xC5B4;&#xB9C1;&#xC5D0;&#xC11C; p38 MAPK&#xC758; CAV.&#xB97C; &#xBC29;&#xC9C0; &#xAC83;&#xC774; &#xAC00;&#xC124; &#xC6B0;&#xB9AC; &#xC5EC;&#xAE30; &#xBCF4;&#xACE0; &#xADF8; &#xBD09;&#xC1C4; p38 MAPK, apoptosis, &#xC138;&#xD3EC; &#xBD84;&#xC5F4;&#xC5D0; &#xAD00;&#xB828; &#xB41C; &#xC2E0;&#xD638; &#xBD84;&#xC790;&#xC758; &#xC138;&#xD3EC; &#xC8FD;&#xC74C;, &#xD604;&#xC800; &#xD558; &#xAC8C; &#xC5B5;&#xC81C; CAV. P38 MAPK&#xC758; &#xC800;&#xD574; &#xC6B0;&#xB9AC;&#xC758; &#xD604;&#xC7AC; &#xC5F0;&#xAD6C; &#xACB0;&#xACFC; &#xBA74;&#xC5ED; &#xC9C8;&#xD658;&#xC758; &#xCE58;&#xB8CC;&#xB97C; &#xC704;&#xD55C; &#xC720;&#xB9DD;&#xD55C; &#xC811;&#xADFC;&#xBC95;&#xC744; &#xB098;&#xD0C0;&#xB0B4;&#xB294; &#xCD5C;&#xADFC; &#xB370;&#xC774;&#xD130;&#xB97C; &#xAC10;&#xC548;&#xD560; &#xB54C;, p38 MAPK &#xBD09;&#xC1C4; &#xAE30;&#xAC11; &#xBD80; &#xB300;&#xC5D0; &#xB300; &#xD55C; &#xC784;&#xC0C1; &#xC751;&#xC6A9; &#xD504;&#xB85C;&#xADF8;&#xB7A8;&#xC5D0; &#xB300; &#xD55C; &#xACE0;&#xB824;&#xC5D0; &#xB300; &#xD55C; &#xD569;&#xB9AC;&#xC801;&#xC778; &#xC811;&#xADFC; &#xAC83;&#xC73C;&#xB85C; &#xBCF4;&#xC778;&#xB2E4;.

P38 MAPK&#xC758; &#xBD09;&#xC1C4; &#xB9CC;&#xC131; allograft vasculopathy&#xC744; &#xC5B5;&#xC81C; &#xD55C;&#xB2E4;.

Supervivencia a largo plazo despu&eacute;s de trasplante de &oacute;rgano s&oacute;lido se ve obstaculizado por cambios cr&oacute;nicos en las arterias de los injertos, llamado aloinjerto cr&oacute;nica vasculopathy (CAV). Las lesiones consisten principalmente de proliferar las c&eacute;lulas de m&uacute;sculo liso vascular que causan estrechamiento de los vasos; Estas lesiones pueden desarrollar dentro de unos meses. No hay ning&uacute;n tratamiento eficaz para prevenir la CAV. Anteriormente, observamos que la inhibici&oacute;n farmacol&oacute;gica de p38 quinasa de prote&iacute;nas activadas por mit&oacute;genos (MAPK) suprime la proliferaci&oacute;n de c&eacute;lulas musculares lisas vasculares. Presumimos que en vivo inhibici&oacute;n de p38 MAPK en ratones alog&eacute;nicos aloinjertos a&oacute;rticas impedir&iacute;a CAV. Nos informe aqu&iacute; ese bloqueo de p38 MAPK, una mol&eacute;cula de se&ntilde;alizaci&oacute;n implicada en la divisi&oacute;n celular, apoptosis, muerte celular y suprime marcadamente CAV. Teniendo en cuenta los datos recientes que indican que la inhibici&oacute;n de la p38 MAPK es un enfoque prometedor para el tratamiento de enfermedades autoinmunes m&aacute;s nuestros resultados actuales, bloqueo de p38 MAPK para CAV parece un enfoque razonable considerar para uso cl&iacute;nico.

Bloqueo de p38 MAPK inhibe vasculopathy aloinjerto cr&oacute;nica.

&#x7F3A;&#x8840;&#x98DF;&#x7BA1;&#x764C;&#x5207;&#x9664;&#x672F;&#x540E;&#x53EF;&#x80FD;&#x4F1A;&#x5BFC;&#x81F4;&#x5728;&#x98DF;&#x7BA1;&#x80C3;&#x543B;&#x5408;&#x53E3;&#x6F0F;&#x3002;&#x8FD9;&#x9879;&#x7814;&#x7A76;&#x7684;&#x76EE;&#x7684;&#x662F;&#x8C03;&#x67E5;&#x80C3;&#x5FAE;&#x5FAA;&#x73AF;&#x7684;&#x65F6;&#x7A0B;&#x53D8;&#x5316;&#x540E;&#x7F3A;&#x8840;&#x6027;&#x7A7A;&#x8C03;&#x3002;

&#x7F3A;&#x8840;&#x6027;&#x7A7A;&#x8C03;&#x529F;&#x80FD;&#x6BDB;&#x7EC6;&#x8840;&#x7BA1;&#x5BC6;&#x5EA6;&#xFF1A; &#x5BF9;&#x98DF;&#x7BA1;&#x764C;&#x5207;&#x9664;&#x672F;&#x80C3;&#x901A;&#x9053;&#x7684;&#x5F71;&#x54CD;&#x3002;

Ischemia may lead to leakage at the esophagogastric anastomosis after esophagectomy. The aim of this study was to investigate time dependent changes of gastric microcirculation after ischemic conditioning.

Functional capillary density in ischemic conditioning: implications for esophageal resection with the gastric conduit.

Isch&eacute;mie peut entra&icirc;ner des fuites &agrave; l&#39;anastomose esophagogastric apr&egrave;s OESOPHAGECTOMIE. Le but de cette &eacute;tude &eacute;tait d&#39;&eacute;tudier les modifications d&eacute;pendant de l&#39;heure de la microcirculation gastrique apr&egrave;s conditionnement isch&eacute;mique.

Fonctionnelle de densit&eacute; capillaire dans le conditionnement isch&eacute;mique : implications pour la r&eacute;section oesophagienne avec le tube gastrique.

Isch&auml;mie f&uuml;hren zu Leckage an der Esophagogastric Anastomose nach &Ouml;sophagektomie. Ziel dieser Studie war Zeit abh&auml;ngigen Ver&auml;nderungen der Magen Mikrozirkulation nach isch&auml;mische Konditionierung zu untersuchen.

Funktionale Kapillar Dichte in isch&auml;mische Konditionierung: Implikationen f&uuml;r esophageal Resektion mit dem Magen Conduit.

Ischemia pu&ograve; portare a perdite all&#39;anastomosi seppure dopo esofagectomia. Lo scopo di questo studio era di indagare i cambiamenti di tempo dipendente della microcircolazione gastrico dopo Condizionamento ischemico.

Funzionale densit&agrave; capillare nel condizionamento ischemico: implicazioni per la resezione esofagea con tubo gastrico.

&#x865A;&#x8840;&#x306F;&#x98DF;&#x9053;&#x764C;&#x624B;&#x8853;&#x5F8C;&#x98DF;&#x9053;&#x80C3;&#x543B;&#x5408;&#x90E8;&#x6F0F;&#x6D29;&#x3059;&#x308B;&#x53EF;&#x80FD;&#x6027;&#x304C;&#x3042;&#x308A;&#x307E;&#x3059;&#x3002;&#x5F8C;&#x306E;&#x865A;&#x8840;&#x6027;&#x306E;&#x30B3;&#x30F3;&#x30C7;&#x30A3;&#x30B7;&#x30E7;&#x30CB;&#x30F3;&#x30B0;&#x80C3;&#x5FAE;&#x5C0F;&#x5FAA;&#x74B0;&#x306E;&#x6642;&#x9593;&#x4F9D;&#x5B58;&#x5909;&#x5316;&#x3092;&#x8ABF;&#x67FB;&#x3057;&#x305F;.

&#x865A;&#x8840;&#x6027;&#x306E;&#x30A8;&#x30A2;&#x30B3;&#x30F3;&#x3067;&#x6A5F;&#x80FD;&#x7684;&#x306A;&#x6BDB;&#x7D30;&#x8840;&#x7BA1;&#x5BC6;&#x5EA6;: &#x98DF;&#x9053;&#x5207;&#x9664;&#x80C3;&#x7BA1;&#x306E;&#x305F;&#x3081;&#x306E;&#x542B;&#x610F;&#x3002;

&#xD5C8; &#xD608; &#xD6C4; esophagectomy esophagogastric &#xBB38; &#xD569;&#xC5D0; &#xB204;&#xC124; &#xB420; &#xC218; &#xC788;&#xC2B5;&#xB2C8;&#xB2E4;. &#xC774; &#xC5F0;&#xAD6C;&#xC758; &#xBAA9;&#xD45C;&#xB294; &#xD5C8; &#xD608; &#xC131; &#xCEE8;&#xB514;&#xC154;&#xB2DD; &#xD6C4; &#xC704; &#xBBF8;&#xC138; &#xD608;&#xAD00;&#xC758; &#xC2DC;&#xAC04; &#xC885;&#xC18D; &#xBCC0;&#xD654;&#xB97C; &#xC870;&#xC0AC; &#xD588;&#xB2E4;.

&#xC5D0; &#xD5C8; &#xD608; &#xC131; &#xCEE8;&#xB514;&#xC154;&#xB2DD; &#xAE30;&#xB2A5; &#xBAA8; &#xC138;&#xAD00; &#xBC00;&#xB3C4;: &#xC704; &#xB3C4;&#xAD00;&#xC73C;&#xB85C; &#xC2DD;&#xB3C4; &#xC808;&#xC81C;&#xC220;&#xC5D0; &#xB300; &#xD55C; &#xC758;&#xBBF8;.

La isquemia puede producir fugas en la anastomosis esofagog&aacute;strica despu&eacute;s esofagectom&iacute;a. El objetivo de este estudio fue investigar los cambios dependientes del tiempo de la microcirculaci&oacute;n g&aacute;strica despu&eacute;s de condicionar isqu&eacute;mica.

Funcional densidad capilar en acondicionado isqu&eacute;mica: implicaciones para la resecci&oacute;n del es&oacute;fago con el conducto g&aacute;strico.

Prolonged ischemia (I) times caused by organ procurement and transport are main contributors to a decrease in organ function, which is further enhanced during reperfusion (R). This combined damage, referred to as ischemia-reperfusion injury (IRI), is a main contributor to delayed graft function, which leads to costly and lengthy follow-up treatments or even organ loss. Methods to monitor the status of a graft prior to transplantation are therefore highly desirable to optimize the clinical outcome. Here, we propose the use of fine needle biopsies, which are analyzed by real-time live confocal microscopy. Such a combination provides information about the functional and structural integrity of an organ within a few minutes. To confirm the feasibility of this approach, we obtained fine needle biopsies from rodent kidneys and exposed them to various stress conditions. Following the addition of a range of live stains, biopsies were monitored for mitochondrial function, cell viability, and tissue integrity using confocal live cell imaging. Our data demonstrate that this procedure requires minimal time for sample preparation and data acquisition and is well suitable to record organ damage resulting from unphysiological stress.

Biopsychronology: live confocal imaging of biopsies to assess organ function.

FOXO transcription factors control cellular levels of reactive oxygen species (ROS) which critically contribute to cell survival and cell death in neuroblastoma. In the present study we investigated the regulation of C10orf10/DEPP by the transcription factor FOXO3. As a physiological function of C10orf10/DEPP has not been described so far we analyzed its effects on cellular ROS detoxification and death sensitization in human neuroblastoma cells.

C10ORF10/DEPP, a transcriptional target of FOXO3, regulates ROS-sensitivity in human neuroblastoma.

Methods to monitor the status of a graft prior to transplantation are highly desirable to avoid unnecessary surgical interventions and follow-up treatments and to optimize the clinical outcome as delayed graft function may lead to costly and lengthy follow-up treatments or even organ loss. As a promising step in this direction we present a method which combines the use of fine needle biopsies, the staining of living cells with dyes suitable to monitor mitochondrial status/cellular integrity, and live confocal real-time analysis.This approach provides information about the functional and structural intactness of an organ within a few minutes. To confirm the feasibility of this approach, we recently published a pilot study using rodent kidneys. The results demonstrated that this method is suitable to monitor organ damage caused by ischemia or short periods of reperfusion. This procedure required minimal time for sample preparation and data acquisition and is suitable for recording damage resulting from unphysiological stress to the organ.

Biopsychronology: A Method Using Live Tissue Staining to Image Cell Function in the Kidney.

The aim of study was to investigate whether cell-penetrating peptides could amplify cellular uptake of plasmid DNA (pDNA) loaded self-nanoemulsifying drug delivery systems (SNEDDS) by mucosal epithelial cells, thereby enhancing transfection efficiency.

Cell-penetrating self-nanoemulsifying drug delivery systems (SNEDDS) for oral gene delivery.

We herein investigate critical ischemia times and the effect of novel preservation solutions such as new histidine-tryptophan-ketoglutarate (HTK-N) and TiProtec on the individual tissues of a rat limb isograft.

Article	Year
Blockade of p38 MAPK inhibits chronic allograft vasculopathy. Transplantation\| PubMed ID: 18212636	2008
Functional capillary density in ischemic conditioning: implications for esophageal resection with the gastric conduit. American journal of surgery\| PubMed ID: 18367142	2008
Biopsychronology: live confocal imaging of biopsies to assess organ function. Transplant international : official journal of the European Society for Organ Transplantation\| PubMed ID: 24750326	2014
C10ORF10/DEPP, a transcriptional target of FOXO3, regulates ROS-sensitivity in human neuroblastoma. Molecular cancer\| PubMed ID: 25261981	2014
Biopsychronology: A Method Using Live Tissue Staining to Image Cell Function in the Kidney. Methods in molecular biology (Clifton, N.J.)\| PubMed ID: 26676129	2016
Cell-penetrating self-nanoemulsifying drug delivery systems (SNEDDS) for oral gene delivery. Expert opinion on drug delivery\| PubMed ID: 27458781	2016
Critical Ischemia Times and the Effect of Novel Preservation Solutions HTK-N and TiProtec on Tissues of a Vascularized Tissue Isograft. Transplantation\| PubMed ID: 28658200	2017

Martin Hermann

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