Licentiatavhandling (sammanfattning) Linköping : Linköpings universitet, 2009. / Härtill 2 uppsatser.

Le pancréas est constitué de deux tissus : exocrine et endocrine. Le tissu endocrine est organisé en îlots de Langerhans, comprenant 5 sous-types cellulaires dont les deux principaux (α et β) sécrètent respectivement le glucagon et l’insuline. Le diabète de type 1 est une maladie auto-immune caractérisée par la perte des cellules β et donc une hyperglycémie chronique. Les thérapies actuelles sont efficaces mais contraignantes, amenant une partie de la recherche actuelle à déchiffrer les mécanismes de la genèse des cellules β et/ou de leur régénération pour tenter d’établir des thérapies alternatives. Des études ont permis de caractériser la cascade de facteurs de transcription différentiant les cellules progénitrices pancréatiques durant le développement, dont Neurog3 spécifiant le lignage endocrine et le gène Pax4 favorisant le lignage β. De précédents résultats nous ont amenés à établir l’hypothèse que les cellules canalaires pancréatiques contiendraient une source potentielle de précurseurs, qui par la réexpression de Neurog3 pourraient devenir endocrine, ce que nous avons analysé in vivo après avoir généré les souris transgéniques correspondantes. Nous avons observé un accroissement considérable de la taille des îlots, dû à une augmentation du nombre de chaque sous-type cellulaire endocrine. Nous démontrons que ces cellules endocrines supplémentaires ont bien une origine canalaires, tandis que des études physiologiques indiquent une réponse fonctionnelle de l’insuline suite à une injection de glucose. Finalement, nos analyses apportent également la preuve que le devenir de ces nouvelles cellules endocrines peut être modulé en agissant sur l’activité du gène Pax4. / The pancreas can be divided into two tissue types: exocrine and endocrine. The endocrine tissue is organized into clusters of cells named islets of Langerhans, comprising five cell subtypes of which the two main (α and β) secrete respectively glucagon and insulin. Type 1 diabetes is an auto-immune disease resulting in the loss of pancreatic β-cells and, consequently, in chronic hyperglycemia. Current therapies are efficient but remain highly binding, leading current research to aim at deciphering the β-cell genesis and/or regeneration to potentially establish new therapies. Many studies characterized the specific cascade of transcription factors differentiating pancreatic progenitor cells during development, including Neurog3 specifying the endocrine lineage and Pax4 favoring the β-cell lineage. Previous results obtained in the lab led us to establish the hypothesis that pancreatic ducts may contain a potential source of progenitor cells, which could become endocrine cells through re-expression of Neurog3. Thus, we investigated the consequences of the ectopic misexpression of Neurog3 in pancreatic duct cells in vivo. Using this strategy, we observed a dramatic increase in islet size, due to an augmentation in all endocrine cells types. Lineage tracing allowed us to demonstrate that the new endocrine cells have a ductal origin, while physiological studies displayed functional insulin response upon a glucose bolus. Finally, our analyses also demonstrated that the fate of these newly generated endocrine cells could be modulated by acting on the Pax4 gene.

Submitted by Ana Maria Fiscina Sampaio (fiscina@bahia.fiocruz.br) on 2016-09-12T13:42:31Z No. of bitstreams: 1 Manuela dos Santos Caldas Alterações Iniciais...2016.pdf: 7635538 bytes, checksum: 6a93fba431df86f82cdcef4c267b57b0 (MD5) / Approved for entry into archive by Ana Maria Fiscina Sampaio (fiscina@bahia.fiocruz.br) on 2016-09-12T13:54:54Z (GMT) No. of bitstreams: 1 Manuela dos Santos Caldas Alterações Iniciais...2016.pdf: 7635538 bytes, checksum: 6a93fba431df86f82cdcef4c267b57b0 (MD5) / Made available in DSpace on 2016-09-12T13:54:54Z (GMT). No. of bitstreams: 1 Manuela dos Santos Caldas Alterações Iniciais...2016.pdf: 7635538 bytes, checksum: 6a93fba431df86f82cdcef4c267b57b0 (MD5) Previous issue date: 2014-02-07 / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / O espaço-porta é o local de origem da fibrose em muitas doenças crônicas hepáticas. Essa área do fígado participa da drenagem linfática hepática e abriga diversos elementos celulares potencialmente fibrogênicos. Estudos sobre a fibrose hepática relacionados à infecção experimental de ratos pelo helminto Capillaria hepatica têm demonstrado que a fibrose começa em áreas portais com a distribuição de septos que sulcam o parênquima hepático se desenvolvendo em áreas próximas ao espaço de Disse. Entretanto, apesar de esta fibrose ocorrer de forma paralela aos sinusóides, estudos têm revelado que não apenas as células estreladas hepáticas participam da fibrose septal, mas também outros tipos celulares residentes nos espaços-porta. Diante destes aspectos, o presente estudo desenvolveu-se com o intuito de investigar a contribuição das células potencialmente fibrogênicas dos espaços-porta, nas fases iniciais da infecção, onde a fibrose se concentra. Para isso, foram utilizados fragmentos de fígado, em blocos parafinados, disponíveis nos arquivos do Laboratório de Patologia Experimental (CPqGM/Fiocruz) provenientes de ratos infectados com 800 ovos de Capillaria hepatica e foi possível observar que ocorreu a proliferação de colangiócitos e a concentração de miofibroblastos em áreas portais, além da ativação de células estreladas hepáticas, sendo todos os resultados vistos por meio da coloração de rotina HE, Picro-sírius vermelho e imunohistoquímica para α-actina de músculo liso, CD31 e GFAP. / Portal space is the local of origin for fibrosis in many chronic liver diseases. This area is involved with lymph drainage and contains several cell types, potentially fibrogenic. Experimental studies related to hepatic fibrosis during Capillaria hepatica infection in rats have suggested that the septal fibrosis indeed takes origin from portal spaces, with the distribution of the septs in the parenchymal region in proximity areas of Disse space. However, despite this fibrosis occurs in parallel to sinusoids, studies have revealed that not only the hepatic stellate cells participate in septal fibrosis, but also other resident cell types in the portal spaces. In face these aspects, the goal of present study was investigate the contribution of the cells potentially fibrogenic in the portal space, in the early phases of the infection. For this, blocks in paraffin available of the liver of rats infected with 800 eggs of Capillaria hepatica archived in the Laboratory of Experimental Pathology (Research Center Gonçalo Moniz, Fiocruz - BA), were utilized and it was observed that proliferation of colangiocytes and concentration of myofibroblasts occurred portal areas, in addition to the activation of hepatic stellate cells. All results were analised by routine staining HE, Sirius red and immunohistochemistry for α-SMA, GFAP and CD31

abstract: Fingerprints have been widely used as a practical method of biometrics authentication or identification with a significant level of security. However, several spoofing methods have been used in the last few years to bypass fingerprint scanners, thus compromising data security. The most common attacks occur by the use of fake fingerprint during image capturing. Imposters can build a fake fingerprint from a latent fingerprint left on items such as glasses, doorknobs, glossy paper, etc. Current mobile fingerprint scanning technology is incapable of differentiating real from artificial fingers made from gelatin molds and other materials. In this work, the adequacy of terahertz imaging was studied as an alternative fingerprint scanning technique that will enhance biometrics security by identifying superficial skin traits. Terahertz waves (0.1 – 10 THz) are a non-ionizing radiation with significant penetration depth in several non-metallic materials. Several finger skin features, such as valley depth and sweat ducts, can possibly be imaged by employing the necessary imaging topology. As such, two imaging approaches 1) using quasi-optical components and 2) using near-field probing were investigated. The numerical study is accomplished using a commercial Finite Element Method tool (ANSYS, HFSS) and several laboratory experiments are conducted to evaluate the imaging performance of the topologies. The study has shown that terahertz waves can provide high spatial resolution images of the skin undulations (valleys and ridges) and under certain conditions identify the sweat duct pattern. / Dissertation/Thesis / Masters Thesis Electrical Engineering 2017

Made available in DSpace on 2014-10-09T12:50:37Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T13:58:52Z (GMT). No. of bitstreams: 1 00621.pdf: 16649575 bytes, checksum: 34a61ca5ff67945244a79765b98ddb45 (MD5) / Tese (Doutoramento) / IEA/T / University of London

Made available in DSpace on 2014-10-09T12:50:37Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T13:58:52Z (GMT). No. of bitstreams: 1 00621.pdf: 16649575 bytes, checksum: 34a61ca5ff67945244a79765b98ddb45 (MD5) / Tese (Doutoramento) / IEA/T / University of London

Orientadores: Antonio Marcos Orsi, Sergio Luis Felisbino / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-09T10:45:56Z (GMT). No. of bitstreams: 1 Domeniconi_RaquelFantin_D.pdf: 10868266 bytes, checksum: 8bdfe8a912508f6afd1b6131f9f8934e (MD5) Previous issue date: 2007 / Resumo: Estudos recentes têm identificado família de proteínas denominadas aquaporinas (AQP), relacionadas à alta permeabilidade de água em várias membranas biológicas. As AQP1, AQP2, AQP7, AQP8 e AQP9 são as principais AQPs identificadas no sistema genital masculino, sendo a sua localização espécie-específica e região-específica. Em vista da importância do fluido luminal na via espermática para a integridade morfofuncional dos espermatozóides, bem como dos componentes que os constituem, tais como a água e proteínas, é importante estudar a distribuição das AQPs ao longo da via espermática. Assim, este trabalho teve como objetivos principais estudar no cão as AQP1, AQP2, AQP7, AQP8 e AQP9, visando identificá-las e localizá-las, através de imuno-histoquímica e ¿Western blotting¿ na via espermática. No cão, a AQP1 foi notada na rede testicular, ductos eferentes e em vasos, sugerindo sua importância na rápida absorção de fluido testicular. Pela primeira vez a AQP2 foi detectada na rede testicular, ductos eferentes e epidídimo, e a AQP7 no epitélio epididimário e ducto deferente em mamíferos. Porém, o papel funcional dessas AQPs no sistema genital masculino do cão permanece desconhecido. A AQP8 não foi detectada ao longo dos ductos extratesticulares do cão. A AQP9 foi abundantemente expressada ao longo da via espermática do cão, que representa um importante caminho apical para o fluxo transmembrana de água e solutos. Portanto, os resultados confirmam o padrão de expressão espécie-específica e região-específica das AQPs, sugerindo variações de atividades de absorção de fluidos e solutos ao longo da via espermática. O conhecimento destas variações torna-se relevante para estudos clínicos de infertilidade, bem como para tecnologias de reprodução assistida / Abstract: Recent studies have identified proteins called aquaporins (AQP) related to the fast water permeability in some biological membranes. AQPs are small, intrinsic membrane proteins that are present in many cell types involved in fluid transport. AQP1, AQP2, AQP7, AQP8 and AQP9 had been the main AQPs identified in the male reproductive tract, being their localization species-specific and region-specific. In view of the importance of the luminal fluid to sperm maturation and integrity of the spermatozoa, it is important to study the distribution of the AQPs throughout the spermatic way. Thus, the aim of this study was to examine the expression of AQP1, AQP2, AQP7, AQP8 e AQP9 in epithelial cells in the adult dog efferent ducts, epididymis and vas deferens, using immunohistochemistry and estern blotting methods to characterize the aquaporins in male reproductive tract. In dog, AQP1 was noted in rete testis, efferent ducts and in vessels in intertubular space, suggesting that AQP1 is important for rapid absorption of testicular fluid. For the first time the AQP2 was detected in rete testis, efferent ducts and epididymis and the AQP7 was expressed in the epithelium epididymidis and in vas deferens in mammals. But its functional role in the male dog reproductive tract, remain unknown. No specific staining for AQP8 was detected in epithelial cells of excurrent ducts in dog testis. AQP9 was abundantly expressed in dog male reproductive tract, in which it is an important apical pathway for transmembrane flow of water and neutral solutes. Thus the results confirm that the AQPs are species-specific and region-specific, suggesting activity variations related with the fluid and solute absorption throughout male excurrent ducts. Investigations of AQP biology could be relevant to clinical studies of the male reproductive tract, as well as to technologies for assisted procreation / Doutorado / Anatomia / Doutor em Biologia Celular e Estrutural

O fígado é um órgão importante para se analisar como o animal reage a agressões químicas. Um dos métodos utlizado para estudar a regeneração hepática é a hepatectomia parcial (HP). Assim, nosso objetivo foi verificar a influência da hepatectomia de 30% e de 70% sobre a taxa de proliferação das células hepática medida pela incorporação de BrdU na região da incisão e no resto do fígado e a proliferação de ductos biliares e de células epiteliais pré-ductulares biliares (CEPDBs) com o uso de uma combinação de 2 anticorpos específicos para citoqueratinas humanas, AE1/AE3. O pico de proliferação nos animais que sofreram HP de 30% do parênquima hepático deu-se após 1 dia da cirurgia enquanto que os animais que sofreram a HP de 70% o pico ocorreu no terceiro dia após a cirurgia.O índice de proliferação foi semelhante para a região próxima ou distante do corte. Para ambas as HP não houve diferença na regeneração do tecido retirado próximo ou distante da área de incisão. Nas regiões distantes da HP havia maior número de ductos havendo o pico do número de ductos coincidindo com o pico de proliferação celular de ambas as HP. Depois da HP o número de CEPDBs cresce consideravelmente. Os pico de proliferação também ocorreram no primeiro e terceiro dia para a HP de 30% e de 70% respectivamente, sendo mais altos na região distante do corte. Assim, durante a regeneração do fígado de C. gariepinus ocorre hiperplasia compensatória por proliferação de hepatócitos, de ductos biliares e de CEPDBs. A hepatectomia de 30% gerou uma resposta regenerativa intensa e é menos traumática para o animal, a região distante do corte reage mais intensamente que a região próxima do corte no que se refere aos ductos biliares e as CEPDBs. / The liver is an important organ in studies aimed to the verification of animals reactions to chemical injuries. The partial hepatectomy (PH) is one of the methods that are usually employed in hepatic regeneration experiments. Our objectives in this work were to verify the influence of 30% and 70% PH on the hepatic cells proliferation index as it is measured by BrdU nuclear uptake in two regions: close to the hepatic surgery region and in a farther region. The biliary ducts and bile preductular epithelial cells (BPDECs) proliferation was quantified with a combination of two antibodies against the human cytokeratins AE1/AE3. The proliferation index peak in 30% hepatectomy animals occurred one day after the surgery, but in 70% hepatectomy animals the peak was only observed after three days from the surgery. Differences between the proliferation index of the close and the far region were not observed and likewise histological differences were absent. In the regions far from the PH site more biliary ducts were counted than in closer regions, but the peaks were coincident in both regions with the hepatocytes proliferation index. It was also observed that the quantity of BPDECs increased. The peaks occurred in the first and third days for the 30% and 70% PH respectively, and both peaks were higher in the region far from the PH site. We may conclude that C. gariepinus liver regeneration after 30% and 70% PH occurs by means of compensatory hyperplasia by hepatocytes, biliary ducts and BPDECs proliferation. The 30% HP stimulated a strong regenerative response and is less traumatic to the animals. The regions far from the PH site reacts more intensely that the close region concerning the stimulation of biliary ducts and BPDECs proliferation.

Orientador: Elinton Adami Chaim / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-26T00:49:38Z (GMT). No. of bitstreams: 1 Machado_RicardoRossetto_M.pdf: 1957576 bytes, checksum: 8139974c79a4445e5f71c069dd543c8a (MD5) Previous issue date: 2014 / Resumo: Contexto: As lesões iatrogênicas da via biliar são de difícil manejo e requerem equipes com experiência para a reconstrução da via biliar. O objetivo desse estudo foi avaliar tardiamente os 21 anos de experiência em um centro de referência terciário das reconstruções bileodigestivas após a lesão iatrogênica da via biliar pós-colecistectomia e os fatores envolvidos na estenose da anastomose bileodigestiva. Métodos: Análise retrospectiva de 91 pacientes submetidos a hepaticojejunostomia em Y de Roux entre 1993 e 2013. Dados pré-operatórios, sintomas clínicos após a lesão, reoperações, classificação da lesão e evolução ambulatorial foram avaliados. O teste de qui-quadrado e a regressão logística foram usados para determinar os fatores envolvidos na estenose da anastomose bileodigestiva. Resultados: Mulheres eram 84,5% dos pacientes, média de idade de 43 anos. Foi observada associação entre fístula biliar e derivação bileodigestiva no serviço de origem (p=0,009). Colangite e sintomas clínicos no seguimento ambulatorial foram associadas com a classificação de Bismuth (p=0,008 e p<0,001). O aumento em uma unidade na aspartato aminotransferase em 12 meses de pós-operatório, aumentou a chance de apresentar sintomas clínicos no ambulatório em 4,8% (IC 95%=1,003-1,096). A derivação bileodigestiva no serviço de origem aumentou a chance de associação com fístula biliar em 5,9 vezes (IC 95%=1,132-31,142). Conclusão: A reconstrução da via biliar após a lesão iatrogênica no tratamento cirúrgico da colecistectomia deve ser realizado por cirurgiões experientes e, de preferência, em centros de referência terciário / Abstract: Background: Iatrogenic bile duct injuries are difficult to manage and require surgical teams with experience in bile duct repair. The aim of the study was to describe and correlate factors associated with biliary-enteric anastomosis stricture in a tertiary referral center. Methods: A retrospective analysis of 91 patients undergoing Roux-en-Y hepaticojejunostomy from 1993 to 2013 was carried out. Preoperative data, symptoms following injury, reoperations, classification of lesions and outpatient outcome were evaluated. The chi-square test and logistic regression were used to determine factors involved in biliary-enteric anastomosis stricture. Results: Women comprised 84.5% of patients (mean age: 43 years). An association between bile leakage and biliary-enteric anastomosis at the original health care facility (p=0.009) was observed. Cholangitis and symptoms in the outpatient facility were associated with Bismuth classification (p=0.008 and p<0.001). For each additional unit increase in aspartate aminotransferase values in the 12-month postoperative period, the likelihood of outpatient symptoms increased by 4.8% (95% CI=1.003-1.096). A biliary-enteric anastomosis performed at the original health care facility increased 5.9-fold the chance that a bile leakage was associated (95% CI=1.132-31.142). Conclusion: Bile duct reconstruction due to iatrogenic injury is challenging. To achieve success, repair must be performed by experienced surgeons in tertiary referral centers / Mestrado / Fisiopatologia Cirúrgica / Mestre em Ciências

O fígado é um órgão importante para se analisar como o animal reage a agressões químicas. Um dos métodos utlizado para estudar a regeneração hepática é a hepatectomia parcial (HP). Assim, nosso objetivo foi verificar a influência da hepatectomia de 30% e de 70% sobre a taxa de proliferação das células hepática medida pela incorporação de BrdU na região da incisão e no resto do fígado e a proliferação de ductos biliares e de células epiteliais pré-ductulares biliares (CEPDBs) com o uso de uma combinação de 2 anticorpos específicos para citoqueratinas humanas, AE1/AE3. O pico de proliferação nos animais que sofreram HP de 30% do parênquima hepático deu-se após 1 dia da cirurgia enquanto que os animais que sofreram a HP de 70% o pico ocorreu no terceiro dia após a cirurgia.O índice de proliferação foi semelhante para a região próxima ou distante do corte. Para ambas as HP não houve diferença na regeneração do tecido retirado próximo ou distante da área de incisão. Nas regiões distantes da HP havia maior número de ductos havendo o pico do número de ductos coincidindo com o pico de proliferação celular de ambas as HP. Depois da HP o número de CEPDBs cresce consideravelmente. Os pico de proliferação também ocorreram no primeiro e terceiro dia para a HP de 30% e de 70% respectivamente, sendo mais altos na região distante do corte. Assim, durante a regeneração do fígado de C. gariepinus ocorre hiperplasia compensatória por proliferação de hepatócitos, de ductos biliares e de CEPDBs. A hepatectomia de 30% gerou uma resposta regenerativa intensa e é menos traumática para o animal, a região distante do corte reage mais intensamente que a região próxima do corte no que se refere aos ductos biliares e as CEPDBs. / The liver is an important organ in studies aimed to the verification of animals reactions to chemical injuries. The partial hepatectomy (PH) is one of the methods that are usually employed in hepatic regeneration experiments. Our objectives in this work were to verify the influence of 30% and 70% PH on the hepatic cells proliferation index as it is measured by BrdU nuclear uptake in two regions: close to the hepatic surgery region and in a farther region. The biliary ducts and bile preductular epithelial cells (BPDECs) proliferation was quantified with a combination of two antibodies against the human cytokeratins AE1/AE3. The proliferation index peak in 30% hepatectomy animals occurred one day after the surgery, but in 70% hepatectomy animals the peak was only observed after three days from the surgery. Differences between the proliferation index of the close and the far region were not observed and likewise histological differences were absent. In the regions far from the PH site more biliary ducts were counted than in closer regions, but the peaks were coincident in both regions with the hepatocytes proliferation index. It was also observed that the quantity of BPDECs increased. The peaks occurred in the first and third days for the 30% and 70% PH respectively, and both peaks were higher in the region far from the PH site. We may conclude that C. gariepinus liver regeneration after 30% and 70% PH occurs by means of compensatory hyperplasia by hepatocytes, biliary ducts and BPDECs proliferation. The 30% HP stimulated a strong regenerative response and is less traumatic to the animals. The regions far from the PH site reacts more intensely that the close region concerning the stimulation of biliary ducts and BPDECs proliferation.