endotracheal-intubation-rabbits-using-polypropylene-guide

Endotracheal Intubation of Rabbits Using a Polypropylene Guide Catheter

Endotracheal intubation in rabbits can be challenging due to their unusual anatomy. Achieving a patent airway during anesthesia is critical for the ...

Mayo Clinic

P-&#x9009;&#x62E9;&#x7D20;&#x6291;&#x5236;&#x88AB;&#x8BC4;&#x4E3A;&#x6CBB;&#x7597;&#x9884;&#x9632;&#x548C;&#x6CBB;&#x7597;&#x9759;&#x8109;&#x8840;&#x6813;&#x5F62;&#x6210;&#x3002;&#x5728;&#x6B64;&#x7814;&#x7A76;&#x4E2D;&#xFF0C;&#x53E3;&#x670D;&#x5C0F;&#x5206;&#x5B50;&#x6291;&#x5236;&#x5242; P-&#x9009;&#x62E9;&#x7D20;&#xFF0C;&#x9632;&#x6269;&#x6563;&#x5B89;&#x5168;&#x5021;&#x8BAE;-421 &#x8BC4;&#x4E3A;&#x7600;&#x81F4;&#x6DF1;&#x9759;&#x8109;&#x8840;&#x6813; (DVT) &#x7684;&#x72D2;&#x72D2;&#x6A21;&#x578B;&#x4E2D;&#x3002;&#x5B9E;&#x9A8C;&#x7EC4;&#x5305;&#x62EC;&#x6211;&#xFF09; &#x63A5;&#x6536; 1 &#x6BEB;&#x514B;/&#x516C;&#x65A4; PSI 421 &#x5355;&#x6B21;&#x53E3;&#x670D;&#x4E24;&#x5929;&#x4E8B;&#x5148;&#x548C;&#x6301;&#x7EED;&#x516D;&#x5929;&#x540E;&#x8840;&#x6813;&#x5F62;&#x6210;&#x7684;&#x7075;&#x957F;&#x7C7B;&#x52A8;&#x7269; &#xFF08;n = 3&#xFF09; &#xFF1B;&#x4E8C;&#xFF09; &#x63A5;&#x6536;&#x6BCF;&#x65E5;&#x76AE;&#x4E0B;&#x5355;&#x6B21; 0.57 &#x6BEB;&#x514B;/&#x5343;&#x514B;&#x4F4E;&#x5206;&#x5B50;&#x91CF;&#x809D;&#x7D20;&#x94A0;&#x4E24;&#x5929;&#x4E8B;&#x5148;&#x548C;&#x6301;&#x7EED;&#x516D;&#x5929;&#x540E;&#x8840;&#x6813;&#x5F62;&#x6210;&#x7684;&#x7075;&#x957F;&#x7C7B;&#x52A8;&#x7269; &#xFF08;n = 3&#xFF09; &#xFF1B;&#x548C;&#x4E09;&#xFF09; &#x7075;&#x957F;&#x7C7B;&#x52A8;&#x7269;&#x6CA1;&#x6709;&#x6CBB;&#x7597; &#xFF08;n = 3)&#x3002;&#x9632;&#x6269;&#x6563;&#x5B89;&#x5168;&#x5021;&#x8BAE; 421 &#x5904;&#x7406;&#x7075;&#x957F;&#x7C7B;&#x52A8;&#x7269;&#x5728;&#x7B2C; 6 &#x5929;&#x4E86;&#x66F4;&#x5927;&#x767E;&#x5206;&#x6BD4;&#x9759;&#x8109;&#x91CD;&#x65B0;&#x5F00;&#x653E;&#x548C;&#x66F4;&#x5C11;&#x9759;&#x8109;&#x58C1;&#x708E;&#x75C7;&#x6BD4;&#x4F4E;&#x5206;&#x5B50;&#x91CF;&#x809D;&#x7D20;&#x548C;&#x63A7;&#x4EF6;&#x3002;&#x5FAE;&#x7C92;&#x5B50;&#x7EC4;&#x7EC7;&#x56E0;&#x5B50;&#x6D3B;&#x6027; (MPTFA) &#x662F;&#x5F88;&#x4F4E;&#x7684;&#x5728;&#x8FD9;&#x4E9B;&#x52A8;&#x7269;&#x4E2D;&#x7684;&#x8840;&#x6813;&#x5F62;&#x6210;&#x8840;&#x6813;&#x5F62;&#x6210; &#xFF08;T + 6 &#x5C0F;&#x65F6;&#x5929; 0&#xFF09; &#x5EFA;&#x8BAE;&#x4F4E;&#x6F5C;&#x529B;&#x540E;&#x7ACB;&#x5373;&#x63A5;&#x6536; PSI 421 &#x7684;&#x52A8;&#x7269;&#x3002;&#x5728; T + 6 &#x5C0F;&#x65F6;&#x5929; 0&#xFF0C;&#x9632;&#x6269;&#x6563;&#x5B89;&#x5168;&#x5021;&#x8BAE; 421 &#x4E5F;&#x51CF;&#x5C11;&#x4E86;&#x53EF;&#x6EB6;&#x6027; P-&#x9009;&#x62E9;&#x7D20;&#x6C34;&#x5E73;&#x4E0E;&#x63A7;&#x4EF6; 2 &#x548C;&#x7B2C; 6 &#x5929;&#x3002;&#x5B9E;&#x9A8C;&#x52A8;&#x7269;&#x5728;&#x4EFB;&#x4F55;&#x7EC4;&#x4E2D;&#x7684;&#x663E;&#x793A;&#x5BF9;&#x51DD;&#x8840;&#x529F;&#x80FD;&#x65E0;&#x4E0D;&#x826F;&#x5F71;&#x54CD;&#x3002;&#x8FD9;&#x9879;&#x7814;&#x7A76;&#x662F;&#x7B2C;&#x4E00;&#x6B21;&#x8BC1;&#x660E;&#x51CF;&#x5C11; MPTFA &#x4E0E;&#x9759;&#x8109;&#x91CD;&#x65B0;&#x5173;&#x8054;&#x548C;&#x964D;&#x4F4E; DVT &#x72D2;&#x72D2;&#x6A21;&#x578B;&#x4E2D;&#x7684;&#x53E3;&#x5934; P-&#x9009;&#x62E9;&#x7D20;&#x6291;&#x5236;&#x9759;&#x8109;&#x708E;&#x75C7;&#x3002;

&#x9632;&#x6269;&#x6563;&#x5B89;&#x5168;&#x5021;&#x8BAE; 421 &#x9884;&#x9632; P-&#x9009;&#x62E9;&#x7D20;&#x6291;&#x5236;&#x4FC3;&#x8FDB;&#x4E0D;&#x6297;&#x51DD;&#x9759;&#x8109;&#x8840;&#x6813;&#x5F62;&#x6210;&#x7684;&#x51B3;&#x8BAE;&#x3002;

P-selectin inhibition has been evaluated as a therapeutic for prevention and treatment of venous thrombosis. In this study, a novel oral small-molecule inhibitor of P-selectin, PSI-421, was evaluated in a baboon model of stasis induced deep vein thrombosis (DVT). Experimental groups included i) primates receiving a single oral dose of 1 mg/kg PSI-421 two days prior and continued six days after thrombosis (n = 3); ii) primates receiving a single daily subcutaneous dose of 0.57 mg/kg enoxaparin sodium two days prior and continued six days post thrombosis (n = 3); and iii) primates receiving no treatment (n = 3). PSI-421 treated primates had greater percent vein reopening and less vein wall inflammation than the enoxaparin and controls at day 6. Microparticle tissue factor activity (MPTFA) was significantly lower in the animals receiving PSI-421 immediately after thrombosis (T+6 hours day 0) suggesting lower potential for thrombogenesis in these animals. PSI-421 also reduced soluble P-selectin levels versus controls at T+6 hours day 0, day 2 and 6. Experimental animals in any group showed no adverse effects on coagulation. This study is the first to demonstrate a reduction in MPTFA associated with vein reopening and reduced vein inflammation due to oral P-selectin inhibition in a baboon model of DVT.

Prophylactic P-selectin inhibition with PSI-421 promotes resolution of venous thrombosis without anticoagulation.

Inhibition de la P-s&#xE9;lectine a &#xE9;t&#xE9; &#xE9;valu&#xE9;e comme une th&#xE9;rapeutique pour la pr&#xE9;vention et le traitement de la thrombose veineuse. Dans cette &#xE9;tude, un roman &#xE0; petite mol&#xE9;cule orale inhibiteur de la P-s&#xE9;lectine, PSI-421, a &#xE9;t&#xE9; &#xE9;valu&#xE9;e dans un mod&#xE8;le de babouin de stase induite par la thrombose veineuse profonde (TVP). Les groupes exp&#xE9;rimentaux i inclus) des primates trait&#xE9;s par une dose orale unique de 1 mg / kg PSI-421 deux jours avant et a continu&#xE9;, six jours apr&#xE8;s une thrombose (n = 3); ii) les primates recevoir un dose unique sous-cutan&#xE9;e quotidienne de 0,57 mg / kg &#xE9;noxaparine sodique deux jours avant et a continu&#xE9; six une thrombose jours apr&#xE8;s (n = 3), et iii) les primates ne recevant aucun traitement (n = 3). PSI-421 primates trait&#xE9;s avaient une plus grande veine pour cent et moins r&#xE9;ouverture inflammation de la paroi veineuse que l&#x26;#39;&#xE9;noxaparine et les contr&#xF4;les au jour 6. L&#x26;#39;activit&#xE9; du facteur tissulaire microparticules (MPTFA) &#xE9;tait significativement plus faible chez les animaux recevant PSI-421 imm&#xE9;diatement apr&#xE8;s la thrombose (T 6 jours heures 0) sugg&#xE9;rant moindre potentiel de thrombog&#xE9;n&#xE8;se chez ces animaux. PSI-421 a &#xE9;galement r&#xE9;duit P-s&#xE9;lectine soluble niveaux par rapport aux t&#xE9;moins &#xE0; T 6 jours heures 0, jour 2 et 6. Les animaux de laboratoire dans n&#x26;#39;importe quel groupe n&#x26;#39;a pas montr&#xE9; des effets n&#xE9;fastes sur la coagulation. Cette &#xE9;tude est la premi&#xE8;re &#xE0; d&#xE9;montrer une r&#xE9;duction de MPTFA associ&#xE9;e &#xE0; la veine et la r&#xE9;ouverture inflammation d&#x26;#39;une veine par voie orale r&#xE9;duite en raison de l&#x26;#39;inhibition de la P-s&#xE9;lectine dans un mod&#xE8;le de babouin de la TVP.

Prophylactique P-s&#xE9;lectine inhibition avec PSI-421 favorise la r&#xE9;solution des thromboses veineuses Sans anticoagulation

P-selectin Hemmung wurde als eine therapeutische f&uuml;r Pr&auml;vention und Behandlung von ven&ouml;sen Thrombosen evaluiert. In dieser Studie eine neuartige orale klein-Molek&uuml;l-Inhibitor der P-selectin, wurde PSI-421, in einem Pavian-Modell des Stillstands induzierte tiefe Venenthrombose (TVT) ausgewertet. Experimentelle Gruppen enthalten i) Primaten Erhalt einer einzigen oralen Dosis von 1 mg/kg PSI-421 zwei Tage vorher und weitere sechs Tage nach Thrombose (n = 3); II) erhalten eine t&auml;gliche subkutane Einzeldosis 0,57 mg/kg Enoxaparin-Natrium zwei Tage vor und weitere sechs Tage Thrombose Post Primaten (n = 3); und Iii) Primaten, die keine Behandlung (n = 3). PSI-421 behandelte Primaten hatte gr&ouml;&szlig;ere Prozent Vene Gef&auml;&szlig;er&ouml;ffnende und weniger Vene Wand Entz&uuml;ndungen als die Enoxaparin und Steuerelemente am Tag 6. Mikropartikel-Gewebe-Faktor-Aktivit&auml;t (MPTFA) war in den Tieren empfangen von PSI-421 unmittelbar nach Thrombose (T + 6 Stunden Tag 0) vorschlagen niedrigeren Potenzial f&uuml;r Thrombogenese bei diesen Tieren erheblich niedriger. PSI-421 reduziert auch l&ouml;sliche P-selectin Ebenen im Vergleich zu Kontrollen bei T + 6 Stunden Tag 0, Tag 2 und 6. Experimentelle Tiere in jeder Gruppe zeigte keine negativen Auswirkungen auf die Blutgerinnung. Diese Studie ist die erste zeigen ein R&uuml;ckgang der MPTFA Vene Wiederer&ouml;ffnung zugeordnet und Ader Entz&uuml;ndung aufgrund m&uuml;ndlicher P-selectin Hemmung in einem Pavian-Modell TVT reduziert.

Prophylaktische P-selectin Hemmung mit PSI-421 f&ouml;rdert die Aufl&ouml;sung von ven&ouml;sen Thrombosen ohne Antikoagulation.

L&#39;inibizione di P-Selectina &egrave; stata valutata come un terapeutico per la prevenzione e il trattamento della trombosi venosa. In questo studio, un inibitore orale del piccolo-molecola romanzo di P-Selectina, PSI-421, &egrave; stata valutata in un modello di babbuino di stasi indotta da trombosi venosa profonda (TVP). Gruppi sperimentali incluse i) ricevere una singola dose orale di 1 mg/kg PSI-421 due giorni precedenti e continuato sei giorni dopo trombosi primati (n = 3); II) primati ricevere una singola dose sottocutanea giornaliera di sodio enoxaparina 0.57 mg/kg due giorni precedenti e continui sei giorni post trombosi (n = 3); e iii) primati non ricevendo alcun trattamento (n = 3). PSI-421 primati trattati avevano una maggiore percentuale vena riapertura e meno vena parete infiammazione rispetto l&#39;enoxaparina e controlli al giorno 6. Microparticelle tessuto fattore attivit&agrave; (MPTFA) era significativamente pi&ugrave; basso negli animali ricevendo PSI-421 immediatamente dopo suggerendo potenziale inferiore di trombosi (T + 6 ore giorno 0) per trombogeno in questi animali. PSI-421 anche ridotti livelli di P-Selectina solubili versus controlli al giorno T + 6 ore 0, giorno 2 e 6. Animali da esperimento in ogni gruppo ha mostrato effetti negativi sulla coagulazione. Questo studio &egrave; il primo a dimostrare una riduzione di MPTFA associati con la riapertura della vena e ridotta infiammazione vena a causa della inibizione di P-Selectina orale in un modello di babbuino della TVP.

L&#39;inibizione di P-Selectina profilattica con PSI-421 favorisce la risoluzione della trombosi venosa profonda senza anticoagulazione.

P-&#x30BB;&#x30EC;&#x30AF;&#x30C1;&#x30F3;&#x963B;&#x5BB3;&#x306F;&#x3001;&#x4E88;&#x9632;&#x3068;&#x9759;&#x8108;&#x8840;&#x6813;&#x75C7;&#x306E;&#x6CBB;&#x7642;&#x306E;&#x305F;&#x3081;&#x306E;&#x6CBB;&#x7642;&#x85AC;&#x3068;&#x3057;&#x3066;&#x8A55;&#x4FA1;&#x3055;&#x308C;&#x3066;&#x3044;&#x307E;&#x3059;&#x3002;&#x672C;&#x7814;&#x7A76;&#x3067;&#x306F;&#x3001;P-&#x30BB;&#x30EC;&#x30AF;&#x30C1;&#x30F3;&#x306E;&#x65B0;&#x898F;&#x7D4C;&#x53E3;&#x4F4E;&#x5206;&#x5B50;&#x963B;&#x5BB3;&#x5264;&#x3001;PSI-421&#x306F;&#x3001;&#x9759;&#x6B62;&#x72B6;&#x614B;&#x8A98;&#x5C0E;&#x6DF1;&#x90E8;&#x9759;&#x8108;&#x8840;&#x6813;&#x75C7;&#xFF08;DVT&#xFF09;&#x306E;&#x30D2;&#x30D2;&#x306E;&#x30E2;&#x30C7;&#x30EB;&#x3067;&#x8A55;&#x4FA1;&#x3057;&#x305F;&#x3002;&#x5B9F;&#x9A13;&#x7FA4;&#xFF09;&#x306F;&#x524D;&#x306B;1 mg / kg&#x306E;&#x5358;&#x56DE;&#x7D4C;&#x53E3;&#x6295;&#x4E0E;&#x3057;&#x305F;PSI-421&#x4E8C;&#x65E5;&#x9593;&#x3092;&#x53D7;&#x4FE1;&#x3057;&#x305F;&#x970A;&#x9577;&#x985E;&#x306E;&#x79C1;&#x304C;&#x542B;&#x307E;&#x308C;&#x3066;&#x304A;&#x308A;&#xFF08;n = 3&#xFF09;&#x3067;&#x8840;&#x6813;&#x75C7;&#x5F8C;&#x3001;6&#x65E5;&#x7D9A;&#x3051;&#x3066;&#x3001;&#x2171;&#xFF09;&#x970A;&#x9577;&#x985E;&#x306F;0.57 mg / kg&#x306E;&#x30A8;&#x30CE;&#x30AD;&#x30B5;&#x30D1;&#x30EA;&#x30F3;&#x30CA;&#x30C8;&#x30EA;&#x30A6;&#x30E0;1&#x65E5;1&#x56DE;&#x76AE;&#x4E0B;&#x6295;&#x4E0E;&#x3092;&#x53D7;&#x3051;&#x304A;&#x3088;&#x3073;iii&#xFF09;&#x970A;&#x9577;&#x985E;&#x3067;&#x306F;&#x7121;&#x6CBB;&#x7642;&#xFF08;n = 3&#x306E;&#xFF09;&#x3092;&#x53D7;&#x4FE1;&#x3057;&#x307E;&#x305B;&#x3093;&#x3002;2&#x65E5;&#x524D;&#x3001;6&#x65E5;&#x5F8C;&#x306E;&#x8840;&#x6813;&#x75C7;&#xFF08;N = 3&#xFF09;&#x3092;&#x7D9A;&#x3051;&#x305F;&#x3002; PSI-421&#x51E6;&#x7406;&#x3055;&#x308C;&#x305F;&#x970A;&#x9577;&#x985E;&#x304C;&#x5927;&#x304D;&#x3044;&#x30D1;&#x30FC;&#x30BB;&#x30F3;&#x30C8;&#x9759;&#x8108;&#x518D;&#x958B;&#x3068;6&#x65E5;&#x76EE;&#x3067;&#x306F;&#x30A8;&#x30CE;&#x30AD;&#x30B5;&#x30D1;&#x30EA;&#x30F3;&#x3068;&#x30B3;&#x30F3;&#x30C8;&#x30ED;&#x30FC;&#x30EB;&#x672A;&#x6E80;&#x9759;&#x8108;&#x58C1;&#x306E;&#x708E;&#x75C7;&#x3092;&#x6301;&#x3063;&#x3066;&#x3044;&#x305F;&#x3002;&#x5FAE;&#x7C92;&#x5B50;&#x7D44;&#x7E54;&#x56E0;&#x5B50;&#x6D3B;&#x6027;&#xFF08;MPTFA&#xFF09;&#x306F;&#x3001;&#x8840;&#x6813;&#x75C7;&#xFF08;T 6&#x6642;&#x9593;0&#x65E5;&#x76EE;&#xFF09;&#x306F;&#x3001;&#x3053;&#x308C;&#x3089;&#x306E;&#x52D5;&#x7269;&#x306B;&#x304A;&#x3051;&#x308B;&#x8840;&#x6813;&#x5F62;&#x6210;&#x306E;&#x305F;&#x3081;&#x306E;&#x3088;&#x308A;&#x4F4E;&#x3044;&#x53EF;&#x80FD;&#x6027;&#x3092;&#x793A;&#x5506;&#x3057;&#x305F;&#x76F4;&#x5F8C;&#x306B;PSI-421&#x3092;&#x53D7;&#x4FE1;&#x3057;&#x305F;&#x52D5;&#x7269;&#x3067;&#x306F;&#x6709;&#x610F;&#x306B;&#x4F4E;&#x304B;&#x3063;&#x305F;&#x3002; PSI-421&#x306F;&#x3001;0&#x3001;2&#x65E5;&#x76EE;&#x3068;6&#x65E5;T 6&#x6642;&#x9593;&#x5F8C;&#x306B;&#x53EF;&#x6EB6;&#x6027;P-&#x30BB;&#x30EC;&#x30AF;&#x30C1;&#x30F3;&#x306E;&#x30EC;&#x30D9;&#x30EB;&#x5BFE;&#x7167;&#x7FA4;&#x3092;&#x6E1B;&#x5C11;&#x3055;&#x305B;&#x305F;&#x3002;&#x4EFB;&#x610F;&#x306E;&#x30B0;&#x30EB;&#x30FC;&#x30D7;&#x306E;&#x5B9F;&#x9A13;&#x52D5;&#x7269;&#x306F;&#x3001;&#x8840;&#x6DB2;&#x51DD;&#x56FA;&#x306B;&#x60AA;&#x5F71;&#x97FF;&#x3092;&#x53CA;&#x307C;&#x3055;&#x306A;&#x304B;&#x3063;&#x305F;&#x3002;&#x672C;&#x7814;&#x7A76;&#x3067;&#x306F;&#x3001;&#x9759;&#x8108;&#x518D;&#x958B;&#x3068;&#x7D4C;&#x53E3;P-&#x30BB;&#x30EC;&#x30AF;&#x30C1;&#x30F3;DVT&#x306E;&#x30D2;&#x30D2;&#x30E2;&#x30C7;&#x30EB;&#x306E;&#x6291;&#x5236;&#x306E;&#x305F;&#x3081;&#x306E;&#x6E1B;&#x5C11;&#x9759;&#x8108;&#x306E;&#x708E;&#x75C7;&#x306B;&#x95A2;&#x9023;&#x4ED8;&#x3051;&#x3089;&#x308C;&#x3066;&#x3044;&#x308B;MPTFA&#x306E;&#x524A;&#x6E1B;&#x3092;&#x5B9F;&#x8A3C;&#x3059;&#x308B;&#x6700;&#x521D;&#x306E;&#x3082;&#x306E;&#x3067;&#x3059;&#x3002;

PSI-421&#x306E;&#x4E88;&#x9632;P-&#x30BB;&#x30EC;&#x30AF;&#x30C1;&#x30F3;&#x963B;&#x5BB3;&#x306F;&#x3001;&#x6297;&#x51DD;&#x56FA;&#x305B;&#x305A;&#x306B;&#x9759;&#x8108;&#x8840;&#x6813;&#x75C7;&#x306E;&#x89E3;&#x6C7A;&#x3092;&#x4FC3;&#x9032;&#x3059;&#x308B;

P selectin &#xC5B5;&#xC81C; &#xC815; &#xB9E5; &#xD608;&#xC804; &#xC99D;&#xC758; &#xCE58;&#xB8CC;&#xC640; &#xC608;&#xBC29;&#xC744; &#xC704;&#xD55C; &#xCE58;&#xB8CC; &#xC801;&#xC73C;&#xB85C; &#xD3C9;&#xAC00; &#xD558;&#xACE0;&#xC788;&#xB2E4;. P selectin&#xC758; &#xC18C;&#xC124; &#xAD6C;&#xAC15; &#xC791;&#xC740; &#xBD84;&#xC790; &#xC5B5;&#xC81C; &#xBB3C;&#xC774;&#xC774; &#xC5F0;&#xAD6C;&#xC5D0;&#xC11C;&#xB294; PSI-421, &#xAC1C; &#xCF54; &#xC6D0;&#xC22D;&#xC774; &#xBAA8;&#xB378; &#xC2A4;&#xD14C;&#xC774; &#xC2DC;&#xC2A4; &#xC720;&#xB3C4; &#xAE4A;&#xC740; &#xC815; &#xB9E5; &#xD608;&#xC804; &#xC99D; (DVT)&#xC758; &#xD3C9;&#xAC00; &#xBC1B;&#xC558;&#xB2E4;. &#xC2E4;&#xD5D8; &#xADF8;&#xB8F9;&#xC774; &#xB098; &#xD3EC;&#xD568;) &#xC601;&#xC7A5;&#xB958; &#xBC1B;&#xB294; PSI-421 1 mg/kg&#xC758; &#xB2E8;&#xC77C; &#xACBD;&#xAD6C; &#xD22C;&#xC5EC; 2 &#xC77C; &#xC774;&#xC804; &#xBC0F; &#xC9C0;&#xC18D;&#xC801;&#xC778; &#xD608;&#xC804; &#xC99D; &#xD6C4;&#xC5D0; 6 &#xC77C; (n = 3); ii) &#xC601;&#xC7A5;&#xB958; &#xBC1B;&#xB294; 0.57 m g/k g enoxaparin &#xB098;&#xD2B8;&#xB968;&#xC758; &#xB2E8;&#xC77C; &#xB9E4;&#xC77C; &#xD53C;&#xD558; &#xD22C;&#xC5EC; 2 &#xC77C; &#xC774;&#xC804; &#xBC0F; &#xC9C0;&#xC18D;&#xC801;&#xC778; 6 &#xC77C; &#xAC8C;&#xC2DC;&#xBB3C; &#xD608;&#xC804; &#xC99D; (n = 3); &#xADF8;&#xB9AC;&#xACE0; iii) &#xC601;&#xC7A5;&#xB958; &#xC544;&#xBB34; &#xCE58;&#xB8CC;&#xB97C; &#xBC1B;&#xACE0; (n = 3). PSI-421 &#xB300;&#xC6B0; &#xC601;&#xC7A5;&#xB958; &#xC8FC; 6&#xC5D0; &#xB354; &#xD070; &#xBC31;&#xBD84;&#xC728; &#xC815; &#xB9E5; reopening &#xBC0F; &#xB354; &#xC801;&#xC740; &#xC815; &#xB9E5; &#xBCBD; &#xC5FC;&#xC99D;&#xC744; enoxaparin &#xCEE8;&#xD2B8;&#xB864; &#xBCF4;&#xB2E4; &#xD588;&#xB2E4;. Microparticle &#xC870;&#xC9C1; &#xC694;&#xC18C; &#xD65C;&#xB3D9; (MPTFA) thrombogenesis&#xC774;&#xC774; &#xB3D9;&#xBB3C;&#xC5D0; &#xB300; &#xD55C; &#xD608;&#xC804; (T + 6 &#xC2DC;&#xAC04; &#xD558;&#xB8E8; 0) &#xC81C;&#xC548; &#xB0AE;&#xC740; &#xC7A0;&#xC7AC;&#xB825; &#xC9C1;&#xD6C4; PSI-421 &#xBC1B;&#xB294; &#xB3D9;&#xBB3C;&#xC5D0;&#xC11C; &#xC0C1;&#xB2F9;&#xD788; &#xB0AE;&#xC740; &#xD588;&#xB2E4;. PSI-421 &#xB610;&#xD55C; &#xAC10;&#xC18C; &#xCEE8;&#xD2B8;&#xB864; &#xB300; &#xC218;&#xC6A9; &#xC131; P selectin &#xB808;&#xBCA8; T + 6 &#xC2DC;&#xAC04; &#xD558;&#xB8E8;&#xC5D0; 0, 2-6 &#xC77C;. &#xC5B4;&#xB5A4; &#xADF8;&#xB8F9;&#xC5D0;&#xC11C; &#xC2E4;&#xD5D8; &#xB3D9;&#xBB3C; &#xC751;&#xACE0;&#xC5D0; &#xC544;&#xBB34;&#xB7F0; &#xBD80;&#xC791;&#xC6A9;&#xC744; &#xBCF4;&#xC5EC;&#xC8FC;&#xC5C8;&#xB2E4;. &#xC774; &#xC5F0;&#xAD6C;&#xB294; &#xBA3C;&#xC800; MPTFA &#xAC10;&#xC18C; &#xC815; &#xB9E5; &#xC7AC;&#xAC1C;&#xC640; &#xAD00;&#xB828; &#xB41C; &#xBC0F; &#xAD6C;&#xAC15; P selectin &#xC800;&#xD574; DVT&#xC758; &#xAC1C; &#xCF54; &#xC6D0;&#xC22D;&#xC774; &#xBAA8;&#xB378;&#xC5D0; &#xB530;&#xB978; &#xC815; &#xB9E5; &#xC5FC;&#xC99D; &#xAC10;&#xC18C;.

PSI-421&#xC640; &#xC608;&#xBC29; P selectin &#xC800;&#xD574; anticoagulation &#xC5C6;&#xC774; &#xC815; &#xB9E5; &#xD608;&#xC804; &#xC99D;&#xC758; &#xD574;&#xACB0;&#xC744; &#xCD09;&#xC9C4;&#xD569;&#xB2C8;&#xB2E4;.

P-selectina inhibici&#xF3;n se ha evaluado como un agente terap&#xE9;utico para la prevenci&#xF3;n y tratamiento de la trombosis venosa. En este estudio, un nuevo anticanceroso oral de mol&#xE9;cula peque&#xF1;a inhibidor de la P-selectina, PSI-421, se evalu&#xF3; en un modelo de babuinos de la inmovilizaci&#xF3;n trombosis venosa inducida por la profunda (TVP). Los grupos experimentales i incluido) los primates que recibieron una dosis oral &#xFA;nica de 1 mg / kg PSI-421 dos d&#xED;as antes y continu&#xF3; seis d&#xED;as despu&#xE9;s de la trombosis (n = 3), ii) los primates que recibieron una dosis &#xFA;nica diaria subcut&#xE1;nea de 0,57 mg / kg de enoxaparina s&#xF3;dica dos d&#xED;as antes y continu&#xF3; seis d&#xED;as despu&#xE9;s de la trombosis (n = 3), y iii) los primates que no recibieron tratamiento (n = 3). 421 PSI-primates tratados ten&#xED;an mayor sentido por ciento de la reapertura y menos inflamaci&#xF3;n de la pared venosa que la enoxaparina y los controles en el d&#xED;a 6. Micropart&#xED;culas actividad del factor tisular (MPTFA) fue significativamente menor en los animales que recibieron PSI-421 inmediatamente despu&#xE9;s de la trombosis (T +6 horas de d&#xED;a 0) lo que sugiere un menor potencial de la trombog&#xE9;nesis en estos animales. PSI-421 tambi&#xE9;n se reduce solubles selectina P-niveles frente a los controles en T 6 d&#xED;as las 0, 2 y 6 d&#xED;as. Los animales experimentales en cualquier grupo no mostr&#xF3; efectos adversos sobre la coagulaci&#xF3;n. Este estudio es el primero en demostrar una reducci&#xF3;n en MPTFA asociada con la vena y la reapertura de inflamaci&#xF3;n de las venas reducida debido a la oral, la inhibici&#xF3;n de la P-selectina en un modelo de babuinos de la TVP.

Profil&#xE1;ctica de P-selectina inhibici&#xF3;n con PSI-421 promueve la resoluci&#xF3;n de la trombosis venosa sin anticoagulaci&#xF3;n

The use of automated watering systems for providing drinking water to rodents has become commonplace in the research setting. Little is known regarding bacterial biofilm growth within the water piping attached to the racks (manifolds). The purposes of this project were to determine whether the mouse oral flora contributed to the aerobic bacterial component of the rack biofilm, quantify bacterial growth in rack manifolds over 6 mo, assess our rack sanitation practices, and quantify bacterial biofilm development within sections of the manifold. By using standard methods of bacterial identification, the aerobic oral flora of 8 strains and stocks of mice were determined on their arrival at our animal facility. Ten rack manifolds were sampled before, during, and after sanitation and monthly for 6 mo. Manifolds were evaluated for aerobic bacterial growth by culture on R2A and trypticase soy agar, in addition to bacterial ATP quantification by bioluminescence. In addition, 6 racks were sampled at 32 accessible sites for evaluation of biofilm distribution within the watering manifold. The identified aerobic bacteria in the oral flora were inconsistent with the bacteria from the manifold, suggesting that the mice do not contribute to the biofilm bacteria. Bacterial growth in manifolds increased while they were in service, with exponential growth of the biofilm from months 3 to 6 and a significant decrease after sanitization. Bacterial biofilm distribution was not significantly different across location quartiles of the rack manifold, but bacterial levels differed between the shelf pipe and connecting elbow pipes.

Quantification, distribution, and possible source of bacterial biofilm in mouse automated watering systems.

Toxicology studies were performed in rats and rhesus macaques to establish a safe starting dose for intratumoral injection of an oncolytic vesicular stomatitis virus expressing human interferon-beta (VSV-hIFNbeta) in patients with hepatocellular carcinoma (HCC). No adverse events were observed after administration of 7.59 x 10(9) TCID(50) (50% tissue culture infective dose) of VSV-hIFNbeta into the left lateral hepatic lobe of Harlan Sprague Dawley rats. Plasma alanine aminotransferase and alkaline phosphatase levels increased and platelet counts decreased in the virus-treated animals on days 1 and 2 but returned to pretreatment levels by day 4. VSV-hIFNbeta was also injected into normal livers or an intrahepatic McA-RH7777 HCC xenograft established in Buffalo rats. Buffalo rats were more sensitive to neurotoxic effects of VSV; the no observable adverse event level (NOAEL) of VSV-hIFNbeta in Buffalo rats was 10(7) TCID(50). Higher doses were associated with fatal neurotoxicity and infectious virus was recovered from tumor and brain. Compared with VSV-hIFNbeta, toxicity of VSV-rIFNbeta (recombinant VSV expressing rat IFN-beta) was greatly diminished in Buffalo rats (NOAEL, >10(10) TCID(50)). Two groups of two adult male rhesus macaques received 10(9) or 10(10) TCID(50) of VSV-hIFNbeta injected directly into the left hepatic lobe under computed tomographic guidance. No neurological signs were observed at any time point. No abnormalities (hematology, clinical chemistry, body weights, behavior) were seen and all macaques developed neutralizing anti-VSV antibodies. Plasma interleukin-6, tumor necrosis factor-alpha, and hIFN-beta remained below detection levels by ELISA. On the basis of these studies, we will be proposing a cautious approach to dose escalation in a phase I clinical trial among patients with HCC.

Safety studies on intrahepatic or intratumoral injection of oncolytic vesicular stomatitis virus expressing interferon-beta in rodents and nonhuman primates.

Focal cortical epilepsy is currently studied most effectively in humans. However, improvement in cortical monitoring and investigational device development is limited by lack of an animal model that mimics human acute focal cortical epileptiform activity under epilepsy surgery conditions. Therefore, we assessed the swine model for translational epilepsy research. Swine were used due to their cost-effectiveness, convoluted cortex, and comparative anatomy. The anatomy has all the same brain structures as the human, and in similar locations. Focal subcortical injection of benzyl-penicillin produced clinical seizures correlating with epileptiform activity demonstrating temporal and spatial progression. Swine were evaluated under five different anesthesia regimens. Of the five regimens, conditions similar to human intraoperative anesthesia, including continuous fentanyl with low dose isoflorane, was the most effective for eliciting complex, epileptiform activity after benzyl-penicillin injection. The most complex epileptiform activity (spikes, and high frequency activity) was then repeated reliably in nine animals, utilizing 14 swine total. There were 20.1 ± 10.8 [95% confidence interval (CI) 11.8-28.4] epileptiform events with > 3.5 Hz activity occurring per animal. Average duration of each event was 46.3 ± 15.6 (95% CI 44.0-48.6) s, ranging from 20-100 s. In conclusion, the acute swine model of focal cortical epilepsy surgery provides an animal model that mimics human surgical conditions with a large brain and gyrated cortex, and is relatively inexpensive among animal models. Therefore, we feel this model provides a valuable, reliable, and novel platform for translational studies of implantable hardware for intracranial monitoring.

Article	Year
Prophylactic P-selectin inhibition with PSI-421 promotes resolution of venous thrombosis without anticoagulation. Thrombosis and haemostasis\| PubMed ID: 18278184	2008
Quantification, distribution, and possible source of bacterial biofilm in mouse automated watering systems. Journal of the American Association for Laboratory Animal Science : JAALAS\| PubMed ID: 18351724	2008
Safety studies on intrahepatic or intratumoral injection of oncolytic vesicular stomatitis virus expressing interferon-beta in rodents and nonhuman primates. Human gene therapy\| PubMed ID: 19911974	2010
Swine model for translational research of invasive intracranial monitoring. Epilepsia\| PubMed ID: 21627648	2011

Thomas R Meier

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