Thesis (doctoral)--Universität, Münster (Westfalen), 2003.

Thesis (M. S.)--University of Hong Kong, 2005. / Title proper from title frame. Also available in printed format.

FundaÃÃo Cearense de Apoio ao Desenvolvimento Cientifico e TecnolÃgico / As cirurgias de transplante de ÃrgÃos sÃlidos foram um dos principais avanÃos da medicina no Ãltimo sÃculo, tornando-se viÃveis apenas com o advento das drogas imunossupressoras, que possuem a capacidade de inibir a resposta do receptor contra o enxerto. Juntamente à evoluÃÃo dos fÃrmacos imunossupressores e das tÃcnicas cirÃrgicas, os riscos pÃs-operatÃrios passaram a ser mais conhecidos, sendo a infecÃÃo, principalmente a bacteriana, um dos principais motivos do insucesso do transplante. Dessa maneira, microorganismos orais tornam-se uma ameaÃa em potencial, embora estes nÃo sejam comumente citados como promotores de infecÃÃes pÃs-transplante na literatura. Dessa forma, à fundamental que o cirurgiÃo-dentista esteja ciente das principais alteraÃÃes orais encontradas nestes pacientes, e que conheÃa suas necessidades de tratamento, a fim de adotar condutas visando à remoÃÃo dos focos infecciosos e eliminaÃÃo do risco pÃs-operatÃrio. O objetivo deste trabalho foi descrever as condiÃÃes de saÃde oral e necessidade de tratamento odontolÃgico de um grupo de pacientes prÃ-transplante de ÃrgÃos sÃlidos. Foi realizado um estudo transversal observacional, mediante de coleta de dados e por exame intra-oral feito por um examinador calibrado. Foram examinados 113 pacientes, sendo 71 (62,83%) indicados para transplante renal, 37 (32,74%) para o hepÃtico e 05 (4,43%) para o cardÃaco. A mÃdia de idade foi de 42,13 anos e a comorbidade mais prevalente foi a hipertensÃo. O Ãndice CPOD mÃdio da amostra foi de 17,27 e o Ãndice Periodontal ComunitÃrio (CPI) mais prevalente durante o exame foi o 02, encontrado em 56 (49,6%) pacientes, indicando alta prevalÃncia de sangramento à sondagem gengival e presenÃa de cÃlculo. A maioria dos pacientes do estudo (81,32%) nÃo mostrou lesÃes de tecidos moles. Avaliando os exames radiogrÃficos, 56 (49,5%) dos indivÃduos apresentavam reabsorÃÃo Ãssea alveolar horizontal e 05 (4,43%) pacientes possuÃam terceiros molares parcialmente erupcionados. Quanto à necessidade de tratamento odontolÃgico, terapia periodontal era indicada em 81,5% dos pacientes, 69,9% possuÃam indicaÃÃo restauradora, 48,6% necessitavam realizar procedimentos cirÃrgicos e 9,7% com indicaÃÃo para tratamento endodÃntico. NÃo houve diferenÃa estatÃstica das variÃveis analisadas entre as trÃs indicaÃÃes de transplantes. Este estudo permitiu concluir que os pacientes examinados possuÃam alta prevalÃncia de doenÃas orais, como cÃrie e gengivite/periodontite, e, consequentemente, grande necessidade de tratamento odontolÃgico. Criteriosa avaliaÃÃo clÃnica deve ser realizada para submeter tais pacientes a procedimentos cruentos, minimizando os riscos hemorrÃgicos. AlÃm disso, hà a necessidade do enfoque à saÃde oral dentro dos serviÃos mÃdicos em pacientes portadores de graus diferentes de insuficiÃncia renal, hepÃtica ou cardÃaca, e nÃo somente durante a fase prÃ-transplante, minimizando as complicaÃÃes clÃnicas no curso do tratamento odontolÃgico trazidas pela doenÃa-base. / The replacement of diseased solid organs by healthy ones was one of the greatest advances in medicine in the last century, becoming viable only with the advent of immunosuppressive drugs, which have the ability to inhibit the response of the recipient against the graft. With the development of immunosuppressive drugs and surgical techniques, post-operative risks have become more known, being infection, mainly bacterial, one of the main reasons for the failure of the transplant. Then, microorganisms present in oral infections become a potential threat, even though they are not commonly cited as post-transplant infections promoters on literature. So, it is essential that dentists known the major oral alterations in these patients, and their needs for treatment in order to adopt a conduct to remove oral infections, and eliminating the postoperative risk. The objective of this study was to assess the oral health status and necessity of dental procedures in a group of solid organ transplant candidates. A cross sectional observational study was realized, collecting data from medical records and by an intra-oral exam, realized by a calibrated examiner. A total of 113 patients were examined, being 71 (62.83%) indicated for renal transplantation, 37 (32.74%) for hepatic and 05 (4.43%) for cardiac. The mean age was 42.13 years, and the most prevalent comorbidity was hypertension. The average DMFT index was 17.27 and the most prevalent Community Periodontal Index (CPI) was 02, found in 56 (49.6%) patients, indicating a high prevalence of gingival bleeding on probing and presence of calculus. Most patients in the study (81.32%) showed no soft-tissue lesions. Evaluating the radiographic exams, 56 (49.5%) individuals had horizontal alveolar bone resorption, and 05 (4.43%) patients had partially erupted third molars. Assessing the necessity of dental treatment, periodontal therapy was indicated in 81.5% of patients, 69.9% had restorative indication, 48.6% needed surgical procedures, and 9.7% had indication for endodontic treatment. There was no statistical difference of variables between the three transplant indications. This study concluded that the examined patients had high prevalence of oral diseases, such as caries and gingivitis/periodontitis, and, therefore, a high indication for dental treatment. Careful clinical evaluation should be performed for patients with indication for surgical procedures, minimizing the hemorrhagic risk. Moreover, there is a necessity to focus on oral health promotion within the medical services in patients with different degrees of renal, liver or heart failure, not only during the pre-transplant period, reducing the clinical complications caused by the systemic disease during dental treatment.

M. Tech. / Stem cells are regarded as undifferentiated cells that are capable of selfrenewal, proliferation, production of a great number of differentiated progeny, and regeneration of tissues (Blau et al., 2001). The therapeutic potential of multilineage stem cells for tissue engineering (TE) applications is vast. Two general types of stem cells are potentially useful for this application: embryonic stem cells (ESCs) and adult (autologous) stem cells (Zuk et al., 2001). Traditionally, ESCs are isolated from the inner cell mass (ICM) of blastocysts, however harvesting of these cells results in the death of the embryo, which has led to ethical, religious and political issues (Moore, 2007). In contrast, adult stem cells, by virtue of their nature, are immunocompatible and have no ethical issues associated with their use (Zuk et al., 2001). Subcutaneous adipose tissue is an active and highly complex tissue composed of several different cell types, and is derived from the mesodermal germ layer and contains a supportive stromal vascular fraction (SVF) that can be easily isolated. This SVF contains a heterogeneous mixture of cells including preadipocytes (Raposio et al., 2007; Schäffler and Büchler, 2007; Jurgens et al., 2008). The preadipoctyes are considered as the multipotent stem cells termed adipose derived stem cells (ADSCs) that have similar properties to bone marrow mesenchymal stem cells (BM-MSCs) (Fraser et al., 2006). ADSCs are idyllic for cellular therapy applications due to various factors: they can be harvested, multiplied and handled easily, efficiently and noninvasively, they have a pluripotential and proliferative capacity comparable to BM-MSCs, and morbidity to donors is considerably less, requiring only local anaesthesia and a short wound healing time. Human ADSCs (hADSCs) can be expanded in an undifferentiated state and have multipotential differentiation capacity along the classical mesenchymal lineages of adipogenesis, osteogenesis, chondrogenesis and myogenesis (de Villiers et al., 2009).

As rising sea temperatures and increases in the frequency, duration, and intensity of marine heatwaves threaten coral survival at a global scale, research on the capacity of corals to acclimatize and adapt to changing environments has become a high priority. Understanding how environmental parameters shape coral thermal performance across habitats is crucial to identify populations with high vulnerability or high thermal tolerance to future ocean warming. In recent studies, corals from high temperature variable environments (HVE) have shown increased thermal tolerance compared to corals from low temperature variable environments (LVE). Here, I investigate if these phenotypes are shaped by acclimatization, habitat-specific adaptation, or a combination of both, in the branching coral, Acropora hemprichii, by reciprocally transplanting individuals between a back (HVE) and front reef (LVE). After ten months of acclimatization, comparisons of photosynthetic efficiency (photosystem II), mortality, and bleaching recovery was assessed for > 2 months between coral ramets following a natural bleaching event in the central Red Sea. In tandem, coral bleaching severity and recovery in each reef environment was assessed to genus level by photographic surveys of fixed belt transects. Bleaching between reef sites was compared against bleaching in treatments to differentiate the role of habitat specific adaptation and acclimatization in the corals. This study aims to elucidate the evolutionary mechanisms driving coral habitat-specific thermal stress tolerances, which may inform coral reef management and restoration efforts.

Indiana University-Purdue University Indianapolis (IUPUI) / Solid organ transplantation is severely limited by a shortage of available donor allografts. Pig-to-human xenotransplantation offers a potential solution to this growing problem. For xenotransplantation to achieve clinical relevance, both immunologic and physiologic barriers must be understood. Genetic modification of pigs has proven to be a valuable means of both studying and eliminating these barriers. The present body of work describes a method for greatly increasing the efficiency and precision of genome editing within the porcine genome. By combining non-integrating selection and homologous recombination of exogenous oligonucleotides, a method for rapidly creating genetic modification without reliance on phenotypic sorting was achieved. Furthermore this work employs the technique of CRISPR/Cas9-directed mutagenesis to create and analyze several new animal models of porcine-to-human xenotransplantation with respect to both immunologic and physiologic parameters. First, Isoglobotrihexosylceramide -a controversial glycan to the field of xenotransplantation- was studied in a knockout model and found not to affect human-anti-porcine humoral reactions. Second, a new combination of glycan modifications is described that significantly lowers the human anti-porcine humoral immune response. This model animal suggests that glycan-deletion alone will be sufficient to promote clinical application, and that conventional immunosuppression will be successful in mediating the human cellular response. Finally, two potential physiologic barriers to xenotransplantation are studied in genetically modified model animals. Xenogenic consumption of human platelets was studied across hepatic and renal organ systems; xenogenic platelet consumption was reduced by glycan modifications to the porcine liver while human platelet sequestration was not identified in the study of renal endothelium. Porcine FcRN –an essential receptor expressed in kidneys to maintain serum proteostasis- was studied as a final potential barrier to pig-to human renal transplantation. Because albumin is the primary driver of serum oncotic pressure, the protein-protein interaction of endogenous porcine FcRN and human albumin was studied. Porcine FcRN was found capable of binding human albumin under physiologic parameters. In summary, the results of the present work suggest that the salient barriers to clinical xenotransplantation have been removed and that porcine-to human renal transplantation may soon offer an answer to the current organ shortage.

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

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