Submitted by JÚLIO HEBER SILVA (julioheber@yahoo.com.br) on 2017-05-26T19:06:37Z No. of bitstreams: 2 Tese - Eduardo Sugizaki - 2011.pdf: 1614665 bytes, checksum: c1512eaa0135859f4c7c6fa48dfb2d02 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2017-05-30T10:20:42Z (GMT) No. of bitstreams: 2 Tese - Eduardo Sugizaki - 2011.pdf: 1614665 bytes, checksum: c1512eaa0135859f4c7c6fa48dfb2d02 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2017-05-30T10:20:42Z (GMT). No. of bitstreams: 2 Tese - Eduardo Sugizaki - 2011.pdf: 1614665 bytes, checksum: c1512eaa0135859f4c7c6fa48dfb2d02 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2011-12-05 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / This doctoral thesis is a historical and epistemological research of the clinical age of Carrion's disease (1842-1885) and of the early age of his bacteriologic study (1885-1913). That´s a disease born within a historical narrative about the medical effects of experimental inoculation that the medical student Daniel Alcides Carrión, was made to do in August 1885. According to the peruvian historical narrative about the origins and consequences of the medical experiment, the student was inoculated with the blood of a disease known as Peruvian wart, but developed and died, in October five, from the disease called Oroya fever. The experiment would then have shown that there are not two diseases, but only one, that which, since then, bears his name as a tribute to the heroic gesture of inoculation. According to current knowledge about the disease, it has two stages in its evolution or syndromes. A febrile phase, anemiante, acute and of high risk for the patient's life; another phase, which follows the first, is the development of a characteristic skin neoformation, with the form of papules blood, called Peruvian wart. The historiography of the disease, after 1940, suggests that this duality of pathological manifestation represented the clinical difficulty explaining the genesis and outcome of the experiment of Carrion. However, research of documents relevant to the experiment of 1885, made in the first chapter of our thesis, showed that the experiment was not aimed at overcoming the dichotomy of two diseases. The student already had an advanced understanding of the overall clinical progression of the disease, including its two stages. From our investigation, moreover, we conclude that the peruvian medicine considered demonstrated that the inoculation produced Oroya fever, but the peruvian medicine does not present anywhere the ways in which one can recognize the Oroya fever. Due to these problems was undertaken in the second chapter, the study of the period of foundation of Peruvian wart clinic (1842-1872) and came to the conclusion that at this time there already was a complete understanding of the evolution of disease, including its stages and forms of development. At this point in our investigation, the existence of the notion of Oroya fever has appeared as unnecessary for the clinical knowledge of the disease. Therefore, the third chapter of our thesis investigated the period from 1872 to 1885, a time when the notion of Oroya fever appears in medical literature. Our investigation has shown that the notion appeared in Peruvian medicine because it regarded the disease as being a strictly benign, afebrile rash. Consequently, the Peruvian nosological dualism appears as a result of its inability to explain the phenomena of the general economy’s commitment that anticipate the eruption of Peruvian wart. With this new understanding of the clinical description of disease, we retake, in the fourth chapter, what happened in the study of disease, after the experiment of Carrión. A review of medical literature of the period between 1885 and 1898 showed that the historical narrative of Lima on the 7 experiment of Carrion became a guiding discipline of all research on the disease of this new period. During one stage of that Peruvian research (1885-1898), required to remain still only clinic, the study of disease was a prisoner of its assumptions - it became necessary, to keep the interpretation of the experiment as true, to define the concept of Oroya fever. But the final solution was not reached because the effort of maintaining doctrinal assumptions was placed above the results of observation. This closed circle began to be broken with the discovery of Tamayo, in 1905, that part of what physicians called Oroya fever was the result of a very common complication of severe cases of Peruvian wart with paratyphoid bacilli. The fourth chapter is concerned, yet, to the period after the discovery of Tamayo, from 1905 to 1913, to know the fate of Oroya fever. This research shows that the Peruvian medicine did not give up of the traditional historical narrative about the Carrion’s experiment. After Tamayo’s explanation of the reasons of part of what is called Oroya fever, the Peruvian medicine refused to give up of the use of this notion. Arce, the main Peruvian defender of the traditional historical narration about the disease, in 1913, meaning to seek the recovery of significance of Oroya fever that kept alive the dual polarity needed to remain true to the idea that, in 1885, has been demonstrated the unity between the two diseases. This doctoral thesis has obtained, thus, the construction of a new history of knowledge of Carrion’s disease, for the period 1842 to 1913. / Esta tese doutoral é uma investigação histórica e epistemológica da idade clínica da doença de Carrión (1842-1885) ao início da idade bacteriológica de seu estudo (1885-1913). Trata-se de uma doença nascida no interior de uma narrativa histórica médica sobre os efeitos da inoculação experimental que o estudante de medicina Daniel Alcides Carrión, se fez fazer em agosto de 1885. Segundo a narrativa médica limenha sobre o experimento, suas origens e suas consequências, o estudante inoculara-se com o sangue de uma doença conhecida como verruga peruana, mas desenvolveu e morreu, em cinco de outubro daquele mesmo ano, da doença chamada febre de Oroya. O experimento teria, assim, demonstrado que não há duas doenças, mas uma só que, desde então, leva seu nome, como homenagem ao gesto heroico da inoculação. Segundo o conhecimento atual sobre a doença, ela possui duas fases ou síndromes em sua evolução. Uma febril, anemiante, aguda e de alto risco para a vida do doente. Outra, que sucede a primeira, é o desenvolvimento de uma neoformação cutânea característica, com a forma de pápulas sanguíneas, chamada verruga peruana. A historiografia sobre a doença, posterior a 1940, sugere de que esta dualidade de manifestação patológica representou a dificuldade clínica que explica a gênese e o resultado do experimento de Carrión. Entretanto, a investigação dos documentos pertinentes ao experimento de 1885, feita no primeiro capítulo de nossa tese, mostrou que o experimento não visava a ultrapassar a dicotomia de duas doenças. O estudante já detinha uma compreensão clínica global avançada da evolução da doença, incluindo as suas duas etapas. Da nossa investigação, ademais, resultou que a medicina limenha deu por demonstrado que a inoculação produziu a febre de Oroya, mas ela não apresentou, em lugar algum, os modos pelos quais se pode reconhecer a febre de Oroya. Em função destes problemas, empreendeu-se, no capítulo segundo, o estudo do período de fundação da clínica da verruga peruana (1842 a 1872) e chegou-se à conclusão de que, nesta época, já havia uma compreensão global da evolução completa da doença, incluindo as suas etapas e formas de desenvolvimento. A esta altura da nossa investigação, a existência da noção de febre de Oroya já aparecia como desnecessária para o conhecimento clínico da doença. Por isso, o capítulo terceiro de nossa tese investigou o período de 1872 a 1885, época em que a noção de febre de Oroya aparece na literatura médica. Nossa investigação mostrou que a noção surgiu na medicina limenha porque esta concebia a doença como sendo estritamente uma erupção cutânea, apirética e benigna. Consequentemente, o dualismo nosológico peruano aparece como resultado da sua incapacidade de explicar os fenômenos de comprometimento geral da economia que antecipam a erupção da verruga peruana. Com essa nova compreensão da descrição clínica da doença, retoma-se, no quarto capítulo, o que aconteceu, no estudo da doença, depois do experimento de Carrión. A análise da literatura médica do período de 1885 a 1898, aí realizada, mostrou que a narrativa 5 histórica limenha sobre o experimento de Carrión tornou-se uma disciplina ordenadora de toda pesquisa sobre a doença deste novo período. Durante uma etapa da pesquisa (1885-1898), obrigada a ainda permanecer apenas clínica, o estudo da doença esteve prisioneiro de seus pressupostos. Tornou-se necessário, para manter como verdadeira a interpretação do experimento, definir o conceito de febre de Oroya. Mas não se chegava à solução definitiva porque o esforço de manutenção dos pressupostos doutrinários era colocado acima dos resultados da observação. Este círculo fechado começou a ser quebrado com a descoberta de Tamayo, em 1905, de que parte daquilo que os clínicos chamavam de febre de Oroya era resultado de uma complicação muito frequente dos casos graves de verruga peruana por bacilos paratifoides. O capítulo quarto ocupa-se, ainda, do período posterior à descoberta de Tamayo, de 1905 a 1913, para conhecer o destino da febre de Oroya. Desta investigação resulta que a medicina peruana não abriu mão da narrativa histórica tradicional do experimento de Carrión. Depois que Tamayo deu a explicação das razões de parte daquilo a que se chamara de febre de Oroya, a medicina peruana não aceitou desistir do uso desta noção. Arce, o principal defensor da narração histórica tradicional sobre a doença, em 1913, procurou recuperar uma significação para a febre de Oroya que mantivesse viva a polaridade dualista necessária para que permanecesse verdadeira a ideia de que, em 1885, foi demonstrada a unidade entre duas doenças. A presente tese doutoral obteve, assim, a construção de uma nova história do conhecimento da doença de Carrión, relativa ao período de 1842 a 1913.

Bacillary angiomatosis (BA), one of the clinical manifestations resulting from infection with the facultative intracellular bacterium Bartonella henselae, is characterized by angiogenic lesions. Endothelial cells have been identified as host cells for this pathogen and are presumed important for pathogenesis as lesions contain bacteria in direct contact with the endothelium. Lesions also contain infiltrating macrophages, which contribute to the angiogenic process during B. henselae infection by secreting vascular endothelial growth factor (VEGF). While virulence factors have been characterized, and the role for macrophages in B. henselae infection has been established, endothelial cell mediators of angiogenesis have not been well defined. We investigated three potentially important pathways that are triggered by the bacterial interactions with endothelial cells. We examined the ability of endothelial cells to upregulate the chemokines monocyte-macrophage chemoattracta nt protein-1 (MCP-1) and CXCL8 and the mechanism by which B. henselae secreted proteins (BHSP) induce endothelial cell proliferation. We determined that MCP-1 production is upregulated in response to B. henselae infection, which very likely contributes to angiogenic lesion formation by recruiting the VEGF-secreting macrophage. The chemokine CXCL8 is an important mediator of angiogenesis which can cause endothelial cell survival, proliferation, and capillary tube formation. We determined that CXCL8 is secreted from B. henselae-infected cells and contributes to B. henselae-induced angiogenesis in an autocrine manner. We also investigated the role of Ca2+ signaling during B. henselae infection. We determined that BHSP induce a robust intracellular Ca2+ response in HUVEC which originates from intracellular Ca2+ pools. Additionally, endothelial cell proliferation in response to BHSP required Ca2+ activity, indicating a role for intracellular Ca2+ pools during B. henselae-induced angio genesis. Endothelial cell proliferation during B. henselae infection possibly indicates a mechanism by which a pathogen induces proliferation of its host cell in order to propagate its own survival. Numerous factors culminate in the vascular lesions that are characteristic of BA. B. henselae infection represents an important and unique model for pathogen-triggered angiogenesis, and studies into the specific mechanisms of this process may elucidate host cell-pathogen interactions as well as pathways of pathogenic angiogenesis.

Submitted by Renan Bressianini do Amaral null (renan.amaral@yahoo.com.br) on 2018-03-22T10:21:41Z No. of bitstreams: 1 Dissertação_Renan_Bressianini_do_Amaral.pdf: 3486446 bytes, checksum: e5ed9f21e12655ff3bf5b939acdfd4c6 (MD5) / Approved for entry into archive by Alexandra Maria Donadon Lusser Segali null (alexmar@fcav.unesp.br) on 2018-03-22T10:58:45Z (GMT) No. of bitstreams: 1 amaral_rb_me_jabo.pdf: 3486446 bytes, checksum: e5ed9f21e12655ff3bf5b939acdfd4c6 (MD5) / Made available in DSpace on 2018-03-22T10:58:45Z (GMT). No. of bitstreams: 1 amaral_rb_me_jabo.pdf: 3486446 bytes, checksum: e5ed9f21e12655ff3bf5b939acdfd4c6 (MD5) Previous issue date: 2018-02-21 / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Dentre os ectoparasitas encontrados em morcegos, destacam-se as mocas Streblidae e ácaros Macronyssidae e e Spinturnicidae. A família Streblidae compreende um grupo monofilético de dípteros hematófagos Hippoboscoidea que parasitam morcegos. Enquanto ácaros da família Spinturnicidae são ectoparasitas exclusivos de quirópteros, aqueles da família Macronyssidae também parasitam outras espécies de mamíferos. Embora a ocorrência de Bartonella spp. tenha sido relatada em morcegos amostrados na Europa, África, Ásia e América Central e do Sul, poucos são os estudos acerca da ocorrência e diversidade genética de Bartonella spp. em moscas Hippoboscoidea e ácaros parasitas de quirópteros. O presente trabalho teve como objetivo investigar a ocorrência e traçar inferências filogenéticas de Bartonella spp. em moscas Streblidae e ácaros de Spinturnicidae e Macronyssidae parasitas de morcegos no Brasil. Entre maio de 2011 a abril de 2012 e setembro de 2013 a dezembro de 2014, 404 moscas de Streblidae, 100 Macronyssidaes e 100 ácaros de Spinturnicidae foram coletadas de duas localidades no município de Nova Iguaçu, estado do Rio de Janeiro, no sudeste do Brasil. Todos os 20 pools de ácaros e 202 (50%) mostraram-se positivos na PCR para o gene endógeno cox-1 de invertebrados. Quarenta (19,8%) de 202 moscas Streblidae foram positivas para Bartonella spp. em ensaios de qPCR baseados no gene nuoG. : 6/32 (18%) Paratrichobius longicrus, 7/24 (29%) Strebla guajiro, 2/5 (40%) Aspidoptera phyllostomatis, 5/43 (11%) Aspidoptera falcata, 1/10 (10%) Trichobius anducei, 1/4 (25%) Megistopoda aranea e 18/55 (32%) Trichobius joblingi, coletados das seguintes espécies: Artibeus lituratus, Carollia perspicillata, Artibeus planirostris, Sturnira lilium, Artibeus obscurus. Foram obtidas seis sequências para Bartonella (nuoG [n = 2], gltA [n = 2], rpoB [n = 1], ribC [= 1]). Nenhum dos ácaros Macronyssidae e Spinturnicidae amostrados mostrou-se positivo para Bartonella spp. As análises filogenéticas das sequências, suportadas pela baixa identidade pelo BLAST, sugerem a circulação de mais de um genótipo/espécie de Bartonella em moscas da família Streblidae no Rio de Janeiro, Brasil, os quais mostraram-se filogeneticamente próximos àqueles previamente detectados em morcegos e roedores na América, e em ruminantes na Europa. Tal fato evidenciando um possível intercâmbio de espécies de Bartonella entre hospedeiros vertebrados pertencentes às ordens Chiroptera, Rodentia e Artiodactyla. / Among the ectoparasites found in bats, stand out Streblidae flies and Macronyssidae and Spinturnicidae mites. The Streblidae family comprises a monophyletic group of Hippoboscoidea hematophagous dipterans that parasitize bats. While mites of the Spinturnicidae family are ectoparasites unique to chiropterans, those of the Macronyssidae family also parasitize other species of mammals. Although the occurrence of Bartonella spp. has been reported in bats sampled in Europe, Africa, Asia and Central and South America, there are few studies on the occurrence and genetic diversity of Bartonella spp. in Hippoboscoidea flies and mites parasites of bats. This study aimed to investigate the occurrence and perform phylogenetic inferences of Bartonella spp. in Streblidae flies and Spinturnicidae and Macronyssidae mites parasites of bats in Brazil. Between May 2011 to April 2012 and September 2013 to December 2014, 404 Streblidae flies, 100 Macronyssidae and 100 Spinturnicidae mites were collected from two locations in the district of Nova Iguaçu, state of Rio de Janeiro, in southeastern Brazil. All 20 mite pools and 202 (50%) Streblidae flies showed to be positive in PCR assays targeting cox-1 gene. Forty (19.8%) of 202 Streblidae flies were positive for Bartonella spp. in qPCR assays based on the nuoG gene: Paratrichobius longicrus, 7/24 (29%) Strebla guajiro, 2/5 (40%) Aspidoptera phyllostomatis, 5/43 (11%) Aspidoptera falcata, 1/10 (10%) Trichobius anducei, 1/4 (25%) Megistopoda aranea and 18/55 (32%) Trichobius joblingi, collected from the following species: Artibeus lituratus, Carollia perspicillata, Artibeus planirostris, Sturnira lilium, Artibeus obscurus. Six Bartonella sequences were obtained (nuoG [n=2], gltA [n=2], rpoB [n=1], ribC [n=1]). None of the sampled Macronyssidae and Spinturnicidae mites were positive for Bartonella spp. Phylogenetic analyzes of the sequences, supported by low BLAST identity, suggest the circulation of more than one Bartonella genotype/species in family Streblidae flies in Rio de Janeiro, Brazil, which were shown to be phylogenetically close to those previously detected in bats and rodents in America, and in ruminants in Europe. This fact evidences a possible interchange of Bartonella species among vertebrate hosts belonging to the orders Chiroptera, Rodentia and Artiodactyla. / 2016/12574-0

Tick-borne diseases are caused by a group of pathogenic microorganisms which are transmitted between animal and human population by vector which is most frequently tick. Evaluation of danger and perils of these diseases is important due to prevention and monitoring of current situation development. The most common tick-borne diseases in the Czech Republic are borreliosis, tick-borne encephalitis and ehrlichiosis. Rarely can we encounter bartonellosis, babesiosis, rickettsiosis and tularemia. All these diseases can have serious consequences and in critical cases they can result in death of the infected person. One of the basic and the most important of preventive measures which lower the risk of the infection by any tick-borne disease is prevention of tick encounter and eventually vaccination. Due to continual global warming we can expect that in near future ticks will spread even to locations which have been so far not suitable for their development. We can expect that we will even more frequently encounter tick-borne diseases - including diseases which were formerly not found in our territory or were very rare. As a part of health education it will be needed more to get known basic information of tick-borne diseases and their prevention. Different educational centres are an ideal place for...