Made available in DSpace on 2014-06-11T19:27:22Z (GMT). No. of bitstreams: 0 Previous issue date: 2007-05-28Bitstream added on 2014-06-13T19:35:18Z : No. of bitstreams: 1 rangel_pm_me_jabo.pdf: 202160 bytes, checksum: 7b5c8c75d2c9df10071428271f91da55 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / A um longo tempo a mastite tem sido reconhecida como a doença que provoca as maiores perdas econômicas nos rebanhos leiteiros. De fevereiro a novembro de 2004, 670 amostras de leite mastítico bovino, provenientes de dois estados brasileiros foram coletadas, das quais foram isoladas 231 cepas de Escherichia coli. Estas cepas foram analisadas para a detecção dos genes de produção de Shiga toxina (stx 1 e stx 2) e do gene da intimina (eae). Vinte cepas (8,6%) foram detectadas através de PCR contendo os genes da Shiga toxina (8 stx 1, 12 stx 2 e nenhuma delas ambos os genes). Duas cepas (0,8%) de E. coli eram eae positivo não produtoras de Shiga toxina. As cepas de E. coli foram também examinadas para detectar a resistência a 12 agentes antimicrobianos. As resistências mais comuns foram para tetraciclina (92,2%), estreptomicina (90,4%), ácido nalidíxico (88,3%), amicacina (86,5%) e cefalotina (84,8%). A resistência a múltiplas drogas foi encontrada em 152 cepas (65,8%). . Entre os sorogrupos determinados, O111, O26, O158 e O125 foram os mais comuns, todos sorogrupos EPEC clássicos. / Mastitis has been recognized for some time as the most costly disease in dairy herds. From February to November 2004, 670 samples of bovine mastitic milk were collected from two Brazilian states, from which 231 Escherichia coli strains were isolated. These strains were screened for the presence of Shiga toxin-producing (stx 1 and stx 2) and intimin (eae) genes. Twenty (8.6%) strains were detected by PCR to harbor the Shiga toxin genes (8 the stx 1 gene, 12 the stx 2 gene and none both of them) Two (0.8%) of the E. coli strains studied were eae positive non Shiga toxin-producing. The E coli strains were also examined for resistance to 12 antimicrobial agents. The most commonly observed resistance was to tetracycline (92.2%), streptomycin (90.4%), nalidixic acid (88.3%), amikacin (86.5%) and cephalothin (84.8%). Multidrug resistance was found among 152 isolates (65.8%). Among the serogroups determined O111, O26, O158 and O125 were the most commonly, all of them classic EPEC serogroups.

Orientador: José Moacir Marin / Banca: Alessandra Aparecida Medeiros / Banca: Maria de Fátima Martins / Resumo: A um longo tempo a mastite tem sido reconhecida como a doença que provoca as maiores perdas econômicas nos rebanhos leiteiros. De fevereiro a novembro de 2004, 670 amostras de leite mastítico bovino, provenientes de dois estados brasileiros foram coletadas, das quais foram isoladas 231 cepas de Escherichia coli. Estas cepas foram analisadas para a detecção dos genes de produção de Shiga toxina (stx 1 e stx 2) e do gene da intimina (eae). Vinte cepas (8,6%) foram detectadas através de PCR contendo os genes da Shiga toxina (8 stx 1, 12 stx 2 e nenhuma delas ambos os genes). Duas cepas (0,8%) de E. coli eram eae positivo não produtoras de Shiga toxina. As cepas de E. coli foram também examinadas para detectar a resistência a 12 agentes antimicrobianos. As resistências mais comuns foram para tetraciclina (92,2%), estreptomicina (90,4%), ácido nalidíxico (88,3%), amicacina (86,5%) e cefalotina (84,8%). A resistência a múltiplas drogas foi encontrada em 152 cepas (65,8%). . Entre os sorogrupos determinados, O111, O26, O158 e O125 foram os mais comuns, todos sorogrupos EPEC clássicos. / Abstract: Mastitis has been recognized for some time as the most costly disease in dairy herds. From February to November 2004, 670 samples of bovine mastitic milk were collected from two Brazilian states, from which 231 Escherichia coli strains were isolated. These strains were screened for the presence of Shiga toxin-producing (stx 1 and stx 2) and intimin (eae) genes. Twenty (8.6%) strains were detected by PCR to harbor the Shiga toxin genes (8 the stx 1 gene, 12 the stx 2 gene and none both of them) Two (0.8%) of the E. coli strains studied were eae positive non Shiga toxin-producing. The E coli strains were also examined for resistance to 12 antimicrobial agents. The most commonly observed resistance was to tetracycline (92.2%), streptomycin (90.4%), nalidixic acid (88.3%), amikacin (86.5%) and cephalothin (84.8%). Multidrug resistance was found among 152 isolates (65.8%). Among the serogroups determined O111, O26, O158 and O125 were the most commonly, all of them classic EPEC serogroups. / Mestre

Orientador: José Moacir Marin / Banca: Everlon Cid Rigobelo / Banca: Maria Cristina Monteiro de Souza-Gugelmin / Resumo: O objetivo deste estudo foi investigar a ocorrência de cepas de Escherichia coli produtoras de Shiga toxina (STEC) em queijos mussarela produzidos artesanalmente. Foram analisadas 59 amostras de queijo, produzidas no Vale do Jequitinhonha (Nordeste de Minas Gerais, Brasil). Isolando-se 147 cepas de E. coli e através da técnica de PCR, foram investigadas a presença dos genes da Shiga toxina (stx 1 e stx 2) e da intimina (eae). Dezesseis cepas bacterianas (10,8%) apresentaram o gene stx ( todas portavam o gene stx 1) e 13 delas também se mostraram eae positivas. Os isolados de E. coli foram também examinados para a detecção dos genes codificadores de adesinas (pap, sfa e afa). Não foram identificados nenhum desses genes.Todas as cepas STEC isoladas foram pesquisadas para resistência a 12 agentes antimicrobianos. As resistências predominantes detectadas foram de 37,5% para estreptomicina, 37,5% para a tetraciclina, 31,2% para a ampicilina e 31,2% para a amicacina. A resistência a múltiplas drogas foi encontrada em 5 cepas (31,2%). A presença dos genes codificadores dos fatores de virulência indica que o queijo mussarela produzido artesanalmente pode representar um risco à saúde dos consumidores. / Abstract: The aim of the present study was to investigate the occurrence of Escherichia coli strains presenting the Shiga toxin gene (probably STEC strains) in mussarela cheese produced by artesanal method in the Jequitinhonha Valey (Northeast of Minas Gerais State, Brazil). Fifty-nine cheese samples were analyzed and a hundred forty seven strains of E. coli were isolated. Using the PCR method the strains were screened for the Shiga toxin (stx 1 and stx 2) and the intimin (eae) genes. Sixteen isolates (10,8%) carried the stx gene (all of them showed the stx 1 gene ) and thirteen also presented the eae gene. Using the same method the strains were screened for the presence of pap, afa, and sfa genes, adhesin genes caracteristics of the E. coli extraintestinal pathogenic strains (ExPEC). None of them showed these adhesin genes and could not be classified as an ExPEC strains. The susceptibility of the probably STEC strains to twelve antimicrobial drugs were evaluated. The most important resistance was detected to the streptomycin (37,5%), tetracycline (37,5%), ampicillin (31,2%) and amikacin (31,2%). The multidrug resistance was detected in 5 isolates (31,2%). The presence of coding genes for virulence factors in the E. coli isolates recovered from mussarela cheese produced by artesanal method could represent a risk for the human health. / Mestre

Submitted by Renata Lopes (renatasil82@gmail.com) on 2016-06-01T13:56:25Z No. of bitstreams: 1 caiocesardesouzaalves.pdf: 1713151 bytes, checksum: fa162d2abe08bab5803054d440f9df69 (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2016-07-02T12:58:48Z (GMT) No. of bitstreams: 1 caiocesardesouzaalves.pdf: 1713151 bytes, checksum: fa162d2abe08bab5803054d440f9df69 (MD5) / Made available in DSpace on 2016-07-02T12:58:48Z (GMT). No. of bitstreams: 1 caiocesardesouzaalves.pdf: 1713151 bytes, checksum: fa162d2abe08bab5803054d440f9df69 (MD5) Previous issue date: 2012-08-28 / CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico / A mitoxantrona é um agente antineoplásico da família das antracenodionas, capaz de reduzir o número de células T, suprimir a imunidade humoral e in vivo ativar células T supressoras. A Esclerose Múltipla (EM) afeta mais de um milhão de pessoas em todo o mundo, caracterizando-se por ser uma doença inflamatória crônica desmielinizante do sistema nervoso central, de natureza auto-imune, sendo, na maioria dos casos, grave e incapacitante. Além disso, a terapêutica atual para a EM freqüentemente tem efeitos insatisfatórios, mostrando-se ainda ineficaz em relação à sua cura e total recuperação dos pacientes em fase avançada. A asma é uma doença inflamatória crônica das vias aéreas que afeta cerca de 300 milhões de pessoas em todo o mundo. Atualmente, os medicamentos disponíveis para o tratamento da asma apenas controlam da doença e apresentam efeitos colaterais sistêmicos que, em geral, são observados com a utilização de doses elevadas por tempo prolongado. Dentro deste contexto, este trabalho teve por objetivo avaliar o efeito de uma série de derivados antraquinônicos análogos da mitoxantrona na modulação da resposta in vitro de macrófagos murinos ativados com lipopolissacarídeo e IFN-g, e verificar a ação na modulação da resposta imune in vivo no modelo de encefalomielite autoimune experimental (EAE) e de alergia pulmonar (AP). Na etapa in vitro foi avaliada a citotoxicidade dos compostos e nos sobrenadantes da cultura foram quantificados os níveis de óxido nítrico. Na etapa in vivo foi investigado o uso do derivado O,O’-di-(3’-iodopropil)-1,4-dihidroxiantraquinona (CS56) na evolução da EAE induzida em camundongos C57Bl/6 através da aplicação do MOG35–55, e na modulação da AP e da exacerbação por vírus da AP, induzidas em camundongos BALB/c por inalação de alérgenos da poeira. Os resultados obtidos demonstraram que as modificações estruturais realizadas nos derivados antraquinônicos originaram análogos menos citotóxicos, com elevada capacidade de inibir a concentração de NO. Os dados obtidos in vivo indicam que o tratamento da EAE com o CS56 melhora o escore clínico da doença e isto pode ser correlacionado com uma redução na liberação de citocinas inflamatórias e quimiocinas envolvidas no aumento de células no sistema nervoso central. Os resultados obtidos do modelo de AP demonstram que o tratamento com CS56 melhora o quadro respirátorio dos camundongos através da redução dos parâmetros da alergia pulmonar, como hiperresponsividade brônquica, hipersecreção de muco e infiltração de eosinófilos. Desta forma, os dados sugerem um papel imunomodulatório do derivado na EAE e na AP com potencial aplicabilidade terapeutica para a asma e a esclerose múltipla. / Mitoxantrone is an antineoplasic agent of the anthracenedione family, capable of reduce T cell numbers, suppress humoral immunity and in vivo activate suppressor T cells. Multiple Sclerosis (MS) affects about one million people worldwide, is characterized by an autoimmune chronic inflammatory demyelinating disease of the central nervous system, and, in most cases, severe and disabling. Moreover, the current therapy for MS has often unsatisfactory effects, being still ineffective in relation to its healing and full recovery of patients in advanced stages. Asthma is a chronic inflammatory disease of the airways that affects approximately 300 million people worldwide. Currently, the treatment of asthma is intended to control the disease and the drugs used show systemic side effects that are generally observed with the use of high doses for long time. In this context, this study aimed to evaluate the effect of a series of anthraquinone derivatives, analogs of mitoxantrone, in the modulation of in vitro response of murine macrophages activated with lipopolysaccharide and IFN-g, and check the action in the modulation of the in vivo immune response of experimental autoimmune encephalomyelitis (EAE) and pulmonary allergy (PA). In the in vitro stage was evaluated the cytotoxicity of the compounds and the levels of nitric oxide produced. In the in vivo stage, the O,O’-bis-(3’-iodopropyl)-1,4-dihidroxyanthraquinone (CS56) derivative was investigated in the evolution of EAE induced in C57Bl/6 mice by applying MOG35-55, and in the modulation of PA and PA exacerbation by Rhinovirus, induced in BALB/c mice by inhalation of dust allergens. The results showed that the structural modifications performed on the anthraquinone derivatives produced less cytotoxic analogs with high ability to inhibit the NO concentration. The data obtained in vivo indicate that treatment of EAE with CS56 improves the clinical score of disease and this may be correlated with a reduction in the release of inflammatory cytokines and chemokines involved in the increase of cells in the central nervous system. The results of PA model demonstrate that treatment with CS56 improves respiratory mice by reducing the parameters of pulmonary allergy, such as bronchial hyperresponsiveness, mucus hypersecretion and infiltration of eosinophils. Thus, the data suggest an immunomodulatory role of the derivative in EAE and PA with potential therapeutic applicability for asthma and multiple sclerosis.

No description available.

Die Multiple Sklerose (MS) ist eine entzündliche Autoimmunerkrankung des Zentralnervensystems. Die klinisch und pathologisch heterogene Erkrankung wird im Tiermodell am besten durch eine experimentelle Autoimmunenzephalomyelitis (EAE) abgebildet. Entzündliche Läsionen einer EAE sind neben Lymphozyten durch Monozyten/ Makrophagen gekennzeichnet. Der in dieser Arbeit untersuchte Chemokinrezeptor CX3CR1 findet sich auf murinen Monozyten des Blutes und wird dort unterschiedlich hoch exprimiert. Im ZNS werden der Rezeptor auf Mikroglia und der Ligand Fraktalkin (CX3CL1) konstitutiv und somit entzündungsunabhängig auf Neuronen exprimiert. In verschiedenen Tiermodellen neurologischer Erkrankungen wurden unterschiedliche Auswirkungen dieser Interaktion beschrieben. Die vorliegende Studie untersucht die Fragestellung, ob sich in einem spontanen EAE-Modell CX3CR1-defiziente OSE-Mäuse von CX3CR1-kompetenten OSEMäusen hinsichtlich spontaner EAE-Inzidenz, Erkrankungsverlauf und Läsionspathologie unterscheiden. CX3CR1-defiziente OSE-Mäuse zeigen in diesem Modell eine erhöhte Inzidenz (54% vs. 32%), aber einen milderen Krankheitsverlauf gegenüber Rezeptor-Wildtypen. Dem milderen Krankheitsverlauf entsprechend weisen OSE CX3CR1-defiziente Mäuse histopathologisch in der akuten Phase kleinere demyelinisierte Läsionen der spinalen weißen Substanz und geringere meningeale spinale entzündliche Infiltrate auf mit einer signifikant geringeren Makrophageninfiltration in den Läsionen. In der spinalen grauen Substanz zeigen sie eine mildere neuronale Schädigung. In der chronischen Krankheitsphase findet sich eine reduzierte Infiltration von Entzündungszellen ohne signifikanten Unterschied zwischen OSE CX3CR1-defizienten Mäusen und Rezeptorwildtypen. Molekularbiologisch zeigen OSE CX3CR1-defiziente Mäuse eine verstärkte Expression von IL-17a in der akuten Krankheitsphase. Die erhöhte EAE-Inzidenz in CX3CR1-defizienten OSE-Mäusen ist am ehesten auf ein vermehrte Generierung von enzephalitogenen 2D2 T-Zellen im Darm in diesem spontanen EAE-Modell zurückzuführen. Der mildere Krankheitsverlauf bei CX3CR1- defizienten Mäusen weist auf eine Bedeutung von CX3CR1 in der Migration von Monozyten in das entzündete ZNS hin. Die vorliegende Arbeit ist die Grundlage für weiterführende Studien, in welchen die Bedeutung der Fraktalkin-CX3CR1-Interaktion für kortikale Pathologie bei der EAE untersucht werden wird.

No description available.

Th17 cells are pro-inflammatory cells that are characterized by the production of their signature cytokine, IL-17. Although they are thought to have arisen to protect against extracellular bacteria and fungi they have been shown to mediate autoimmune diseases such as EAE and psoarisis. Notch protein is a cell-surface receptor that has been widely conserved among species. It plays an essential role in determining multiple cell fates. More recently, it has been implicated in regulating peripheral CD4+ T-cell responses. In these studies, we report that blockade of Notch signaling significantly down-regulates the production of IL-17 and associated cytokines in both mouse and human in-vitro polarized Th17 cells, suggesting an intrinsic requirement for Notch during Th17 differentiation in both species. We also present evidence, using promoter reporter assays, knockdown studies as well as chromatin immunoprecipitation, that IL-17 and RORt are direct transcriptional targets of Notch signaling in Th17 cells, with Notch 1 being the responsible Notch family member important in regulating the differentiation of human Th17 cells. In-vivo inhibition of Notch signaling reduced IL-17 production and Th17 mediated disease progression in experimental autoimmune encephalomyelitis, a mouse model of multiple sclerosis. In addition, by using Notch1 and Notch3 knockout mice, we have shown that Notch 3 is the Notch family member that is essential for murine Th17 differentiation. We have also investigated noncanonical Notch signaling in Th17 cells by using CD4+ T-cells from CSL/RBP-Jk knockout mice. Based on data obtained, we have concluded that canonical Notch signaling is dispensable in Th17 responses. Thus, this study highlights the importance of different Notch family members in Th17 differentiation and indicates that selective targeted therapy against Notch may be an important tool to treat autoimmune disorders, including multiple sclerosis.

No description available.

No description available.