Diss. (sammanfattning) Uppsala : Univ., 2003. / Härtill 4 uppsatser.

Diss. (sammanfattning) Umeå : Univ., 2004. / Härtill 5 uppsatser.

Thesis (Ph.D.)--University of Wollongong, 2005. / Typescript. Bibliography: leaf 141-157.

Thesis (Ph. D.)--University of California, Riverside, 2009. / Includes abstract. Available via ProQuest Digital Dissertations. Title from first page of PDF file (viewed March 10, 2010). Includes bibliographical references. Also issued in print.

Thesis (Ph.D.) -- McMaster University, 2001. / Includes bibliographical references (leaves 204-228). Also available via World Wide web.

Orientador: Hamilton de Almeida Rollo / Banca: Ana Terezinha Guillaumon / Banca: Edwaldo Edner Joviliano / Banca: Marcone Lima Sobreira / Banca: Paulo de Almeida Silvares / Resumo: Após cerca de 50 anos de experiência com a heparina e antagonistas da vitamina K (AVK), pesquisas e estudos com novos anticoagulantes vem evoluindo de forma crescente nos últimos anos. Embora consagrados pelo uso, os anticoagulantes tradicionais tem limitações importantes em termos de controle laboratorial, complicações, efeitos colaterais, interações com medicamentos e dieta. A heparina não fracionada (HNF) tem interação com proteínas plasmáticas e parede vascular, pode desencadear trombocitopenia induzida pela heparina (TIH), só pode ser administrada por via parenteral, exige controle laboratorial pelo teste da tromboplastina parcial ativada (TTPa), pode provocar osteoporose e alopecia quando usada por períodos prolongados e sua produção tem origem biológica. A AVK tem a vantagem de poder ser ministrada por via oral (VO), mas o controle (feito pela razão normatizada internacional - RNI) pode ser difícil em alguns casos, tem início de ação e eliminação demorados, tem janela terapêutica estreita, e interação com dieta e grande número de medicamentos, pode provocar necrose de pele em portadores de deficiência de antitrombina e de proteínas C e S, e pode induzir alterações fetais quando usada na gravidez. Na década de 80, surgiram as heparinas de baixo peso molecular (HBPM), que foram uma evolução da HNF, pois apresentaram maior biodisponibilidade, dosagem por peso corporal, sem necessidade de controle laboratorial, administração por via subcutânea (SC), menor risco de TIH, e eficácia e segurança similares à HNF. Na última década surgiram, então, uma série de novos anticoagulantes no mercado, os quais vem apresentando resultados promissores em várias situações de profilaxia e tratamento do tromboembolismo venoso (TEV). Nesta revisão, são apresentados as novas HBPM, as heparinas de ultra-baixo peso molecular, os pentassacarídeos, os novos inibidores diretos do fator Xa e inibidores do Fator IIa / Abstract: After about 50 years of experience with heparin and vitamin K antagonists (VKA), researches and studies have evolved in recent years with new anticoagulants. Although recognized by usage, the traditional anticoagulants have important limitations in terms of control, complications, side effects and interactions with medications and diet. The unfractionated heparin (UFH) has interaction with plasma proteins and vascular wall, may trigger heparin-induced thrombocytopenia (HIT), can only be administered parenterally, it requires control by the laboratory test of partial thromboplastin time (aPTT), may cause osteoporosis and alopecia when used for long periods and its production has a biological origin. The AVK has the advantage of being administered orally, but the control (made by the international normalized ratio - INR) can be difficult in some cases, have delayed onset and metabolism, has a narrow therapeutic window and interaction with diet and large number of medicines, can cause skin necrosis in patients with antithrombin and protein C and S deficiencies, and may induce fetal changes when prescribed in pregnancy. In the '80s came the low molecular weight heparins (LMWH), which were an evolution of UFH, because they showed greater bio-availability, fixed dosage per body weight, no need for laboratory control, subcutaneous administration, lower risk of HIT, and efficacy and safety similar to UFH. In the last decade, a series of new anticoagulants appeared in the market, which has shown promising results in various situations of prophylaxis and treatment of VTE. In this review, new LMWH, ultra-low molecular weight heparin, pentasaccharides, the new direct inhibitors of Factor Xa and Factor IIa inhibitors are presented / Doutor

The composition and conformational state of biological molecules have a profound influence on cell behavior and large-scale processes including development and disease progression. Fibronectin fibers are a prevalent component of the extracellular matrix that are believed to adopt a wide array conformations with different functions. Two factors that are hypothesized to regulate fibronectin conformation, and hence fibronectin biological function, are allosteric regulators, such as heparan sulfates, and mechanical strain. However, the relative influence of allosteric regulators and mechanical forces on fibronectin conformation has not been determined. This conformational regulation is especially important in the context of the heparin 2 binding domain (modules III12 to III14), which is known to bind and present numerous growth factors, such as vascular endothelial growth factor, to cells. This thesis will highlight three contributions to this field. First, a new, and remarkably simple technique was developed that permits the detection of the non-equilibrium fibronectin conformations. This technique is founded on the identification of monoclonal antibodies that have altered affinities for fibronectin based on heparin treatment or mechanical strain dependence, or that bind fibronectin equally well in all conditions. Second, the impact of both heparin and mechanical strain on the binding of VEGF to the hep2 region of fibronectin was investigated. It was discovered that both strain and heparin co-regulate VEGF binding. Finally, studies of cell attachment and migration on single fibers of fibronectin with controlled strain states provided the first direct evidence that mechanical strain regulates cell attachment, spreading, and migration on a fibronectin matrix. This body of work demonstrating that the conformational changes in fibronectin lead to altered biological activity has broad impact in a number of fields due to the ubiquitous presence and requirement of fibronectin in cell and tissue function.

Made available in DSpace on 2014-06-11T19:32:44Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-02-21Bitstream added on 2014-06-13T20:04:11Z : No. of bitstreams: 1 yoshida_ra_dr_botfm.pdf: 660337 bytes, checksum: 25d0f7db1a4139f44f3c1a6c4496df7b (MD5) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Universidade Estadual Paulista (UNESP) / Após cerca de 50 anos de experiência com a heparina e antagonistas da vitamina K (AVK), pesquisas e estudos com novos anticoagulantes vem evoluindo de forma crescente nos últimos anos. Embora consagrados pelo uso, os anticoagulantes tradicionais tem limitações importantes em termos de controle laboratorial, complicações, efeitos colaterais, interações com medicamentos e dieta. A heparina não fracionada (HNF) tem interação com proteínas plasmáticas e parede vascular, pode desencadear trombocitopenia induzida pela heparina (TIH), só pode ser administrada por via parenteral, exige controle laboratorial pelo teste da tromboplastina parcial ativada (TTPa), pode provocar osteoporose e alopecia quando usada por períodos prolongados e sua produção tem origem biológica. A AVK tem a vantagem de poder ser ministrada por via oral (VO), mas o controle (feito pela razão normatizada internacional - RNI) pode ser difícil em alguns casos, tem início de ação e eliminação demorados, tem janela terapêutica estreita, e interação com dieta e grande número de medicamentos, pode provocar necrose de pele em portadores de deficiência de antitrombina e de proteínas C e S, e pode induzir alterações fetais quando usada na gravidez. Na década de 80, surgiram as heparinas de baixo peso molecular (HBPM), que foram uma evolução da HNF, pois apresentaram maior biodisponibilidade, dosagem por peso corporal, sem necessidade de controle laboratorial, administração por via subcutânea (SC), menor risco de TIH, e eficácia e segurança similares à HNF. Na última década surgiram, então, uma série de novos anticoagulantes no mercado, os quais vem apresentando resultados promissores em várias situações de profilaxia e tratamento do tromboembolismo venoso (TEV). Nesta revisão, são apresentados as novas HBPM, as heparinas de ultra-baixo peso molecular, os pentassacarídeos, os novos inibidores diretos do fator Xa e inibidores do Fator IIa / After about 50 years of experience with heparin and vitamin K antagonists (VKA), researches and studies have evolved in recent years with new anticoagulants. Although recognized by usage, the traditional anticoagulants have important limitations in terms of control, complications, side effects and interactions with medications and diet. The unfractionated heparin (UFH) has interaction with plasma proteins and vascular wall, may trigger heparin-induced thrombocytopenia (HIT), can only be administered parenterally, it requires control by the laboratory test of partial thromboplastin time (aPTT), may cause osteoporosis and alopecia when used for long periods and its production has a biological origin. The AVK has the advantage of being administered orally, but the control (made by the international normalized ratio - INR) can be difficult in some cases, have delayed onset and metabolism, has a narrow therapeutic window and interaction with diet and large number of medicines, can cause skin necrosis in patients with antithrombin and protein C and S deficiencies, and may induce fetal changes when prescribed in pregnancy. In the '80s came the low molecular weight heparins (LMWH), which were an evolution of UFH, because they showed greater bio-availability, fixed dosage per body weight, no need for laboratory control, subcutaneous administration, lower risk of HIT, and efficacy and safety similar to UFH. In the last decade, a series of new anticoagulants appeared in the market, which has shown promising results in various situations of prophylaxis and treatment of VTE. In this review, new LMWH, ultra-low molecular weight heparin, pentasaccharides, the new direct inhibitors of Factor Xa and Factor IIa inhibitors are presented

Made available in DSpace on 2014-06-11T19:23:41Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-01-18Bitstream added on 2014-06-13T18:51:07Z : No. of bitstreams: 1 borghesan_ac_me_botfmvz.pdf: 1646300 bytes, checksum: 839e649d17087393e054d28018df89fe (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Fundação para o Desenvolvimento da UNESP (FUNDUNESP) / A tromboflebite jugular é uma das principais doenças vasculares em eqüinos, podendo levar a edema de cabeça, diminuição do desempenho atlético e até causar o óbito. A heparina é um dos medicamentos utilizados para o tratamento dessa enfermidade com o objetivo de minimizar a evolução do trombo. O objetivo desse experimento foi avaliar, por exames clínicos, laboratoriais, ultra-sonográficos e venográficos as alterações provocadas pela administração de heparina no tratamento da tromboflebite experimental em eqüinos. Dez eqüinos foram submetidos à indução de tromboflebite jugular unilateral. Os animais foram divididos em grupo controle e grupo tratado, composto por cinco animais que receberam durante 10 dias a administração de heparina. Previamente à indução da tromboflebite e diariamente após o estabelecimento da mesma foram realizados exames clínicos e ultra-sonográficos até o 18º dia. Os exames laboratoriais tempo de tromboplastina parcial ativada (TTPA), tempo de protrombina (TP) e contagem total de plaquetas foram determinados no dia anterior à indução da tromboflebite, durante o período de indução e mensurados diariamente, até o 12º dia pós-indução. Hemogramas foram realizados no período pré-indução, imediatamente após a cirurgia para a indução do trombo e no 3°, 7° e 10° dia após a tromboflebite induzida. Medidas diárias do comprimento dos trombos foram submetidas à comparação estatística pelo método de análise de variância. Venografias foram realizadas nos momentos pré-indução, imediatamente à indução, após a indução e a cada seis dias até o 18° dia. No grupo controle, os trombos cresceram até o 9° dia pós-indução, quando foi possível observar diminuição do comprimento dos trombos e aumento de fluxo lateral. No grupo tratado com heparina observou-se a interrupção no crescimento do trombo após... / Jugular thrombophlebitis is a major vascular disease in horses which can lead to head edema, decreased athletic performance and even death. Heparin is used for the treatment of this disease in order to minimize the development of thrombus. The aim of this experiment was to evaluate clinical, laboratory, ultrasound and venographic changes caused by administration of heparin in the treatment of experimental thrombophlebitis in horses. Ten horses were subjected to induction of unilateral jugular thrombophlebitis. The animals were divided into control group and the treated group, composed of five animals each that received during 10 days the administration of heparin. Prior to the induction of thrombophlebitis and daily after the establishment of the same physical examinations and ultrasound were performed until the 18th day. The laboratory tests activated partial thromboplastin (APTT), prothrombin time (PT) and total count platelet were determined the day before the induction of thrombophlebitis, during the induction period and measured daily until the 12th day post-induction. Red blood cells counts were performed in the pre-induction, immediately after surgery for the induction of thrombus in the 3rd, 7th and 10th day after induced thrombophlebitis. Daily measurements of the length of the thrombi were subjected to statistical comparison with analysis of variance. Venographs were performed in the pre-induction, immediately before induction, after induction and every six days until the 18th day. In the control group, the thrombi to grow until the 9th day post-induction, when we observed a shortening of the thrombi and increased lateral flow. In the group treated with heparin there was a break in the growth of the thrombus after the start of administration of the drug and decrease in length of the thrombus with the appearance of flow down the sides of the cranial portion of the thrombus ...(Complete abstract click electronic access below)

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