During the independence era in West Africa (1958–1980) many nations embarked on ambitious programmes aimed at rejuvenating their traditional art forms. These programmes were realised through new cultural policies, with music the prime target of the governments’ campaigns. I contend that in the search for an appropriate voice West African governments focussed on one group of musicians, the Mande griots. It was through their musical compositions that the State communicated ideology and doctrine to the public. I assert that to focus on a specific ethnic group and promote them as cultural ambassadors was a policy that conflicted with the core principles of West Africa’s governments, who upheld a doctrine that promoted nationalism over ethnocentrism. It was a neo-colonialist strategy designed to consolidate the rule of the governing party, a contention which I support through an analysis of the role of griots in West African society and an appraisal of the careers of musicians, musical recordings, and musical styles. This thesis represents a historical account of Mande griots in West Africa with respect to their influence on local and national politics. Part of the aim of this thesis is to create a comprehensive and accurate catalogue of West African musical recordings and groups, the results of which are located in the appendices.

Zugl.: Diss. Universität Basel, 1991. / Based on the author's thesis, Universitaet Basel, 1991. Originaltitel: Falsch gehandelt - schwer erkrankt. Includes bibliographical references (p. 313-325) and index.

Made available in DSpace on 2016-06-02T20:39:15Z (GMT). No. of bitstreams: 1 4621.pdf: 10468707 bytes, checksum: c38c3ca9cf60dac2e6bad351d4f51f79 (MD5) Previous issue date: 2012-06-11 / Financiadora de Estudos e Projetos / The study describes and analyzes sociologically, from a qualitative approach, the social representations of the people of the island of Formosa Bijagó about possible threats related to climate change, its consequences in terms of the form of territorial occupation and way of life characteristic of that group. For this, we adopted the following methodological procedures: a) A review of the state of the art about the concepts of vulnerability related to climate change, the increasing vulnerability, risk and social representations, b) documentary research and fieldwork. For Bijagó the natural and the social are inextricably linked, to the extent that a crisis in the social system would have negative effects on natural sistem. Thus, the adverse changes that are occurring in nature around them, would be signs of displeasure from their ancestors about the differences and crises with the community, which are in power to control and manipulate the events of nature. / A pesquisa descreve e analisa sociologicamente, a partir de uma abordagem qualitativa, as representações sociais do povo Bijagó da ilha de Formosa acerca das possíveis ameaças relacionadas às mudanças do clima, seus desdobramentos em relação ao lugar, isto é, em termos da forma de ocupação territorial e correspondente modo de vida característico do referido grupo. Para isso, foram adotados os seguintes procedimentos metodológicos: a) uma revisão do estado da arte acerca dos conceitos de vulnerabilidade relacionados às mudanças climáticas, à vulnerabilização, ao risco e às representações sociais; b) uma pesquisa documental e o trabalho de campo. Para os Bijagó o meio natural e o meio social são indissociáveis, na medida em que uma crise no sistema social teria reflexos negativos no sistem natural. Conclui identificando que, nas representações dos Bijagó, as mudanças adversas que vêm ocorrendo no meio natural, seriam sinais de desagrado de seus ancestrais com relação as divergências e crises dentro da comunidade, sendo estes os detentores do poder de controlar e manipular os eventos da natureza.

Made available in DSpace on 2015-05-14T12:59:47Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 2456836 bytes, checksum: 09d3f72dc7985812ae8e5dab865bed8c (MD5) Previous issue date: 2013-02-19 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Solanum paludosum Moric. (Solanaceae), popularly known as "jurubeba roxa" in Brazil Northeast, is used as a substitute for Solanum paniculatum ( jurubeba-verdadeira ) in folk medicine to treat hypertension and gastrointestinal disorder. In previous studies performed by Monteiro (2009) with total alkaloid fraction obtained from the root bark of this species (FAT-SP) was shown that its presented spasmolytic activity on smooth muscle, being more potent on guinea pig ileum and rat aorta. On guinea pig ileum, the relaxing effect involved antimuscarinic activity, and on rat aorta the NO/GC pathways. As the fraction has constituted by glycoalkaloids and many are known to exhibit cytotoxic activity, this activity was assessed in longitudinal layer myocytes from guinea pig ileum. In this work, we found that FAT-SP has no cytotoxic activity in these cells even the highest concentration tested (750 μg/mL), then we proceeded with the investigation of the relaxant action mechanism of FAT-SP on guinea pig ileum and rat aorta until that concentration. FAT-SP showed a relaxant effect on guinea pig ileum resistant simultaneous blockade of cholinergic and adrenergic pathways with guanethidine and atropine, respectively, suggesting there is involvement of NANC pathway; L-NAME (NOS competitive inhibitor) reduced FAT-SP relaxing potency, which was reversed in the presence of L-arginine, the substrate for NOS, suggesting that NO may be via NANC neurotransmitter. However, no reduction of the relaxing potency in the presence of ODQ, selective inhibitor of GC soluble, suggesting no participation of the GC in the FAT-SP relaxant action mechanism on guinea pig ileum. In the other hand, K+ channels participation (BKCa and SKCa) was evidenced by FAT-SP relaxing potency reduction on CsCl 5 mM presence (K+ channels nonselective blocker), TEA+ 1 mM (BKCa selective blocker) or apamin 100 nM (SKCa selective blocker). On rat aorta, it was observed participation pathway NO/cGMP/PKG, as can be evidenced by FAT-SP relaxing potency reduction in L-NAME 3 x 10-4 or 10-4 M presence and by inhibitory effect reversibility in L-arginine presence, as well as relaxing potency reduction in Rp-8-Br-cGMP 3 x 10-5 M presence, PKG selective inhibitor. Also, it was shown endothelial calmodulin participation because FAT-SP relaxing potency was reduced in presence calmidazolium 10-5 M, endothelial calmodulin selective inhibitor. The channel K+ participation (KV, SKCa and KATP) was evidenced by experiments with TEA+ 10 mM (K+ channels nonselective blocker), 4-AP 1 mM (KV selective blocker), apamin 5 x 10-8 M, glibenclamide 10-5 M (KATP selective blocker). Further, was showed partial inhibition of Ca2+ mobilization induced by IP3 of RS, but not by caffeine (20 mM). Thus, FAT-SP relaxing effect involves NO, BKCa and SKCa participation, on guinea pig ileum and endothelial calmodulin, NO/cGMP/PKG pathway and K+ channels (KV, SKCa and KATP) on rat aorta. / Solanum paludosum Moric. (Solanaceae), conhecida popularmente como jurubeba-roxa no Nordeste do Brasil, é utilizada como sucedânea de Solanum paniculatum ( jurubeba-verdadeira ) na medicina popular para tratamento de hipertensão e desordem gastrintestinal. Estudos anteriores, realizados por Monteiro (2009) com a fração de alcaloides totais obtida da casca da raiz desta espécie (FAT-SP) demonstraram que a mesma apresentou atividade espasmolítica em músculos lisos, sendo mais potente em íleo de cobaia e aorta de rato. Em íleo de cobaia, o efeito relaxante envolve atividade antimuscarínica e, em aorta de rato, a participação da via NO/GC. Como a fração possui na sua composição glicoalcaloides e muitos destes são conhecidos por apresentar atividade citotóxica, avaliou-se esta atividade em miócitos da camada longitudinal do íleo de cobaia. Neste trabalho, observou-se que a FAT-SP não apresenta atividade citotóxica nessas células na concentração máxima testada (750 μg/mL), portanto prosseguiu-se com a investigação do mecanismo de ação relaxante da FAT-SP em íleo de cobaia e aorta de rato até essa concentração. A FAT-SP apresentou um efeito relaxante em íleo de cobaia resistente ao bloqueio simultâneo das vias adrenérgica e colinérgica com guanetidina e atropina, respectivamente, sugerindo-se que há a participação da via NANC; o L-NAME (inibidor competitivo da NOS), reduziu a potência relaxante da FAT-SP, que foi revertida na presença da L-arginina, substrato para a NOS, sugerindo que o neurotransmissor da via NANC pode ser o NO. Porém, não houve redução da potência relaxante na presença de ODQ, inibidor seletivo da GC solúvel, o que sugere a não participação da GC no mecanismo de ação relaxante da FAT-SP em íleo de cobaia. Por outro lado, a participação dos canais de K+ (BKCa e SKCa) foi evidenciada pela redução da potência relaxante da FAT-SP na presença de 5 mM de CsCl (bloqueador não seletivo dos canais de K+), de 1 mM de TEA+ (bloqueador seletivo dos BKCa) ou 100 nM de apamina (bloqueador seletivo dos SKCa). Em aorta de rato, observou-se que há a participação da via NO/GMPc/PKG, como evidenciado pela redução da potência relaxante da FAT-SP na presença de 10-4 ou 3 x 10-4 M de L-NAME, e da reversibilidade do efeito inibidor na presença da L-arginina, bem como, da redução da potência relaxante na presença de 3 x 10-5 M de Rp-8-Br-cGMPS, inibidor seletivo da PKG. Ademais, foi demonstrado que há a participação da calmodulina endotelial, pois houve redução da potência relaxante da FAT-SP na presença de 10-5 M de calmidazolium, inibidor seletivo da calmodulina endotelial; participação dos canais de K+ (KV, SKCa e KATP) evidenciado pelos experimentos com 10 mM de TEA+ (bloqueador não seletivo dos canais de K+), 1 mM de 4-AP (bloqueador seletivo dos KV), 5 x 10-8 M de apamina e 10-5 M de glibenclamida (bloqueador seletivo dos KATP). Observou-se ainda a inibição parcial da mobilização do Ca2+ do RS induzida pelo IP3, mas não por cafeína (20 mM). Assim, o efeito relaxante da FAT-SP envolve a participação do NO e dos BKCa e SKCa em íleo de cobaia, e da calmodulina endotelial, bem como da via NO/GMPc/PKG e canais de K+ (KV, SKCa e KATP) em aorta de rato.

Lorsqu’elle s’inscrit dans un contexte tel que celui des pays en développement, la notion de handicap se caractérise par des tendances bien singulières. C’est notamment en République de Guinée que nous avons décidé de centrer notre travail, traitant des problématiques liées aux handicaps physiques et plus particulièrement aux déficiences des membres inférieurs. Les objectifs fixés dans cette recherche consistent à expliquer les causes et les conséquences de la prédominance de ce type de déficiences à Conakry. De plus, parmi d’autres problématiques que soulève notre travail, nous nous intéressons aux représentations que reflètent les handicaps et aux influences qu’elles subissent de la part des croyances traditionnelles et religieuses. Notre travail s’inscrit donc à la fois dans la volonté d’établir un état des lieux de la situation actuelle et dans la réalisation d’un important travail de terrain qui a été mené à Conakry entre 2008 à 2011 auprès d’un millier de personnes. D’après nos résultats, la principale cause des déficiences des membres inférieurs est liée aux séquelles de la poliomyélite et à la présence d’autres facteurs de risques tels que l’insécurité routière. De plus, selon nos analyses, près de 80% des personnes atteintes de ce type de déficience résidant à Conakry sont issues de l’exode rural. Une fois installées à Conakry, elles optent pour les trois modes de subsistance à savoir : la pratique de la mendicité (48%), l’occupation d’un emploi (16%) et la prise en charge familiale (18%). Par ailleurs, chaque mode semble déterminer leur participation et leur intégration au sein de la société. Enfin, nos résultats montrent que près de la moitié des Guinéens croit en la sorcellerie et en la nature maléfique des handicaps. Comme nous l’expliquons, ces croyances influencent négativement les représentations des handicaps. Pour conclure, selon nos analyses la majorité des Guinéens s’accorde à définir le handicap comme un phénomène biomédical et le considère comme un problème individuel et non social. / While dealing with the context of the developing countries, the notion of handicap is characterized in a specific way. We carried out our study in the Republic of Guinea, particularly related to the problems of the handicap, more specifically with the disability of inferior members. The main objectives of this research consist in explaining the causes and the consequences of the ascendancy of this type of deficiencies in Conakry. Furthermore, among the other problems analyzed in this work, we are interested in the representations which reflect the handicaps and the influence of traditional and religious beliefs on handicap. Our work is aimed to present the current conditions of the situation and to carry out a significant work on the site. In this framework, we organized two surveys during 2008 and 2009, dealing with approximately 1000 persons. According to our results, the main cause of the deficiencies of lower limbs is associated to the aftereffects of the poliomyelitis and to the presence of the other risk factors, such as the lack of safety on the roads. Furthermore, according to our analyses, about 80 % of the people questioned, belonged to the rural depopulation. Once installed in Conakry, they opt for three modes of subsistence: the practice of begging (48 %), working (16 %) and the family care (18 %). Moreover, each mode seems to determine the participation and the integration of these individuals in the society. Finally, our results show that nearly half of the Guineans believe in the witchcraft and in the malefic nature of the handicaps. Consequently, the faith influences negatively on the interpretation of the handicaps. To conclude, according to our analyses, the majority of the Guineans agrees to define the handicap as a biomedical phenomenon and considers it as an individual and not a social problem.

Les marges transformantes, formées par le coulissage des plaques lors des premières étapes de l’ouverture océanique, ont été peu étudiées relativement aux marges divergentes. La marge de Côte d’Ivoire-Ghana fait figure d’exemple-type, et l’absence d’inventaire exhaustif ainsi que le peu d’étude de marges transformantes conjuguées entraîne une méconnaissance de la véritable diversité de ce type de marge. Deux approches ont été abordées dans ce mémoire. La première a consisté à les inventorier dans le monde à partir d’une méthodologie simple. Elles ont ensuite été comparées (physiographie et structure). La deuxième s’est concentrée sur l’étude tectono-sédimentaire des marges transformantes conjuguées des plateaux de Demerara et de Guinée. L’inventaire des marges transformantes a montré que les marges transformantes représentent 30% des marges passives. Leur distribution au sein de domaines océaniques ouverts de façon très oblique ou à l’intersection entre grands domaines reflète des conditions d’initiation spécifiques. 30% des marges transformantes se trouvent notamment en bordure d’un plateau marginal ; un type de bassin à l’histoire double nouvellement défini, qui semble associé à un fort amincissement crustal. Par ailleurs, on montre que les marges transformantes présentent des architectures diverses et sont souvent segmentées. L’étude des plateaux marginaux de Demerara et Guinée a permis de montrer qu’elles se mettent en place au niveau d’un domaine pré-aminci, sans doute guidées par des structures préexistantes. La nature du soubassement des plateaux est discutée : éventails sédimentaires ou volcaniques type SDR. La formation et l’évolution des marges transformantes en bordure des deux plateaux a été accompagnée de déformations intenses à l’approche des frontière océan-continents ainsi que de plusieurs épisodes de soulèvement et subsidence successifs de la bordure transformante, dont les origines et mécanismes sont discutés. / Transform margins form by transform motion between plates during early stages of oceanic spreading. They have been poorly studied in comparison with divergent margins, at least for the last 15 years. The Côte d’Ivoire-Ghana margin represents the best known example of a transform margin and is often considered as a model. However, the lack of a global complete inventory of such margins may lead to underestimate their diversity. Two approaches have been developed in this work. The first one consisted in a compiling world transform margins using a systematic and simple methodology. Those margins have then been compared (physiography, structure). In a second approach we analysed the tectono-sedimentary evolution of the Demerara and Guinea conjugated transform-derived plateaus. The worldwide review of transform margins shows that those represent 30% of the existing passive margins. Their distribution inside very oblique oceanic domains, and at the intersection between oceanic domains of contrasted ages, reflects specific initiation conditions. 30% of those transform margins locate on the edge of marginal plateaus —newly defined type of basins— that seem to be associated with important crustal thinning. Furthermore, this inventory shows that transform margins display a great variety of architectures. The Demerara and Guinea marginal plateaus are bounded by transform margins that occur on an already thinned crust, probably along a preexisting structure. The nature of these plateaus basement is discussed: sedimentary or volcanic SDRs fan-shaped units? During the Equatorial Atlantic opening, the formation and evolution of Demerara and Guinea transform margins were accompanied by intense deformations close to the continent-ocean boundary and by several successive uplift and subsidence phases along the plateaus borders. Their origin and mechanisms are discussed.

Made available in DSpace on 2015-07-22T20:49:55Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-05-26 / Objetivo: Determinar o efeito do ácido ursodesoxicólico e o papel da mucosa no aparecimento de alterações motoras, na musculatura esofagiana de cobaias. Métodos: Trabalho experimental realizado com 18 cobaias albinas do sexo masculino pesando entre 200 e 250g. Os animais foram distribuídos em 03 grupos, sendo assim constituídos: Grupo (A)- 06 animais formaram o grupo experimental – Esôfago com mucosa, Grupo (B)- 06 animais formaram o grupo experimental – Esôfago sem mucosa e Grupo (C)- 06 animais formaram o grupo controle. Os animais foram sacrificados e o esôfago distal foi removido. Após identificação da transição epitelial escamo-colunar, foi realizada a secção ao nível da mesma desprezando-se a câmara gástrica. Os espécimes de esôfago foram encaminhados para prova de avaliação contrátil, utilizando-se câmaras de perfusão de órgãos e um sistema de aquisição de dados com o programa KITCAD 8. Os espécimes foram mantidos em solução salina oxigenada por 01 hora, com estiramento de 01 grama a fim de readquirirem sua tensão basal e foram estimulados com 40mM de KCl. Após a verificação da manutenção contrátil e avaliação da amplitude contrátil inicial, os fragmentos foram banhados na solução de 100 mM de ácido ursodesoxicólico, nos grupos A e B, e em solução salina fisiológica, no grupo C, por 01 hora, e, então, novamente estimulados com 40mM de KCl, e realizados cinco estímulos com intervalo de cinco minutos para o registro da amplitude contrátil. Resultados: A média da amplitude de contração antes da incubação (pré) variou entre os grupos (p=0,006) com médias de 1,319(A), 0,306(B) e 1,795(C). Após a incubação (pós), a média da amplitude de contração foi de 0,709 , 0,278 e 1,353 para os grupos A, B e C, respectivamente. Antes da incubação, não houve diferença na amplitude de contração entre os grupos A e C (p=0,633) e houve diferença entre os grupos A e B (p=0,039) e B e C (p=0,048). Após a incubação, quando comparamos as diferenças das médias dentro dos grupos nos momentos pré e pós, encontramos apenas diferenças no grupo A (p=0,030). Conclusões: A exposição esofagiana ao ácido ursodexosicólico, componente da bile, induz a uma diminuição da amplitude de contração esofagiana. A mucosa esofagiana desempenha importante papel na motilidade esofagiana. / Background and Aims: Esophageal motor abnormalities are frequently found in patients with gastroesophageal reflux disease. The role of bile in reflux-induced dysmotility is still elusive. Furthermore, it is questionable weather mucosal or muscular stimulation leads to motor modification. The aims of this study were: (a) analyze the effect of bile infusion in the amplitude of esophageal contractions and (b) analyze the effect of mucosal vs muscular stimulation. Methods: 18 guinea-pig esophagi were isolated and its contractility assessed with force transducers. Three groups were studied. In group A (n= 6) the entire esophagus was used and incubated in 100 ìML ursodeocycholic acid for 2 hours. In group B (n=6) the mucosal layer was removed and the muscular layer incubated in 100 ìML ursodeocycholic acid for 1 hours. In group C (n=6) (control group) the entire esophagus was used and incubated in saline solution. In all groups, five sequential contractions spaced by 1 minute were measured before and after incubation. Contractions were recorded after KCl 40 mM stimulation. Results: Contractions before incubation did differed among groups (p= 0,006) and averaged 1,319(A),0,306(B) and 1,795(C). After incubation amplitude of contraction was 0,709 , 0,278 and 1,353 for groups A, B and C respectively. Before incubation there were no diferrences between groups A and C (p=0,633) there was difference between groups A and B (p=0,039) and B and C (p=0,048). After incubation when we compare average within groups (before and after) there was difference only in group A (p=0,030). Conclusion: Our results show that bile exposure may induce ineffective esophageal motility and the mucosa seems to take an important role in esophageal motility. Disclosure Statement: No author has commercial associations that might create a conflict of interest. No competing financial interests exist. / TEDE / BV UNIFESP: Teses e dissertações

Cette thèse se propose d’examiner les représentations de la femme dans Ekomo (1985) de María Nsue Angüe et Hija de la fortuna (1998) d’Isabel Allende. Dans l’un comme dans l’autre texte, la femme est marginalisée en tant que fille, mère et épouse. Dans Ekomo, María Nsue Angüe soutient que cette situation perdure depuis la fondation des tribus fang par l’ancêtre, Afrikara. Une période durant laquelle, la femme s’illustrait tantôt par sa traîtrise, tantôt par sa sorcellerie. L’enseignement de la généalogie des tribus destiné aux jeunes hommes, conforte cette idée. Ainsi, alors que les jeunes hommes sont préparés pour dominer, les jeunes filles de leur côté, sont éduquées pour obéir et se soumettre. Une image de paria dont la femme tant dans Hija de la fortuna que dans Ekomo ne parvient que rarement à défaire. Cependant, deux événements vont accélérer la prise de conscience des femmes de cette marginalisation et favoriser leur libération. D’abord le contact de la tradition fang avec la culture occidentale et l’école en particulier et, ensuite le voyage ou l’éloignement de la femme de la famille. Chez María Nsue Angüe tout comme chez Isabel Allende, la libération de la femme suscite des interrogations tant leurs propositions paraissent inappropriées. / The aim of this thesis is to consider women representations in the books Ekomo (1985) and Hija de la fortuna, respectively written by María Nsue Angüe and Isabel Allende. In both books, women are marginalized. In Ekomo, María Nsue Angüe states that the situation has not been changing since the Fang tribe foundation by the ancestor, Afrikara. During this period women were renowned for treachery and witchcraft. The genealogical teachings given to boys, venerate the male ancestors and dishonor females. Therefore, while boys are trained to dominate and to carry out noble tasks, girls are educated to obey and to be obsequious. Women rarely manage to get rid of this ancestral and historic pariah image in Hija de la fortuna and Ekomo. Two events will accelerate women's awareness of their marginalization and will help them to get free. Firstly, the contact between the Fang tradition and the European culture and particularly school and then the journey and the estrangement of women from their family. With both María Nsue Angüe and Isabel Allende, women freedom gives rise to so many questions because their statements are inappropriate.

The biology and epidemiology of bovine herpesvirus 2 (BoHV-2), the agent of bovine herpetic mammillitis (BHM), remain largely unknown. Thus, the present study aimed at addressing selected aspects of BoHV-2 epidemiology and pathogenesis in sheep and guinea pigs. A serological survey for BoHV-2 antibodies in 2.213 samples from cattle > 24-months-old from 136 counties of seven different mesoregions of Rio Grande do Sul (RS) revealed an overall prevalence of 24.5% (543/2.213). These results demonstrate that BoHV-2 infection is widespread among cattle in RS, and potentially involved in cases of mammillitis frequently described in dairy cows. A second experiment was conducted to characterize the latent BoHV-2 infection in a sheep model. Lactating ewes inoculated with BoHV-2 in the skin of the udder shed virus for up to five days, developed mammillitis and seroconverted. However, attempts to reactivate latent infection by dexamethasone (Dx) administration at day 40 post infection (pi) failed. Nevertheless, viral DNA was detected by PCR in several nerve ganglia and/or regional lymph nodes (LNs) of all animals at day 40 post-reactivation (pr). Lambs previously inoculated with BoHV-2 in the nose also harbored latent viral DNA in trigeminal ganglia, tonsils and regional LNs. These results demonstrated that BoHV-2 establishes latent infection in nerve ganglia and in regional lymphoid tissues, yet virus reactivation is not easily achieved by standard protocols used for other alphaherpesvirus. A third experiment was conducted to evaluate guinea pigs (Cavia porcellus) as an experimental model to study the biology of BoHV-2 infection. Weanling (30-40 daysold) guinea pigs inoculated into the genital area and over the skin of the udder and teats with a viral suspension developed moderate to severe clinical signs, noticeably more pronounced in the genital area. Infectious virus was recovered from swabs collected between days 3 and 7 from genital area (8/12) and less frequently (1/12) from teat skin. All animals seroconverted to BoHV-2 developing neutralizing titers from 16 to 128 at day 30 pi. Histological examination of skin biopsies collected from genital lesions showed intranuclear inclusion bodies and perivascular infiltrates composed by lymphocytes and plasmocytes. PCR examination of tissues collected from animals euthanized at day 35 pi revealed the presence of latent viral DNA in nerve ganglia and LNs. Dx administration at day 35 pi was followed by mild recrudescence of genital disease in some animals, yet virus isolation and/or seroconversion which are usually taken as indicators of virus reactivation were not observed. These results show that guinea pigs may be used as models to study BoHV-2 acute and latent infection and confirm that BoHV-2 reactivation is not easily achieved by using the standard protocols for other alphaherpesviruses. Taken together, these results demonstrate that both sheep and guinea pigs are suitable animal models for BoHV-2 infection. / A biologia e a epidemiologia da infecção pelo herpesvírus bovino tipo 2 (BoHV-2), agente da mamilite herpérica bovina, são pouco conhecidas. Com isso, o presente estudo teve como objetivos elucidar alguns aspectos da epidemiologia e estudar a patogenia da infecção pelo BoHV-2 em ovinos e cobaias. Um estudo sorológico pesquisando anticorpos para o BoHV-2 em 2.213 amostras de bovinos com mais de 2 anos, provenientes de 136 municípios distribuídos em 7 mesoregiões do Rio Grande do Sul (RS), determinou uma soroprevalência de 24,5% (543/2.213). Os resultados demonstram que o BoHV-2 está disseminado no rebanho bovino no RS, com potencial envolvimento em casos de mamilite freqüentemente relatados em rebanhos leiteiros. Um segundo experimento visou caracterizar a infecção latente em ovinos, propostos como modelo experimental. Ovelhas lactantes inoculadas com o BoHV-2 na pele do úbere excretaram o vírus por até 5 dias, desenvolveram mamilite e soroconverteram. Entretanto, a tentativa de reativar a infecção latente pela administração de dexametasona (Dx) no dia 40 pós-infecção (pi) não resultou em reativação. Não obstante, o DNA viral latente foi detectado por PCR em gânglios neurais e/ou em diversos linfonodos (LNs) de todos os animais no dia 40 pós reativação (pr). Cordeiros que haviam sido inoculados com o BoHV-2 pela via nasal igualmente albergavam o DNA viral latente nos gânglios trigêmeos, tonsilas e LNs regionais. Esses resultados demonstram que o BoHV-2 estabelece infecção latente em gânglios neurais e tecidos linfóides regionais, embora a reativação viral não seja facilmente obtida com os protocolos usados em outros alfaherpesvírus. Um terceiro experimento foi realizado para validar cobaias (Cavia porcellus) como modelo experimental para estudo da biologia da infecção com o BoHV-2. Cobaias lactentes (30- 40 dias) inoculadas com o BoHV-2 nas regiões genital e intra-dérmico no tetos e úbere desenvolveram sinais clínicos moderados a severos, notadamente mais pronunciados na região genital. O vírus foi isolado de suabes coletados entre os dias 3 e 7 pi da região genital (8/12) e em menor freqüência da região dos tetos (1/12). Todos os animais soroconverteram para o BoHV-2, apresentando títulos de anticorpos neutralizantes entre 16 e 128 no dia 30 p.i. A análise histológica de biópsias de pele coletada de lesões revelou corpúsculos de inclusão e infiltrado linfocitário e plasmocitário perivascular. PCR realizada com DNA total extraído dos tecidos coletados no dia 35 pi revelou a presença de DNA viral latente em gânglios neurais lombo-sacrais e LNs regionais. A administração de Dx no dia 35 pi cursou com recrudescência clínica na região genital, porém não foram detectados excreção viral nem soroconversão, indicadores de reativação da infecção latente. Estes resultados demonstram que cobaias podem ser usados como modelo para a infecção aguda e latente pelo BoHV- 2, e confirmam que a reativação viral não é facilmente obtida pelo uso de protocolos usuais para outros alfaherpesvírus. Em conjunto, os resultados demonstram a utilidade de ovinos e cobaias como modelo experimental para a infecção pelo BoHV-2.

Submitted by Clebson Anjos (clebson.leandro54@gmail.com) on 2016-03-29T19:52:46Z No. of bitstreams: 1 arquivototal.pdf: 2685795 bytes, checksum: 4ec45796766163ba90a711b655c68fbf (MD5) / Made available in DSpace on 2016-03-29T19:52:46Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 2685795 bytes, checksum: 4ec45796766163ba90a711b655c68fbf (MD5) Previous issue date: 2014-03-06 / Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Xylopia frutescens Aubl. species, popularly known as “embira”, “semente-de-embira” and “embira-vermelha”, is used in folk medicine as antidiarrhoeal. From leaves of these species was extract the essential oil (XF-OE), that in previous studies, showed spasmolytic activity on phasic contractions induced by CCh or histamine on guinea pig ileum. Considering this premise, the aim of this study was to characterize the mechanism of spasmoliytic action of XF-OE on intestinal smooth muscle. For this, were used functional and cellular methodologies. XF-OE inhibited cumulative concentration-response curves to histamine, and these were shifted to the right, in a non-parallel manner, with Emax reduction, discarding thus a competitive type antagonism and relaxed the guinea pig ileum contracted by KCl (40 mM) or histamine (10-6 M). How the relaxant potency of the essential oil was smaller in organ pre-contracted by KCl, it was hypothesized that XF-OE would be acting as a K+ channels positive modulator. In presence of CsCl (5 mM), a non-selective blocker of these channels, the relaxant potency of XF-OE was not altered, showed a non-participation of K+ channels on the essential oil spasmolytic effect. Thus, we decided to check whether the essential oil would prevent calcium influx through CaV, for this were obtained cumulative concentration-response curves to CaCl2 in depolarizing medium (70 mM KCl) nominally without Ca2+ in absence (control) and presence of different concentrations of XF-OE. The essential oil shifted to the right CaCl2 control curves, with reduction of its Emax, in addition to relaxed the ileum pre-contracted by S-(-)-Bay K8644 (3 x 10-7 M), a CaV1 selective agonist, demonstrating that the essential oil inhibited Ca2+ influx through CaV1. As the Ca2+ mobilization mechanisms into circular and longitudinal muscle layers are differentiated, it was hypothesized that XF-OE would preventing Ca2+ mobilization from intracellular stores in order to promote its spasmolytic effect. To test this hypothesis, in experiments with ileum circular layer, the essential oil antagonized phasic contractions induced by histamine (10-5 M), negatively modulates the Ca2+ release to exert their spasmolytic effect. In cellular experiments, the viability of longitudinal layer myocytes from guinea pig ileum was not altered in XF-OE (81 μg/mL) presence and the fluorescence intensity in these intestinal myocytes stimulated by histamine was reduced by the essential oil, indicating a [Ca2+]c reduction. Thus, the XF-OE spasmolytic action mechanism on guinea pig ileum involves blocking the Ca2+ influx, by CaV1, in addition to negative modulation of Ca2+ release mechanisms from intracellular stores, that lead to reduction of this ion cytosolic levels and consequently muscle relaxation. / A espécie Xylopia frutescens Aubl., conhecida popularmente como “embira”, “semente-de-embira” e “embira-vermelha”, é utilizada na medicina popular como antidiarreica. Das folhas dessa espécie foi extraído o óleo essencial (XF-OE), que, em estudos anteriores, apresentou atividade espasmolítica frente às contrações fásicas induzidas por CCh ou por histamina em íleo de cobaia. Diante dessa premissa, o objetivo desse trabalho foi caracterizar o mecanismo de ação espasmolítica do XF-OE em musculatura lisa intestinal. Para isso, foram utilizadas metodologias funcionais e celulares. O XF-OE inibiu as curvas concentrações-resposta cumulativas à histamina, desviando-as para a direita, de maneira não paralela e com redução do seu Emax, descartando um antagonismo do tipo competitivo, além de relaxar o íleo pré-contraído com KCl (40 mM) ou com histamina (10-6 M). Como a potência relaxante do óleo essencial foi menor quando as contrações foram induzidas por KCl, hipotetizou-se que o XF-OE estaria atuando como um modulador positivo de canais de K+. Na presença do CsCl (5 mM), bloqueador não seletivo desses canais, a potência relaxante do XF-OE não foi alterada, sendo descartada a participação dos canais de K+ no efeito espasmolítico do óleo essencial. Diante disso, decidiu-se verificar se o óleo essencial estaria inibindo o influxo de cálcio através dos CaV, para isso foram obtidas curvas concentrações-resposta cumulativas ao CaCl2 em meio despolarizante (KCl 70 mM) nominalmente sem Ca2+ na ausência (controle) e na presença de diferentes concentrações do XF-OE. O óleo essencial deslocou para a direita as curvas controle de CaCl2 com redução do seu Emax, além de relaxar o íleo pré-contraído com o S-(-)-Bay K8644 (3 x 10-7 M), um agonista dos CaV1, demonstrando que o óleo essencial inibe o influxo de Ca2+ através dos CaV1. Sendo os mecanismos de mobilização de Ca2+ em células musculares das camadas circular e longitudinal diferenciados, hipotetizou-se que o XF-OE estaria impedindo a mobilização de Ca2+ dos estoques intracelulares para promover seu efeito espasmolítico. Para testar essa hipótese, em experimentos utilizando a camada circular do íleo, o óleo essencial antagonizou as contrações fásicas induzidas por histamina (10-5 M), modulando negativamente a liberação de Ca2+ para exercer seu efeito espasmolítico. Nos experimentos celulares, a viabilidade dos miócitos da camada longitudinal do íleo de cobaia não foi alterada na presença do XF-OE (81 μg/mL) e a intensidade de fluorescência nos miócitos intestinais estimulados por histamina foi reduzida pelo óleo essencial, indicando a redução na [Ca2+]c. Assim, o mecanismo de ação espasmolítica do XF-OE em íleo de cobaia envolve bloqueio do influxo de Ca2+, via CaV1, além da modulação negativa dos mecanismos de liberação de Ca2+ dos estoques intracelulares, levando à redução dos níveis citosólicos desse íon e, consequente, relaxamento muscular.