Made available in DSpace on 2014-03-29T02:01:33Z (GMT). No. of bitstreams: 1 000455917-Texto+Completo-0.pdf: 2015931 bytes, checksum: 9c232dbbf603a1ea4db4fc35a200c003 (MD5) Previous issue date: 2013 / INTRODUCTION: Studies have shown that LAIV is more effective than TIV for prevention of influenza infection in young children, but the underlying mechanisms associated with protection are still not well defined. OBJECTIVES: To assess differences in cellular immunity and gene expression profiles in children after immunization with LAIV or TIV. METHODS: Peripheral blood of previously healthy children was collected pre and postvaccination and analyzed for B cells measurement and antibodies production. Microarray analyses were applied to assess the gene expression profiles. RESULTS: LAIV vaccinees showed number of naïve, memory and transitional B cells increased on day 1 compared to baseline (p<0. 05). TIV vaccinees showed the number of plasmablasts increased on day 7 post-vaccination (p≤0. 01). In addition, the titers for the three strains of the vaccine (H1N1, H3N2 and B) were significantly elevated on the TIV group when compared with the LAIV group. Regarding the transcriptional profiles presented, both vaccines induced interferon signaling, but in different time points, TIV 1 day postvaccination and LAIV 7 days post-vaccination, the last only in children younger than 5 years old. CONCLUSIONS: These results indicate that LAIV and TIV induced different immune responses in peripheral blood of vaccinated children and that both vaccines induce interferon signaling post-vaccination. / INTRODUÇÃO: Estudos têm demonstrado que a vacina contra os vírus influenza LAIV é mais eficiente que a formulação TIV para a prevenção de infecção em crianças, porém os mecanismos envolvidos ainda não estão bem definidos. OBJETIVOS: Acessar as diferenças na imunidade celular humoral e de expressão de perfis gênicos em crianças imunizadas com LAIV ou TIV.MÉTODOS: Sangue periférico de crianças previamente hígidas foi coletado pré e pósvacinação e analisado para mensuração de células B e para titulação de anticorpos. Análise pela técnica de microarranjos foi empregada para avaliação dos perfis de expressão gênica. RESULTADOS: Vacinação com LAIV induziu aumento do número absoluto de células B naïve, de memória e transicionais no após 30 dias comparado aos valores medidos antes da vacinação (p<0. 05). Vacinação com TIV, no entanto, induziu aumento de plasmoblastos no dia 7 pós-vacinação (p<0. 01). Os títulos de anticorpos para os três antígenos da vacina (H1N1, H3N2 e B) encontraram-se significativamente elevados no grupo vacinado com TIV quando comparado ao grupo que recebeu LAIV. Ambos os grupos vacinados induziram sinalização de genes relacionados ao interferon, porém em diferentes momentos: TIV induziu-os 1 dia pós-vacinação, enquanto LAIV 7 dias pós-vacinação, especialmente em crianças com menos de cinco anos de idade. CONCLUSÕES: Esses resultados sugerem que as vacinas LAIV e TIV induzem resposta celular imune diferente em crianças e que ambas induzem sinalização de interferon pós-vacinação.

Patógenos associados a aves migratórias podem causar doenças em aves domésticas. As aves de subsistência são possíveis fontes de disseminação destes patógenos pela ausência de biossegurança na criação e pelo contato com aves silvestres. A região do Parque Nacional da Lagoa do Peixe (PNLP), no Rio Grande do Sul, se caracteriza como um importante sítio de aves migratórias. Devido a isto, é possível uma interface entre aves migratórias e aves de subsistência criadas na região. A influenza aviária (AI) é a principal doença associada a aves migratórias que afeta o sistema respiratório, sendo estas os principais disseminadores do vírus. Estudos prévios indicam que há risco de introdução de um vírus de AI de alta patogenicidade (HPAIV) na região. Porém, o padrão e impacto do espalhamento deste patógeno na região é desconhecido, visto a ausência de relatos. Cabe ressaltar que outras enfermidades respiratórias, como a Doença de Newcasle (ND) e a micoplasmose por Mycoplasma gallisepticum (MG), também são associadas a aves migratórias e podem causar doenças em aves domésticas. Neste contexto, o objetivo deste trabalho é realizar um inquérito epidemiológico de doenças respiratórias associadas a aves migratórias em aves de subsistência e propor um modelo de espalhamento de HPAIV na região do PNLP. Com esta finalidade, realizamos uma avaliação (i) da presença de anticorpos contra AI, ND e MG nas aves de subsistência por ELISA, (ii) da presença dos agentes de AI e ND por RT-PCR em tempo real nas aves de subsistência, (iii) dos possíveis fatores de risco associados aos patógenos e (iv) das consequências da introdução de HPAIV na região através de um modelo matemático de espalhamento. Nas propriedades de aves de subsistência amostradas da região, foi detectada a presença de anticorpos contra AI, ND e MG na frequência de 4,2%, 87,5% e 58,3%, respectivamente. Todas as amostras foram negativas no RT-PCR em tempo real realizado para AI e ND. A avaliação de fatores de risco foi possível nas propriedades soropositivas para ND e MG, possibilitando realizar-se a primeira análise de fatores de risco para estes agentes em aves de subsistência no Brasil. Para ND, o risco foi maior nas propriedades nas quais os criadores adotam a prática de reposição própria para manter a criação (PR=1,64; 95% IC: 1,11 – 2,42). Além disso, o aumento na distância das granjas em relação ao estuário da Laguna do Peixe diminui o risco para ND (PR=0,94; 95% IC: 0,90 – 0,99). Já para MG, foram considerados fatores de risco a prática de confinar as aves (PR = 3,40, 95% IC: 1,93 – 5,99) e a interação entre a “troca de aves ou ovos com outros produtores e vizinhos possuírem aves” (PR = 2,16, 95% IC: 1,24 – 3,76). Nas simulações da modelagem matemática de espalhamento de HPAIV na região, a maioria das propriedades se tornaria infectada até o 30º dia de infecção. Além disso, na média das simulações, a infecção atingiria em torno de 80 a 90% das propriedades, alcançando até 30 km de distância do caso índice. Os resultados indicam a circulação de patógenos associados a aves migratórias na região do PNLP. Devido à detecção destes nas aves de subsistência, estas podem ser consideradas sentinelas destes agentes na região. Além disso, os dados obtidos incrementam o conhecimento sobre o espalhamento e a dinâmica dessas doenças em propriedades com aves de subsistência, bem como sobre os indicadores de risco para ocorrência. Estes dados podem ser utilizados para o estabelecimento de medidas de biossegurança e de manejo adequados para este tipo de criação e de programas de monitoria visando à contenção da disseminação de patógenos. / Pathogens associated with migratory birds can cause disease in domestic birds. Backyard poultry are possible source of pathogens dissemination due to the lack of biosecurity measures and the contact with wild birds. The region of Lagoa do Peixe National Park (PNLP), in Rio Grande do Sul state, Brazil, is characterized as an important site for migratory birds. Thus, it is a possible interface place for migratory and backyard birds. Avian influenza (AI) is the most important respiratory disease associated with migratory birds, the main virus disseminating agents. Previous studies have indicated a risk for introduction of higly pathogenic avian influenza virus (HPAIV) in PNLP region. However, the impact and spreading pattern of AI virus in this region is unknown due to the lack of disease reports. It is noteworthy that other respiratory diseases, such Newcastle Disease (ND) and micoplasmosis due to Mycoplasma gallisepticum (MG), are also associated with migratory birds and can cause disturbances in domestic poultry. In this context, the aims of this work are to perform an epidemiological survey of respiratory diseases associated with migratory birds in backyard poultry and to propose a model of HPAIV spreading in PNLP region. For this, it was evaluated (i) the presence of antibodies against AI, ND and MG in backyard poultry by ELISA, (ii) the presence of AI and ND virus in backyard poultry by real time RT-PCR, (iii) the potential risk factors associated with these pathogens, and (iv) the consequences of HPAIV introduction in PNLP region using a mathematical model of virus spreading. In the sampled properties, frequency of antibodies against AI, ND and MG were 4.2%, 87.5% and 58.3%, respectively. All samples were negative for AI and ND in real time RT-PCR analysis. The first evaluation of risk factors associated to ND or MG in backyard poultry from Brazil was performed in this work. For ND, the risk was increased in the properties in which farmers used their own replacement poultry to restock their flock (PR=1.64; 95% CI: 1.11–2.42). Furthermore, the increasing distance of the household flock to the “Laguna do Peixe” estuary is associated with decreasing NDV seropositivity (PR=0.94; 95% CI: 0.90 – 0.99). For MG, seropositivity was significantly associated with bird confinement (PR = 3.40, 95% CI: 1.93 – 5.99) and with interaction between “poultry/egg exchange and neighbors have poultry” (PR = 2.16, 95% CI: 1.24 – 3.76). In the simulations from the mathematical model of HPAIV spreading in PNLP region, most of the properties of this region would become infected up to 30 days outbreak beginning. Moreover, the infection would affect about 80 to 90% of the properties from the region, reaching up to 30 km distance from the index case. The results showed the circulation of pathogens associated with migratory birds in PNLP region. Since these pathogens were detected in backyard poultry, these birds can be considered sentinels for these agents in this region. Additionally, the data obtained improve the knowledge on spreading and dynamics of these diseases in properties with backyard poultry, as well as on potential risk factors. The set of these results can be useful to development of adequate biosecurity procedures for backyard flocks and surveillance programs to avoid pathogen dissemination.

Les proprotéines convertases (PC) sont d’importantes enzymes impliquées dans l’activation par clivage de précurseurs protéiques dans la voie de sécrétion cellulaire et qui permettent la régulation de la physiologie animale. Toutefois, les PC ont un rôle particulier lors d’infections, puisqu’elles participent à la fois à l’activation de pathogènes et au contrôle de la réponse immunitaire qu’ils induisent. Cette thèse présente le développement d’un inhibiteur peptidique de PC à des fins thérapeutiques contre les pathogènes et se penche sur le rôle de PC1/3, une PC dite neuroendocrinienne, dans le contrôle de la réponse immunitaire au sein des macrophages. Dans un premier temps, l’inhibiteur de PC a été optimisé par peptidomimétique afin de bloquer l’activation de deux pathogènes activés par les PC, l’un viral et l’autre bactérien. Dans un second temps, l’utilisation de shRNA sur un modèle de macrophages en culture NR8383 et du modèle de souris où PC1/3 est inactivée ont permis de déterminer les conséquences physiologiques et moléculaires de l’inactivation de PC1/3 au sein des macrophages grâce au développement d’une approche par spectrométrie de masse. L’approche par spectrométrie de masse s’est avérée être un catalyseur dans cette recherche et a pu être appliquée à l’étude de tissus de patientes atteintes du cancer de l’ovaire, démontrant ainsi tous les avantages de cet outil. En somme, les résultats de cette thèse montrent la faisabilité d’inhiber les PC pour contrôler les infections et ouvrir de nouvelles perspectives sur le contrôle de l’immunité en établissant les bases moléculaires du rôle de PC1/3 dans le maintien de l’homéostasie immunitaire. / The proprotein convertases (PCs) are important enzymes mainly involved in the activation of protein precursors into the cell secretory pathway. This critical activation step that generates various biologically active polypeptides makes the PCs a cornerstone in a variety of biological process, including the neuroendocrine system. However, the PCs are described as very special players during infection, since they both activate various pathogens and control the immune response they induce. This thesis presents the development of a PCs peptide inhibitor for therapeutic purposes against pathogens and examines the role of PC1/3, which is mainly associated with the neuroendocrine system, in the control of the immune response in macrophages. As a first step, the PC inhibitor has been optimized by a peptidomimetic approach to block pathogens activation by PC for both a viral pathogen and a bacterial pathogen. In a second step, gene expression control tools have been used (shRNA) on a macrophage NR8383 cell line combined with the use of PC1/3 inactivated mouse (KO) to determine the physiological and molecular consequences of PC1/3 inactivation in macrophages by the mean of mass spectrometry approaches. The mass spectrometry approaches were proven to be a catalyst in this research and were further applied on ovarian cancer tissues studies, demonstrating the benefits of these tools. Overall, the results of this thesis demonstrate the feasibility of inhibiting PC to control infections and establish new avenues to modulate immunity by laying the foundations of PC1/3 molecular functions in the maintenance of immune homeostasis.

M.Tech. (Homoeopathy) / Influenza is a highly infectious illness caused by the influenza A or B viruses. Together with the high infectivity rates, relatively short incubation period and the genetic lability of the influenza virus, influenza can cause overwhelming epidemics and thus become extremely problematic to world public health (Bannister et al., 1996: 131-134). Influenza and influenza-like syndromes are responsible for one third of absenteeism in the workplace and it is due to this that prophylactic and curative measures have become necessary (papp et al., 1998: 69-76). In homoeopathyit is known that treatment of an epidemic with the genus epidemicus remedy should be effective in the majority of cases (Kent, 1979: 33-39). This remedy is carefully chosen on account of its similarity to the main presenting symptoms displayed in all cases of the respective year's influenza picture. The aim of this study . was to demonstrate the effectiveness of the genus epidemicus remedy indicated for the current year's influenza epidemic, namely Arsenicum album. It was administered in a 30CH potency. The efficacy of the genus epidemicus remedy in the treatment of influenza was assessed by investigating the intensity and duration of influenza symptoms over a specified period of time, this being four days, in a suitable sample group. The sample group was selected and obtained in a clinical setting. The sample group was randomly divided into an experimental group and a control group of fifteen participants respectively. Symptoms were monitored with the use of a questionnaire (Appendix C). Placebos were administered to the control group and Arsenicum album 30CH was administered to the experimental group. The medication was administered as a single dose of five pillules three times daily. The first dose of medication was administered in the clinician's office on commencement of the study and the following. six doses were to be taken three times daily, in the morning, at lunch and in the evening, by the participants themselves. Data was analysed by means of the Mann-Whitney statistical test. The experimental and control groups were analysed separately. Group A was determined to be the control group and Group B was determined to be the experimental group. Effectiveness ofArsenicum album 30CH in the treatment of influenza was defined as a statistically significant greater decrease in the symptom severity over time in the experimental group, Group B, as compared with the control group, Group A. From statistical evaluation it was determined that the homoeopathic remedy, Arsenicum album 30CH, was the indicated genus epidemicus remedy for the influenza epidemic of the winter of 2001. It was further determined that Arsenicum album 30CH was effective in reducing the severity of symptoms of influenza or influenza-like syndrome and was thus effective in the treatment of influenza and influenza-like syndrome.

Influenza viral infection causes several hospitalizations and claims the lives of many people each year. The threat of epidemic and pandemic are more pressing than ever with newly mutated strains developing every year. Understanding the mechanism of infection of influenza can help identify new potential drug targets and help progress the development of antivirals. Currently there are two classes of FDA approved drugs, neuraminidase inhibitors and M2 ion channel inhibitors, to combat influenza infection. Unfortunately, viral resistance to M2 ion channel blockers has caused them to stop being used for treatment. This paper focuses on understanding influenzas ability to mutate and it mechanism of infection to develop new M2 ion channel blockers.

Dissertation submitted in partial compliance with the requirements for the Masters Degree in Technology: Homoeopathy at Durban Institute of Technology, 2003. / The purpose of this double blind randomised study is to evaluate the efficacy of homoeopathic simillimum versus high doses of vitamin C in the treatment of Influenza Type Syndrome in terms of subjective symptoms assessed by the patient, and objective clinical signs assessed by the researcher / M

No description available.

In systems biology and genomics, epistasis characters the impact that a substitution at a particular location in a genome can have on a substitution at another location. This phenomenon is often implicated in the evolution of drug resistance or to explain why particular ‘disease-causing’ mutations do not have the same outcome in all in- dividuals. Hence, uncovering these mutations and their locations in a genome is a central question in biology. However, epistasis is notoriously difficult to uncover, es- pecially in fast-evolving organisms. Here, we present a novel statistical approach that takes inspiration from a model developed in ecology and that we adapt to analyze genetic data in a typically fast-evolving system: the influenza A virus. We validate the approach using experimentally-validated data: known interactions are recovered. We further evaluate the ability of our approach to detect epistasis during antigenic shifts or at the emergence of drug resistance. We show that in all cases, epistasis is prevalent in influenza A viruses, involving many pairs of sites linked together in chains, a hallmark of historical contingency. Strikingly, interacting sites are sepa- rated by large physical distances, which entail either long-range structural effects or functional tradeoffs, for which we find support with the emergence of drug resistance. Our work paves a new way for the unbiased detection of epistasis in a wide range of organisms by performing whole-genome scans.

Patógenos associados a aves migratórias podem causar doenças em aves domésticas. As aves de subsistência são possíveis fontes de disseminação destes patógenos pela ausência de biossegurança na criação e pelo contato com aves silvestres. A região do Parque Nacional da Lagoa do Peixe (PNLP), no Rio Grande do Sul, se caracteriza como um importante sítio de aves migratórias. Devido a isto, é possível uma interface entre aves migratórias e aves de subsistência criadas na região. A influenza aviária (AI) é a principal doença associada a aves migratórias que afeta o sistema respiratório, sendo estas os principais disseminadores do vírus. Estudos prévios indicam que há risco de introdução de um vírus de AI de alta patogenicidade (HPAIV) na região. Porém, o padrão e impacto do espalhamento deste patógeno na região é desconhecido, visto a ausência de relatos. Cabe ressaltar que outras enfermidades respiratórias, como a Doença de Newcasle (ND) e a micoplasmose por Mycoplasma gallisepticum (MG), também são associadas a aves migratórias e podem causar doenças em aves domésticas. Neste contexto, o objetivo deste trabalho é realizar um inquérito epidemiológico de doenças respiratórias associadas a aves migratórias em aves de subsistência e propor um modelo de espalhamento de HPAIV na região do PNLP. Com esta finalidade, realizamos uma avaliação (i) da presença de anticorpos contra AI, ND e MG nas aves de subsistência por ELISA, (ii) da presença dos agentes de AI e ND por RT-PCR em tempo real nas aves de subsistência, (iii) dos possíveis fatores de risco associados aos patógenos e (iv) das consequências da introdução de HPAIV na região através de um modelo matemático de espalhamento. Nas propriedades de aves de subsistência amostradas da região, foi detectada a presença de anticorpos contra AI, ND e MG na frequência de 4,2%, 87,5% e 58,3%, respectivamente. Todas as amostras foram negativas no RT-PCR em tempo real realizado para AI e ND. A avaliação de fatores de risco foi possível nas propriedades soropositivas para ND e MG, possibilitando realizar-se a primeira análise de fatores de risco para estes agentes em aves de subsistência no Brasil. Para ND, o risco foi maior nas propriedades nas quais os criadores adotam a prática de reposição própria para manter a criação (PR=1,64; 95% IC: 1,11 – 2,42). Além disso, o aumento na distância das granjas em relação ao estuário da Laguna do Peixe diminui o risco para ND (PR=0,94; 95% IC: 0,90 – 0,99). Já para MG, foram considerados fatores de risco a prática de confinar as aves (PR = 3,40, 95% IC: 1,93 – 5,99) e a interação entre a “troca de aves ou ovos com outros produtores e vizinhos possuírem aves” (PR = 2,16, 95% IC: 1,24 – 3,76). Nas simulações da modelagem matemática de espalhamento de HPAIV na região, a maioria das propriedades se tornaria infectada até o 30º dia de infecção. Além disso, na média das simulações, a infecção atingiria em torno de 80 a 90% das propriedades, alcançando até 30 km de distância do caso índice. Os resultados indicam a circulação de patógenos associados a aves migratórias na região do PNLP. Devido à detecção destes nas aves de subsistência, estas podem ser consideradas sentinelas destes agentes na região. Além disso, os dados obtidos incrementam o conhecimento sobre o espalhamento e a dinâmica dessas doenças em propriedades com aves de subsistência, bem como sobre os indicadores de risco para ocorrência. Estes dados podem ser utilizados para o estabelecimento de medidas de biossegurança e de manejo adequados para este tipo de criação e de programas de monitoria visando à contenção da disseminação de patógenos. / Pathogens associated with migratory birds can cause disease in domestic birds. Backyard poultry are possible source of pathogens dissemination due to the lack of biosecurity measures and the contact with wild birds. The region of Lagoa do Peixe National Park (PNLP), in Rio Grande do Sul state, Brazil, is characterized as an important site for migratory birds. Thus, it is a possible interface place for migratory and backyard birds. Avian influenza (AI) is the most important respiratory disease associated with migratory birds, the main virus disseminating agents. Previous studies have indicated a risk for introduction of higly pathogenic avian influenza virus (HPAIV) in PNLP region. However, the impact and spreading pattern of AI virus in this region is unknown due to the lack of disease reports. It is noteworthy that other respiratory diseases, such Newcastle Disease (ND) and micoplasmosis due to Mycoplasma gallisepticum (MG), are also associated with migratory birds and can cause disturbances in domestic poultry. In this context, the aims of this work are to perform an epidemiological survey of respiratory diseases associated with migratory birds in backyard poultry and to propose a model of HPAIV spreading in PNLP region. For this, it was evaluated (i) the presence of antibodies against AI, ND and MG in backyard poultry by ELISA, (ii) the presence of AI and ND virus in backyard poultry by real time RT-PCR, (iii) the potential risk factors associated with these pathogens, and (iv) the consequences of HPAIV introduction in PNLP region using a mathematical model of virus spreading. In the sampled properties, frequency of antibodies against AI, ND and MG were 4.2%, 87.5% and 58.3%, respectively. All samples were negative for AI and ND in real time RT-PCR analysis. The first evaluation of risk factors associated to ND or MG in backyard poultry from Brazil was performed in this work. For ND, the risk was increased in the properties in which farmers used their own replacement poultry to restock their flock (PR=1.64; 95% CI: 1.11–2.42). Furthermore, the increasing distance of the household flock to the “Laguna do Peixe” estuary is associated with decreasing NDV seropositivity (PR=0.94; 95% CI: 0.90 – 0.99). For MG, seropositivity was significantly associated with bird confinement (PR = 3.40, 95% CI: 1.93 – 5.99) and with interaction between “poultry/egg exchange and neighbors have poultry” (PR = 2.16, 95% CI: 1.24 – 3.76). In the simulations from the mathematical model of HPAIV spreading in PNLP region, most of the properties of this region would become infected up to 30 days outbreak beginning. Moreover, the infection would affect about 80 to 90% of the properties from the region, reaching up to 30 km distance from the index case. The results showed the circulation of pathogens associated with migratory birds in PNLP region. Since these pathogens were detected in backyard poultry, these birds can be considered sentinels for these agents in this region. Additionally, the data obtained improve the knowledge on spreading and dynamics of these diseases in properties with backyard poultry, as well as on potential risk factors. The set of these results can be useful to development of adequate biosecurity procedures for backyard flocks and surveillance programs to avoid pathogen dissemination.

Orientador: Maria Marluce dos Santos Vilela / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-07-19T08:26:02Z (GMT). No. of bitstreams: 1 Silva_MarcosTadeuNolascoda_M.pdf: 3136388 bytes, checksum: 55e005bb4732584ad379e5d556b31897 (MD5) Previous issue date: 1994 / Resumo: Foi avaliada a imunidade humoral para o Haemophilus influenzae do tipo b (Hib) em 68 crianças brasileiras saudáveis com idades entre 15 e 19 meses. Foram analisados os títulos naturais de anticorpos contra o polissacáride capsular do Hib (PRP) bem como os títulos estimulados por uma dose de 0,5 ml por via intramuscular da vacina conjugada do PRP com o toxóide diftérico (PRP-D) contendo 25ug de PRP e 18 ug de toxicóide diftérico por dose).Observação: O resumo, na íntegra, poderá ser visualizado no texto completo da tese digital / Abstract: Humoral immunity to Haemophilus influenzae type b HIB) was studied in 68 healthy Brazilian children between 15 and 19 month of age. Ehe evaluation was done by the measure, by radioiminoassay, of the levels of antibodies against the capsular polysaccharide of Hib (PRP). The children enrolled in the trial received one intramuscular dose of the conjugate vaccine of the capsular polysaccharide of HIB and diphtheria toxoid. Note: The complete abstract is available with the full electronic digital thesis or dissertations / Mestrado / Mestre em Pediatria