Diss. (sammanfattning) Linköping : Univ., 2002. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 7 uppsatser.

Thesis (Ph. D.)--Duke University, 2008.

Thesis (M.S.)--University of Texas at El Paso, 2008. / Title from title screen. Vita. CD-ROM. Includes bibliographical references. Also available online.

Thesis (M.S.)--University of North Carolina Wilmington, 2009. / Title from PDF title page (February 23, 2010) Includes bibliographical references (p. 55-61)

Thesis (Ph. D.)--University of Virginia, 2002. / Includes bibliographical references (leaves 160-197). Also available online through Digital Dissertations.

abstract: Thrombus (blood clot) formation is at the roots of hemostasis and pathological thrombosis. Although many studies have successfully elucidated the cellular and molecular mechanisms underlying thrombus formation, there is still a void in understanding the processes limiting thrombus growth beyond that needed for stabilization. As a hemostatic thrombus grows, its surface consisting primarily of platelets changes to that composed of fibrin, which mechanically stabilizes the thrombus. Formation of fibrin ceases after some time; however, it is unclear why this fibrin is non-thrombogenic. This is puzzling since fibrin is known to support strong integrin-mediated adhesion of both platelets and leukocytes in vitro. Therefore, it would be expected that the fibrin surface of hemostatic thrombi in the circulation also support accumulation of these cells and thus continuous thrombus growth or degradation. Nevertheless, many in vivo studies did not detect any accumulation of blood cells including platelets at the fibrin surfaces of thrombi. This finding suggests the existence of natural processes that modulate the adhesive properties of fibrin to ensure proper regulation of thrombus growth, stability and degradation. In this dissertation, I document and discuss the findings supporting the existence of anti-adhesive mechanisms and their physiological relevance in surface-mediated control of thrombus growth and stability. The studies discussed in my dissertation have the potential to establish a novel aspect of hemostasis. Furthermore, it may provide new insights into the intricate and dynamic interplay between the mechanisms underlying hemostatic balance, which is essential to understanding the dysfunction of this process during pathological conditions. / Dissertation/Thesis / Doctoral Dissertation Molecular and Cellular Biology 2016

Natural therapies such as Aged Garlic Extract (AGE) have displayed cardioprotective properties, with studies indicating that AGE can inhibit platelet aggregation both in vivo and in vitro. The mechanism of inhibition induced by AGE is proposed to be due to AGE exerting effects upon several targets within platelets, including calcium and cyclic adenosine monophosphate (cAMP). The effect of AGE upon the other cyclic nucleotide, cyclic guanosine monophosphate (cGMP) is currently unknown. The aims therefore of this project are to identify the effect of AGE upon platelet cGMP, as well as associated signaling molecules including nitric oxide (NO) and cAMP.It was found that the NO donor 3-morpholinosydnonimine (Sin-1) in high concentrations along with the presence of specific inhibitors inhibited platelet aggregation independently of cGMP. Experimentation using chemical inhibitors also displayed erratic results in the presence of high concentrations of AGE, indicating that AGE was influencing the binding of such inhibitors. The results of in vitro experiments indicated that AGE moderately increases intraplatelet cGMP, whereas intraplatelet cAMP is significantly increased. it is proposed that the main mechanism of inhibition caused by AGE is due to increases in cAMP. As intraplatelet cAMP can also be influenced by intraplatelet cGMP, it is likely that cAMP is increased directly and indirectly by AGE.Evidence provided in the present study supports the proposed theory that the mechanisms of inhibition of platelet aggregation by AGE is multimechanistic. More specifically inhibition of platelet aggregation by AGE is due to AGE increasing intraplatelet cyclic nucleotides, reducing the expression of key receptors such as GPIIb/IIIa and inhibiting agonist induced platelet shape change. As AGE can inhibit platelet aggregation, which is a key risk factor in cardiovascular disease, the consumption of AGE would be beneficial to those who are at risk of cardiovascular episodes.

Made available in DSpace on 2014-06-11T19:27:58Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-02-13Bitstream added on 2014-06-13T18:07:21Z : No. of bitstreams: 1 silva_lfn_me_botfmvz.pdf: 253354 bytes, checksum: 346237b24c0c8bb40efc79358dd2a8ab (MD5) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / O objetivo do presente estudo foi avaliar a importância das plaquetas reticuladas nas condições trombocitopênicas associadas a hipoplasia de megacariócitos e a outras etiologias sem alteração no número de megacariócitos. Para tanto foram utilizados 30 cães sadios adultos (Grupo controle); 15 cães com trombocitopenia (< 100.000 plaquetas/mL), por causas diversas que não sejam por hipoplasia megacariocítica (Grupo A) e 15 cães com trombocitopenia (< 100.000 plaquetas/mL) e com hipoplasia megariocítica (Grupo B), constatadas por meio de citologia aspirativa de medula óssea. Foi coletado sangue e extraído o plasma rico em plaquetas para a realização da quantificação das plaquetas reticuladas em citometria de fluxo e colheita de medula óssea para a análise do número de megacariócitos por duas técnicas distintas e correlação com as plaquetas reticuladas. Não foi observada diferença estatística (p>0,05) entre as duas técnicas de quantificação de megacariócitos. Foi observada diferença estatística (p<0,05) para as plaquetas reticuladas, sendo superior nos grupos A e B, em relação ao grupo controle. Não houve correlação entre plaqueta reticulada e megacariócitos medulares. A ausência de correlação observada não nos permite estabelecer relações de contagem de PR com o aumento do número de megacariócitos na medula óssea. / The aim of this study was to evaluate the reticulated platelet importance in evaluation of platelet production in thrombocytopenic conditions associated with megakaryocytic hypoplasia and other conditions with adequate number of bone marrow megacaryocytes. These study were obtained from 30 healthy dogs (control group), 15 thrombocytopenic dogs (< 100,000 platelets/μL) without megakaryocytic hipoplasia (group A) and 15 thrombocytopenic dogs (< 100,000 platelets /μL) with megakaryocytic hipoplasia (group B). Blood samples were collected and the platelet rich plasma (PRP) was extracted for quantification of reticulated platelets in flow cytometry, megakaryocytes were quantified in marrow particles, collected from aspiration cytology and correlated to reticulated platelets counts. No statistical significance (p>0.05) was observed between two megakaryocytes quantification techniques. For reticulated platelets was observed statistical significance difference (p<0.05), values from groups A and B were higher than control group. No correlation was verified between reticulated platelets and marrow megakaryocytes. The absence of correlation do not allow us to establish relationship of reticulated platelets with increase production of bone marrow megakaryocytes.

Orientador: Luís Carlos Spolidorio / Banca: Joni Augusto Cirelli / Banca: Raquel Fernanda Gerlach / Resumo: O objetivo deste trabalho foi avaliar o efeito da administracao da aspirina (Asp), do clopidogrel (Clo) e da ticlopidina (Tic) sobre o processo de reparacao dos tecidos periodontais apos inducao experimental de periodontite em ratos. Primeiramente avaliou-se a acao destas drogas sobre a expressao das citocinas pro-inflamatorias: TNF-α, IL-6 e TXA2 no tecido gengival de 25 ratos subdivididos em 5 grupos (n=5), 15 dias apos a instalacao da ligadura ao redor do primeiro molar inferior. Para avaliacao do reparo dos tecidos periodontais, setenta e dois ratos (Rattus norvegicus albinus, Holtzman) foram distribuídos aleatoriamente em 6 grupos (n=12), sendo 1 controle e 5 submetidos a periodontite atraves da instalacao de ligadura bilateral na regiao de primeiro molar inferior. Apos 15 dias, o grupo controle e um grupo com periodontite foram sacrificados. Para a inducao do reparo dos tecidos periodontais, as ligaduras dos animais dos outros 4 grupos foram removidas e os ratos foram tratados com solucao de NaCl 0.9%, Asp (30mg/kg), Clo (75 mg/kg) e Tic (300 mg/kg), diariamente, via gavagem. Apos 15 dias de tratamento, os animais foram sacrificados, as hemi- mandibulas do lado direito removidas para analise histologica e as do lado esquerdo para avaliacao macroscopica, microtomografia computadorizada e analise da expressao, atividade especifica e co-localizacao das metaloproteinases de matriz (MMPs) -2 e -9 atraves de zimograma e zimografia in situ. Apos a retirada da ligadura, houve reparacao do osso alveolar e reparacao do tecido gengival representado pela recomposicao da arquitetura tecidual do epitélio e do tecido conjuntivo. O tratamento com Asp comprometeu a reparacao óssea alveolar na face mesial e acelerou na area de furca, ao passo que nao influenciou na recomposicao da arquitetura do tecido epitelial e... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The aim of this study was to evaluate the effect of administration of aspirin (Asp), clopidogrel (Clo) and ticlopidine (Tic) in the process of periodontal tissue repair after induction of experimental periodontitis in rats. First, we evaluated the action of these drugs on the expression of pro-inflammatory cytokines: TNF-α, IL-6 and TXA2 in the gingival tissue of 25 rats randomly distributed in five equal groups (n=5), 15 days after ligature placement around lower first molars. For periodontal tissue evaluation, seventy-two rats (Rattus norvegicus albinus, Holtzman) were randomly distributed in 6 equal groups (n=12). One control and 5 submitted to a ligature-induced periodontitis model in the region of lower first molar bilaterally. After 15 days, the control group and a group with periodontitis were sacrificed. To induce periodontal tissue repair, ligatures from the other 4 groups were removed and the rats treated with NaCl 0.9%, Asp (30 mg/kg), Clo (75 mg/kg) and Tic (300 mg/kg) daily by gavage. After 15 days of treatment, animals were killed, the right mandibles were removed for histological analysis and the left side to macroscopic, microtomography evaluation and expression, activity and colocalization of matrix metalloproteinases (MMPs) -2 and -9 by zymogram and in situ zymography. After removal of the ligature, there was repair of the alveolar bone and gingival tissue represented by the restoration of tissue architecture of the epithelium and connective tissue. Treatment with Asp undertook the repair of the mesial alveolar bone and accelerated the repair of furcation area, while not influenced the restoration of tissue architecture and epithelial tissue. Treatment with Tic undertook the repair of mesial alveolar bone and furcation the area, as well as the repair of gingival epithelial... (Complete abstract, click electronic access below) / Mestre