988 resultados para Proteína C-FOS : Imunorreatividade : Nocicepção
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Gene expression is frequently regulated by multiple transcription factors (TFs). Thermostatistical methods allow for a quantitative description of interactions between TFs, RNA polymerase and DNA, and their impact on the transcription rates. We illustrate three different scales of the thermostatistical approach: the microscale of TF molecules, the mesoscale of promoter energy levels and the macroscale of transcriptionally active and inactive cells in a cell population. We demonstrate versatility of combinatorial transcriptional activation by exemplifying logic functions, such as AND and OR gates. We discuss a metric for cell-to-cell transcriptional activation variability known as Fermi entropy. Suitability of thermostatistical modeling is illustrated by describing the experimental data on transcriptional induction of NF?B and the c-Fos protein.
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O crescimento demográfico de idosos é um fenômeno mundial e exerce influência sobre o desenvolvimento e funcionamento das sociedades. Fatores sociais, econômicos, ambientais, biológicos e culturais influenciam o processo de envelhecimento, que pode vir acompanhado de contínua perda na capacidade de adaptação do indivíduo ao meio ambiente, de maior vulnerabilidade ao estresse, limitações funcionais e diminuição da qualidade de vida do indivíduo. Todavia, ao longo do curso da vida, o indivíduo vivencia múltiplas exposições adversas à saúde, e o declínio da mobilidade surge como um dos primeiros sinais do envelhecimento, repercutindo na saúde física e mental do indivíduo. Para contribuir com o conhecimento sobre os desfechos relacionados ao envelhecimento e mobilidade, o estudo IMIAS investiga idosos em quatro países com diferentes perfis epidemiológicos. O presente estudo abordou os possíveis fatores associados ao declínio físico em idosos de distintas sociedades, sobre a perspectiva epidemiológica do curso da vida e dos biomarcadores da inflamação e do estresse. Objetivos: 1) Analisar as relações entre as adversidades sociais e econômicas, vivenciadas durante a infância, a fase adulta e a velhice, com o baixo desempenho físico em populações idosas, de diferentes contextos sociais, econômicos e culturais. 2) Verificar a associação entre os níveis elevados da proteína c-reativa (PCR) com o desempenho físico em idosos de diferentes populações. 3) Avaliar se a desregulação nos níveis de cortisol diurno exerce influência sobre o desempenho físico em idosos com distintos perfis epidemiológicos. Métodos: Foram utilizados dados da linha de base do IMIAS – Estudo Internacional de Mobilidade no Envelhecimento, composto por 1.995 indivíduos entre 65 e 74 anos de idade, residentes em comunidades de quatro países (Albânia, Brasil, Canadá, Colômbia). O desempenho físico foi avaliado através do Short Physical Performance Battery (SPPB) e da força de preensão manual. As adversidades durante o curso da vida foram estimadas a partir de eventos e exposições sociais, econômicas e culturais ocorridas durante a infância, fase adulta e velhice. Para avaliar o percurso biológico e suas associações com a mobilidade, a proteína c-reativa e o cortisol foram considerados como biomarcadores da inflamação e do estresse, respectivamente. No sentido de responder as questões de investigações, foram conduzidas análises de estatística descritiva, bivariada e multivariada, mediante técnicas de distribuição de frequências, teste qui-quadrado, odds ratio e regressões logística, linear e multinível. Resultados: O desempenho físico foi menor nos participantes que vivem na Colômbia, Brasil e Albânia do que nos que vivem no Canadá, mesmo quando ajustados por idade, sexo e adversidades durante o curso da vida. O baixo nível de desempenho físico (SPPB < 8) foi associado a ter sofrido adversidade social e econômica na infância, ter tido ocupação semiqualificada na fase adulta, morar sozinho e possuir renda insuficiente na velhice. A PCR esteve associada com a baixa força de preensão manual e com o SPPB<8. Entretanto, a associação entre a PCR e a força de preensão manual não se manteve quando ajustada por fatores socioeconômicos e hábitos de saúde. As associações negativas entre SPPB e PCR permaneceram significativas mesmo após ajustes por idade, sexo, escolaridade, local de pesquisa e condições de saúde. O baixo desempenho físico (SPPB ≤ 8) foi associado com uma significativa diminuição nos níveis de cortisol ao acordar, em comparação com os níveis de cortisol de idosos com bom desempenho físico (SPPB > 8), mesmo após modelos controlados por local de estudo, sexo, depressão, hábitos de saúde, uso de psicotrópicos e índice de massa corporal. Conclusões: Os resultados evidenciaram associação entre a inflamação, o estresse e as desigualdades sociais e econômicas na infância, sobre o desempenho físico de idosos com diferenciados perfis epidemiológicos. Enfatizamos que a promoção do envelhecimento saudável requer considerar políticas e práticas que favoreçam o bem-estar econômico e social para crianças, adultos e idosos.
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The polycystic ovary syndrome (PCOS) is considered the most common endocrine disorder in reproductive age women, with a prevalence ranging from 15 to 20%. In addition to hormonal and reproductive changes, it is common in PCOS the presence of risk factors for developing cardiovascular disease (CVD) and diabetes mellitus, insulin resistance (IR), visceral obesity, chronic low-grade inflammation and dyslipidemia. Due to the high frequency of obesity associated with PCOS, weight loss is considered as the first-line treatment for the syndrome by improving metabolic and normalizes serum androgens, restoring reproductive function of these patients. Objectives: To evaluate the inflammatory markers and IR in women with PCOS and healthy ovulatory with different nutritional status and how these parameters are displayed after weight loss through caloric restriction in with Down syndrome. Methods: Tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and C-reactive protein (CRP) were assessed in serum samples from 40 women of childbearing age. The volunteers were divided into four groups: Group I (not eutrophic with PCOS, n = 12); Group II (not eutrophic without PCOS, n = 10), Group III (eutrophic with PCOS, n = 08) and Group IV (eutrophic without PCOS, n = 10). The categorization of groups was performed by body mass index (BMI), according to the World Health Organization (WHO) does not eutrophic, overweight and obesity (BMI> 25 kg / m²) and normal weight (BMI <24.9 kg / m²). IR was determined by HOMA-IR index. In the second phase of the study a controlled dietary intervention was performed and inflammatory parameters were evaluated in 21 overweight and obese women with PCOS, before and after weight loss. All patients received a low-calorie diet with reduction of 500 kcal / day of regular consumption with standard concentrations of macronutrients. Results: Phase 1: PCOS patients showed increased levels of CRP (p <0.01) and HOMAIR (p <0.01). When divided by BMI, both not eutrophic group with PCOS (I) as eutrophic with PCOS (III) showed increased levels of CRP (I = 2.35 ± 0,55mg / L and 2.63 ± III = 0,65mg / L; p <0.01) and HOMA-IR (I = 2.16 ± 2.54 and III = 1.07 ± 0.55; p <0.01). There were no differences in TNF-α and IL-6 between groups. Step 2: After the weight loss of 5% of the initial weight was reduced in all of the components of serum assessed inflammatory profile, PCR (154.75 ± 19:33) vs (78.06 ± 8.9) TNF α (10.89 ± 5.09) vs (6:39 ± 1:41) and IL6 (154.75 ± 19:33) vs (78.06 ± 08.09) (p <0:00) in association with improvement some hormonal parameters evaluated. Conclusion: PCOS contributed to the development of chronic inflammation and changes in glucose metabolism by increasing CRP, insulin and HOMA-IR, independent of nutritional status. The weight loss, caloric restriction has improved the inflammatory condition and hormonal status of the evaluated patients.
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The dog-eating fox (Cerdocyon thous - Linnaeus, 1766) is a medium sized canid widely distributed in South America and occurs in almost all of Brazil. Among the main threats to their conservation are the roadkill mainly caused by habitat loss. The shortage of laboratory bush dogs data affect the veterinary medical care hindering the application of appropriate therapies. This study aimed to evaluate the levels of C-reactive protein, albumin, pre-albumin, ceruloplasmin, haptoglobin and Afla 1 acid glycoprotein and the Prognostic Index Inflammatory Nutritional (IPIN) in this species, thus obtaining a first description of these prognostic markers. They collected 1.5 ml of blood by jugular access 8 of Mato Dogs copies (thous thous) from the Laboratory of collection of Teaching and Research in Wildlife (limpets), Faculty of Veterinary Medicine, Federal University of Uberlândia for exams routine. The samples were collected via the jugular vein after physical restraint of animals and trichotomy of the region. After statistical analysis, the values were: albumin: between 2.7 and 3.0 g / dl, alpha 1-acid glycoprotein: between 0.19 and 0.21 g / l, C-reactive protein: between 1.7 and 2 2, prealbumin between 30 and 35 mg / l haptoglobin: between 0.078 and 0.156 and IPIN ≤ 0.006 being considered normal and values ≥ 0.006 considered high. This press description will serve as a basis for studies where animals may be used with specific diseases and, after analysis, compared with the values found in this study and verified the behavior follows the likeness of domestic dogs.
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The Overactive Bladder (OAB) and Bladder Pain Syndrome (BPS) are debilitating disorders for which the pathophysiological mechanisms are poorly understood. Injury or dysfunction of the protective urothelial barrier layer, specifically the proteoglycan composition and number, has been proposed as the primary pathological characteristic of BPS. For OAB, the myogenic theory with dysfunction of the muscarinic receptors is the most reiterated hypothesis. For both over activity of the inflammatory response has been posited to play a major role in these diseases. We hypothesise that BPS and OAB are peripheral sensory disorders, with an increase in inflammatory mediators, such as cytokines and chemokines, which are capable of activating, either directly or indirectly, sensory nerve activity causing the disease. The aim of the PhD is to identify potential new therapeutic targets for the treatment of BPS and OAB. We used medium throughput quantitative gene expression analysis of 96 inflammation associated mediators to measure gene expression levels in BPS and OAB bladder biopsies and compared them to control samples. Then we created a novel animal model of disease by specific proteoglycan deglycosylation of the bladder mucosal barrier, using the bacterial enzymes Chondroitinase ABC and Heparanase III. These enzymes specifically remove the glycosaminoglycan side chains from the urothelial proteoglycan molecules. We tested role of the identified mediators in this animal model. In addition, in order to determine on which patients peripheral treatment strategies may work, we assessed the effect of local anaesthetics on patients with bladder pain. Gene expression analysis did not reveal a difference in inflammatory genes in the OAB versus control biopsies. However, several genes were upregulated in BPS versus control samples, from which two genes, FGF7 and CLL21 were correlated with patient clinical phenotypes for ICS/PI symptom and problem indices respectively. In order to determine which patients are likely to respond to treatment, we sought to characterise the bladder pain in BPS patients. Using urodynamics and local anaesthetics, we differentiated patients with peripherally mediated pain and patients with central sensitisation of their pain. Finally to determine the role of these mediators in bladder pain, we created an animal model of disease, which specifically replicates the human pathology: namely disruption in the barrier proteoglycan molecules. CCL21 led to an increase in painrelated behaviour, while FGF7 attenuated this behaviour, as measured by cystometry, spinal c-fos expression and mechanical withdrawal threshold examination. In conclusion, we have identified CCL21 and FGF7 as potential targets for the treatment of BPS. Manipulation of these ligands or their receptors may prove to be valuable previously unexploited targets for the treatment of BPS.
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Increased osteoclast (OC) bone resorption and/or decreased osteoblast (OB) bone formation contribute to bone loss in osteoporosis and rheumatoid arthritis (RA). Findings of the basic and translational research presented in this thesis demonstrate a number of mechanisms by which cytokine-induced NF-κB activation controls bone resorption and formation: 1) Tumour necrosis factor-α (TNF) expands pool of OC precursors (OCPs) by promoting their proliferation through stimulation of the expression of macrophage colony stimulating factor (M-CSF) receptor, c-Fms, and switching M-CSF-induced resident (M2) to inflammatory (M1) macrophages with enhanced OC forming potential and increased production of inflammatory factors through induction of NF-κB RelB; 2) Similar to RANKL, TNF sequentially activates transcriptional factors NF-κB p50 and p52 followed by c-Fos and then NFATc1 to induce OC differentiation. However, TNF alone induces very limited OC differentiation. In contrast, it pre-activates OCPs to express cFos which cooperates with interleukin-1 (IL-1) produced by these OCPs in an autocrine mechanism by interacting with bone matrix to mediate the OC terminal differentiation and bone resorption from these pre-activated OCPs. 3) TNF-induced OC formation is independent of RANKL but it also induces NF-κB2 p100 to limit OC formation and bone resorption, and thus p100 deletion accelerates joint destruction and systemic bone loss in TNF-induced RA; 4) TNF receptor associated factor-3 (TRAF3) limits OC differentiation by negatively regulating non-canonical NF-κB activation and RANKL induces TRAF3 ubiquitination and lysosomal degradation to promote OC differentiation. Importantly, a lysosomal inhibitor that inhibits TRAF3 degradation prevents ovariectomy-induced bone loss; 5) RelB and Notch NICD bind RUNX2 to inhibit OB differentiation and RelB:p52 dimer association with NICD inhibit OB differentiation by enhancing the binding of RBPjκ to Hes1. These findings suggest that non-canonical NF- κB signaling could be targets to develop new therapies for RA or osteoporosis. For example 1) Agents that degrade TNF-induced RelB could block M1 macrophage differentiation to inhibit inflammation and joint destruction for the therapy of RA; 2)Agents that prevent p100 processing or TRAF3 degradation could inhibit bone resorption and also stimulate bone formation simultaneously for the therapy of osteoporosis.
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Analisar se o pré-tratamento com sinvastatina em modelo experimental de sepse abdominal é benéfico em ratos diabéticos. Métodos: Cinquenta e seis ratos Wistar foram aleatoriamente distribuídos em: grupo não diabético (n-28) e grupo diabetes induzido por estreptozotocina (n=28). Sepse abdominal por ligadura e punção do ceco foi induzida em 14 ratos diabéticos e em 14 não diabéticos. Os demais 28 animais foram alocados em grupo sham. Os grupos de ratos com sepse e os sham (cada com sete animais) foram tratados com microemulsão oral de simvastatina (20 mg kg-1 day-1) e solução salina 0,9%, respectivamente. Sangue periférico foi usado para dosagem de TNFa, IL-1b, IL-6, proteína C reativa, procalcitonina, contagem de leucócitos e neutrófilos em todos os animais. A análise estatística foi realizada pela ANOVA e teste de Tukey, com p<0,05. Resultados: A sinvastatina reduziu a mortalidade nos ratos diabéticos. Os valores séricos de TNF-a, IL-1b, IL-6, proteína C reativa, procalcitonina, leucócitos e neutrófilos mostraram-se mais baixos nos ratos diabéticos e não diabéticos com sepse, tratados com sinvastatina, do que nos tratados com solução salina. Conclusão: A sinvastatina teve efeito antiinflamatório, que pode ter resultado em proteção contra a sepse em ratos diabéticos
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Human exposure to Bisphenol A (BPA) results mainly from ingestion of food and beverages. Information regarding BPA effects on colon cancer, one of the major causes of death in developed countries, is still scarce. Likewise, little is known about BPA drug interactions although its potential role in doxorubicin (DOX) chemoresistance has been suggested. This study aims to assess potential interactions between BPA and DOX on HT29 colon cancer cells. HT29 cell response was evaluated after exposure to BPA, DOX, or co-exposure to both chemicals. Transcriptional analysis of several cancer-associated genes (c-fos, AURKA, p21, bcl-xl and CLU) shows that BPA exposure induces slight up-regulation exclusively of bcl-xl without affecting cell viability. On the other hand, a sub-therapeutic DOX concentration (40 nM) results in highly altered c-fos, bcl-xl, and CLU transcript levels, and this is not affected by co-exposure with BPA. Conversely, DOX at a therapeutic concentration (4 μM) results in distinct and very severe transcriptional alterations of c-fos, AURKA, p21 and CLU that are counteracted by co-exposure with BPA resulting in transcript levels similar to those of control. Co-exposure with BPA slightly decreases apoptosis in relation to DOX 4 μM alone without affecting DOX-induced loss of cell viability. These results suggest that BPA exposure can influence chemotherapy outcomes and therefore emphasize the necessity of a better understanding of BPA interactions with chemotherapeutic agents in the context of risk assessment.
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Analisar se o pré-tratamento com sinvastatina em modelo experimental de sepse abdominal é benéfico em ratos diabéticos. Métodos: Cinquenta e seis ratos Wistar foram aleatoriamente distribuídos em: grupo não diabético (n-28) e grupo diabetes induzido por estreptozotocina (n=28). Sepse abdominal por ligadura e punção do ceco foi induzida em 14 ratos diabéticos e em 14 não diabéticos. Os demais 28 animais foram alocados em grupo sham. Os grupos de ratos com sepse e os sham (cada com sete animais) foram tratados com microemulsão oral de simvastatina (20 mg kg-1 day-1) e solução salina 0,9%, respectivamente. Sangue periférico foi usado para dosagem de TNFa, IL-1b, IL-6, proteína C reativa, procalcitonina, contagem de leucócitos e neutrófilos em todos os animais. A análise estatística foi realizada pela ANOVA e teste de Tukey, com p<0,05. Resultados: A sinvastatina reduziu a mortalidade nos ratos diabéticos. Os valores séricos de TNF-a, IL-1b, IL-6, proteína C reativa, procalcitonina, leucócitos e neutrófilos mostraram-se mais baixos nos ratos diabéticos e não diabéticos com sepse, tratados com sinvastatina, do que nos tratados com solução salina. Conclusão: A sinvastatina teve efeito antiinflamatório, que pode ter resultado em proteção contra a sepse em ratos diabéticos
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Introducción: La periodontitis crónica y la artritis reumatoide (AR) son desórdenes inflamatorios crónicos caracterizados por la destrucción de tejidos, la reabsorción ósea y la producción de citoquinas proinflamatorias. Objetivos: Analizar la relación entre ambas enfermedades y la posible influencia del tratamiento de una sobre la otra. Material y métodos: Se realiza una revisión bibliográfica acerca de la patogénesis de la AR y la EP y los aspectos relacionados. Resultados: La patogénesis de ambas enfermedades muestra semejanzas notables. Bacterias periodontopatógenas, como Porphyromonas gingivalis, y mediadores inflamatorios, como el factor de necrosis tumoral y la proteína C reactiva, juegan un papel importante en la AR. La EP es un factor importante en la respuesta a la terapia en pacientes con AR. Conclusiones: Ambas enfermedades tienen una patogenia común. La prevalencia de enfermedad periodontal (EP) es mayor en pacientes con AR y viceversa. Aunque el control de la EP mediante tratamiento periodontal no quirúrgico parece mejorar los signos y síntomas en ambas enfermedades, hacen falta estudios más rigurosos con mayor número de casos y de mayor tiempo de evolución.
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American visceral leishmaniasis (AVL), caused by Leishmania infantum chagasi (L.i.chagasi), stands as a public health problem in Brazil, with human and canine cases related in all states..Lipid metabolism can be modified in several status of infection. For example, experimental studies show that the cholesterol is necessary to internalization and replication of L.i.chagasi in macrophages through caveolar domains. Patients with AVL present low levels of cholesterol and a visible triglycerides increase. This work aimed to evaluate the lipid metabolism in several post-infection status by L.i.chagasi, including individuals with symptomatic infection (AVL), and asymptomatic. The levels of cholesterol, triglycerides, HDL and reactive C protein, were measured. Individuals with AVL were compared with individuals with assymptomatic infection and presented low levels of total cholesterol (128 ± 6.180 mg/dL vs. 158 ±5.733 mg/dL, p=0.0001), HDL (29 ± 1.746 mg/dL vs. 37 ± 1.647 mg/dL, p=0.0001), increased levels of triglycerides (149.5 mg/dL ± 12.72 vs. 78.00 ± 10.43 mg/dL, p=0.0095) and higher levels of reactive C protein (1.750± 0.4939 mg/dL vs. 0.40 ± 0.1707 mg/dL; p=0.0001). The expression of genes related to lipid metabolism, such as LXR-a, LXR-b, PPAR-a, PPAR-d, PPAR-g and APOE was evaluated by real time PCR. A reduction in the expression of those genes was found in the group of AVL patients corroborating the serum levels of the metabolites earlier quantified. Our findings suggest a modulation of metabolism of lipids, in the chronic phase of AVL, this could facilitate the survival of leishmania, due to the known reduction on the ability of macrophages in presenting antigens efficiently to the T cells due to the reduction in the cholesterol available, it results in a subversion of the host immunity.
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The seeds are excellent sources of proteinase inhibitors and have been highlighted owing to various applications. Among these applications are those in effect on food intake and weight gain that stand out because of the increasing number of obese individuals. This study evaluated the effects of trypsin inhibitor present in the seed of tamarind (Tamarindus indica L.) reduction in weight gain, biochemical and morphological alterations in Wistar rats. For this, we partially purified a trypsin inhibitor tamarind seed. This inhibitor, ITT2 at a concentration of 25 mg / kg body weight, over a period of 14 days was able to reduce food intake in rats (n = 6) by approximately 47%, causing a reduction in weight gain approximately 70% when compared with the control group. With the evaluation of the in vivo digestibility was demonstrated that the animals lost weight due to satiety, presented by the reduction of food intake, since there were significant differences between true digestibility for the control group (90.7%) and the group treated with inhibitor (89.88%). Additionally, we checked the deeds of ITT2 on biochemical parameters (glucose, triglycerides, total cholesterol, high-density lipoprotein, low-density lipoprotein, glutamic-pyruvic transaminase, glutamic oxaloacetic transaminase, gamma glutamyl transferase albumin, globulin, total protein and C-reactive protein) and these, when assessed in the study groups showed no statistically significant variations. We also evaluate the histology of some organs, liver, stomach, intestine, and pancreas, and showed no changes. And to evaluate the effect of trypsin inhibitor on food intake due to the satiety is regulated by cholecystokinin (CCK) were measured plasma levels, and it was observed that the levels of CCK in animals receiving ITT2 were significantly higher ( 20 + 1.22) than in animals receiving only solution with casein (10.14 + 2.9) or water (5.92 + 1.15). Thus, the results indicate that the effect caused ITT2 satiety, reducing food intake, which in turn caused a reduction in weight gain in animals without causing morphological and biochemical changes, this effect caused by the elevation of plasma levels CCK
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Tese de Doutoramento em Biologia Comportamental apresentada ao ISPA - Instituto Universitário
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La fiebre chikunguña es una enfermedad emergente producida por un alfavirus perteneciente a la familia Togaviridae, transmitida por miembros de diferentes especies de mosquitos del género Aedes: Aedes aegypti y Aedes albopictus. La enfermedad del chikunguña se manifiesta de forma aguda con fiebre, rash cutáneo y poliartritis (dolores en varias articulaciones) es por ello que EL OBJETIVO de la investigación fue realizar el Perfil Reumatoideo a estudiantes de nuevo ingreso de Tecnología Médica presentaron en el año 2014 la Fiebre del chikunguña de la Facultad Multidisciplinaria Oriental. METODOLOGÍA: La investigación que se realizó es retroprospectiva porque se evaluaron los datos de una enfermedad que se cursó en el año 2014 y se realizaron las pruebas en el año 2015, transversal porque se realizó en un período sin seguimiento posterior, descriptiva por que permitió conocer si existe o no una alteración en el Perfil Reumatoideo y de laboratorio porque se utilizaron técnicas de laboratorio para determinar los valores del Perfil Reumatoideo. La recopilación de la información se realizó a través de una cédula de entrevista dirigida a los estudiantes que presentaron en el año 2014 la fiebre del chikunguña con el propósito de descartar las interferencias que se pueden presentar en el momento de obtener los resultados clínicos. RESULTADOS: del total de las muestras (100) estudiadas el 51% presentó los valores normales en las pruebas del Perfil Reumatoideo realizadas, por lo tanto el 49% presentó valores positivos o alterados. CONCLUSIONES: el 49% de la población se encontró afectada por la enfermedad presentando positivas una, dos o más pruebas, el 18% presentó resultados positivos de la Proteína "C" reactiva, otro 18% para el Factor reumatoideo, un 38% para la Antiestreptolisina "O" y un 16% de resultados alterados para el Ácido Úrico.
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Dissertação de Mestrado, Qualidade em Análises - Erasmus Mundus, Faculdade de Ciências e Tecnologia, Universidade do Algarve, 2015