Dados epidemiológicos documentaram a associação entre elevação moderada dos níveis da proteína C-reativa (PCR) pela técnica hipersensível (PCRhs), dentro da variação normal, e risco cardiovascular em indivíduos sem doença clínica vascular. A potencial aplicação da PCRhs, como uma ferramenta auxiliar na avaliação global, de risco requer conhecimento de sua distribuição na população e das características clínicas envolvidas. Há carência de dados sobre a influência sobre a genética na concentração da PCR. Formulamos a hipótese de que variações alélicas (polimorfismo) no gene que codifica a PCR poderiam interferir na sua concentração sérica. Avaliamos a distribuição da concentração sérica da proteína C-reativa determinada pela técnica hipersensível em indivíduos de uma população brasileira sem evidências clínica e laboratorial de cardiopatia, e as variações desta concentração e, relação às características clínicas, variáveis laboratoriais e ao polimorfismo G1059C do gene da PCR. Realizamos um estudo de coorte, de indivíduos assintomáticos com exames clínico e cardiológico normais, atendidos na Unidade Clínica de Ambulatório Geral do Instituto do Coração (InCor) do Hospital das Clínicas da Universidade de São Paulo, no período de julho de 1998 a julho de 2001. Critérios de inclusão: indivíduos assintomáticos com exame físico normal, eletrocardiograma de repouso e esforço normais e radiografia do tórax normal. Foram excluídos aqueles com glicemia superior a 125 md/dl, alterações na concentração sérica do hormônio tíreo-estimulante (TSH) e sorologia positiva para doença de Chagas. Foram elegíveis 684 indivíduos: 295 (43,1%) do sexo masculino e 389 (56,9%) do feminino. Suas idades variaram entre 14 e 74 anos (média 40,6; desvio-padrão 11,5); 513 (75,0%) eram brancos, 117 (17,1%) mulatos, 32 (4,7%) amarelos e 22 (3,2%) negros. O tabagismo foi relatado por 160 (23,4%) indivíduos e 524 (76,6%) não eram tabagistas. A avaliação laboratorial incluiu a dosagem de glicemia, colesterol total e frações, triglicérides e ácido úrico. Foram colhidas amostras de sangue para dosagem sérica da PCRhs e genotipagem de PCR. A ecocardiografia bidimencional com Doppler foi realizada em 634 indivíduos, com resultado normal. A concentração sérica da PCRhs foi distribuída por quartis da população em estudo, os valores mínimo e máximo por quartil foram: 1º quartil 0,014-0,037 mg/dl; 2º quartil 0,0384,07 mg/dl; 3º quartil 0,080-0,187 mg/dl e 4º quartil 0,188-1,31 mg/dl. Num modelo de regressão múltipla as variáveis independentes correlacionadas ao log da PCRhs foram: idade (p=0,03), índice de massa corpórea (IMC) (p<0,01), razão colesterol total/HDL colesterol (ColT/HDL-C) (P<0,01) e frequência cardíaca (p<0,01). Para avaliar o comportamento das variáveis significativas deste modelo de regressão, a amostra foi estratificada em quatro grupos, segundo sexo e tabagismo, e foram estimados quatro modelos múltiplos. Nos homens tabagistas foram variáveis significativas a idade (p=0,04) e a razão ColT/HDL-C (p<0,01); nos homens não tabagistas foram o IMC (p<0,01) e a razão ColT/HDL-C (p<0,01); nas mulheres tabagistas o IMC (p<0,01) e nas mulheres não tabagistas foram o IMC (p<0,01), a razão ColT/HDL-C (p=0,01) e a frequência cardíaca (p=0,02). Não houve diferença estatisticamente significativa (p<0,05) na concentração da PCRhs entre os diferentes genótipos do gene da PCR. Portanto as variáveis idade, IMC, razão ColT/HD1-C e frequência cardíaca, não se relacionam com a concentração sérica da PCRhs de maneira homogênea, mas sim de acordo com o subgrupo analisado, referente ao sexo e tabagismo; e as concentrações da PCRhs não diferiram quanto a presença ou ausência do polimorfismo G1059C do gene da PCR. / Epidemiologic data have documented the association between moderate elevation, within the normal range, of the C-reactive protein (CPR) serum levels measured by high-sensitivity assays (hs-CRP), and cardiovascular risk among individuals without clinical evidence of vascular disease. The potential use of hs-CRP as a new auxiliary tool in the assessment of overall risk requires that its distribution in the population and the related clinical characteristics are known. There is few data about the influence of genetics upon CRP concentration. The hypothesis that allele variations in the gene responsible for coding CRP (polymorphism) could interfere with CRP serum concentration has been posed. The aim of this study was to assess the distribution of C-reactive protein (CRP) serum concentration measured by high-sensitivity assay (hs-CRP), in a Brazilian population of individuals without heart disease, as well as the association of variations of that concentration with clinical characteristics and laboratory variables, and with the CRP gene G1059C polymorphism. A cohort of asymptomatic patients visiting the Outpatient Clinic of the Heart Institute (InCor) of the University of São Paulo Medical School between July 1998 and July 2001, all with normal results in the clinical and cardiological evaluations, was studied. The inclusion criteria were: asymptomatic individuals with normal results in the physical evaluation, normal electrocardiography and stress test, and normal chest X-ray examination. Individuals with glucose level above 125mg/dl, changes in the thyroid-stimulating hormone (TSH) serum concentration, and positive serology for Chagas\' disease, were excluded. Thus, 684 individuals, 295 men (43.1 %) and 389 women (56.9%), ages 14 to 74 (mean 40.6, SD 11.5) years, were eligible. White people in the cohort were 513 (75.0%), mulatto 117 (17.1%), eastern people 32 (4.7%) and 22 of black color (3.2%) 160 individuals (23.4%) reported as currently smoking, while 524 (76.6%) were non-smokers Laboratory screening consisted of dosing of glucose, total and partial: cholesterol, triglycerides and uric acid plasma levels. Doppler two-dimensional echocardiography was performed in 636 individuals, all with normal results. Serum hs-CRP concentration of the study population was distributed in quartiles, with minimum and maximum values per quartile as follows: 1st quartil, 0.014-0.037mg/dl; 2nd quartile: 0.038-0.078mg/dl; 3rd quartile 0.080-0.\'187mg/dl; and 4th quartile: 0.188-1,31mg/dl. Multiple regression analysis has shown that the independent variables correlating with hs-CRP-log were age (p=0.03), body mass index (p<0.01), total/HOL cholesterol ratio (p<0.01) and heart rate (p<0.01). The study population was stratified in 4 groups according to gender and smoking status, to verify the behavior of the significant variables in this regression model, with estimation of 4 multiple models. Significant variables were: among currently smoking men, age (p=0.04) and Total/HDL cholesterol ratio (p<0.01); among non-smoking men, BMI (p<0.01) and Total/HDL cholesterol ratio (p<0.01). Among currently smoking women, only BMI (p<0.01) was significant, and among non-smoking women, BMI (p<0.01), Total/HDL cholesterol ratio (p=001) and heart rate (p=0.02) were significant. There was no statistically significant difference (p<005) of the hs-CRP serum concentration in the groups with GG genotypes or the CRP gene G1059C polymorphism. Our findings led to the conclusion that the variables age, BMI, Total/HDL cholesterol: ratio and heart rate do not correlate homogeneously with the hs-CRP serum concentration in this study population, but according to the specific gender or smoking status subgroup being studied this is verified. Additionally, hs-CRP concentrations did not differ according to the presence or the absence of the CRP gene G1059C polymorphism.

Dados epidemiológicos documentaram a associação entre elevação moderada dos níveis da proteína C-reativa (PCR) pela técnica hipersensível (PCRhs), dentro da variação normal, e risco cardiovascular em indivíduos sem doença clínica vascular. A potencial aplicação da PCRhs, como uma ferramenta auxiliar na avaliação global, de risco requer conhecimento de sua distribuição na população e das características clínicas envolvidas. Há carência de dados sobre a influência sobre a genética na concentração da PCR. Formulamos a hipótese de que variações alélicas (polimorfismo) no gene que codifica a PCR poderiam interferir na sua concentração sérica. Avaliamos a distribuição da concentração sérica da proteína C-reativa determinada pela técnica hipersensível em indivíduos de uma população brasileira sem evidências clínica e laboratorial de cardiopatia, e as variações desta concentração e, relação às características clínicas, variáveis laboratoriais e ao polimorfismo G1059C do gene da PCR. Realizamos um estudo de coorte, de indivíduos assintomáticos com exames clínico e cardiológico normais, atendidos na Unidade Clínica de Ambulatório Geral do Instituto do Coração (InCor) do Hospital das Clínicas da Universidade de São Paulo, no período de julho de 1998 a julho de 2001. Critérios de inclusão: indivíduos assintomáticos com exame físico normal, eletrocardiograma de repouso e esforço normais e radiografia do tórax normal. Foram excluídos aqueles com glicemia superior a 125 md/dl, alterações na concentração sérica do hormônio tíreo-estimulante (TSH) e sorologia positiva para doença de Chagas. Foram elegíveis 684 indivíduos: 295 (43,1%) do sexo masculino e 389 (56,9%) do feminino. Suas idades variaram entre 14 e 74 anos (média 40,6; desvio-padrão 11,5); 513 (75,0%) eram brancos, 117 (17,1%) mulatos, 32 (4,7%) amarelos e 22 (3,2%) negros. O tabagismo foi relatado por 160 (23,4%) indivíduos e 524 (76,6%) não eram tabagistas. A avaliação laboratorial incluiu a dosagem de glicemia, colesterol total e frações, triglicérides e ácido úrico. Foram colhidas amostras de sangue para dosagem sérica da PCRhs e genotipagem de PCR. A ecocardiografia bidimencional com Doppler foi realizada em 634 indivíduos, com resultado normal. A concentração sérica da PCRhs foi distribuída por quartis da população em estudo, os valores mínimo e máximo por quartil foram: 1º quartil 0,014-0,037 mg/dl; 2º quartil 0,0384,07 mg/dl; 3º quartil 0,080-0,187 mg/dl e 4º quartil 0,188-1,31 mg/dl. Num modelo de regressão múltipla as variáveis independentes correlacionadas ao log da PCRhs foram: idade (p=0,03), índice de massa corpórea (IMC) (p<0,01), razão colesterol total/HDL colesterol (ColT/HDL-C) (P<0,01) e frequência cardíaca (p<0,01). Para avaliar o comportamento das variáveis significativas deste modelo de regressão, a amostra foi estratificada em quatro grupos, segundo sexo e tabagismo, e foram estimados quatro modelos múltiplos. Nos homens tabagistas foram variáveis significativas a idade (p=0,04) e a razão ColT/HDL-C (p<0,01); nos homens não tabagistas foram o IMC (p<0,01) e a razão ColT/HDL-C (p<0,01); nas mulheres tabagistas o IMC (p<0,01) e nas mulheres não tabagistas foram o IMC (p<0,01), a razão ColT/HDL-C (p=0,01) e a frequência cardíaca (p=0,02). Não houve diferença estatisticamente significativa (p<0,05) na concentração da PCRhs entre os diferentes genótipos do gene da PCR. Portanto as variáveis idade, IMC, razão ColT/HD1-C e frequência cardíaca, não se relacionam com a concentração sérica da PCRhs de maneira homogênea, mas sim de acordo com o subgrupo analisado, referente ao sexo e tabagismo; e as concentrações da PCRhs não diferiram quanto a presença ou ausência do polimorfismo G1059C do gene da PCR. / Epidemiologic data have documented the association between moderate elevation, within the normal range, of the C-reactive protein (CPR) serum levels measured by high-sensitivity assays (hs-CRP), and cardiovascular risk among individuals without clinical evidence of vascular disease. The potential use of hs-CRP as a new auxiliary tool in the assessment of overall risk requires that its distribution in the population and the related clinical characteristics are known. There is few data about the influence of genetics upon CRP concentration. The hypothesis that allele variations in the gene responsible for coding CRP (polymorphism) could interfere with CRP serum concentration has been posed. The aim of this study was to assess the distribution of C-reactive protein (CRP) serum concentration measured by high-sensitivity assay (hs-CRP), in a Brazilian population of individuals without heart disease, as well as the association of variations of that concentration with clinical characteristics and laboratory variables, and with the CRP gene G1059C polymorphism. A cohort of asymptomatic patients visiting the Outpatient Clinic of the Heart Institute (InCor) of the University of São Paulo Medical School between July 1998 and July 2001, all with normal results in the clinical and cardiological evaluations, was studied. The inclusion criteria were: asymptomatic individuals with normal results in the physical evaluation, normal electrocardiography and stress test, and normal chest X-ray examination. Individuals with glucose level above 125mg/dl, changes in the thyroid-stimulating hormone (TSH) serum concentration, and positive serology for Chagas\' disease, were excluded. Thus, 684 individuals, 295 men (43.1 %) and 389 women (56.9%), ages 14 to 74 (mean 40.6, SD 11.5) years, were eligible. White people in the cohort were 513 (75.0%), mulatto 117 (17.1%), eastern people 32 (4.7%) and 22 of black color (3.2%) 160 individuals (23.4%) reported as currently smoking, while 524 (76.6%) were non-smokers Laboratory screening consisted of dosing of glucose, total and partial: cholesterol, triglycerides and uric acid plasma levels. Doppler two-dimensional echocardiography was performed in 636 individuals, all with normal results. Serum hs-CRP concentration of the study population was distributed in quartiles, with minimum and maximum values per quartile as follows: 1st quartil, 0.014-0.037mg/dl; 2nd quartile: 0.038-0.078mg/dl; 3rd quartile 0.080-0.\'187mg/dl; and 4th quartile: 0.188-1,31mg/dl. Multiple regression analysis has shown that the independent variables correlating with hs-CRP-log were age (p=0.03), body mass index (p<0.01), total/HOL cholesterol ratio (p<0.01) and heart rate (p<0.01). The study population was stratified in 4 groups according to gender and smoking status, to verify the behavior of the significant variables in this regression model, with estimation of 4 multiple models. Significant variables were: among currently smoking men, age (p=0.04) and Total/HDL cholesterol ratio (p<0.01); among non-smoking men, BMI (p<0.01) and Total/HDL cholesterol ratio (p<0.01). Among currently smoking women, only BMI (p<0.01) was significant, and among non-smoking women, BMI (p<0.01), Total/HDL cholesterol ratio (p=001) and heart rate (p=0.02) were significant. There was no statistically significant difference (p<005) of the hs-CRP serum concentration in the groups with GG genotypes or the CRP gene G1059C polymorphism. Our findings led to the conclusion that the variables age, BMI, Total/HDL cholesterol: ratio and heart rate do not correlate homogeneously with the hs-CRP serum concentration in this study population, but according to the specific gender or smoking status subgroup being studied this is verified. Additionally, hs-CRP concentrations did not differ according to the presence or the absence of the CRP gene G1059C polymorphism.

Motivation: C-reactive protein (hs-CRP) and other risk factors such as cortisol and obesity in the diagnosis of cardiovascular dysfunction (CVD) in African and Caucasian women has become increasingly imperative when one considers the escalation of hypertension among these groups. Recent studies have explored some aspects of these risk factors and the roles that they play within hypertension and possible future risk for cardiovascular disease. Hs-CRP has been associated with the increased prevalence of hypertension and obesity. Cortisol per se has also been linked with the development of both hypertension and the hypothalamic-pituitary adrenal cortex (HPA) response. Nevertheless, the exact mechanism remains rather uncertain due to conflicting outcomes of research within different ethnic groups. Several recent investigations have, however, linked hypocortisolism with both urbanisation and a subsequent increased likelihood of hypertension within African women as they have presented increased vascular blood pressure responses. Conversely, Caucasian women have displayed an increased central cardiac reactivity. The lack of data regarding the relationship between the above-mentioned parameters within both African and Caucasian women serves as the motivation for conducting this study. Objective: To investigate hs-CRP, cortisol and hypertension as contributors to the increased likelihood of cardiovascular dysfunction in both African and Caucasian women within South Africa. hs-CRP use this through whole document please Methodology: The manuscript presented in Chapter 2 has been compiled using data obtained from the POWIRS (Profiles of Obese Women with Insulin Resistance Syndrome) study. Apparently healthy African (N=102) and Caucasian (N=115) women, matched for age and body mass index, were recruited from the North-West Province of South Africa for participation within this study. Subjects were divided into normotensive (NT) and hypertensive (HT) groups according to the mean resting cardiovascular values that were taken using a Finometer device. High-sensitivity C-reactive protein (hs-CRP) and cortisol blood serum values were determined by immunochemistry and ELISA analyses. Significant differences within each ethnic group and between each of the groups (NT and HT) were determined by analysis of covariance (ANCOVA), for anthropometric, cardiovascular, hs-CRP and cortisol variables, while adjusting for cardiovascular covariates (age, smoking and alcohol consumption). Partial correlations analyses were used to examine the relationship between hs-CRP, cortisol, anthropometric and cardiovascular parameters adjusting for cardiovascular covariates. Logistic regression analyses was used within each ethnic group to determine the relationship between anthropometric, cardiovascular, hs-CRP and cortisol as independent variables and hypertension as dependent variable. This study was approved by the Ethics Committee of the North-West University and all subjects gave informed consent in writing. For a more detailed description of the subjects, study design and analytical procedures please refer to the Materials and Methods section within Chapter 2 of this dissertation. Results and Conclusion: Both ethnic groups presented higher hs-CRP and lower cortisol levels compared to normal values. Lower waist circumference (WC) and cortisol as well as higher blood pressure (BP) and vascular values were evident in Africans compared to Caucasians. Both HT ethnic groups were older and more visceral obese compared to their NT counterparts. HT Caucasians indicated higher central adrenergic responses whilst HT Africans showed vascular adrenergicresponses. Only NT Africans had lower cortisol values than NT Caucasians but the Africans (NT and HT) responded with higher diastolic blood pressure responses compared to their Caucasian counterparts. Moreover, hs-CRP within African women significantly correlated with all BP and obesity variables whilst hs-CRP only associated with stroke volume (SV) and compliance (Cw) within HT Caucasian women. Cortisol in both ethnic groups was strongly associated with vascular BP responses. Only BP contributed to the higher prevalence of HT in both ethnic groups. In conclusion, these results suggest the possible diverse roles of HPA axis dysregulation associated with higher inflammatory responses. This happens in conjunction with cardiac and vascular responses within more obese Caucasian and especially African women, respectively. / MSc (Physiology), North-West University, Potchefstroom Campus, 2009

Motivation: C-reactive protein (hs-CRP) and other risk factors such as cortisol and obesity in the diagnosis of cardiovascular dysfunction (CVD) in African and Caucasian women has become increasingly imperative when one considers the escalation of hypertension among these groups. Recent studies have explored some aspects of these risk factors and the roles that they play within hypertension and possible future risk for cardiovascular disease. Hs-CRP has been associated with the increased prevalence of hypertension and obesity. Cortisol per se has also been linked with the development of both hypertension and the hypothalamic-pituitary adrenal cortex (HPA) response. Nevertheless, the exact mechanism remains rather uncertain due to conflicting outcomes of research within different ethnic groups. Several recent investigations have, however, linked hypocortisolism with both urbanisation and a subsequent increased likelihood of hypertension within African women as they have presented increased vascular blood pressure responses. Conversely, Caucasian women have displayed an increased central cardiac reactivity. The lack of data regarding the relationship between the above-mentioned parameters within both African and Caucasian women serves as the motivation for conducting this study. Objective: To investigate hs-CRP, cortisol and hypertension as contributors to the increased likelihood of cardiovascular dysfunction in both African and Caucasian women within South Africa. hs-CRP use this through whole document please Methodology: The manuscript presented in Chapter 2 has been compiled using data obtained from the POWIRS (Profiles of Obese Women with Insulin Resistance Syndrome) study. Apparently healthy African (N=102) and Caucasian (N=115) women, matched for age and body mass index, were recruited from the North-West Province of South Africa for participation within this study. Subjects were divided into normotensive (NT) and hypertensive (HT) groups according to the mean resting cardiovascular values that were taken using a Finometer device. High-sensitivity C-reactive protein (hs-CRP) and cortisol blood serum values were determined by immunochemistry and ELISA analyses. Significant differences within each ethnic group and between each of the groups (NT and HT) were determined by analysis of covariance (ANCOVA), for anthropometric, cardiovascular, hs-CRP and cortisol variables, while adjusting for cardiovascular covariates (age, smoking and alcohol consumption). Partial correlations analyses were used to examine the relationship between hs-CRP, cortisol, anthropometric and cardiovascular parameters adjusting for cardiovascular covariates. Logistic regression analyses was used within each ethnic group to determine the relationship between anthropometric, cardiovascular, hs-CRP and cortisol as independent variables and hypertension as dependent variable. This study was approved by the Ethics Committee of the North-West University and all subjects gave informed consent in writing. For a more detailed description of the subjects, study design and analytical procedures please refer to the Materials and Methods section within Chapter 2 of this dissertation. Results and Conclusion: Both ethnic groups presented higher hs-CRP and lower cortisol levels compared to normal values. Lower waist circumference (WC) and cortisol as well as higher blood pressure (BP) and vascular values were evident in Africans compared to Caucasians. Both HT ethnic groups were older and more visceral obese compared to their NT counterparts. HT Caucasians indicated higher central adrenergic responses whilst HT Africans showed vascular adrenergicresponses. Only NT Africans had lower cortisol values than NT Caucasians but the Africans (NT and HT) responded with higher diastolic blood pressure responses compared to their Caucasian counterparts. Moreover, hs-CRP within African women significantly correlated with all BP and obesity variables whilst hs-CRP only associated with stroke volume (SV) and compliance (Cw) within HT Caucasian women. Cortisol in both ethnic groups was strongly associated with vascular BP responses. Only BP contributed to the higher prevalence of HT in both ethnic groups. In conclusion, these results suggest the possible diverse roles of HPA axis dysregulation associated with higher inflammatory responses. This happens in conjunction with cardiac and vascular responses within more obese Caucasian and especially African women, respectively. / MSc (Physiology), North-West University, Potchefstroom Campus, 2009

Background: This study examined the association of 25-hydroxyvitamin D (25(OH)D) and C-reactive protein (CRP) with postoperative medical complications and one year mortality of elderly patients sustaining a low-energy cervical hip fracture scheduled for surgery. We hypothesized that vitamin D deficiency and CRP in these patients might be associated with an increased 1-year mortality. Methods: The prospective single-center cohort study included 209 patients with a low-energy medial femoral neck fracture; 164 women aged over 50 years and 45 men aged over 60 years. Referring to 1-year mortality and postoperative medical complications multiple logistic regression analysis including 10 co-variables (age, sex, BMI, ASA, creatinine, CRP, leukocytes hemoglobin, 25(OH)D, vitamin D supplementation at follow-up) was performed. Results: Vitamin D deficiency was prevalent in 87 % of all patients. In patients with severe (<10 ng/ml) and moderate (10–20 ng/ml) vitamin D deficiency one year mortality was 29 % and 13 %, respectively, compared to 9 % in patients with > 20 ng/ml 25(OH)D levels (p =0.027). Patients with a mild (CRP 10–39.9 mg/l) or active inflammatory response (CRP ≥ 40 mg/l) showed a higher one year mortality of 33 % and 40 % compared to 16 % in patients with no (CRP < 10 mg/l) inflammatory response (p = 0.002). Multiple logistic regression analysis identified CRP (OR 1.01, 95 % CI 1.00- 1.02; p = 0.007), but not 25(OH)D (OR 0.97, 95 % CI 0.89-1.05; p = 0.425) as an independent predictor for one year mortality. 20 % of patients suffered in-hospital postoperative medical complications (i.e. pneumonia, thromboembolic events, etc.). 25(OH)D (OR 0.89, 95 % CI 0.81–0.97; p = 0.010), but not CRP (OR 1.01, 95 % CI 1.00-1.02; p = 0.139), was identified as an independent risk factor. Conclusion: In elderly patients with low-energy cervical hip fracture, 25(OH)D is independently associated with postoperative medical complications and CRP is an independent predictor of one year mortality.

Background: Obesity-related diseases are arising as a major problem among children. inflammation has recently been identified to play an important role in the relationship between obesity.- as well as stunting-related diseases. Objectives: The aim of this study was to assess the association between serum tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and C-reactive protein (CRP) concentrations and a variety of cardiometabolic and anthropometric indices of children in a township outside Potchefstroom, South Africa. Methods: Blood samples of 115 girls and 78 boys (mean age 15.6 ± 1.35) in the Physical Activity in the Young (PLAY) study were cross-sectionally analysed. Trained fieldworkers collected the demographic, Tanner growth stage and habitual physical activity information. Physiologists measured the children’s blood pressure. Anthropometric measurements were taken by. trained post-graduate students with level 1 or 2 qualifications in anthropometrics. A standard test battery was administered by trained postgraduate students in Human Movement Science to assess muscular strength. flexibility and endurance of the children. Blood samples were collected, centrifuged and stored frozen until further analyses. Results: Stunted girls had a significantly higher serum TNF-α concentration than the non-stunted girls (p=0.03). The factor analyses showed that the inflammatory. status clustered with the height for age-z-scores (HAZ) scores and the waist-hip-ratio (WHR). The HAZ-score of the over-fat boys (- 1.46) was significantly smaller than the lean boys (- 1.14, p=0.0 1). whereas the over-fat girls had a trend for a smaller HAZ-score (-1.07) than the lean girls (-0.89). No significant differences were found between the over-fat and the lean children-s inflammatory status. TNF-α and CRP levels tended to be higher in the over-fat children than in lean children. The girls' scrum IL-6 and CRP concentrations correlated significantly with their body mass index (BMI) and WHR (p<0.05 )and their TNF-α and IL-6 concentrations correlated significantly with their WHR (p<0.01 and p<0.05, respectively). Conclusion: In comparison to the non-stunted girls, stunted girls had a statistically significantly higher TNF-α concentration. Unusual fat distribution that is found in over-fat and stunted children may be associated with low-grade inflammation in children. More research is needed on these associations with markers of inflammation in a long-term longitudinal study. / Thesis (M.Sc. (Nutrition))--North-West University, Potchefstroom Campus, 2007.

De nombreuses études ont contribué à dévoiler les mécanismes à la base de l’athérosclérose. Cette maladie est médiée par un important déséquilibre homéostatique, qui entraine une inflammation vasculaire contribuant à sa progression. Plusieurs équipes de recherche ont axé leurs investigations sur l’étude d’importants biomarqueurs inflammatoires telle que la protéine C-réactive (CRP). Considérée comme facteur de risque de maladies cardiovasculaires, cette dernière participe aussi aux différents stades du développement de l’athérosclérose. Notre étude révèle pour la toute première fois un processus d’auto-induction de l’expression de la CRP régit par les CE vasculaires. Ce mécanisme représente une nouvelle cible thérapeutique potentielle pour la prévention de l’athérosclérose. L’estrogène (E2) est une hormone féminine qui possède un rôle athéroprotecteur via entre autres, la modulation de la réponse inflammatoire. Ainsi, nous avons cherché à déterminer si elle avait un effet bénéfique sur le profil athérogénique de la CRP exprimée par les cellules endothéliales (CE). En effet, nos travaux ont démontré que l’E2 a la capacité de moduler le rétrocontrôle positif de l’expression de la CRP, contribuant à diminuer également le profil inflammatoire de cette dernière. De plus, nous avons établi que l’E2 restitue une importante voie pro-angiogénique impliquant la réponse migratoire des CE au VEGF, en contrant l’effet d’inhibition de la CRP. Cette nouvelle découverte nous a permis d’éclaircir un important mécanisme de guérison vasculaire de cette hormone dans un contexte inflammatoire. Ainsi, ces données contribuent à mieux comprendre la production endogène de la CRP par les CE vasculaires et l’activité cardioprotectrice de l’E2. / Numerous studies have contributed to reveal the mechanisms underlying cardiovascular diseases such as atherosclerosis. This disease is mediated by an important homeostatic imbalance, which causes vascular inflammation contributing to its progression. Several research groups have focused their studies on inflammatory biomarkers such as C-reactive protein (CRP). Considered as a risk factor for cardiovascular diseases, it also participates in various stages of atherosclerosis development. Our study shows for the first time a process of self-induction of the CRP expression regulated by vascular EC. This mechanism represents a new potential therapeutic target for the prevention of atherosclerosis formation. Estrogen (E2) is a female hormone which has an atheroprotective role through various vascular regulation mechanisms including modulation of the inflammatory response. Thus, we sought to determine whether it had a beneficial effect on atherogenic profile of CRP expressed by endothelial cells (EC). Indeed, our work has demonstrated for the first time that E2 has the ability to modulate the CRP expression positive feedback identified in our study, which also helps to reduce the inflammatory profile of the latter. In addition, we determined that E2 restores an important proangiogenic response involving migration of vascular EC to VEGF, by countering the inhibition effect of CRP. This new discovery has enabled us to clarify an important vascular healing mechanism of this hormone in an inflammatory context. Thus, these data provide further advances that contribute to a better understanding of the endogenous CRP production by vascular EC and the cardioprotective activity of E2.

INTRODUÇÃO: A proteína C-reativa de alta sensibilidade (PCR-as) é comumente utilizada na prática clínica para avaliar o risco cardiovascular. O seio coronário (SC) é considerado o local ideal para estudos de marcadores inflamatórios e circulação coronária, até o momento. A correlação entre os níveis séricos de PCR-as (valores absolutos) periférico versus (vs.) central ainda não foi feita. Avaliou-se a correlação entre os níveis séricos de PCR-as (mg/L) em veia periférica do antebraço esquerdo (VPAE) vs. SC, em pacientes portadores de doença arterial coronária (DAC) aterosclerótica com diagnóstico de angina estável (AE) ou angina instável (AI). Avaliou-se, também, se os níveis de PCR-as na VPAE e no SC diferem na AE e AI. MÉTODOS e RESULTADOS: 40 pacientes com DAC e estenose >= 70 % do diâmetro da luz vascular em uma das principais artérias coronárias foram incluídos no estudo e classificados em AE (n = 20) e, AI (n = 20). Coletaram-se amostras de sangue simultaneamente na VPAE e no SC, antes da angiografia coronária. A média dos níveis séricos absolutos de PCR-as na VPAE nos pacientes com AE foi de 2,97 ± 2,66, log 0,53 ± 1,24 e, com AI foi de 3,04 ± 3,29, log 0,67 ± 0,94, p = 0,689; e no SC, na AE foi de 2,71 ± 2,46, log 0,46 ± 1,18 e na AI, foi de 2,65 ± 3,08, log 0,41 ± 0,97, p = 0,898 e, portanto, não foram observadas diferenças significativas. A análise de correlação entre os níveis séricos de PCR-as em VPAE vs. SC mostrou uma forte correlação linear tanto para AE (r = 0,993, p < 0,001), para AI (r = 0,976, p < 0,001) e em toda amostra (r = 0,985, p < 0,001). CONCLUSÃO: Os nossos dados sugeriram uma forte correlação linear entre os níveis séricos de PCR-as na VPAE vs. SC na AE e AI; e esses níveis na VPAE e no SC na AE e AI foram semelhantes e não revelaram diferentes influências biológicas / BACKGROUND: The high-sensitivity C-reactive protein (hs-CRP) is commonly used in clinical practice to assess cardiovascular risk. The coronary sinus (CS) is considered the ideal location for studies of inflammatory markers and coronary circulation, until the moment. The correlation between peripheral versus (vs.) central serum levels of hs-CRP (absolute values) has not been done. We evaluated the correlation between serum levels of hs-CRP (mg/L) in the left forearm peripheral vein (LFPV) vs. CS in patients with atherosclerotic coronary artery disease (CAD) and diagnosis of stable angina (SA) or unstable angina (UA). We also evaluated whether the hs-CRP levels in LFPV and CS differ in SA and UA. METHODS and RESULTS: 40 patients with CAD and >= 70 % stenosis of the diameter of the vascular lumen in one of the main coronary arteries were included in the study and, classified into SA (n = 20) and, UA (n = 20). Blood samples from in the LFPV and CS were simultaneously collected before coronary angiography. The mean serum levels of hs-CRP in LFPV in the patients with SA was 2.97 ± 2.66, log 0.53 ± 1.24 and, in the UA was 3.04 ± 3.29, log 0.67 ± 0.94, p = 0.689. In CS in SA, it was 2.71 ± 2.46, log 0.46 ± 1.18 and in UA it was 2.65 ± 3.08, log 0.41 ± 0.97, p = 0.898; therefore, no significant differences were observed. The correlation analysis between the serum levels of hs-CRP in LFPV vs. CS showed a strong linear correlation in both for SA (r = 0.993, p < 0.001), for UA (r = 0.976, p < 0.001) and in the whole sample (r = 0.985, p < 0.001). CONCLUSIONS: Our data suggested that in SA as well as in UA there was a strong linear correlation between the serum levels of hs-CRP in LFPV vs. CS and, these levels in VPAE and SC in AE and AI were similar and did not reveal different biological influences

Linfomas pertencem a um grupo de neoplasias que têm em comum a origem em células linforreticulares, manifestando-se geralmente em tecidos linfóides. Em sua evolução, há uma reação generalizada do organismo de forma não específica contra as alterações sistêmicas que comprometem a homeostase, conhecida como resposta de fase aguda, a qual leva a uma importante alteração na síntese de proteínas pelo fígado, resultando no aumento de algumas proteínas conhecidas como proteínas de fase aguda, sendo as de maior relevância a amiloide sérica A, &alpha;-1 glicoproteína ácida e proteína C reativa. Foram objetivos deste estudo, definir o perfil eletroforético do felino com linfoma e avaliar as concentrações séricas de amilóide sérica A (ASA), &alpha;-1 glicoproteína ácida (GPA) e proteína C reativa (PCR) destes animais durante a quimioterapia, avaliando-se como possíveis indicadores de remissão de doença. Os grupos de estudo foram constituídos por 20 felinos clinicamente normais (controle) e 16 felinos com linfoma (experimental). Foram excluídos pacientes que apresentavam tratamentos prévios e/ou doenças concomitantes. A eletroforese das proteínas séricas foi realizada em tiras de acetato de celulose. Para as mensurações de ASA, GPA e PCR utilizaram-se kits comerciais, sendo as mesmas determinadas no grupo controle, uma única vez e, no grupo experimental, quando do diagnóstico e a cada 2 semanas durante 3 meses de tratamento. A análise estatística foi realizada com testes paramétricos, sendo o teste t não pareado utilizado para comparações entre os grupos controle e experimental no momento do diagnóstico e análise de variância simples (ANOVA), seguida do teste de comparações múltiplas de Tukey, para comparar o grupo experimental no diagnóstico e semanas de tratamento. Foram observadas diferenças significantes entre os grupos controle e experimental no momento do diagnóstico, com relação à GPA (p<0,0001), ASA (p=0,0028), PCR (p=0,0003), globulina (p=0,0087), relação albumina: globulinas (p<0,0001) e &alpha;-2 globulinas (p=0,0082). Quando se compararam os achados do grupo experimental no diagnóstico e nas semanas de tratamento houve diferença nos resultados referente à GPA (p=0,0021) e ASA (p=0,0053), enquanto os níveis de PCR não se alteraram significativamente (p=0,4510). Concluiu-se que os felinos com linfoma apresentaram uma expressiva resposta de fase aguda, caracterizada por aumento das concentrações séricas de &alpha;-1 glicoproteína ácida, amiloide sérica A e proteína C reativa, sendo a amilóide sérica A e &alpha;-1 glicoproteína ácida potenciais indicadores de remissão de doença naqueles pacientes que estavam com suas concentrações elevadas quando do diagnóstico. / Lymphoma belongs to a group of malignancies that have in common their origin in lymphoreticular cells, and is generally manifested in lymphoid tissues. In its evolution, there is a generalized reaction of the organism against a non-specific systemic conditions that compromises the homeostasis, known as acute phase response, which leads to a significant change in protein synthesis by the liver, resulting in an increase of some proteins known as acute phase proteins, and the most relevant are serum amyloid A, &alpha;-1 acid glycoprotein and C-reactive protein. This study was designed to define the electrophoretic profile of feline lymphoma and to evaluate serum concentrations of serum amyloid A (ASA), &alpha;-1 acid glycoprotein (GPA) and C-reactive protein (PCR) of these animals during chemotherapy, evaluated as possible indicators of disease remission. The study groups consisted of 20 clinically normal cats (control) and 16 cats with lymphoma (experimental). We excluded patients who had previous treatments and/or concomitant diseases. Electrophoresis of serum proteins was conducted on strips of cellulose acetate. For measurements of ASA, GPA and PCR we used commercial kits, which are then determined, in the control group, only once and, in the experimental group, at diagnosis and every 2 weeks during 3 months of treatment. Statistical analysis was performed with parametric tests, where unparied t test was used for comparisons between control and experimental groups at diagnosis and simple analysis of variance (ANOVA) test followed by Tukey\'s multiple comparisons to compare the experimental group in the diagnosis and weeks of treatment. There were significant differences between control and experimental groups at diagnosis of &alpha;-1 acid glycoprotein (p<0,0001), serum amyloid A (p=0,0028), C-reactive protein (p=0,0003), total globulin (p=0,0087), albumin: globulin (p<0,0001) and &alpha;-2 globulins (p=0,0082). When comparing the experimental group in the diagnosis and weeks of treatment was significant in the results of &alpha;-1 acid glycoprotein (p=0,0021) and serum amyloid A (p=0,0053), whereas C-reactive protein did not change significantly (p=0,4510). It is concluded that cats with lymphoma have an expressive acute phase response, characterized by increased in serum concentrations of serum amyloid A, &alpha;-1 acid glycoprotein and C-reactive protein, and the serum amyloid A and alpha-1 acid glycoprotein reference potential indicators of remission in those patients who were with their high concentrations at diagnosis.

INTRODUÇÃO: Sepse e choque séptico são doenças comuns em pacientes gravemente enfermos, evoluindo muitas vezes com síndrome de disfunção de múltiplos órgãos (SDMO) e morte. Este trabalho investiga a eficácia da administração precoce de dexametasona em evitar a progressão do choque séptico para SDMO e morte e o comportamento da proteína amilóide A sérica (SAA) e da proteína C-reativa (PCR) como marcadores da evolução e gravidade dos pacientes em choque séptico no período pós-operatório. MÉTODOS: Estudo prospectivo, aleatório, duplamente encoberto, realizado na Unidade de Terapia Intensiva pós-operatória do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, com 29 pacientes que no período pós-operatório evoluíram com choque séptico. Os participantes foram divididos de forma aleatória em dois grupos, de acordo com a solução administrada: dexametasona 0,2 mg/kg (grupo D) ou placebo (grupo P), repetidas a cada 36 horas. Os pacientes foram acompanhados durante sete dias de internação na UTI através do escore SOFA (Sequential Organ Failure Assessment) e dosagens séricas diárias de PCR, SAA e lactato. RESULTADOS: Os pacientes do grupo D, quando comparados aos pacientes do grupo P, permaneceram mais dias sem necessidade do uso do vasopressor (respectivamente 2,9±2,7 e 0,7±0,6, p=0,01) e mais tempo livre de ventilação mecânica (respectivamente 2,6±2,5 e 0,6±0,5, p=0,03). A mortalidade no grupo P foi de 67% (10 em 15) e no grupo D foi de 21% (3 em 14) (Risco Relativo=0,31, IC95% 0,11-0,88). Os valores de PCR e SAA apresentaram forte correlação durante o período de observação (R=0,91/p=0,002). PCR e SAA não tiveram correlação com o escore SOFA (respectivamente R=0,71/p=0,05 e R=0,52/p=0,18), nem com o lactato (p=0,88 e p=0,67). CONCLUSÕES: O tratamento precoce com dexametasona nos pacientes com choque séptico reduziu a mortalidade em 7 dias de acompanhamento. Os níveis séricos de PCR e SAA apresentaram-se elevados nos pacientes em choque séptico e tiveram forte correlação, porém não foram preditores de disfunção orgânica nem de mortalidade. / INTRODUCTION: Sepsis and septic shock are a very common condition in critically ill patients, leading to multiple organ dysfunction syndrome (MODS) and death. This study aimed at investigating the efficacy of early administration of dexamethasone in patients with septic shock in order to block the evolution to MODS and death. It also evaluated serum amyloid A protein (SAA) and C-reactive protein (CRP) as evolution and organ dysfunction markers in postoperative septic shock patients. METHODS: Prospective, randomized, double-blind study, developed in a surgical intensive care unit of Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo that involved 29 patients with septic shock. All eligible patients were prospectively randomized to receive either a dose of 0.2 mg/kg of dexamethasone (group D) or placebo (group P), repeated every 36 hours intervals. Patients were monitored over a 7- day period by Sequential Organ Failure Assessment score (SOFA) and daily measurements of CRP, SAA and lactate. RESULTS: Patients treated with dexamethasone had more vasopressor therapy-free days (2.9±2.7 versus 0.7±0.6, p=0.01) and more mechanical ventilation-free days (2.6±2.5 e 0.6±0.5, p=0.03). Mortality in group P was 67% (10 in 15) and in group D was 21% (3 in 14) (Relative Risk=0.31, 95%CI 0.11 to 0.88). CRP and SAA were strongly correlated during the 7 day period of observation (R=0.91/p=0.002). CRP and SAA did not correlate with SOFA (respectively R=0.71/p=0.05 and R=0.52/p=0.18) and lactate (p=0.88 and p=0.67). CONCLUSIONS: Early treatment with dexamethasone reduced 7-day mortality in septic shock patients. CRP and SAA levels were significantly elevated in septic shock and were strongly correlated to each other, but did neither correlate with organ dysfunction nor predict mortality.