Objectifs : Les lymphocytes T régulateurs de par leur rôle primordial dans l'homéostasie de la réponse immune sont des cellules idéales pour une immunothérapie antigène-spécifique dans les maladies auto-immunes. Les lymphocytes T régulateurs de type 1 ou Tr1 sont caractérisées par une forte sécrétion d'IL-10, cytokine qui joue un rôle déterminant dans leur capacité à supprimer des réponses immunes pathologiques dans différents contextes. L'objectif de ma thèse est d'évaluer le potentiel thérapeutique de cellules Tr1 spécifiques du collagène de type II (col-Treg) dans deux modèles de polyarthrite rhumatoïde (PR) chez la souris. Méthode : Les clones Col-Treg ne possèdent pas de marqueurs membranaires spécifiques mais sont caractérisés par un profil cytokinique particulier (IL10highIL4negIFN-γint) et par leur capacité de suppression in vitro. Tout comme les Tregs naturels, ils expriment une quantité importante de GITR, de CD39 et de Granzyme B. Une simple injection de cellules Col-Treg réduit l'incidence et les symptômes cliniques de l'arthrite à la fois de manière préventive et curative, avec un impact significatif sur les anticorps anti-collagène de type II. En outre, l'injection de Tr1 antigène spécifique in vivo diminue de manière significative la prolifération des cellules T antigène spécifique. Conclusion : Nos résultats démontrent le potentiel thérapeutique des cellules Col-Treg dans deux modèles d'arthrite expérimentale prouvant que les cellules Col-Treg représente une nouvelle approche thérapeutique de choix pour le traitement des patients atteint de polyarthrite et réfractaires aux traitements actuels. / Objectives : Regulatory T (Treg) cells play a crucial role in preventing autoimmune diseases and are an ideal target for therapies to suppress inflammation in an antigen-specific manner. Type 1 Treg cells (Tr1) are defined by their capacity to produce high levels of IL10, which contributes to their ability to suppress pathological immune responses in several settings. The aim of my PhD was to evaluate the therapeutic potential of collagen type II-specific Tr1 (Col-Treg) cells in two models of rheumatoid arthritis (RA) in mice. Methods : Col-Treg clones were isolated and expanded from Collagen-specific TCR transgenic mice. Their cytokine secretion profile and phenotype characterization were studied. The therapeutic potential of Col-Treg cells was evaluated after adoptive transfer in collagen-antibodies- and collagen-induced arthritis models. The in vivo suppressive mechanism on effector T cell proliferation was also investigated. Results : Col-Treg clones are characterized by a cytokine profile (IL10highIL4negIFN-γint) and mediate contact-independent immune suppression. They also share with natural Tregs high expression of GITR, CD39 and Granzyme B. Single infusion of Col-Treg cells reduced incidence and clinical symptoms of arthritis both in preventive and curative settings, with a significant impact on collagen type II antibodies. Importantly, injection of antigen-specific type 1 Treg cells decreases significantly the proliferation of antigen-specific effector T cells in vivo. Conclusion : Our results demonstrate the therapeutic potential of Col-Treg cells in two models of RA, providing evidence that Col-Treg could be an efficient cell-based therapy for RA patients refractory to current treatments.

Sammanfattning Bakgrund: Kronisk ledgångsreumatism eller Reumatoid Artrit (RA) är en kronisk inflammatorisk ledsjukdom och är den vanligaste artritsjukdomen vars huvudsymtom är ledvärk. RA finns i alla folkgrupper, dock med varierande prevalens. I Skandinavien ligger prevalensen på ca 0,7 %. Etnologin till RA är en blandning av genetiska och omgivningsrelaterade faktorer. Att leva med RA påverkar patienten fysiskt, känslomässigt, psykologiskt och även socialt vilket leder till att hela livssituationen påverkas. Syfte: Syftet med litteraturstudien var att beskriva erfarenheter av sjuksköterskeledd mottagning hos patienter med reumatoid artrit samt beskriva undersökningsgruppen i de inkluderade artiklarna. Metod: En litteraturstudie med beskrivande design. Huvudresultat: Patienternas erfarenhet av sjuksköterskeledd mottagning var möten i en varm, vänlig och familjär atmosfär. Vården beskrevs som personcentrerad och kompetent och var baserad utifrån varje individs speciella behov. Sjuksköterskans specialistkunskaper värderades högt och uppgavs skapa en känsla av trygghet hos patienten. Den sjuksköterskeledda mottagningen upplevdes som lättillgänglig, flexibel och skapade kontinuitet i vården. Tillgängligheten medförde också att patienten visste när och hur de skulle kontakta sjuksköterskan. Patientens erfarenhet var att en god kommunikation med vårdpersonalen, gav en ömsesidig respekt och ingav patienten ökat förtroende. Slutsats: Slutsatsen av denna studie är att sjuksköterskeledd mottagning kan skapa ett mervärde för patientens omvårdnad. Den erbjudna vården representerade för deltagarna trygghet, hopp och förtroende. För att ett mervärde ska skapas är det av största vikt med god kommunikation och relationskapande, vilket i sin tur ger trygghet och skapar en grundläggande möjlighet för hälsofrämjande omvårdnad. / Abstract Background: Chronic arthritis rheumatism or rheumatoid arthritis (RA) is a chronic inflammatory joint disease and is the most common arthritis disease, in which headache is joint pain. RA is present in all populations, with varying prevalence. In Scandinavia, the prevalence is approximately 0.7%. The ethnology of RA is a combination of genetic and environmental factors. Living with RA affect the patient physically, emotionally, psychologically and socially, meaning that the whole life situation is affected. Aim: The purpose of the literature study was to describe the experiences of nurse-led clinics for patients with rheumatoid arthritis and to present the study groups described in the articles included. Methods: A descriptive literature study Main results: Patients' experiences of nurse-led clinics were encounters in a warm, friendly and familiar atmosphere. The care was described as person-centered and competent provided and based on each individual's special needs. The nursing specialist skills were highly valued and described to create a sense of security for the patient. The nurse-led clinic was reported readily available, flexible and to create stability in the care. The accessibility also meant that the patients were aware of when and how to contact the nurse. The patient's experience was that good communication with the healthcare staff provided a mutual respect and instilled an increased patient confidence. Conclusion: The conclusion of this study was that nurse-led clinics could add value for the patient nursing care. This offered care represented familiarity, hope and confidence for the patients. To achieve added value, good communication and relationship are of the utmost importance, which in turn provide security and create a fundamental possibility in health-promoting care.

<p>Post-traumatic arthritis (PTA) is arthritis that develops following joint injury, including meniscus and ligament tears. Current treatments for PTA range from over-the-counter medication to knee replacement; however, in the presence of obesity, the levels of pro-inflammatory cytokines, such as interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF-α,) are more elevated than in non-obese individuals. The role of fatty acids, obesity, and PTA has been examined, with omega-3 fatty acids showing promise as an anti-inflammatory after injury due to its ability to suppress IL-1 and TNF-α. Due to the difficulty in switching patients’ diets, an alternative solution to increasing omega-3 levels needs to be developed. The Fat-1 enzyme, an omega-3 desaturase that has the ability to convert omega-6 to omega-3 fatty acids, may be a good target for increasing the omega-3 levels in the body. </p><p>In the first study, we examined whether Fat-1 transgenic mice on a high-fat diet would exhibit lower levels of PTA degeneration following the destabilization of the medial meniscus (DMM). Both male and female Fat-1 and wild-type (WT) littermates were put on either a control diet (10% fat) or an omega-6 rich high-fat diet (60% fat) and underwent DMM surgery. Arthritic changes were examined 12 weeks post-surgery. Fat-1 mice on both the control and high-fat diet showed protection from PTA-related degeneration, while WT mice showed severe arthritic changes. These findings suggest that the omega-6/omega-3 ratio plays an important role in reducing PTA following injury, and demonstrates the potential therapeutic benefit of the Fat-1 enzyme in preventing PTA in both normal and obese patients following acute injury.</p><p>Following this, we needed to establish a translatable delivery mechanism for getting the Fat-1 enzyme, which is not present in mammalian cells, into patients. In the second study, we examined whether anti-inflammatory gene delivery of the Fat-1 enzyme would prevent PTA following DMM surgery. In vitro testing of both lentivirus (LV) and adeno-associated virus (AAV) was completed to confirm functionality and conformation of the Fat-1 enzyme after transduction. Male WT mice were placed on an omega-6 rich high-fat diet (60% fat) and underwent DMM surgery; either local or systemic AAV injections of the Fat-1 enzyme or Luciferase, a vector control, were given immediately following surgery. 12 weeks post-surgery, arthritic changes were assessed. The systemic administration of the Fat-1 enzyme showed protection from synovial inflammation and osteophyte formation, while administration of Luciferase did not confer protection. These findings suggest the utility of gene therapy to deliver the Fat-1 enzyme, which has potential as a therapeutic for injured obese patients for the prevention of PTA.</p> / Dissertation

Die Juvenile Idiopathische Arthritis ist eine der häufigsten Ursachen von Gelenkbeschwerden im Kindesalter. Die Pathogenese der Erkrankung ist bisher wenig verstanden. Da sich jedoch bei einigen Subtypen der JIA Antinukleäre Antikörper (ANA) nachweisen lassen, liegt eine Beteiligung von B-Lymphozyten nahe. Mittels einer Kombination aus phänotypischer Zuordnung bestimmter B-Zell Differenzierungsstadien sowie Einzelzellsortierung, Amplifikation und Sequenzierung des rearrangierten Immunglobulingens individueller B-Zellen wurde der Frage nach klonaler Verwandschaft unterschiedlich differenzierter B-Zell Stadien und Selektion innerhalb des Gelenkes nachgegangen. / Juvenile idiopathic arthritis is one of the most common reasons for joint problems in childhood. Still the pathogenesis is rarely understood. Since antinuclear antibodies can be found in some subtypes of JIA, an involvement of b-cells can be suggested. By combining phenotypical assignment of specific b-cell subsets and single cell sorting, amplification and sequencing of the rearranged immunoglobulin-gene of individual b-cells, indication for clonal relationship of different b-cell subsets and selection in the joints was examined.

Rheumatoid arthritis (RA) is a worldwide problem representing one of the most prevalent autoimmune diseases in the world. Despite the commonness of the disea- se, its pathogenesis has not been fully described. Immune cells ranging from antigen- presenting cells to T, B and NK cells playing various roles participate in the rheumatic process. In this work we concentrated on NK cells expressing a repertoire of activating and inhibitory receptors which influence their function in health and disease. We focused on the analysis of NK cell function and described its possible modulation by rheumatic autoantigens and multivalent glycodendrimers bearing 4 (GN4C) or 8 (GN8P) N-acetyl glucosamine moieties. The effect on NK cells and the glycosylation pathways was further studied in vitro. Finally, an in vivo study was performed on an animal model of RA - col- lagen-induced arthritis (CIA) to assess the effect of the compounds on clinical develop- ment of the disease and selected immune parameters. Comparison of NK cell cytotoxicity in patients suffering from RA, other inflam- matory diseases and healthy donors showed its impairment particularly in RA patients. Peripheral blood NK cells reacted to GN8P glycoconjugate by inhibition of their effector function in CD161 high-expressing samples. The MGAT5...

A artrite reumatoide (AR) é uma doença inflamatória crônica, caracterizada por inflamação das articulações e se manifesta por inchaço e incapacidade funcional das mesmas. A patologia da doença envolve a produção excessiva de radicais livres pelos neutrófilos ativados, podendo induzir à peroxidação lipídica nas membranas celulares o que leva ao aumento da inflamação. Nesse sentido, o selênio (principal fonte é a castanha-do-brasil) é um importante fator por diminuir a atividade dos hidroperóxidos por meio da ação da enzima antioxidante glutationa peroxidase (GPx). No entanto, estudos que avaliem a associação do estado nutricional relativo ao selênio em pacientes com AR com os biomarcadores do estresse oxidativo e de inflamação são escassos na literatura. Desse modo, a avaliação do efeito potencial in vivo da suplementação com castanha-do-brasil, como fonte de selênio, sobre os parâmetros descritos anteriormente e sua relação com o polimorfismo Pro198Leu no gene da GPx1, em pacientes com artrite reumatoide (AR), vêm a suprir essa lacuna. Inicialmente foi realizada a caracterização da castanha-do-brasil quanto à composição de macronutrientes e teor de selênio. O estudo em pacientes com artrite reumatoide foi de natureza longitudinal. Foram avaliados 46 pacientes com AR, com idade média de 55,2 ± 10,9 anos, atendidos no Setor de Reumatologia da Universidade Federal de São Paulo. O estudo foi dividido em duas fases: antes (T0) e após a suplementação (T1) com 1 nóz de castanha-do-brasil. Foi realizada a avaliação da composição corporal e do consumo alimentar. Além disso, foram avaliados parâmetros bioquímicos relativos ao status de selênio por espectrofotometria de absorção atômica por geração de hidretos; atividades da GPx e SOD com uso de kits comerciais; concentração da GPx1 por kits comerciais, sua expressão gênica (qRT-PCR) e genotipagem do Pro198Leu no referido gene por PCR em tempo real; determinação de 8-isoprostanos por kit comercial, assim como níveis circulantes de fibrinogênio, proteína C reativa, IL-6, IL-10, TNF-&#945;, IL-1&#946;, IL-2, VCAM, ICAM, PAI-1 e sE-selectina pelo ensaio ELISA. O genótipo selvagem (Pro/Pro) foi observado em 57,63% das participantes; 35,59% para as heterozigotas para o alelo variante (Pro/Leu) e 6,78% apresentaram os dois alelos variantes. As pacientes com artrite reumatoide apresentaram baixa ingestão de selênio e, após a intervenção, o consumo aumentou significantemente. Em relação ao status de selênio, houve um aumento em sua concentração no plasma e eritrócitos após o período de intervenção com castanha-do-brasil, assim como na atividade da GPx, na concentração da GPx1 e em sua expressão gênica. Níveis urinários reduzidos de 8-isoprostano e nenhuma alteração quanto à capacidade antioxidante total plasmática e quanto aos marcadores inflamatórios foram observados após o período de intervenção. Por outro lado, houve um aumento nas concentrações séricas das moléculas de adesão celulares. Portanto, pode-se concluir que a suplementação com castanha-do-brasil mostrou-se efetiva em melhorar o estado nutricional relativo ao selênio dos pacientes e os marcadores de estresse oxidativo, todavia a ingestão de 350 &#181;gSe/dia não foi suficiente para promover uma melhora do quadro inflamatório. Além disso, a presença do polimorfismo Pro198Leu modificou as respostas dos indivíduos CT e TT em relação à suplementação, sendo inferior à dos indivíduos CC. / Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by joint inflammation, manifested by swelling and joint impairment. These pathology involves excessive free radicals production by activated neutrophils leading to lipid peroxidation in cell membranes and increased inflammation. Accordingly, selenium (Brazil-nut as main source) is an important factor reducing hydroperoxides through the improvement of glutathione peroxidase (GPx) activity. However, studies evaluating their association with oxidative stress biomarkers and inflammation in RA patients are scarce. Thus, the assessment of the in vivo potential Brazil nut supplementation on the parameters described above and its relationship to the polymorphism Pro198Leu in GPx1 gene in patients with rheumatoid arthritis, come to fill this gap. First of all, we analysed macronutrients and selenium content in Brazil nut. This is a longitudinal study with 46 RA patients attending rheumatologic treatment at Federal University of São Paulo and whose mean age were 55.2 ± 10.9 years. The present study was carried out by two phases, before and after one Brazil ingestion. We evaluated selenium status by spectrophotometry absorption with hydride generation; body composition, SOD, GPx activites, GPx1 concentration and 8- isoprostane levels, using commercial Kits; gene expression by RT-PCR and genotyping using real time PCR. Besides, inflamatory biomarkers were performed (fibrinogen, C reactive protein, IL-6, IL-10, TNF-&#945;, IL-1&#946;, IL-2, VCAM, ICAM, PAI-1 e sE-selectin by ELISA. The wild genotype (Pro/Pro) was observed in 57.63% of the participants, 35.59% were heterozygote for variant allele (Pro/Leu) and 6.78% had two variant alleles. Patients with rheumatoid arthritis had low selenium intake and after the intervention, consumption of this element increased significantly. Selenium status increased significantely after Brazil nut ingestion, as well as GPx activity, GPx1concentration and its gene expression. Reduced urinary levels of 8-isoprostane and no change for total plasma antioxidant capacity and markers for inflammation were observed after the intervention period. On the other hand, there was an increase in serum concentrations of cell adhesion molecules. Therefore, it can be concluded that Brazil-nut supplementation proved to be effective in improving selenium status and markers of oxidative stress in RA patients, however ingestion of 350 &#181;gSe/day wasn\'t enough to ameliorate inflammation. Besides, the presence of Pro198Leu polymorphisms interfere in supllementation response in CT and TT groups, being less responsive than CC ones.

A Artrite Encefalite Caprina (AEC) é uma lentivirose multisistêmica que tem a glândula mamária caprina como um dos alvos lesionais da doença. Pode causar uma manifestação mamária específica, chamada de mastite endurativa, além da mama representar uma importante via de eliminação do vírus, mesmo em animais que não apresentam a forma clínica. Considerando-se a possibilidade desta virose, cuja célula alvo predominante é o monócito, levar a alterações imunológicas que influenciem a susceptibilidade do animal a outras doenças, objetivou-se avaliar essa interação do vírus e da imunidade do hospedeiro por meio de fenotipagem, fagocitose e produção de Espécies reativas de oxigênio (ERO) e dos mecanismos de morte das células sanguíneas e lácteas de cabras naturalmente infectadas. Para isso 200 cabras foram triadas e, destas selecionadas oito fêmeas não sororreagentes e dez sororreagentes na pesquisa de anticorpos séricos para AEC, dentro dos padrões hematológicos da espécie e com dois exames bacteriológicos do leite negativos. O leite e o sangue colhido destes animais foram submetidos às seguintes provas: fenotipagem dos leucócitos CD4+, CD8+, CD14+, PG68A+ e CD45+, fagocitose de Staphylococcus aureus e de Escherichia coli por células CD14+ e PG68A+, produção de ERO e marcação com Anexina-V e Iodeto de Propídeo (PI) por granulócitos e células mononucleares. A infecção pelo VAEC pode ser associada a um aumento de células CD14+ no leite, mas não no sangue. Os outros perfis celulares não sofreram alterações. Quanto a função fagocítica, o vírus reduziu a porcentagem de fagocitose de Staphylococcus aureus por granulócitos PG68A+ do leite. Esta alteração não ocorreu na fagocitose de Escherichia coli e na produção de ERO dessas células, nem na fagocitose e produção de ERO pelas células CD14+ ressaltando que nesses processos a espécie bacteriana pode sofrer interações com o vírus ou mesmo com a resposta imune do organismo infectado. O VAEC não influenciou significativamente os mecanismos de morte ora investigados, mas a tendência dos resultados sugere que possa haver indução de morte por apoptose e/ou por necrose nos granulócitos do sangue e influenciar no processo de necrose destas células no leite, sem alterar esses processos nas células mononucleares. Ressalta-se a importância da interação monócito-neutrófilo na glândula mamária, principalmente nos animais sororreagentes para AEC, mesmo na ausência de mastite bacteriana. / The caprine arthritis encephalitis (CAE) is a multisystem lentivirose that have the goat mammary gland as one target of the lesional disease. May cause a mammary specific expression, called indurative mastitis, beyond these organ represent a major route of virus elimination, even in animals that do not exhibit this clinical manifestation. Considering the possibility of this virus, whose target cell are predominantly monocyte, lead to immunological changes that influence the animal\'s susceptibility to other diseases, this study aimed to evaluate the interaction of virus and host immunity by phenotyping, phagocytosis and production of reactive oxygen species (ROS) and the mechanisms of cell death, in blood and milk of goats naturally infected. For that, 200 goats were screened and was selected eight females non sero-reagents and ten seroreagents for serum antibodies against CAE, with the haematological analises within the species standards and two negative bacteriological tests of milk. Milk and blood from these animals underwent the following tests: phenotyping of leukocytes CD4+, CD8+, CD14+, PG68A+ and CD45+, phagocytosis of Staphylococcus aureus and Escherichia coli ROS production by CD14+ and PG68A+ cells, and labeling with Annexin-V and propidium iodide (PI) for granulocytes and mononuclear cells. CAEV infection may be associated with an increase in CD14+ cells in milk, but not in blood. The other cellular profile did not change. In the phagocytic function, the virus reduced the percentage of phagocytosis of Staphylococcus aureus by granulocytes PG68A+ milk. This change did not occur in the phagocytosis of Escherichia coli and production of ROS in these cells, nor in phagocytosis and ROS production by CD14+ cells, noting that in those cases the bacterial species may undergo interactions with the virus or even with the immune response of the infected organism. The VAEC not significantly affect the mechanism of death now investigated, but the tendency of the results suggests that can induce apoptosis and/or necrosis in the blood granulocytes and influence the process of necrosis of these cells in milk, without changing these processes mononuclear cells. We emphasize the importance of monocyte-neutrophil interaction in the mammary gland, especially in animals seropositive for CAE, even in the absence of bacterial mastitis.

Estudou-se a freqüência da ocorrência de anticorpos antivírus da Artrite-encefalite dos Caprinos, em caprinos de 14 plantéis localizados no Estado de São Paulo, por um período de 2 anos, utilizando-se a técnica de imunodifusão em gel de ágar. A prevalência obtida foi de 26,3%, sendo significativamente maior nos caprinos mantidos em regime intensivo (31,8% - 733/2303) de criação do que no sistema semi-extensivo (13,1% - 128- 977). A infecção pelo vírus da Artrite-encefalite dos Caprinos aumentou gradativa e significativamente após os 6 meses de idade, havendo predominância da infecção nos caprinos mais velhos. Não se detectou influência de fatores sexuais sobre a prevalência da enfermidade determinada em caprinos do sexo feminino (27,9% - 663/2375) e masculino (32,3% - 94/291). A prevalência da doença foi significativamente maior nos caprinos das raças Anglo Nubiana (63,8% - 88/138) e Toggenbourg (56,0% - 28/50) do que nas demais raças estudadas: Saanen (27,4% - 673/2458), Alpina (11,9% - 59/497), Bôer (5,9% - 2/34) e caprinos mestiços (10,7% - 11/103). Paralelamente realizou-se estudo clínico dos animais infectados pelo vírus da Artrite-encefalite dos Caprinos, quando pudemos demonstrar que 17,1% (64/374) dos caprinos sororeagentes apresentavam a forma clínica articular da enfermidade e que 6,6% (17/249) das cabras sororeagentes apresentavam a forma mamária. A possibilidade de transmissão vertical transplacentária foi menor do que 3,8%. Verificou-se ser pequena a possibilidade dos cabritos se infectarem pelo colostro de cabras sororeagentes positivas, mas podem se infectar pelo leite oriundos dessas cabras infectadas (18,8% - 3/16). O tempo de duração dos anticorpos séricos adquiridos passivamente pelo colostro variou de 60 a 120 dias. Demonstrou-se, indiretamente, a presença e a viabilidade do vírus no sangue circulante, colostro e leite de caprinos infectados, bem como a possibilidadede infectar animais susceptíveis por inoculação, sendo o período de incubação de 45 a 60 dias. Não se demonstrou diferenças significativas dos teores séricos de proteína total, gamaglobulina e da atividade enzimática da glutamiltransferase - &gamma;GT em cabritos que receberam colostro de cabras infectadas ou não infectadas pelo mencionado vírus. / The frequency of occurrence of antibodies anti-caprine arthritis-encephalitis virus was studied in 14 herds in the State of São Paulo, during 2 years, using agar gel immunodiffusion. Prevalence was equal to 26.3%, and was significantly higher in animals kept under an intensive management scheme (31.8% - 733/2303), than in animals kept under a semi-extensive one (13.1% - 128- 977). Infection by the caprine arthritis-encephalitis virus increased gradual and significantly after 6 months of age. Infection was predominant in older animals. There was no gender influence on the prevalence of the disease, both in females (27.9% - 663/2375) and males (32.3% - 94/291). In relation to breed, prevalence of the disease was significantly higher in Anglo-Nubian (63.8% - 88/138) and Toggenbourg animals (56.0% - 28/50), than in the rest of the breeds studied: Saanen (27.4% - 673/2458), Alpine (11.9% - 59/497), Boer (5.9% - 2/34) and mixed breed animals (10.7% - 11/103). A clinical study of the animals infected by caprine arthritis-encephalitis virus was also performed. It was observed that 17.1% (64/374) of seroreagents presented the articular form of the disease and that 6.6% (17/249) of the seroreagent females presented the mammary form of the disease. The possibility of vertical, transplacentary transmission was lower than 3.8%. It was observed that the probability of infection of kids by colostrum of infected females was low (18.8% - 3/16). Antibodies passively acquired by colostrum ingestion lasted from 60 to 120 days. The presence and viability of the virus circulating in blood, colostrum and milk of infected animals, as well as the possibility of infection of susceptible animals by inoculation was indirectly demonstrated. Incubation period ranged from 45 to 60 days. There was no significant difference in serum levels of total protein and gammaglobulin, and in enzymatic activity of glutamiltransferase - &gamma;GT in kids that received colostrum from infected and non-infected females.

O estudo da vocalização em animais de produção tem sido uma metodologia amplamente utilizada para avaliar as condições de bem-estar às quais os animais são submetidos. Diante disto, é importante tentar estabelecer novos métodos de identificação do quadro sanitário dos animais, na tentativa de melhorar a qualidade de vida dos mesmos. O presente trabalho tem, como objetivo principal, comparar as características acústicas presentes na vocalização de leitões com artrite e sadios durante a fase de maternidade. Algumas observações mais específicas também foram avaliadas envolvendo a variação da vocalização frente diferentes níveis de lesões proporcionadas pela artrite; a relação de parâmetros inerentes aos animais, tais como peso, idade, gênero e a influência da temperatura do ambiente na vocalização dos mesmos. O experimento foi desenvolvido na fase de maternidade em uma granja comercial de suínos. Durante o processo de aquisição de dados foram utilizados 123 leitões com idades entre 5 e 21 dias de vida; dentre estes, 60 eram animais artríticos e 63 sadios. Todos os animais selecionados foram submetidos a uma análise clínica prévia e a um processo de apreensão manual capaz de estimular a emissão de vocalização. Um microfone digital diretivo foi utilizado para realizar o registro dos sons emitidos por animais diagnosticados positivos bem como o dos negativos. A medida da temperatura ambiental foi feito por um dattalogger posicionado no centro geométrico do galpão. Os níveis de lesões nos animais com artrite foram analisados clinicamente e separados em lesões leves, moderadas e intensas. As chamadas foram editadas pelo software Audacity® versão 1.3 Beta e analisadas pelo software PRAAT®, capaz de fornecer os parâmetros envolvidos no espectro sonoro dos sinais, tais como a duração (s), frequência fundamental (Hz), intensidade sonora (dB) e quatro níveis de formantes (Hz). Os dados foram submetidos à analise de variância (GLM) e teste de significância entre as médias (Tukey). A partir destas medidas do sinal sonoro foi possível verificar que as vocalizações emitidas por leitões com artrite diferiram das vocalizações emitidas por leitões sadios em fase de maternidade, principalmente pelos menores valores médios encontrados na duração das chamadas, intensidade sonora, primeira e segunda formantes presentes na vocalização de animais com artrite. Os resultados relacionados aos níveis de lesão revelaram que os valores médios da intensidade sonora, frequência fundamental, primeira e segunda formantes diminuiram à medida que o nível de lesão aumentou. Para os animais sadios envolvidos no estudo, encontraram-se diferenças significativas em muitas variáveis acústicas presentes na vocalização de animais apresentando diferentes idades, pesos (Kg), gênero e condições fisiológicas em função da temperatura do ar. / The vocalizations study in farm animals has been a methodology used to assess the conditions of welfare which animals are subjected. In front of this, it is important to try to establish new methods to identifying the health situation of animals in an attempt to improve the quality of life for them. The purpose of this study was to analyze the acoustic features of vocalizations piglets vocalization in two different conditions: arthritis and healthy animals during farrowing house. Some specific comments were also evaluated involving calls variation in front of different levels of injuries provided by arthritis; the relation of animals parameters such as weight, age, sex and the influence of environmental temperature. The experiment was conducted in farrowing stage in a commercial farm pigs. During the process of data acquisition, 123 piglets aged between 5 and 21 days of life were used. Sixty were with arthritis and 63 were healthy. All animals selected were submitted to a previous clinical examination and handled to stimulate the emission of vocalization. A steering digital microphone was used for recording the sounds. Measures of ambient temperature were done by a dattalogger positioned at the geometric center of the shed. The levels of lesions in animals with arthritis were clinically analyzed and separated into light, moderate and intense injuries. After sound record, they were quantified as body weight, sex and age. Calls were issued by Audacity® software version 1.3 Beta and analyzed by software PRAAT®, which can provide parameters involved in the sound spectrum of the signals, such as duration (s), fundamental frequency (Hz), loudness (dB) four levels of formants (Hz). The data were submitted to analysis of variance (GLM) and test of significance between means (Tukey). From these measures sound signal was also observed that the vocalizations emitted by piglets differed from arthritis vocalizations emitted by healthy piglets being motherhood, especially by low values found in the average call duration, loudness, first and second formants present in vocalization of animals with arthritis. The results related to the level of injury revealed that the mean values of sound intensity, fundamental frequency, first and second formants were reduced as the level of injury increased. For healthy animals in the study, we found significant differences in many variables present in the acoustic vocalizations of animals with different ages, weights (kg), gender and physiological conditions as a function of air temperature.

Apesar do recente conhecimento do papel anti-inflamatório e anti-nociceptivo do H2S na artrite induzida por carragenina (CGN) em rato, os mecanismos envolvidos ainda não são conhecidos. Tampouco se sabe se compostos híbridos antiinflamatórios não esteroides (AINEs) doadores de H2S possuem vantagens farmacológicas adicionais quando comparados aos doadores de H2S clássicos. Apesar de H2S exercer um efeito anti-nociceptivo em modelos de inflamação e dor aguda, pouco se sabe sobre o papel deste gás na dor crônica. Neste estudo investigou-se os mecanismos do H2S no modelo de sinovite e participação desse gás na dor crônica. Verificou-se que os canais de K+ATP, canais de Ca2+ tipo L ou receptores TRPV1 não estão envolvidos no mecanismo protetor do H2S na sinovite, diminuição da IL-1b e aumento da IL-10 e não houve diferença em relação a participação das enzimas oxidantes GPx e GR. Ainda, o tratamento agudo com o doador de H2S não reverteu o desconforto do teste do Rota Rod e alodinia térmica. / Despite recent knowledge of the anti-inflammatory and anti-nociceptive role of H2S in the carrageenin-induced arthritis (CGN) in rats, the mechanisms involved are not yet known. Nor is it known whether hybrid compounds antiinflammatory drugs (NSAIDs) H2S donors have additional pharmacological advantages when compared to classical H2S donors. Although H2S exert an anti-nociceptive effect in models of inflammation and acute pain, little is known about the role of this gas in chronic pain . In this study we investigated the protective mechanisms of H2S in the model of synovitis and chronic pain . It was found that the K+ATP channel, L type Ca2+ channel or TRPV1 receptors are not involved in the protective mechanism of H2S in synovitis , decreased IL-1b and increased IL-10 and there was no difference in the participation of oxidant enzymes GPx and GR . Still, the acute treatment with H2S donor did not reverse the discomfort of the Rota Rod test and thermal allodynia.