C-reactive protein (CRP) is a protein found in the blood that is synthesized by the liver and has been extensively studied due to its role in inflammatory and atherosclerotic processes. The importance of this biomarker in its role in vascular risk factors is increased with several lines of evidence pointing to its association with cognitive decline. The association between CRP and depression has been increasingly analyzed by various cross-sectional studies. The research between CRP and depressive symptoms in older women has yet to generate consistent trends. In the present study, a series of regression analyses was used to explore the association between CRP and both cognitive function and depressive symptomatology among a group of rural-dwelling women. Associations were evaluated through the use of data from Project FRONTIER, a rural-based research looking at both physical and cognitive aspects of health in rural-dwelling adults and elders. Comparisons were made between Mexican American women and a group of non-Hispanic Caucasian women. CRP was a significant independent predictor of total depression (beta = -.11, t = -1.99, p =.048). CRP was also a significant independent predictor of symptoms associated with meaningless within depression (beta = -.16, t = -2.94, p =.004). Contrary to prediction, CRP was not a significant independent predictor of overall cognitive function or performance in five specific cognitive domains. There is still needed evaluation on racial/ethnic differences present in regard to the impact of varied health factors on mental health within a culturally rich, rural cohort. It is recommended that future studies utilize standardized measurement of cognitive function to facilitate a more thorough understanding and comparison of change in this particular population.

Metabolic syndrome affects approximately 25% of the US population and increases risk for the development of cardiovascular disease, as well as, and Type 2 diabetes. Inorganic arsenite exposure has been associated with cardiovascular disease, insulin resistance and Type 2 diabetes. The mechanisms by which arsenic increases these health risks has not been fully elucidated. In this report we show two pathways by which arsenite may contribute to metabolic syndrome. First through induction of C-Reactive Protein (CRP) and secondly through inhibition of insulin stimulated glucose uptake. CRP is a clinical marker for metabolic syndrome and a predictive clinical marker for cardiovascular disease and type 2 diabetes. Treatment of HepG2 cells with arsenite resulted in elevated CRP production and secretion. In addition, treatment of FvB mice with 100 ppb sodium arsenite via drinking water for six months starting at weaning age resulted in dramatically higher levels of CRP in both the liver and inner medullary region of the kidney. Further, mouse Inner Medullary Collecting Duct cells (mIMCD-3), a mouse kidney cell line, were stimulated with CRP, which resulted in activation of NFkappaB. Pretreatment with Y27632, a Rho kinase inhibitor, prior to CRP stimulation attenuated NFkappaB activation. Additionally, L6 myocytes, an insulin responsive cell line, exposed to arsenite for 4 or 7 days showed decreased insulin-stimulated glucose uptake but no decrease in AKT activation. In addition, we found that ERK activity decreased, while p38 MAPK activity increased, in response to prolonged arsenite treatment. These data support the epidemiological evidence that chronic exposure to low physiologically relevant levels of arsenite can contribute to insulin resistance and type 2 diabetes. These data provide a novel pathway by which arsenic can contribute to metabolic syndrome, cardiovascular disease, insulin resistance and type 2 diabetes.

Obesity is currently the most common and costly nutritional problem in developed countries and ten percent of the world's school-aged children are estimated to be overweight to some extent. Low-grade systemic inflammation is increasingly emerging as a significant component of the metabolic syndrome. Youth in lower income families are particularly vulnerable because of poor diet and limited opportunities for physical activity. In developing countries obesity among youth is rising among the urban poor, possibly due to their exposure to Westernised diets coinciding with a history of under-nutrition. The aim of this study was to assess the association between serum CRP and physical activity and to assess the association between serum CRP and body composition in black high-school children from a township in the North West Province (NWP), South Africa. Methods and results: The study group consisted of 193 school children between the ages 13 to 18 years (78 boys and 115 girls) residing in lkageng, the township outside of Potchefstroom in the North West Province, South Africa. Children were from a black ethnic group, living in a poor socioeconomic setting. Demographic and body composition measurements were taken and fasting blood samples were drawn for serum C-reactive protein (CRP) measurements. The difference between serum CRP of overfat versus girls with a normal fat percentage was non-significant (p = 0.46). Boys with body fat percentage >20% (n=16) had .a mean serum CRP of 1.42 2.16 mg/L and for boys with a normal fat percentage (n=53) mean serum CRP was 0.89 k 1.62 mg/L. The Mann-Whitney U-test for the difference between mean CRP of the two groups of boys was Z=1.39, p=0.16 (no significant difference), but with a trend of higher serum CRP concentration in the boys with higher % body fat. For the boys, the only positive partial correlation was between serum CRP and triceps skinfold (r=0.327, p=0.045). In the girls' group no statistically significant partial correlations were found between CRP and body composition variables. There was no significant difference between serum CRP concentrations of the three physical activity categories of girls. Interestingly, there was an inverse correlation between percentage body fat and fitness in the boys' group (r=-0.509 and p= 0.008). The difference in log CRP between activity groups showed a trend of lower serum CRP with higher physical activity in the girls. Conclusion: This study showed no statistically significant associations between serum CRP and body composition, except for the positive correlation between triceps skin fold and serum CRP in boys, or CRP and physical activity, but clear trends were noted of an inverse association between CRP and physical activity in the girls. / Thesis (M.Sc. (Nutrition))--North-West University, Potchefstroom Campus, 2007

Background.Studies have shown that low-grade chronic inflammation affect muscle mass negatively. Theimpact of inflammation in grip strength is not yet investigated. Existing studies are made on a few populations.This study aims to describe how inflammation, grip strength and muscle mass looks in agroup of 52-year-old men and women and to examine the differences between the sexes.Another aim is to investigate the correlations between low-grade chronic inflammation (n =32) and muscle mass (n = 23) and grip strength (n = 30).Method Data from an ongoing study were analyzed with a non-experimental descriptive, comparativeand correlating design. Lean muscle mass was calculated by subtracting the percentage of fatfrom weight. Grip strength was measured by Jamar dynamometer. CRP as inflammationparameter through blood-samples. Results The populations measured levels was consistent with current reference values för healthyindividuals. Tendencies to positive correlation between CRP and muscle mass could be seenfor both men and women. For men there were tendency towards positive correlation betweenCRP levels and grip strength, while tendency to negative correlation for women. Women hadhigher CRP levels compared to men. Men had higher levels of muscle mass and grip strength. Conclusion No conclusions could be drawn regarding the effect of low-grade chronic inflammation effectin fat-free mass and grip strength. The study has highlighted the need for further research inthe field.

Evidence linking periodontitis and cardiovascular disease points to systemic inflammation as the primary etiology. The investigation into this association has focused on periodontitis as a low grade chronic infection, and subsequently, systemic inflammation and the cascade of numerous markers and mediators integrally involved in the human inflammatory response. The aim of this study was to measure the differences in circulating levels of C-reactive protein and human soluble CD40 ligand as markers and mediators of systemic inflammation in the serum of patients with moderate to severe periodontitis before, during, and after non-surgical periodontal therapy.Twenty-one patients were treated with full mouth scaling and root planing performed on two separate appointments spaced approximately 2 weeks apart. The third visit, an evaluation of non-surgical therapy, occurred 8 weeks after completion of scaling and root planing. Blood samples were procured from each patient at the first and second appointment prior to scaling and root planing and again at a third visit. CRP and sCD40 ligand levels were measured using ELISA. CRP levels remained relatively constant throughout the study maintaining a mean level of 2.44 mg/L at visit 1, 2.53 mg/L at visit 2, and 2.63 mg/L at visit 3. These differences were not statistically significant. sCD40 ligand mean levels were reported to be 847.7 pg/mL, 637.3 pg/mL, and 859.5 pg/mL, respectively for visits 1, 2, and 3. These values were not statistically significant. Within the limitations of this study, no evidence was found to directly relate non-surgical periodontal therapy with the lowering of systemic markers CRP and human soluble CD40 ligand.

My dissertation deals with the significance of C-reactive protein determination in clinical practices. It is divided into three parts. Theorethical part acquaints us with CRP, statistics and statistical methods. Experimental part informs us about the applied machine, data gathering and outcomes valuation procedures.There are results of statistical data processing in the final part of my thesis. CRP was measured with Qucread 101 machine (Oriondignostika) in all cases and biological samples to distinguish between different kinds of infection were collected from all examined patients. I set down all the examination results and patients symptoms into a tab and made statistical data evaluation. The purpose of my work was to find out if CRP level incresed above 50mg/l isdefinitely confirmed by biological samples examination. If we can find possitive cultivation when CRP is lower than 8mg/l and finally to discover the correlation between all investigated atributes. Aftet answering these qeustions we should be able to find out significance of CRP measuring in diagnosis assessment.

Le déclin des hormones sexuelles avec l'âge a été mis en cause dans le développement de nombreuses maladies. Chez les hommes, la baisse de la testostérone circulante est un prédicteur de la mortalité toutes causes mais son impact sur le risque cardiovasculaire est incertain. A partir de l’étude de cohorte des Trois Cités (3C), réalisée en France dans la population générale, j'ai étudié le rôle de la testostérone plasmatique dans la survenue des évènements artériels ischémiques chez les hommes de plus de 65 ans.J'ai montré, dans une première partie, que des taux diminués de testostérone étaient associés à des facteurs de risque cardiovasculaire. J'ai notamment confirmé le rôle central de la masse grasse et du diabète comme déterminants des androgènes. De plus, j'ai mis en évidence une association inverse entre la testostérone et l’épaisseur intima-media (EIM) des artères carotidiennes. J'ai montré que cette relation dépendait du statut inflammatoire systémique avec des variations significatives de l'EIM observées uniquement chez les hommes ayant des niveaux élevés de protéine C-réactive. En revanche, aucune association significative n'a pu être détectée entre les androgènes et la présence de plaques d'athérome.Dans une seconde partie, j'ai mis en évidence une relation originale en forme de J entre la testostérone et le risque de maladies artérielles ischémiques. Les hommes ayant des taux élevés ou diminués de testostérone présentaient un risque accru d’évènements artériels et cette relation ne dépendait pas des principaux facteurs de risque cardiovasculaire. Des résultats similaires étaient observés pour les cardiopathies ischémiques et les accidents vasculaires cérébraux ischémiques.Ces résultats suggèrent que des taux moyens de testostérone totale circulante (4-5 ng/mL) protègent des maladies artérielles ischémiques. Ce rôle modulateur des androgènes pourrait être lié à un processus de vieillissement précoce non spécifique. / The age-related decline in sex hormones has been involved in the development of many diseases. In men, low endogenous testosterone levels predict mortality due to all causes. However, the role of testosterone in the development of cardiovascular disease remains uncertain. In the french Three-City population-based cohort study, I assessed the association of plasma sex hormones with the incidence of ischemic arterial disease in men aged over 65 years.First, I showed that low testosterone levels were associated with cardiovascular risk factors. I confirmed a leading role of obesity and diabetes as determinants of androgens. I also found an inverse association between testosterone and carotid intima-media thickness (IMT). I highlighted that, this relationship was mediated through systemic inflammation as significant changes in IMT were observed only in men with high C-reactive protein levels. However, no significant association was detected between androgens and the presence of carotid plaques.Second, I found an original J-shaped association between testosterone and risk of ischemic arterial disease. Men with elevated or decreased testosterone levels had higher risk of arterial events and this association was independent of major cardiovascular risk factors. Similar results were observed for ischemic heart disease and ischemic stroke.Overall, these results suggest that intermediate testosterone levels (4-5 ng/mL) could protect against cardiovascular events. Androgens could also be involved in general ageing process.

O pênfigo foliáceo inclui-se em um grupo de dermatoses autoimunes vésico-bolhosas da pele e mucosas reconhecido em alguns mamíferos, incluíndo os cães. Muitos autores acreditam que o pênfigo foliáceo (PF) é a dermatopatia autoimune mais frequentemente observada em caninos. Muitas podem ser as enfermidades caninas que devem ser incluídas no diagnóstico diferencial do pênfigo foliáceo, principalmente, a piodermite superficial (PS). A Proteína C Reativa (PCr) é conhecida como a principal proteína de fase aguda em cães. Nesses espécimes, a elevação da PCr tem sido observada em ampla variedade de condições mórbidas. A determinação da PCr tem sido proposta como um marcador inflamatório de algumas doenças autoimunes. O objetivo deste estudo foi determinar se a Proteína C Reativa pode ser utilizada como um marcador biológico precoce para diferenciar o pênfigo foliáceo da piodermite superficial em cães. Esta pesquisa constituiu um estudo clínico observacional prospectivo longitudinal, realizada em cães acometidos pelo PF ou PS. Foram incluídos 59 cães divididos em três Grupos I (Controle) com 31 animais, II (PF) e III (PS), cada um constituído por 14 cães. Submeteram-se, respectivamente, fragmentos cutâneos e soros de caninos, acometidos por PF ou PS, a exames histopatologicos e imunofluorescência direta (IFD) e à determinação de PCr e, também, a imunofluorescência indireta (IFI), utilizando-se para essa última coxins palmo-plantares a título de substrato. O grau de acometimento dos pacientes penfigosos (Grupo II) foi avaliado pelo PEFESI, durante período de até 90 dias, em diferentes momentos em que se realizou a IFI e a avaliação da PCr. Comparando-se os valores de IFD com aqueles da histopatologia obtiveram-se valores geral de concordância de 75% (9/12) e Índice Kappa de 0,77 (p<0,001) e, também, concordância dita substancial entre os dois métodos. Já, na IFI o valor de concordância foi de 100% (14/14), o de Kappa de 1,0 (p<0,001), com concordância considerada perfeita entre a IFI e a histopatologia. O Grupo II apresentou maior valor de mediana de PCr (37,4&micro;g/mL) quando comparado aos Grupos I, com 2,9 &micro;g/mL (p<0,0001) e III, com 3,8 &micro;g/mL (p=0,008). Não houve diferença entre os Grupos I e III (p=0,178). Considerando-se como ponto de corte um valor de PCr > 10,6&micro;g/mL, a chance de um animal estar acometido pelo PF é 5,5 vezes maior àquela de um cão não afetado, o que equivale a uma probabilidade pós-teste de 84,6%, conferindo um acréscimo de 34,6% na capacidade de diagnóstico do PF. Conclui-se que determinação de PCr é de inequívoca valia para o estabelecimento de diferenciação diagnóstica entre a casuística da contumaz piodermite superficial com quadros do pênfigo foliáceo canino / Pemphigus is included in a group of skin and mucous autoimmune vesicobullous dermatoses recognized in some mammals, including dogs. Many authors believe that pemphigus foliaceus (PF) is the autoimmune skin disease most often observed in dogs. Many must be the canine diseases considered in the pemphigus foliaceus differential diagnosis, especially the superficial pyoderma (SP). The C-Reactive Protein (CRP) is known as a major acute phase protein in dogs. The CRP increase has been observed in a wide variety of morbid conditions in dogs. The determination of CRP has been proposed as an inflammatory marker of some autoimmune diseases. This study aimed to determine whether C-Reactive Protein can be used as an early biomarker to differentiate pemphigus foliaceus of superficial pyoderma in dogs. An observational prospective longitudinal clinical study was undertaken including dogs affected by PF or PS. Fifth nine dogs were divided into three groups: Group I (Control) with 31 animals and II (PF) and III (SP), consisting of 14 dogs each. Dogs affected by PF or SP had skin fragments submitted to histopathological examination and direct immunofluorescent reaction (DIF). The blood sera were used to determine the CRP concentration, and also to perform the indirect imunofluorescent reaction (IIF) using canine footpad as substrate. The pemphigus patients (Group II) clinical involvement degree was evaluated by PEFESI, over a period of 90 days, moments in which IFI and evaluation of CRP took place. Comparing the DIF values with the histopathology there was an agreement of 75% (9/12) with a Kappa index of 0.77 (p <0.001) which means a degree of substantial arrangement between the two methods. Considering IIF, the agreement value was 100% (14/14) with Kappa index of 1.0 (p<0.001), showing perfect arrangement between the IIF and the histopathology. Group II showed higher CRP median (37.4 mg / mL) compared to Groups I, with 2.9 mg / mL (p <0.0001) and III with 3.8 mg / mL (p = 0.008 ). There was no statistic difference between groups I and III (p = 0.178). Considering CRP> 10,6&micro;g / mL as a cutoff value, the chance of an animal having PF is 5.5 times higher than not to be, which is equivalent to a post-test probability of 84,6%, giving a 34.6% increase in the PF diagnostic capability. It concludes that determination of CRP is unequivocal asset for the establishment of diagnostic differentiation between the common superficial pyoderma to canine pemphigus foliaceus

A pneumonia nosocomial é uma infecção prevalente e associada com elevados custos e morbi-mortalidade. A maioria destes episódios ocorre em pacientes criticamente doentes em ventilação mecânica. Os biomarcadores, como a proteína C-reativa, tem se mostrado uteis na avaliação da evolução dos pacientes, podendo se descrever padrões de resposta associados ao sucesso da terapia antimicrobiana e ao prognostico de paciente com pneumonia associada a ventilação mecânica. Nesta tese, apresenta-se uma revisão da literatura abordando aspectos da fisiopatologia, diagnostico e manejo da pneumonia associada a ventilação mecânica. Além disso, é feita a análise do uso de biomarcadores em duas populações especificas de pacientes criticamente doentes (pacientes com doença critica cronica e pacientes idosos). Foram avaliados 405 pacientes com diagnostico clínico de pneumonia associada a ventilação mecânica. Descreve-se que pacientes com doença critica crônica apresentam episódios de pneumonia associada a ventilação mecânica com pior prognostico do que pacientes que não apresentam doença critica crônica. Entretanto, esses achados não parecem associados a um comprometimento da resposta inflamatória, uma vez que nao houve diferença significativa nem nos níveis basais, nem na evolução dos níveis de proteína C-reativa comparando episódios de pacientes com doença critica crônica com aqueles sem esta condição, sugerindo que seu uso é válido nessa população de pacientes. Ainda, descreve-se a evolução dos pacientes com pneumonia associada a ventilação mecânica de acordo com a idade. A partir dos 65 anos, parece haver um efeito da idade na mortalidade dos pacientes com PAV. No entanto, não houve alteração na resposta da PCR ou na sua cinética nas primeiras 96h quando comparamos pacientes com diferentes faixas etárias a partir de um ponto de corte de 65 anos, também sugerindo a validade do uso deste biomarcador nesta população de pacientes. Estes achados originais permitem que estudos futuros avaliem intervenções baseadas em biomarcadores em pacientes com pneumonia nosocomial levando em consideração estas populações especificas de pacientes não avaliadas previamente na literatura. / Nosocomial pneumonia is a prevalent infection associated with higher costs and worse outcomes. Most episodes occur in mechanically ventilated critically ill patients. Biomarkers, such as C-reactive protein, are useful to assess patients evolution, allowing identification of patterns associated with antimicrobial treatment success and prognosis in ventilator-associated pneumonia patients. In this thesis, a literature review is presented evaluating aspects of pathopsysiology, diagnosis and management of ventilator-associated pneumonia patients. In addition, biomarker use in two specific populations (chronic critical illness and elderly) was assessed. Four hundred and five patients with ventilator associated pneumonia clinical diagnosis were evaluated. Patients with chronic critical illness presented ventilator-associated pneumonia episodes associated with worse prognosis. However, these findings were not associated with a compromise of inflamatory response, assessed by comparison of C-reactive protein basal levels and kinetis evolution in patients with and wihtout chronic critical illness, suggesting its use remains valid in this specific population. Still, evolution of ventilator-associated pneumonia according to age is described. After 65 years old, our data suggest an effect of age on mortality in ventilator-associated pneumonia patients. However, no change in C-reactive protein basal levels, response or kinetics within 96h was found when comparing patients younger and older than 65 years old, also suggesting this biomarker usefulness in this specific population. These original findings allow that future studies assessing intervention based on biomarkers evolution in patients with nosocomial pneumonia consider these specific populations, never assessed before in literature.

Objetivo: Avaliar o impacto do tratamento periodontal na concentração sérica de proteína C-reativa (PCR), perfil lipídico e hemoglobina glicada em pacientes cardiopatas participantes de um ensaio clínico randomizado com análise de 12 meses de acompanhamento. Métodos: Trata-se de um ensaio clínico randomizado em hospital terciário com pacientes com doença arterial coronariana (DAC) estável e periodontite crônica grave. Foram realizados exames periodontais (seis sítios por dente em toda a boca) para registro de profundidade de sondagem (PS) e perda de inserção (PI), além de índice de placa visível (IPV) e índice de sangramento gengival (ISG). O grupo teste recebeu tratamento periodontal intensivo, sendo inicialmente realizada uma sessão de raspagem, alisamento e polimento supragengival (RAP) com orientação personalizada de higiene bucal. Em seguida, foram realizadas até quatro sessões de raspagem e alisamento radicular subgengival (RASUB) por quadrante, sob anestesia local. O grupo controle recebeu uma única sessão de RAP e orientação de higiene bucal. Foram coletadas amostras para mensuração dos níveis sistêmicos de PCR de alta sensibilidade, perfil lipídico e hemoglobina glicada. Resultados: 60 pacientes foram analisados após 12 meses, 28 no grupo teste e 32 no grupo controle, com idade média de 59 e 61 anos, respectivamente. Não foram observadas diferenças significativas ao longo do tempo, e entre os grupos nos dois tempos experimentais em relação a PCR. Assim como não foram encontradas diferenças significativas entre perfil lipídico e hemoglobina glicada. Conclusão: O tratamento periodontal não adicionou benefício sobre os níveis de PCR, hemoglobina glicada e perfil lipídico em indivíduos cardíacos crônicos tratados em uma unidade terciária. No entanto, foi observada uma tendência de benefício em pacientes cardíacos com níveis basais controlados de PCR. / Objective: To evaluate the impact of periodontal therapy on serum concentration of CRP, lipid profile and glycated hemoglobin in patients with heart disease participating in a randomized clinical trial with 12 months of follow-up. Methods: A randomized clinical trial in a tertiary hospital with patients with stable coronary artery disease (CAD) and severe chronic periodontitis. Whole mouth periodontal examination (six sites per tooth) was performed and comprised probing depth (PD) and attachment loss, in addition to visible plaque (VPI) and gingival bleeding index (GBI) The test group received intensive periodontal treatment. Initially, supragingival scaling with oral hygiene instruction were performed. In sequence, up to four sessions of subgingival scaling root planing per quadrant, under local anesthesia were performed. The control group had supragingival scaling and oral hygiene instruction. Blood samples were collected to assess the serum levels of high sensitivity CRP, lipid profile and glycated hemoglobin. Results: A total of 60 patients were analyzed after twelve moths, 28 (test group) and 32 (control group), with a mean age of 59 and 61 years. No statistically significant differences were observed along the study between groups in CRP. Also, no statistically significant diferences were detected in glycated hemoblobin and lipid profile. Conclusion: Periodontal treatment did not add benefit on CRP and glycated hemoglobina levels as well as in lipid profile in chronic cardiac individuals treated in a tertiary unit. However, a positive trend was observed in cardiac patients with controlled RCP basal levels.