Title of thesis: Ballistic cavity origin characterisation; auxiliary materials of a standardised or a special military ammunition. Aim of thesis: The goal of this work is to provide a regularising framework suggesting structural changes of the auxiliary materials in the impact zone of the various ammunition. Methods: A ballistic experiment based upon the piercing test of various ammunition types. For these tests different barrier materials were used (e.g. glycerine, soap, ballistic gel). A comparative study of the various physical aspects of the cavities was exercised. Several diagnostic methods such as dimensions verification, water volume measurement, projectile speed radar check, computer tomography or the high speed camera were used to determine the secondary cavity specifics. Results: This thesis identified several key parameters determining projectile behaviour in the auxiliary materials. The major determinants were: speed, position or homogeneity of the projectile on the impact. However the major parameter defining the "injury level" was the concluded that the highest Injury level has the prohibited "fragmentation effect ammunition". On the other hand it was pointed out that so called "Black Mamba" projectiles have lower injury effect, although manufactore claims otherwise. Key words:...

A tuberculose (TB) é uma doença infecciosa causada por bactérias do gênero Mycobacterium que acomete principalmente o sistema respiratório. A cepa Beijing 1471 (M. tuberculosis) induz uma resposta altamente pró-inflamatória, enquanto que a cepa MP287/03 (M. bovis) induz uma fraca resposta inflamatória. O receptor P2X7 (P2X7R) é um sensor de ATP extracelular, uma molécula associada ao dano que é liberada a partir de células necróticas. A TB induzida por ambas as cepas hipervirulentas Beijing 1471 e MP287/03 é atenuada em camundongos deficientes do P2X7R. Portanto o objetivo do nosso trabalho foi avaliar o papel do P2X7R na resposta imune da TB induzida por essas cepas hipervirulentas. Nós percebemos que apesar das diferenças na capacidade imunomodulatória induzida pelas cepas Beijing 1471 e MP287/03, o P2X7R exerce um papel importante na severidade da doença induzida por ambas as cepas, e que a ausência desse receptor foi capaz de restabelecer a resposta imune pulmonar a perfis semelhantes ao induzido pela cepa de menor virulência H37Rv de M. tuberculosis. / Tuberculosis (TB) is infectious diseases caused by Mycobacterium tuberculosis (Mtb) that mainly affect the respiratory system. Beijing 1471 strain (Mtb) induce a strong pro-inflammatory response, while MP287/03 strain (M. bovis) induce a weak pro-inflammatory response. The P2X7 receptor (P2X7R) is a sensor of extracellular ATP, a damage-associated molecule that is released from necrotic cells and that induces pro-inflammatory cytokine. TB caused by both hypervirulent strains Beijing 1471 and MP287/03 is attenuated in P2X7R deficient mice (P2X7RKO). Therefore, our aim was to investigate the role of P2X7R in imune response of TB induced by MP287/03 and Beijing 1471 strains. We has note that despite Beijing 1471 and MP287/03 strains have opposite immunomodulatory properties, the P2X7R have an important role in modulating the immune response induced by both strains. Thus, the lung immune responses induced by both hypervirulent infections in the absence of this receptor were similar to that induced by less virulent H37Rv Mtb mycobacteria.

Toxoplasma gondii é um protozoário intracelular obrigatório que causa a toxoplasmose. Em modelo experimental, camundongos C57BL/6 infectados por via oral com 100 cistos de T. gondii, cepa ME-49, desenvolvem sérias lesões intestinais similares as observadas em doenças inflamatórias intestinais. Ao invadir as células epiteliais intestinais, o parasito induz uma resposta inflamatória de padrão T helper (Th) 1 elevada, ativada pela produção de quimiocinas e citocinas envolvidas na migração e ativação celular. Para que ocorra essa migração celular para o sítio de infecção é necessário a presença de receptores de quimiocinas. O receptor de quimiocinas CCR5 é muito importante para o recrutamento celular em algumas infecções e está envolvido com a migração de vários subtipos celulares como células dendríticas, células T e, em particular, células T reguladoras. CCR5 pode estar relacionado também a mecanismos independentes da migração celular, no qual a sinalização intracelular e ativação de NF-B podem levar a intensificação da resposta imunológica. Ainda não está claro o papel do receptor CCR5 no modelo de infecção oral por T. gondii. Dessa forma, animais C57BL/6 e deficientes em CCR5 foram infectados por via oral com 5 cistos de T. gondii, cepa ME-49, e alguns parâmetros imunológicos e bioquímicos foram avaliados no 8º dia de infecção. Os resultados mostraram que animais CCR5-/- apresentaram alta suscetibilidade à infecção oral por T. gondii, exibindo um intenso infiltrado inflamatório no íleo e regiões de ulceração epitelial, quando comparados com animais C57BL/6. Independentemente de serem deficientes ou não de CCR5, os camundongos apresentaram focos inflamatórios dispersos pelo parênquima do fígado, entretanto camundongos CCR5-/- apresentaram uma extensiva vacuolização dos hepatócitos, com excessivo acúmulo de lipídeos no órgão e elevada concentração sérica de triglicérides e de transaminases. A carga parasitária foi significativamente mais elevada no intestino delgado e no fígado dos animais CCR5-/- em comparação com animais C57BL/6. Foi observada também uma menor migração de células NK no intestino delgado, bem como um aumento na frequência de células T CD4+ neste órgão e uma menor concentração de IFN- e IL-12p40 no macerado do fígado dos animais CCR5-/- em comparação com C57BL/6. Análise de expressão gênica no fígado revelou redução na formação de transcritos para PPAR nos animais deficientes em CCR5, e quando os camundongos foram tratados com Gemfibrozil, um agonista de PPAR, houve reversão na vacuolização hepática e na concentração de triglicérides no soro dos animais CCR5-/-. Estes dados sugerem que a migração celular dependente de CCR5 é essencial para a modulação da resposta inflamatória induzida por T. gondii no intestino delgado. Além do mais, a ausência de CCR5 compromete a integridade hepática durante a infecção oral por T. gondii e os mecanismos moleculares envolvidos podem estar relacionados à expressão de PPAR. / T. gondii is an obligate intracellular protozoan parasite which is the causative agent of toxoplasmosis. In experimental model, C57BL/6 mice orally infected with a high parasitic load develop serious intestinal lesions, whose injuries are similar to those observed in Inflammatory Bowel Disease. This inflammation is caused due to parasite invasion of intestinal epithelial cells that elicit a robust Th1 type immune response. Moreover, chemokines produced by intestinal epithelial cells are involved in the migration and activation of inflammatory cells. In particular, the chemokine receptor CCR5 is important for cell recruitment in some infections and is involved with the migration of various cells subsets such as dendritic cells, T cells and, in particular regulatory T cells. CCR5 may also be related to mechanisms independent of cell migration, in which the intracellular signaling and activation of NF-B may lead to intensification of the immune response. The role of CCR5 has not been clear in the experimental oral T. gondii infection. Thus, wild type C57BL/6 mice and CCR5-/- littermates were infected with T. gondii by gavage and immune and biochemical parameters, were analyzed at day 8 after infection. The CCR5-/- mice showed to be highly susceptible to the parasite, with intense inflammatory infiltration in the ilea and regions of epithelial ulcerations in comparison with WT mice. Both strain of mice presented inflammatory foci scattered by parenchyma of the liver, however the CCR5-/- mice presented an extensive hepatocyte vacuolization with an excessive accumulation of lipids in the organ and elevated serum triglycerides and transaminases concentration. The parasite load was significantly higher on small intestine and liver samples of CCR5-/- in comparison with WT mice. There was also a minor migration of NK cells in the small intestine, as well as greater frequency of CD4+ T cells in this organ and a lower IFN- and IL-12p40 levels in liver homogenate samples in the CCR5-/- mice compared with WT mice. Gene expression analysis revealed a reduction in the formation of transcripts for PPAR in mice deficient in CCR5, and when the animals were treated with Gemfibrozil, a PPAR agonist, there was an improvement in the level of vacuolization and reduced triglycerides. These data suggest that a CCR5-dependent cell migration is essential for the modulation of T. gondii-induced inflammatory response in the small intestine. In addition, hepatic integrity during T. gondii oral infection is compromised in the absence of CCR5, and the molecular mechanisms involved can be related to PPAR expression.

Toxoplasma gondii é um protozoário intracelular obrigatório que causa a toxoplasmose. Em modelo experimental, camundongos C57BL/6 infectados por via oral com 100 cistos de T. gondii, cepa ME-49, desenvolvem sérias lesões intestinais similares as observadas em doenças inflamatórias intestinais. Ao invadir as células epiteliais intestinais, o parasito induz uma resposta inflamatória de padrão T helper (Th) 1 elevada, ativada pela produção de quimiocinas e citocinas envolvidas na migração e ativação celular. Para que ocorra essa migração celular para o sítio de infecção é necessário a presença de receptores de quimiocinas. O receptor de quimiocinas CCR5 é muito importante para o recrutamento celular em algumas infecções e está envolvido com a migração de vários subtipos celulares como células dendríticas, células T e, em particular, células T reguladoras. CCR5 pode estar relacionado também a mecanismos independentes da migração celular, no qual a sinalização intracelular e ativação de NF-B podem levar a intensificação da resposta imunológica. Ainda não está claro o papel do receptor CCR5 no modelo de infecção oral por T. gondii. Dessa forma, animais C57BL/6 e deficientes em CCR5 foram infectados por via oral com 5 cistos de T. gondii, cepa ME-49, e alguns parâmetros imunológicos e bioquímicos foram avaliados no 8º dia de infecção. Os resultados mostraram que animais CCR5-/- apresentaram alta suscetibilidade à infecção oral por T. gondii, exibindo um intenso infiltrado inflamatório no íleo e regiões de ulceração epitelial, quando comparados com animais C57BL/6. Independentemente de serem deficientes ou não de CCR5, os camundongos apresentaram focos inflamatórios dispersos pelo parênquima do fígado, entretanto camundongos CCR5-/- apresentaram uma extensiva vacuolização dos hepatócitos, com excessivo acúmulo de lipídeos no órgão e elevada concentração sérica de triglicérides e de transaminases. A carga parasitária foi significativamente mais elevada no intestino delgado e no fígado dos animais CCR5-/- em comparação com animais C57BL/6. Foi observada também uma menor migração de células NK no intestino delgado, bem como um aumento na frequência de células T CD4+ neste órgão e uma menor concentração de IFN- e IL-12p40 no macerado do fígado dos animais CCR5-/- em comparação com C57BL/6. Análise de expressão gênica no fígado revelou redução na formação de transcritos para PPAR nos animais deficientes em CCR5, e quando os camundongos foram tratados com Gemfibrozil, um agonista de PPAR, houve reversão na vacuolização hepática e na concentração de triglicérides no soro dos animais CCR5-/-. Estes dados sugerem que a migração celular dependente de CCR5 é essencial para a modulação da resposta inflamatória induzida por T. gondii no intestino delgado. Além do mais, a ausência de CCR5 compromete a integridade hepática durante a infecção oral por T. gondii e os mecanismos moleculares envolvidos podem estar relacionados à expressão de PPAR. / T. gondii is an obligate intracellular protozoan parasite which is the causative agent of toxoplasmosis. In experimental model, C57BL/6 mice orally infected with a high parasitic load develop serious intestinal lesions, whose injuries are similar to those observed in Inflammatory Bowel Disease. This inflammation is caused due to parasite invasion of intestinal epithelial cells that elicit a robust Th1 type immune response. Moreover, chemokines produced by intestinal epithelial cells are involved in the migration and activation of inflammatory cells. In particular, the chemokine receptor CCR5 is important for cell recruitment in some infections and is involved with the migration of various cells subsets such as dendritic cells, T cells and, in particular regulatory T cells. CCR5 may also be related to mechanisms independent of cell migration, in which the intracellular signaling and activation of NF-B may lead to intensification of the immune response. The role of CCR5 has not been clear in the experimental oral T. gondii infection. Thus, wild type C57BL/6 mice and CCR5-/- littermates were infected with T. gondii by gavage and immune and biochemical parameters, were analyzed at day 8 after infection. The CCR5-/- mice showed to be highly susceptible to the parasite, with intense inflammatory infiltration in the ilea and regions of epithelial ulcerations in comparison with WT mice. Both strain of mice presented inflammatory foci scattered by parenchyma of the liver, however the CCR5-/- mice presented an extensive hepatocyte vacuolization with an excessive accumulation of lipids in the organ and elevated serum triglycerides and transaminases concentration. The parasite load was significantly higher on small intestine and liver samples of CCR5-/- in comparison with WT mice. There was also a minor migration of NK cells in the small intestine, as well as greater frequency of CD4+ T cells in this organ and a lower IFN- and IL-12p40 levels in liver homogenate samples in the CCR5-/- mice compared with WT mice. Gene expression analysis revealed a reduction in the formation of transcripts for PPAR in mice deficient in CCR5, and when the animals were treated with Gemfibrozil, a PPAR agonist, there was an improvement in the level of vacuolization and reduced triglycerides. These data suggest that a CCR5-dependent cell migration is essential for the modulation of T. gondii-induced inflammatory response in the small intestine. In addition, hepatic integrity during T. gondii oral infection is compromised in the absence of CCR5, and the molecular mechanisms involved can be related to PPAR expression.

A tuberculose (TB) é uma doença infecciosa causada por bactérias do gênero Mycobacterium que acomete principalmente o sistema respiratório. A cepa Beijing 1471 (M. tuberculosis) induz uma resposta altamente pró-inflamatória, enquanto que a cepa MP287/03 (M. bovis) induz uma fraca resposta inflamatória. O receptor P2X7 (P2X7R) é um sensor de ATP extracelular, uma molécula associada ao dano que é liberada a partir de células necróticas. A TB induzida por ambas as cepas hipervirulentas Beijing 1471 e MP287/03 é atenuada em camundongos deficientes do P2X7R. Portanto o objetivo do nosso trabalho foi avaliar o papel do P2X7R na resposta imune da TB induzida por essas cepas hipervirulentas. Nós percebemos que apesar das diferenças na capacidade imunomodulatória induzida pelas cepas Beijing 1471 e MP287/03, o P2X7R exerce um papel importante na severidade da doença induzida por ambas as cepas, e que a ausência desse receptor foi capaz de restabelecer a resposta imune pulmonar a perfis semelhantes ao induzido pela cepa de menor virulência H37Rv de M. tuberculosis. / Tuberculosis (TB) is infectious diseases caused by Mycobacterium tuberculosis (Mtb) that mainly affect the respiratory system. Beijing 1471 strain (Mtb) induce a strong pro-inflammatory response, while MP287/03 strain (M. bovis) induce a weak pro-inflammatory response. The P2X7 receptor (P2X7R) is a sensor of extracellular ATP, a damage-associated molecule that is released from necrotic cells and that induces pro-inflammatory cytokine. TB caused by both hypervirulent strains Beijing 1471 and MP287/03 is attenuated in P2X7R deficient mice (P2X7RKO). Therefore, our aim was to investigate the role of P2X7R in imune response of TB induced by MP287/03 and Beijing 1471 strains. We has note that despite Beijing 1471 and MP287/03 strains have opposite immunomodulatory properties, the P2X7R have an important role in modulating the immune response induced by both strains. Thus, the lung immune responses induced by both hypervirulent infections in the absence of this receptor were similar to that induced by less virulent H37Rv Mtb mycobacteria.

Shock waves are generally characterized by a sharp change of the pressure, which causes subsequent changes in properties of the surrounding in which it spreads. In medical applications, it is an acoustic shock wave which is used for the treatment of concrements for more than 25 years. This success naturally led to considerations about the possibility of using shock waves in other areas of medicine. One of the main directions of the research is the possibility of the damage to tumor tissue. In contrast to concrements the tumor tissue is not different from surrounding tissues by its acoustic attributes, so the normal lithotryptor is not appropriate for this application. Therefore, there has been developed a new source of shock waves, which is based on the principle of multichannel discharge on the composite anode. The experiments demonstrated the effect of the new source on the acoustically homogeneous tissue of the thigh muscle at a depth of rabbit in vivo. Then there was observed the damage to tumor tissue in vivo in rats. Finally, there was observed the damage to tumor tissue in vivo in rats in the combination with cisplatin and Photosan. It was found that the new source of shock waves can cause the damage to the acoustically homogeneous tissue in vivo in depth. It also can damage the tumor...

Submitted by Luciana Ferreira (lucgeral@gmail.com) on 2016-03-03T13:38:21Z No. of bitstreams: 2 Tese - Vânia Beatriz Lopes - 2015.pdf: 1571381 bytes, checksum: 95d706025dea6373e88193f8224608f3 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2016-03-03T13:44:17Z (GMT) No. of bitstreams: 2 Tese - Vânia Beatriz Lopes - 2015.pdf: 1571381 bytes, checksum: 95d706025dea6373e88193f8224608f3 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Made available in DSpace on 2016-03-03T13:44:17Z (GMT). No. of bitstreams: 2 Tese - Vânia Beatriz Lopes - 2015.pdf: 1571381 bytes, checksum: 95d706025dea6373e88193f8224608f3 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Previous issue date: 2015-11-09 / Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq / The cysticercosis is endemic and is considered neglected by the World Health Organization. The neurocysticercosis (NCC) is the most common and severe form of cysticercosis, accounting for over 50,000 deaths annually. The use of experimental models in research, has been essential to the advancement of knowledge of various diseases, such as in understanding the pathophysiology, immune response and parasite host reactions. This study aimed to characterize the cellular immune response in situ and systemic, and the role of inflammatory cells in triggering changes in myelin standards. For this, we used an experimental model to evaluate the NCC intraventricular concentrations of cytokine in situ and systemically, by spleen cell culture, and changes in parenchymal patterns and periventricular desmielinizarão throughout the experimental period. No changes were detected in cytokine concentration at the infection site. Systemically, it is observed the presence of IL-10 initially and after 30 days of infection, there is a significant presence of all the cytokines analyzed as IL-4, IL-10, IL-17 and IFN-γ in the infected group. At the end of the infection, the Th2 profile was predominant. In evaluating pathological observed breaking the blood-brain barrier (BBB) allowing the initial influx of inflammatory cells in the two groups. At 30 days, there was a mixed inflammatory process, ventriculomegaly, foamy macrophages and periventricular desmielinizarão. At the end of the infection, predominance of mononuclear cells, ventriculomegaly, foamy macrophages and demyelination in the parenchyma mostly. In conclusion, the systemic immune response of BALB / c mice induced by cysticercus T. crassiceps, was characterized by a Th2-type immune profile and desmielinizarão parenchymal infection possibly at the end of the inflammatory process as well as the compressive effect on the parenchyma of the parasite brain. / A cisticercose é uma doença endêmica e é considerada negligenciada pela Organização Mundial de Saúde. A neurocisticercose (NCC) é a forma mais frequente e grave da cisticercose, sendo responsável por mais de 50 mil mortes anuais. A utilização de modelos experimentais em pesquisa tem sido essencial para o avanço do conhecimento de diversas doenças, como no entendimento da fisiopatologia, da resposta imune e das relações parasito hospedeiro. O presente estudo objetivou a caracterização da resposta imune celular in situ e sistêmica, e o papel das células inflamatórias em desencadear alterações nos padrões de mielina. Para isto, utilizou-se um modelo experimental de NCC intraventricular para avaliar as concentrações de citocinas in situ e sistemicamente, pela cultura de células do baço, e as alterações nos padrões de desmielinizarão periventricular e parenquimal ao longo do período experimental. Não foram detectadas alterações nas concentrações de citocinas no local da infecção. Sistemicamente, observa-se a presença de IL-10 inicialmente e aos 30 dias de infecção, observa-se a presença significante de todas as citocinas analisadas como, IL-4, IL-10, IL-17 e IFN-γ no grupo infectado. No final da infecção, o perfil Th2, foi predominante. Na avaliação anatomopatológica observou quebra da barreira hemato encefálica (BHE), que permitiu o influxo inicial de células inflamatórias nos dois grupos analisados. Aos 30 dias, observou-se processo inflamatório misto, ventriculomegalia, macrófagos espumosos e desmielinizarão periventricular. No final da infecção, predomínio de células mononucleares, ventriculomegalia, macrófagos espumosos e desmielinização no parênquima em sua maioria. Em conclusão, a resposta imune sistêmica dos camundongos BALB/c induzida por cisticercos de T. crassiceps, foi caracterizada por um perfil imune do tipo Th2e desmielinizarão parenquimal no final da infecção possivelmente pelo processo inflamatório como também pelo efeito compressivo do parasito sobre o parênquima encefálico.

Severe extremity trauma often involves significant damage to multiple tissue types, including bones, skeletal muscles, peripheral nerves, and blood vessels. Such injuries present unique challenges for reconstruction, and improving structural and functional outcomes of intervention remains a pressing, unmet clinical need. While tissue engineering/regenerative medicine (TE/RM) therapeutics offer promising potential to overcome the status quo limitations of surgical reconstruction, very few products have transitioned to clinical practice. Improving treatment options will likely require advancing our understanding of the biological interactions occurring in the repair of damaged tissues. Bone tissue is known to be innervated and highly vascularized, and both tissue types are involved in normal bone physiology. However, the degree to which these tissue relationships influence the repair of large, multi-tissue defects remains unknown. Accordingly, the goal of this thesis was to investigate tissue regeneration in two novel composite injury models. First, we characterized interactions in a composite bone and nerve injury model where a segmental bone defect was combined with a peripheral nerve gap. Our results indicated that although tissue regeneration was not impaired, the composite injury group experienced a marked functional deficit in the operated limb compared to single-tissue injury. Second, we developed a model of composite bone and vascular extremity trauma by combining a critically-sized segmental bone defect with surgically-induced hind limb ischemia to evaluate the effects on BMP-2-mediated bone repair. Interestingly, our results demonstrated a stimulatory effect of the recovery response to ischemia on bone regeneration. Finally, we investigated early vascular growth and gene expression as potential mechanisms coupling the response to ischemia with bone defect repair. Although the response to ischemia promoted robust vascular growth in the thigh, it did not directly augment vascularization at the site of bone regeneration. In addition, the stimulatory effects of ischemia on bone regeneration could not be explained by gene expression alone based on the genes and time points investigated. Taken together, this thesis presents pioneering work on a new thrust of TE/RM research – tissue regeneration in models of composite injury. This work has provided new insights on the complexity of composite tissue repair, specifically in regard to the relationship between vascular tissue growth and bone healing. Going forward, successful leverage of models of composite tissue injuries will provide valuable test beds for screening new technologies, advance the understanding of tissue repair biology, and ultimately, may produce new therapeutic interventions for limb salvage and reconstruction that improve outcomes for extremity trauma patients.

No description available.