<p>Serum amyloid A protein (SAA) is an acute phase protein that has recently gained increasing interest as a potential marker for disease and treatment monitoring. We investigated SAA and CRP levels in (a) patients with various common infectious diseases (n=98), (b) patients with pyelonephritis (n=37) versus patients with cystitis (n=32), (c) healthy individuals of varying ages (n=231), (d) very immature newborn infants with or without nosocomial infections (NIs) (n=72) and (e) patients with bacterial infections treated with cefuroxime (n=81). </p><p>SAA significantly correlated with CRP in viral as well as in bacterial infections (for the total group: r²=0.757, p<0.0001) and showed a systemic inflammatory response in 90% of the patients with cystitis as compared with 23% for CRP. Equally high efficiencies (0.96 and 0.94 for SAA and CRP, respectively) were observed in discriminating between pyelonephritis and cystitis. SAA and high sensitive (hs) CRP were lower in umbilical cords (p<0.0001) and higher in elderly adults (p<0.0001-0.03) than in the other age groups; higher in immature newborn infants than in term infants; and higher in the NI group than in the non-NI group. Interindividual variabilities of the time course of the biomarkers SAA and CRP were considerable. Because of the smoothed distribution of SAA and CRP (i.e. elevations were both essentially unchanged during the first 3 days of cefuroxime treatment), these markers were not useful when deciding parenteral-oral switch of therapy, which occurred within this time period in most cases.</p><p>SAA is a sensitive systemic marker in cystitis. SAA and hsCRP in umbilical cord blood are close to the detection limit and increase with age. They increase in relation to NI in very immature newborn infants and might therefore be used in diagnosis and monitoring. Finally, SAA and CRP in adults with bacterial infections could not predict an early parenteral-oral switch of antimicrobial therapy.</p>

Serum amyloid A protein (SAA) is an acute phase protein that has recently gained increasing interest as a potential marker for disease and treatment monitoring. We investigated SAA and CRP levels in (a) patients with various common infectious diseases (n=98), (b) patients with pyelonephritis (n=37) versus patients with cystitis (n=32), (c) healthy individuals of varying ages (n=231), (d) very immature newborn infants with or without nosocomial infections (NIs) (n=72) and (e) patients with bacterial infections treated with cefuroxime (n=81). SAA significantly correlated with CRP in viral as well as in bacterial infections (for the total group: r2=0.757, p&lt;0.0001) and showed a systemic inflammatory response in 90% of the patients with cystitis as compared with 23% for CRP. Equally high efficiencies (0.96 and 0.94 for SAA and CRP, respectively) were observed in discriminating between pyelonephritis and cystitis. SAA and high sensitive (hs) CRP were lower in umbilical cords (p&lt;0.0001) and higher in elderly adults (p&lt;0.0001-0.03) than in the other age groups; higher in immature newborn infants than in term infants; and higher in the NI group than in the non-NI group. Interindividual variabilities of the time course of the biomarkers SAA and CRP were considerable. Because of the smoothed distribution of SAA and CRP (i.e. elevations were both essentially unchanged during the first 3 days of cefuroxime treatment), these markers were not useful when deciding parenteral-oral switch of therapy, which occurred within this time period in most cases. SAA is a sensitive systemic marker in cystitis. SAA and hsCRP in umbilical cord blood are close to the detection limit and increase with age. They increase in relation to NI in very immature newborn infants and might therefore be used in diagnosis and monitoring. Finally, SAA and CRP in adults with bacterial infections could not predict an early parenteral-oral switch of antimicrobial therapy.

No description available.

No description available.

O cachorro-do-mato (Cerdocyon thous - Linnaeus, 1766) é um canídeo de médio porte com distribuição ampla na América do Sul e que ocorre em quase todo o Brasil. Dentre as principais ameaças à sua conservação estão os atropelamentos causados principalmente pela perda de habitat. A escassez de dados laboratoriais de cachorro-do-mato prejudica o atendimento médico veterinário dificultando a aplicação de terapias adequadas. Este trabalho teve como objetivo avaliar os níveis de Proteína C Reativa, Albumina, Pré-albumina, Ceruloplasmina, Haptoglobina e Alfa 1 Glicoproteína Ácida bem como o Indice Prognóstico Inflamatório Nutricional (IPIN) nesta espécie, obtendo portanto uma primeira descrição destes marcadores prognósticos. Foram coletados 1,5 ml de sangue por acesso jugular de oito exemplares de Cachorro-do-mato (Cerdocyon thous) provenientes do acervo do Laboratório de Ensino e Pesquisa em Animais Selvagens (LAPAS) da Faculdade de Medicina Veterinária da Universidade Federal de Uberlândia para exames de rotina. As amostras foram coletadas através da veia jugular após contenção física dos animais e tricotomia da região. Após análise estatística, os valores encontrados foram: albumina: entre 2,7 e 3,0 g/dl, alfa 1 glicoproteína ácida: entre 0,19 e 0,21 g/l, proteína C reativa: entre 1,7 e 2,2, pré-albumina: entre 30 e 35 mg/l e haptoglobina: entre 0,078 e 0,156 e IPIN ≤ 0,006 sendo considerado normal e valores ≥ 0,006 considerados altos. Esta prima descrição servirá como base para estudos utilizando animais com doenças específicas e, após as análises, comparadas com os valores encontrados neste trabalho verificando se o comportamento segue a semelhança de cães domésticos. / 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. / Tese (Doutorado)

Orientadores: Andrei Carvalho Sposito, Valéria Nasser Figueiredo / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-26T20:27:16Z (GMT). No. of bitstreams: 1 Carvalho_LuizSergioFernandesde_D.pdf: 19288751 bytes, checksum: ea3c4fda36c00d542fbe2d8c4f4242e8 (MD5) Previous issue date: 2015 / Resumo: Introdução: A resposta de fase aguda (RFA) transforma a lipoproteína de alta densidade (HDL) em uma partícula disfuncional que pode favorecer o estresse oxidativo/inflamatório e disfunção da enzima óxido nítrico sintase endotelial (eNOS). Ao mesmo tempo, a modulação do metabolismo da HDL pela proteína de transferência de colesteril ester (CETP) parece estar associada a um potencial efeito anti-inflamatório durante a RFA relacionada a sepse. Embora esses mecanismos possam estar envolvidos na disfunção endotelial que se segue ao infarto do miocárdio com supra de ST (IMCSST), essas hipóteses nunca foram testadas em humanos. Método: Plasma foi obtido de pacientes consecutivos com IMCSST (n=116 a 180) nas primeiras 24 horas após o início dos sintomas (D1) e no 5o dia (D5), sendo utilizado para medir: proteína C reativa (PCR), nitrato/nitrito (NOx) e atividade de CETP. As lipoproteínas foram isoladas por ultracentrifugação de gradiente. A oxidabilidade de LDL co-incubada com HDL (HDLaoxLDL) e auto-oxidabilidade da HDL (HDLautox) foram medidas após a incubação com CuSO4. A atividade anti-inflamatória da HDL foi estimada pela secreção de VCAM-1 por células endoteliais da veia umbilical humana, após a incubação com TNF-?. Dilatação mediada por fluxo (FMD) foi avaliada no 30o dia (D30). Resultados: Entre os pacientes no 1o tercil de HDL-colesterol no D1 (<33mg/dL), o incremento de NOx entre D1 e D5 e a FMD ajustada para várias co-variáveis foram maiores do que naqueles no 2o (33- 42mg/dL) e 3o (>42mg/dL) tercis. Do D1 ao D5 houve redução no tamanho e no número de partículas de HDL, bem como aumento da HDLaoxLDL e HDLautox. A secreção de VCAM-1 após estímulo com TNF-? foi reduzida após co-incubação com HDL de voluntários saudáveis, de doentes com IM no D1 e D30, mas não para a HDL do D5. A oxidação da HDL foi medida pela concentração de TBARS em partículas de HDL isoladas, sendo observado aumento entre D1 e D5, e permanecendo elevado no D30. O aumento no conteúdo de TBARS na HDL foi associado com a atividade de CETP (r=0,72; p=0,014), FMD (r =-0,61; p=0,046) e HDL-C (r=0,83; p=0,004). Em paralelo, elevada atividade de CETP na admissão foi associado a menor FMD, menor biodisponibilidade de NOx e a maior incidência de morte súbita e infarto recorrente após 30 (OR=12,8; p=0,032) e 180 dias (OR=3,3; p=0,044). Conclusão: O IMCSST induz mudanças na composição química e função do HDL, bem como alterações na atividade enzimática da CETP que paralelamente contribuem para o aumento da oxidação de partículas de HDL, que se traduz em disfunção endotelial / Abstract: Introduction: Acute phase response (APR) turns high-density lipoprotein (HDL) into a dysfunctional particle that may favor oxidative/inflammatory stress and endothelial nitric oxide (NO) synthase (eNOS) dysfunction. Moreover, modulation of HDL intravascular metabolism by cholesteryl ester transfer protein (CETP) action has also been implicated as a potentially anti-inflammatory and thrombotic mechanism during APR. Although these mechanisms may be involved into endothelial dysfunction that follows acute ST-elevation myocardial infarction (STEMI), these assumptions have never been in investigated in humans. Method: Plasma was obtained in the first 24-hours after STEMI symptoms onset (D1) and after 5 days (D5) in consecutive patients (n=116 to 180), and then used to measure C-reactive protein (CRP), nitrate/nitrite (NOx) and CETP activity. Lipoproteins were isolated by gradient ultracentrifugation. The oxidizability of low-density lipoprotein incubated with HDL (HDLaoxLDL) and the HDL self-oxidizability (HDLautox) were measured after CuSO4 co-incubation. Anti-inflammatory activity of HDL was estimated by VCAM-1 secretion by human umbilical vein endothelial cells after incubation with TNF-?. Flowmediated dilation (FMD) was assessed at the 30th day (D30) after STEMI. Results: Among patients in the first tertile of admission HDL-Cholesterol (<33mg/dL), the increment of NOx from D1 to D5 and the FMD adjusted for multiple covariates were higher than in those in the second (33-42mg/dL) or third (>42mg/dL) tertiles, respectively. From D1 to D5, there was a decrease in HDL size and particle number and increase in both HDLaoxLDL and HDLautox. VCAM-1 secretion after TNF-a stimulation was reduced after co-incubation with HDL from healthy volunteers, from MI patients at D1 and D30 but not from D5. Oxidized HDL was measured by TBARS in isolated HDL particles and increased from D1 to D5, and remaining elevated at D30. The change in TBARS content in HDL was associated with CETP activity (r=0.72;p=0.014), FMD (r=-0.61;p=0.046) and HDL-C (r=0,83,p=0,004). High CETP activity at admission was associated lower FMD, lower NOx bioavailability and with the incidence of sudden death and recurrent MI at 30 days (OR 12.8;p=0.032) and 180 days (OR 3.3;p=0.044). Conclusion: STEMI induces changes in the chemical composition and function of HDL as well as changes in the enzymatic activity of CETP that in parallel contribute to increased oxidation of HDL particles, and thus inducing endothelial dysfunction / Doutorado / Patologia Clinica / Doutor em Ciências Médicas

Le traumatisme craniocérébral léger (TCCL) s'accompagne d'une constellation de symptômes de nature variée, appelés symptômes post-commotionnels (SPC). La majorité des patients se rétablissent complètement et rapidement, à savoir dans le mois qui suit l'accident. Cependant, 10 à 20 % d'entre eux présentent un rétablissement prolongé avec des SPC persistants (SPCP), lesquels entravent la qualité de vie, l'intégration à la communauté et le retour aux activités. Pour la minorité de patients présentant des SPCP, il est donc nécessaire d'intervenir au-delà de la psychoéducation préventive aiguë recommandée par les guides de pratique. Or, il existe très peu d'interventions visant spécifiquement à outiller ces patients afin de diminuer les SPC et ainsi, accélérer le rétablissement. En effet, à l’heure actuelle, les interventions psychologiques et psychoéducatives développées spécifiquement pour la phase post-aiguë, qui prend place entre les phases aiguë (0-1 mois après le TCCL) et chronique (> 6 mois post-accident), sont particulièrement rares. Les quelques études existantes plaident en faveur d'une approche brève de quelques séances de psychoéducation et/ou de soutien. Cependant, il s'agit de données préliminaires et de nombreuses inconnues subsistent encore quant au format idéal (ex. : en personne vs par téléphone, individuel vs en groupe, nombre de séances, contenu précis). En outre, la pauvre qualité méthodologique des études complique significativement les interprétations possibles à ce sujet (ex. : absence de groupe contrôle, groupes non randomisés). L'objectif principal de cette thèse était donc de développer une nouvelle intervention de psychoéducation et de soutien destinée aux personnes en phase post-aiguë du rétablissement post-TCCL, et d’explorer sa faisabilité ainsi que son efficacité. L'objectif du premier article de la thèse (Chapitre 2) était de remédier à la pauvreté de la littérature en ce qui a trait, d'une part, à la description des protocoles d'intervention de psychoéducation et, d'autre part, relativement à leurs assises théoriques. Il avait donc pour objectif de présenter la démarche théorique et méthodologique associée au développement de l'intervention SAAM, un programme de quatre séances d'intervention individuelles d’une heure, données en personne, et visant chacune un type de SPC fréquent en phase post-aiguë : Sommeil/fatigue, Attention, Anxiété/humeur, Mémoire/organisation. Le programme offre de l'information au patient, le rassure sur son rétablissement et l'accompagne vers un retour graduel aux activités, en l'outillant à cet effet. Cette approche est ancrée dans un modèle théorique intégratif de persistance des symptômes (Hou et al., 2012), dont les composantes sont expliquées dans l'article. Celui-ci permet non seulement de mieux saisir les fondements théoriques associés à la création du nouvel outil d'intervention, mais en dévoile également son contenu. Il met donc en lumière une démarche qui s'inscrit parfaitement dans un effort de clarification et de transparence, essentiel au progrès de la recherche interventionnelle. Plus largement, ce travail permettra de faciliter la réplication scientifique et de soutenir le transfert de connaissances vers les milieux cliniques. Le deuxième article de la thèse (Chapitre 3) avait pour objectif d'estimer la faisabilité et d’explorer l'effet de l'intervention SAAM auprès de patients symptomatiques en phase post-aiguë de leur rétablissement. Une étude pilote d’essai contrôlé randomisé à deux groupes parallèles (expérimental, n = 13 et liste d'attente, n = 12) a permis de démontrer la faisabilité et la tolérance à l’intervention SAAM. Les données préliminaires suggèrent un effet de l’intervention sur la diminution des SPC en général. En ce qui a trait plus directement aux SPC visés par l'intervention SAAM, une amélioration des plaintes reliées aux symptômes dépressifs, à la fatigue et à la perception de la qualité du sommeil a été mise en évidence à la suite de l'intervention. Cependant, l’étude n'a pas montré d’effet bénéfique du programme SAAM en termes de plaintes somatiques ni de performance cognitive (attention, mémoire). De plus, aucun effet n'a été observé sur le plan de l'intégration à la communauté. Des analyses supplémentaires (Chapitre 4) suggèrent que l'intervention SAAM pourrait restaurer le besoin de compétence, un besoin psychologique fondamental intimement relié au bien-être des individus. Enfin, des analyses supplémentaires portant sur un questionnaire de satisfaction face à l'intervention confirment un haut taux de satisfaction des participants face à l'intervention, ce qui est de bon augure pour l'implémentation en milieux cliniques. Par son aspect novateur, son format standardisé bref et facilement accessible, ainsi que ses effets objectivés sur plusieurs SPCP particulièrement invalidants à la suite du TCCL, le programme d'intervention SAAM est prometteur. La portée clinique de cette thèse est donc particulièrement importante et est discutée, avec ses limites et les avenues de recherche futures, dans le dernier chapitre. Ces résultats soulignent l'importance de poursuivre la recherche dans le champ des interventions post-TCCL, afin d’outiller les cliniciens et d’offrir les meilleurs soins possibles aux patients ayant subi un TCCL. / Mild traumatic brain injury (mTBI) is accompanied by a constellation of manifestations known as post-concussive symptoms (PCS). The majority of patients recover completely and promptly, i.e. within one month of injury. However, 10-20 % experience prolonged recovery with persistent PCS (PPCS), which impact quality of life, community integration and resumption of activities. For the minority of patients who present PPCS, it is necessary to provide them with resources beyond the acute preventive psychoeducation recommended by practice guidelines. However, there are very few interventions available to reduce PCS and thus enhance recovery. To date, psychological and psychoeducational interventions developed specifically for the post-acute phase, which takes place between the acute (0-1 month after mTBI) and the chronic phase (> 6 months post-injury), are particularly rare. The scarce existing evidence suggests that the optimal intervention should be brief, including a few sessions of psychoeducation and/or counseling. Nevertheless, these are preliminary data and many open questions remain regarding the optimal format (e.g., in person vs. on the phone, individual vs. group, number of sessions, specific content). Moreover, the poor methodological quality of previous intervention studies significantly complicate interpretations (e.g., absence of control groups, non-randomized groups). The main objective of this thesis was therefore to develop and explore the feasibility and treatment effect of a novel psychoeducational and counseling intervention program for the post-acute phase after mTBI. The objective of the first article of the thesis (Chapter 2) was to overcome the paucity of work describing psychoeducational intervention protocols and their theoretical underpinnings. The article therefore aimed to present the theoretical and methodological approach associated with the development of the SAAM intervention. SAAM is a program including four 1-hour individual intervention sessions given in person, each targeting a type of common PCS in the post-acute phase: Sleep/fatigue, Attention, Anxiety/mood, Memory/organization. It informs the patient, provides reassurance about recovery, and supports the gradual resumption of activities by giving the patient the tools to do so. This approach is anchored in an integrative theoretical model of symptom persistence (Hou et al., 2012), the components of which are explained in the article. The latter provides a better understanding of the theoretical rationale behind the development of the SAAM intervention, and includes a detailed description of the protocol. The article is meant to align with efforts to clarify the theoretical underpinnings of the intervention program and enhance transparency in scientific reporting, an essential step in the advancement of interventional research. More broadly, this work will facilitate scientific replication and knowledge transfer in clinical settings. The second article (Chapter 3) aimed to estimate feasibility and explore the treatment effect of the SAAM intervention in symptomatic patients during the post-acute phase. A pilot randomized controlled trial with two parallel groups (experimental, n = 13 and wait list, n = 12) demonstrated the feasibility and tolerability of the intervention. Preliminary data suggest an effect of the intervention in reducing overall PCS. More specifically, regarding the PCS targeted by the SAAM intervention, an improvement in complaints related to depressive symptoms, fatigue, and sleep quality perception was observed post-intervention. However, the intervention failed to show a positive effect in addressing anxiety or somatic complaints, nor was it significantly impactful in improving cognitive performance (attention, memory). No effect was observed in terms of community integration either. Nonetheless, additional analyses (Chapter 4) suggest that SAAM intervention might restore the need for competence, a basic psychological need closely related to the individual's well-being. Finally, additional analyses pertaining to an intervention satisfaction questionnaire confirm that participants report a high level of satisfaction with the intervention, which bodes well for clinical implementation. The SAAM intervention holds promise because of its innovative aspect, its brief and easily accessible standardized format, and its demonstrated effects on several disabling PCS. The clinical significance of this thesis is notable and is discussed, along with study limitations and future avenues of research, in the final chapter. This work emphasizes the importance of pursuing research efforts in the field of post-mTBI interventions, in order to provide clinicians with the tools they need to offer the best possible care to patients who have sustained mTBI.

This study investigated the effects of abomasal infusion of essential fatty acids, especially alpha-linolenic acid, and conjugated linoleic acid on their distribution in milk fat and blood plasma and on the plasma inflammatory response in dairy cows from late to early lactation. The most important essential fatty acids for ruminants are alpha-linolenic acid and linoleic acid. They are abundant in pasture which is nowadays reduced in the ration of dairy cows due to the replacement of fresh feeds by preserved diets. Conjugated linoleic acid is formed as a by-product during ruminal biohydrogenation of essential fatty acids and has been associated with positive effects on the energy metabolism and immune system. Forty rumen-cannulated Holstein Friesian cows were assigned to four treatment groups in their late second lactation. Prior to supplementation, cows were fed a total mixed rations with a low-fat content. In late gestation cows were abomasally treated with coconut oil, linseed and safflower oil, conjugated linoleic acid, or both. Performance data, milk composition and fatty acid pattern in milk and plasma as well as inflammatory response parameters in plasma were measured regularly. Furthermore, liver tissue was tested for the abundance of genes related to the inflammatory response.:TABLE OF CONTENTS ABBREVIATIONS 1. INTRODUCTION 2. LITERATURE OVERVIEW 2.1 Essential Fatty Acids and Conjugated Linoleic Acid 2.1.1 Essential Fatty Acids (EFA) 2.1.2 Conjugated Linoleic Acid (CLA) 2.1.3 EFA in Dairy Cow Nutrition 2.2 Fatty Acid Distribution in Blood, Erythrocyte Membranes, and Milk Fat 2.2.1 Plasma Lipids 2.2.2 EFA and CLA in Plasma Lipids 2.2.3 EFA and CLA in Erythrocyte Membranes 2.2.4 EFA and CLA in Milk Fat 2.3 Effects of EFA and CLA on Inflammatory Processes during the Transition Period 2.3.1 Metabolic and Immunological Challenges during the Transition Period 2.3.2 Effects of EFA on the Metabolism, Inflammatory- and Immune Response 2.3.3 Effects of CLA on the Metabolism, Inflammatory- and Immune Response 2.4 Scope of the Thesis 3. PUBLICATION 4. GENERAL DISCUSSION 4.1 Abomasal Infusion 4.2 Animal Performance 4.3 Distribution of EFA and CLA in Blood and Milk Fat 4.4 Effects of EFA and CLA on Plasma and Hepatic Acute Phase and Inflammatory Response 4.5 Conclusion and Practical Considerations 4.5.1 Summary of EFA effects 4.5.2 Summary of CLA effects 4.5.3 Summary of synergistic effects of EFA and CLA 4.5.4 Summary of Observations apart from Treatments and Practical Considerations 5. SUMMARY 6. ZUSAMMENFASSUNG 7. REFERENCES APPENDIX

INTRODUÇÃO: A endomiocardiofibrose (EMF) é uma doença típica de países tropicais, na qual ocorre a deposição de uma capa fibrosa na região endomiocárdica com graves consequências clínicas. A patogenia da EMF ainda não foi elucidada, mas uma das principais hipóteses etiológicas sugere que a EMF seja consequência de um processo inflamatório crônico com envolvimento de respostas imunes Th2 pós-infestação helmíntica, mediada por eosinófilos nas fases iniciais da doença. Neste estudo avaliamos o perfil da resposta imune e inflamatória, assim como o perfil de proteínas expressas no endomiocárdio afetado, para compreender melhor os mecanismos envolvidos na patogênese da EMF. MÉTODOS: Foram coletadas amostras de plasma e soro de pacientes com diagnóstico de EMF e de indivíduos saudáveis, para dosagens de 6 citocinas plasmáticas do perfil Th1/Th2, Proteína C Reativa ultrassensível (PCRus), IgE total e IgE específico contra aero-alérgenos prevalentes e alérgenos de helmintos. A análise proteômica do endomiocárdio afetado de quatro pacientes com EMF submetidos à ressecção cirúrgica da fibrose, levou à identificação por espectrometria de massas, de proteínas separadas previamente por gel 1D e 2D. Análises in silico de vias funcionais e redes ligando as proteínas identificadas também foram realizadas. Eosinofilia em sangue periférico, assim como dados clínicos e ecocardiográficos, foram avaliados retrospectivamente. RESULTADOS: Foram selecionados 27 pacientes em estágio avançado da EMF, portadores de disfunção diastólica e/ou valvar. Todas as amostras de plasma analisadas apresentaram níveis detectáveis de pelo menos uma das citocinas avaliadas. As citocinas IL-6, TNF-?, IL-10 e IL-4 foram detectadas em pelo menos 74% das amostras, sendo que os níveis de IL-6, TNF-? e IL-10 se apresentaram significantemente elevados em comparação com os detectados nos indivíduos saudáveis. Foi observada correlação positiva entre os níveis de todas as citocinas avaliadas. Apenas 33% dos pacientes apresentaram algum episódio isolado de eosinofilia periférica ao longo do tempo, sendo que 11% apresentaram hipereosinofilia. Os níveis de IgE total foram semelhantes aos observados na população controle. A análise proteômica permitiu identificar 140 proteínas distintas no tecido endomiocárdico, das quais 18 eram provenientes da matriz extracelular. As análises in silico indicaram IL-6 e TNF-? como dois dos principais indutores da expressão das proteínas identificadas e a principal via canônica envolvida nas proteínas identificadas foi a: \"Resposta de Fase Aguda\". Coincidentemente, os níveis de PCRus encontraram-se significativamente aumentados nos portadores de EMF. CONCLUSÕES: Elevados níveis de citocinas pró e anti-inflamatórias e de PCRus sugerem a presença de perfil inflamatório misto (Th1/Th2) nas fases avançadas da patogênese da EMF. A pouca expressão da eosinofilia descarta sua participação ativa na patogênese da fase avançada da doença, mas não é possível excluir sua participação nas fases iniciais. Nossos dados permitem levantar a hipótese que os níveis elevados de citocinas inflamatórias modulem a expressão de proteínas- incluindo as de fase aguda- no tecido endomiocárdico de pacientes portadores de EMF / INTRODUCTION: Endomyocardial fibrosis (EMF) is a typical disease in tropical countries, characterized by the fibrous deposition in the endomyocardium, with severe clinical manifestations. EMF pathogenesis is still unclear, but one of the major hypothesis suggests that EMF could be a consequence of a chronic inflammatory process with possible involvement of a Th2 immune responses after helminthiasis, mediated by eosinophils, which could contribute to pathogenesis in the early stages of the disease. In this study, we evaluated the inflammatory response profile and the protein expression profile of the affected endomyocardium, to understand the mechanisms involved in this pathogenesis. METHODS: Plasma and serum samples were collected from the 27 patients diagnosed with advanced stage EMFand from healthy controls, to mensured plasma levels of 6 cytokines belonging to the Th1/Th2 cytokine profiles, ultrasensitive C Reactive Protein (CRP), total and allergen-specific serum IgE against prevalent and helminthic allergens. Proteomic analysis of tissue samples obtained from 4 EMF patients submitted to surgical resection of affected endomyocardial tissue allowed the identification of proteins by mass spectrometry, after separation by 1D and 2D electroforesis. In silico analysis of functional pathways and networks connecting the proteins identified in the EMF cardiac tissue was also performed. Blood peripheral eosinophilia, clinical and echocardiography data were evaluated retrospectively. RESULTS: All EMF patients displayed detectable plasma levels of at least one of the cytokines tested. We found that TNF-?, IL-6, IL-4 and IL-10 were each detected in at least 74% of tested sera, and plasma levels of IL10, IL6 and TNF-? were significantly higher than controls. Plasma levels of such cytokines positively correlated with each other. Only 33% of the patients presented any episode of blood eosinophilia along time, and 11% of these patients presented hypereosinophilia. Total IgE levels were similar to those from healthy subjects. Proteomic analysis allowed the identification of 140 distinct proteins from the resected endomiocardium of the EMF patients, 18 of which belonging to the extracellular matrix. In silico analysis indicated IL-6 and TNF-? as two of the major gene expression inducers of the identified proteins in our analysis, and the Acute Phase Response was identified as the major canonical pathway involved with the identified set of proteins. Similarly, CRP levels were significantly increased in the EMF patients. CONCLUSIONS: Increased levels of an inflammatory/anti-inflammatory circulating cytokines (Th1/Th2), along with increased CRP levels, suggested the presence of a mixed inflammatory profile in EMF advanced stage. The number of EMF patients with blood eosinophilia does not support the active participation of eosinophils in pathogenesis of advanced EMF. However, it is not possible to exclude the participation in the pathogenesis early stages. Our data support the hypothesis that the increased levels of inflammatory cytokines modulate protein expression -including proteins of the acute phase response - in the endomyocardial tissue of EMF patients

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