Orientador: Marcos Jun Watanabe / Coorientador: Carlos Alberto Husnni / Banca: Juliana de Moura Alonso / Banca: Paula Alessandra Di Filippo / Resumo: Nos equinos, os distúrbios gastrointestinais (GI) são as causas mais comuns de problemas de coagulação, podendo gerar complicações fatais. Atualmente, uma das ferramentas mais sensíveis para avaliação da hipercoagulabilidade e hiperfibrinólise em cavalos é a determinação das concentrações de dímeros-D. Dessa forma, objetivou-se relacionar as concentrações plasmáticas e peritoneais de dímeros-D com as variáveis clínicas (frequência cardíaca, frequência respiratória, cor das membranas mucosas, tempo de preenchimento capilar, temperatura retal, grau de dor e tempo de evolução do quadro) e laboratoriais (hematócrito, proteína plasmática total, plaquetas, fibrinogênio e leucócitos sanguíneos, além de proteína, fibrinogênio, células nucleadas, bactérias e glicose no líquido peritoneal) de equinos com síndrome cólica e com o diagnóstico e prognóstico desses casos. Foram utilizados 86 equinos com idade mediana de 6,5 anos e com peso mediano de 400 Kg. Os animais foram submetidos ao exame clínico e coleta de amostras de sangue e líquido peritoneal (LP) na admissão. As concentrações plasmáticas e peritoneais de dímeros-D foram avaliadas através de um ensaio semiquantitativo de aglutinação em látex. Apesar das concentrações plasmáticas e peritoneais de dímeros-D terem demonstrado um sentido biológico relacionado à gravidade dos casos de cólica na análise descritiva, isso não foi comprovado estatisticamente através da análise multivariada. Portanto, concluímos que a determinação das conc... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: In horses, gastrointestinal (GI) disorders are the most common cause of coagulation problems, which can lead to fatal complications. One of the most sensitive tools for assessing hypercoagulability and hyperfibrinolysis in horses is the determination of D-dimer concentrations. The aim of this study was to correlate the plasma and peritoneal D-dimer concentrations with the clinical variables (heart rate, respiratory rate, mucous membranes color, capillary filling time, rectal temperature, pain degree, and time frame evolution) (hematocrit, total plasma protein, platelets, fibrinogen and blood leukocytes, as well as protein, fibrinogen, nucleated cells, bacteria and glucose in the peritoneal fluid) of horses with colic syndrome and with the diagnosis and prognosis of these cases. A total of 86 horses with a median age of 6.5 years and with a median weight of 400 kg were used. The animals were submitted to clinical examination and collection of blood and peritoneal fluid (LP) samples at admission. Plasma and peritoneal concentrations of D-dimers were evaluated by a semi-quantitative latex agglutination assay. Although plasma and peritoneal concentrations of D-dimers demonstrated a biological significance related to the severity of colic cases in the descriptive analysis, this was not statistically demonstrated through multivariate analysis. Therefore, we concluded that the determination of plasma and peritoneal concentrations of D-dimers using semi-quantitative latex agglutinati... (Complete abstract click electronic access below) / Mestre

INTRODUCTION AND AIM The prevalence of cardiovascular disease (CVD) has increased significantly in the black South African population in recent years. Early in the development of CVD, atherosclerotic plaques form in the vessel wall. When this plaque becomes unstable and ruptures, the coagulation cascade is activated and a blood clot forms. The function of this clot is to stop bleeding. However, it cannot remain in the vasculature indefinitely and has to be lysed again. The ability of the body to lyse clots can be measured with global fibrinolytic potential (GFP) assays and expressed as lysis time. Increased clot lysis time (CLT) has been shown to be significantly associated with various CVD risk factors and CVD events in Caucasian populations while very little information is available for other ethnicities. In this study we investigated plasma GFP and its relation to CVD risk factors in a large black African population. We also determined the effect of three polymorphisms in the promoter area of the plasminogen activator inhibitor-1 (PAI-1) gene on PAI-1act (activity) levels (a main determinant of CLT) and CLT, together with gene-environment interactions and the effect of urbanisation on these interactions. PARTICIPANTS AND METHODS Apparently healthy men and women between the ages of 35 and 65 years were recruited to take part in the South African arm of the Prospective Urban and Rural Epidemiology (PURE) study. Approximately 1000 rural and 1000 urban black African individuals participated. Data and samples were collected during a 12-week collection period in 2005 for cross-sectional analysis. RESULTS Increased PAI-1act levels, body mass index (BMI), glycosylated haemoglobin (HbA1c), triglycerides, fibrinogen concentration, C-reactive protein, female sex, positive HIV-status and the metabolic syndrome were all associated with prolonged CLTs, while increased habitual alcohol consumption was associated with shorter iv CLTs. Urban-rural differences for CLT existed in women only. This is likely due to the larger extent of rural-urban differences in other CVD risk factors observed in women compared to what was observed in men. Of the CVD risk factors measured, PAI-1 explained the largest proportion of the variance in CLT (27%). Owing to the important role PAI-1act plays in CLT, we investigated three polymorphisms in the PAI-1 gene promoter area (the 4G/5G polymorphism, the novel SNP C428T and SNP G429A (previously identified)), and the influence of these polymorphisms on PAI-1act levels and CLT. The frequency of the 5G allele was high (0.85) in comparison with previously reported literature. PAI-1act increased significantly across genotypes in the urban (5G/5G: 3.84 U/ml; 4G/5G: 4.85 U/ml; 4G/4G: 5.96 U/ml p=0.009) but not the rural subgroup, while CLT did not differ. We found significant interactions between the 4G/5G polymorphism and BMI, waist circumference and triglycerides in determining PAI-1act, and between the 4G/5G polymorphism and fibrinogen and fibrinogen gamma prime in determining CLT. Direct relationships with PAI-1act or CLT were not found for the C428T and G429A polymorphisms; they did, however, influence associations of other environmental factors with PAI-1act and CLT. Several of these interactions differed significantly between rural and urban subgroups, particularly in individuals harbouring the mutant alleles. CONCLUSION CLT associated with many of the same CVD risk factors described in the literature for Caucasian populations, but also with other risk factors. Rural-urban differences in CLT are dependent on the association of CLT with other CVD risk factors in the rural-urban setting. Genetic polymorphisms of the PAI-1 gene did not directly influence CLT, despite influencing PAI-1act. The main contributor to PAI-1act variance, however, was (central) obesity. The effect of the 4G/5G polymorphism on PAI-1act, as well as gene–environment interactions for the C428T and G429A genotypes in determining PAI-1act and CLT, were significantly influenced by urbanisation. / Thesis (PhD (Nutrition))--North-West University, Potchefstroom Campus, 2013.

INTRODUCTION AND AIM The prevalence of cardiovascular disease (CVD) has increased significantly in the black South African population in recent years. Early in the development of CVD, atherosclerotic plaques form in the vessel wall. When this plaque becomes unstable and ruptures, the coagulation cascade is activated and a blood clot forms. The function of this clot is to stop bleeding. However, it cannot remain in the vasculature indefinitely and has to be lysed again. The ability of the body to lyse clots can be measured with global fibrinolytic potential (GFP) assays and expressed as lysis time. Increased clot lysis time (CLT) has been shown to be significantly associated with various CVD risk factors and CVD events in Caucasian populations while very little information is available for other ethnicities. In this study we investigated plasma GFP and its relation to CVD risk factors in a large black African population. We also determined the effect of three polymorphisms in the promoter area of the plasminogen activator inhibitor-1 (PAI-1) gene on PAI-1act (activity) levels (a main determinant of CLT) and CLT, together with gene-environment interactions and the effect of urbanisation on these interactions. PARTICIPANTS AND METHODS Apparently healthy men and women between the ages of 35 and 65 years were recruited to take part in the South African arm of the Prospective Urban and Rural Epidemiology (PURE) study. Approximately 1000 rural and 1000 urban black African individuals participated. Data and samples were collected during a 12-week collection period in 2005 for cross-sectional analysis. RESULTS Increased PAI-1act levels, body mass index (BMI), glycosylated haemoglobin (HbA1c), triglycerides, fibrinogen concentration, C-reactive protein, female sex, positive HIV-status and the metabolic syndrome were all associated with prolonged CLTs, while increased habitual alcohol consumption was associated with shorter iv CLTs. Urban-rural differences for CLT existed in women only. This is likely due to the larger extent of rural-urban differences in other CVD risk factors observed in women compared to what was observed in men. Of the CVD risk factors measured, PAI-1 explained the largest proportion of the variance in CLT (27%). Owing to the important role PAI-1act plays in CLT, we investigated three polymorphisms in the PAI-1 gene promoter area (the 4G/5G polymorphism, the novel SNP C428T and SNP G429A (previously identified)), and the influence of these polymorphisms on PAI-1act levels and CLT. The frequency of the 5G allele was high (0.85) in comparison with previously reported literature. PAI-1act increased significantly across genotypes in the urban (5G/5G: 3.84 U/ml; 4G/5G: 4.85 U/ml; 4G/4G: 5.96 U/ml p=0.009) but not the rural subgroup, while CLT did not differ. We found significant interactions between the 4G/5G polymorphism and BMI, waist circumference and triglycerides in determining PAI-1act, and between the 4G/5G polymorphism and fibrinogen and fibrinogen gamma prime in determining CLT. Direct relationships with PAI-1act or CLT were not found for the C428T and G429A polymorphisms; they did, however, influence associations of other environmental factors with PAI-1act and CLT. Several of these interactions differed significantly between rural and urban subgroups, particularly in individuals harbouring the mutant alleles. CONCLUSION CLT associated with many of the same CVD risk factors described in the literature for Caucasian populations, but also with other risk factors. Rural-urban differences in CLT are dependent on the association of CLT with other CVD risk factors in the rural-urban setting. Genetic polymorphisms of the PAI-1 gene did not directly influence CLT, despite influencing PAI-1act. The main contributor to PAI-1act variance, however, was (central) obesity. The effect of the 4G/5G polymorphism on PAI-1act, as well as gene–environment interactions for the C428T and G429A genotypes in determining PAI-1act and CLT, were significantly influenced by urbanisation. / Thesis (PhD (Nutrition))--North-West University, Potchefstroom Campus, 2013.

Made available in DSpace on 2014-06-11T19:23:45Z (GMT). No. of bitstreams: 0 Previous issue date: 2013-07-04Bitstream added on 2014-06-13T19:50:54Z : No. of bitstreams: 1 000760136.pdf: 3009097 bytes, checksum: ab6e7c1fbf6f7224e3b942dec747e608 (MD5) / As afecções do cólon menor são causas frequentes de síndrome cólica, sendo a enterotomia rotineiramente empregada para a remoção de fecalitos, enterólitos e corpos estranhos. O trauma cirúrgico resulta em inflamação difusa e ocorrência de peritonite asséptica devido à manipulação e ao acesso cirúrgico. Objetivou-se estudar a reatividade peritoneal após a realização de enterotomia e abrasão do cólon menor em equinos tratados ou não com heparina sistêmica. Foram utilizados dez equinos com idade média de 9 ± 3,87anos e 358 ± 30,28 Kg de massa corporal, divididos em dois grupos de cinco animais, sendo um grupo o controle (GC) e o outro tratado (GT). Ambos os grupos foram submetidos à laparotomia e enterotomia de cólon menor através da via paralombar direita em posição quadrupedal e receberam flunixin meglumine, gentamicina e associação de penicilinas. Ao GT, acrescentou-se heparina (150 UI/Kg SC, BID, 5 dias). Os animais foram avaliados quanto ao exame físico; hemograma; fibrinogênio; coagulograma; proteínas de fase aguda, séricas e peritoneais; características macroscópicas, físico-químicas e citológicas do líquido peritoneal; concentrações peritoneais do ativador e inibidor do plasminogênio tecidual e dímero D. Para tanto, pradonizaram-se os seguintes momentos de avaliação: M0-prévio à enterotomia; M1-12 horas; M2 - 1dia, M3- 2dias, M4- 4dias e M5- 6 dias; M6- 10 dias e M7- 14 dias após a enterotomia. Observou-se que a heparina resultou em anemia e diminuição da contagem de plaquetas, aumento do tempo de tromboplastina parcial ativada e aumento nas concentrações séricas e peritoneais das proteínas de fase aguda, entretanto diminuiu a formação de dímeros D, sugerindo diminuição da formação de coágulos de fibrina. Após 15 dias da enterotomia, realizou-se o exame laparoscópico, que não demonstrou diferença na deposição de fibrina entre os grupos, entretanto... / Small colon affections are frequent causes of abdominal pain, and enterotomy is routinely employed for removal of fecalith, enteroliths and foreign bodies. Surgical trauma results in diffuse inflammation and aseptic peritonitis occurrence due to handling and surgical access. The aim of this study was to evaluate peritoneal reactivity after small colon enterotomy and abrasion in horses treated or not with systemic heparin. Were used ten horses with a mean age of 9 ± 3.87 years and 358 ± 30,28 body weight, divided into two groups of five animals: one control group (CG) and the other treated (TG). Both groups underwent laparotomy and small colon enterotomy via right paralumbar flank in standing position and received flunixin meglumine, gentamicin and penicillin association. TG received also heparin (150 IU / kg SC BID, 5 days). Animals were evaluated for physiological parameters, hemogram, fibrinogen, coagulation markers, serum and peritoneal acute phase proteins, peritoneal fluid macroscopic, physico-chemical and cytological characteristics, peritoneal concentrations of tissue plasminogen activator and inhibitor and d-dimer. Assessments were performed prior to enterotomy-M0, M1-12 hours after enterotomy; M2 - 1 day, M3 - 2days; M4 - 4days; M5 - 6 days; M6-10 days and M7 - 14 days after the enterotomy. Heparin resulted in anemia and decreased platelet counts, increased in partial thromboplastin activated time and increased serum and peritoneal acute phase proteins, however, resulted in decreased formation of fibrin clots and d dimer formation. After 15 days of enterotomy, laparoscopic examination showed no difference in fibrin deposition between the groups, and a slight diffuse peritoneal reactivity higher to treated group. So, heparin showed as negative effect the development of anemia, significant decrease in platelet count and acting as a proinflammatory agent, however shown to reduce fibrin deposition and formation ...

Orientador: Carloa Alberto Hussni / Banca: Armen Thomassian / Banca: Luis Cláudio Lopes Corrêa da Silva / Resumo: As afecções do cólon menor são causas frequentes de síndrome cólica, sendo a enterotomia rotineiramente empregada para a remoção de fecalitos, enterólitos e corpos estranhos. O trauma cirúrgico resulta em inflamação difusa e ocorrência de peritonite asséptica devido à manipulação e ao acesso cirúrgico. Objetivou-se estudar a reatividade peritoneal após a realização de enterotomia e abrasão do cólon menor em equinos tratados ou não com heparina sistêmica. Foram utilizados dez equinos com idade média de 9 ± 3,87anos e 358 ± 30,28 Kg de massa corporal, divididos em dois grupos de cinco animais, sendo um grupo o controle (GC) e o outro tratado (GT). Ambos os grupos foram submetidos à laparotomia e enterotomia de cólon menor através da via paralombar direita em posição quadrupedal e receberam flunixin meglumine, gentamicina e associação de penicilinas. Ao GT, acrescentou-se heparina (150 UI/Kg SC, BID, 5 dias). Os animais foram avaliados quanto ao exame físico; hemograma; fibrinogênio; coagulograma; proteínas de fase aguda, séricas e peritoneais; características macroscópicas, físico-químicas e citológicas do líquido peritoneal; concentrações peritoneais do ativador e inibidor do plasminogênio tecidual e dímero D. Para tanto, pradonizaram-se os seguintes momentos de avaliação: M0-prévio à enterotomia; M1-12 horas; M2 - 1dia, M3- 2dias, M4- 4dias e M5- 6 dias; M6- 10 dias e M7- 14 dias após a enterotomia. Observou-se que a heparina resultou em anemia e diminuição da contagem de plaquetas, aumento do tempo de tromboplastina parcial ativada e aumento nas concentrações séricas e peritoneais das proteínas de fase aguda, entretanto diminuiu a formação de dímeros D, sugerindo diminuição da formação de coágulos de fibrina. Após 15 dias da enterotomia, realizou-se o exame laparoscópico, que não demonstrou diferença na deposição de fibrina entre os grupos, entretanto ... / Abstract: Small colon affections are frequent causes of abdominal pain, and enterotomy is routinely employed for removal of fecalith, enteroliths and foreign bodies. Surgical trauma results in diffuse inflammation and aseptic peritonitis occurrence due to handling and surgical access. The aim of this study was to evaluate peritoneal reactivity after small colon enterotomy and abrasion in horses treated or not with systemic heparin. Were used ten horses with a mean age of 9 ± 3.87 years and 358 ± 30,28 body weight, divided into two groups of five animals: one control group (CG) and the other treated (TG). Both groups underwent laparotomy and small colon enterotomy via right paralumbar flank in standing position and received flunixin meglumine, gentamicin and penicillin association. TG received also heparin (150 IU / kg SC BID, 5 days). Animals were evaluated for physiological parameters, hemogram, fibrinogen, coagulation markers, serum and peritoneal acute phase proteins, peritoneal fluid macroscopic, physico-chemical and cytological characteristics, peritoneal concentrations of tissue plasminogen activator and inhibitor and d-dimer. Assessments were performed prior to enterotomy-M0, M1-12 hours after enterotomy; M2 - 1 day, M3 - 2days; M4 - 4days; M5 - 6 days; M6-10 days and M7 - 14 days after the enterotomy. Heparin resulted in anemia and decreased platelet counts, increased in partial thromboplastin activated time and increased serum and peritoneal acute phase proteins, however, resulted in decreased formation of fibrin clots and d dimer formation. After 15 days of enterotomy, laparoscopic examination showed no difference in fibrin deposition between the groups, and a slight diffuse peritoneal reactivity higher to treated group. So, heparin showed as negative effect the development of anemia, significant decrease in platelet count and acting as a proinflammatory agent, however shown to reduce fibrin deposition and formation ... / Mestre

INTRODUCTION - Plasminogen activator inhibitor type-1 (PAI-1) has a known relationship with obesity and more specifically with central obesity. Traditionally the physiological contribution of PAI-1 is seen as an indicator of fibrinolysis with increased PAI-1 levels contributing to decreased fibrinolysis. In more recent years, assays have been developed that not only uses proxy markers, such as PA-1, which is considered to be representative of fibrinolysis , but global assays that report on the global fibrinolytic potential of an individual, often reported as clot lysis time (CLT). Investigations into the relationship of CLT with obesity are scarce. Preliminary evidence shows that the relationship of CLT with obesity may differ from that of PAI-1 with obesity although in depth investigations in this regard are lacking. Therefore, the aim of this study was to investigate the association between fibrinolysis markers (PAI-1act and CLT) and various markers of body composition in the South African Prospective Urban and Rural Epidemiology (PURE) data collected during 2010. METHODS - Data collected in the PURE study in 2010 were cross-sectionally analysed. The participants (n = 1288) were apparently healthy black South-African men and women 35 years and older, residing in urban and rural settlements in the North-West Province. Experimental methods included anthropometric measurements such as height, weight, hip circumference, waist circumference, skinfolds (triceps, chest, abdominal, thigh and supra iliac skinfolds) and body composition measurements by means of air-displacement plethysmography and biolelectrical impedance analysis. Laboratory analysis of fibrinolysis markers, PAI-1act and CLT were also performed. MAIN FINDINGS - In men, similarities were seen regarding the relationship between PAI-1act and body composition markers and the relationships observed between CLT and body composition markers. In contrast, in the women more and stronger associations were observed between CLT and body composition markers compared to that observed between PAI-1act and body composition markers. CLT showed a linear relationship with body composition markers where PAI-1act levels plateaued at higher body composition categories. Possible reasons for the observed differences may be related to differences in adipose tissue distribution and sequence of accumulation between men and women. PAI-1 is associated with visceral adipose tissue (VAT) where high amounts of stromal cells are found. In men preferential accumulation of VAT may explain similarities in the relationship of PAI-1act with body composition and that of CLT with body composition. Proportionally less VAT, but more subcutaneous adipose tissue in women may explain the observed increase in CLT compared to PAI-1act levels that plateaued over body composition tertiles and categories. CONCLUSION - PAI-1act has a stronger association with central obesity while CLT has a stronger association with total body fat. In women PAI-1act and CLT showed different associations with body composition markers, whereas associations of PAI-1act and CLT with body composition were similar in men. PAI-1act is strongly influenced by type of body fat accumulation whereas CLT is associated with obesity independent of type and sequence of body fact accumulation. Significant associations observed between CLT and body composition variables are, therefore, at least in part, independent of PAI-1act. Additional factors such as, thrombin activatable fibrinolysis inhibitor (TAFI), α-2-antiplasmin, plasminogen, prothrombin and fibrin clot structure that influence CLT and are also related to obesity may additionally contribute to the link between CLT and obesity. / MSc (Dietetics), North-West University, Potchefstroom Campus, 2014

INTRODUCTION - Plasminogen activator inhibitor type-1 (PAI-1) has a known relationship with obesity and more specifically with central obesity. Traditionally the physiological contribution of PAI-1 is seen as an indicator of fibrinolysis with increased PAI-1 levels contributing to decreased fibrinolysis. In more recent years, assays have been developed that not only uses proxy markers, such as PA-1, which is considered to be representative of fibrinolysis , but global assays that report on the global fibrinolytic potential of an individual, often reported as clot lysis time (CLT). Investigations into the relationship of CLT with obesity are scarce. Preliminary evidence shows that the relationship of CLT with obesity may differ from that of PAI-1 with obesity although in depth investigations in this regard are lacking. Therefore, the aim of this study was to investigate the association between fibrinolysis markers (PAI-1act and CLT) and various markers of body composition in the South African Prospective Urban and Rural Epidemiology (PURE) data collected during 2010. METHODS - Data collected in the PURE study in 2010 were cross-sectionally analysed. The participants (n = 1288) were apparently healthy black South-African men and women 35 years and older, residing in urban and rural settlements in the North-West Province. Experimental methods included anthropometric measurements such as height, weight, hip circumference, waist circumference, skinfolds (triceps, chest, abdominal, thigh and supra iliac skinfolds) and body composition measurements by means of air-displacement plethysmography and biolelectrical impedance analysis. Laboratory analysis of fibrinolysis markers, PAI-1act and CLT were also performed. MAIN FINDINGS - In men, similarities were seen regarding the relationship between PAI-1act and body composition markers and the relationships observed between CLT and body composition markers. In contrast, in the women more and stronger associations were observed between CLT and body composition markers compared to that observed between PAI-1act and body composition markers. CLT showed a linear relationship with body composition markers where PAI-1act levels plateaued at higher body composition categories. Possible reasons for the observed differences may be related to differences in adipose tissue distribution and sequence of accumulation between men and women. PAI-1 is associated with visceral adipose tissue (VAT) where high amounts of stromal cells are found. In men preferential accumulation of VAT may explain similarities in the relationship of PAI-1act with body composition and that of CLT with body composition. Proportionally less VAT, but more subcutaneous adipose tissue in women may explain the observed increase in CLT compared to PAI-1act levels that plateaued over body composition tertiles and categories. CONCLUSION - PAI-1act has a stronger association with central obesity while CLT has a stronger association with total body fat. In women PAI-1act and CLT showed different associations with body composition markers, whereas associations of PAI-1act and CLT with body composition were similar in men. PAI-1act is strongly influenced by type of body fat accumulation whereas CLT is associated with obesity independent of type and sequence of body fact accumulation. Significant associations observed between CLT and body composition variables are, therefore, at least in part, independent of PAI-1act. Additional factors such as, thrombin activatable fibrinolysis inhibitor (TAFI), α-2-antiplasmin, plasminogen, prothrombin and fibrin clot structure that influence CLT and are also related to obesity may additionally contribute to the link between CLT and obesity. / MSc (Dietetics), North-West University, Potchefstroom Campus, 2014