The goal of hematopoietic stem cell transplantation (HSCT) is to induce graft-versus-tumor effect (GVT), which is the recognition of and response against tumor- associated antigens (TAAs) by donor immune cells to clear the recipient of residual tumor. A complication of HSCT as a treatment for hematologic malignancies is graft-versus-host disease (GVHD), which is the recognition and reactivity of donor immune cells against healthy tissues. As of now, the differentiation between GVHD and GVT effects has been a hindrance to the development of effective therapies against GVHD. Certain T cell clones may induce both GVHD and GVT effects, making targeted therapy of GVHD difficult. This project was aimed to uncover differences at a molecular level of the T cell recognition site that exist between patients with GVHD and those with GVHD-free survival following allogeneic HSCT. We found that there are inherent differences in the T cell receptor at a molecular level between patients experiencing GVHD and those that are GVHD-free, suggesting the ability of T cells to distinguish tumor cells from self cells. In addition, the intention was to reveal differences in proportions of engrafted donor T cells and stem cells and the effects of these proportions on the severity, outcome, and prognosis of GVHD. We additionally found that a lower proportion of stem cells to T cells was associated with the trend of GVHD, while a higher frequency of T cells engrafted into host may indicate resistance to treatment and a poor prognosis. These data suggest that allogeneic HSCT may be improved by optimizing the proportion of T cells to stem cells in the transplant as well as developing targeted therapy against GVHD-associated T cell clones while rescuing GVT-associated T cell clones.

Ce travail de thèse porte sur la simulation du déploiement des prothèses vasculaires de type stent-graft (SG) lors de la réparation endovasculaire (EVAR) des anévrismes de l’aorte abdominale (AAA). Cette étude se présente en trois parties: (i) tests mécaniques en flexion et compression de SG couramment utilisés (corps et jambage de marque Cook) ainsi que la simulation numérique desdits tests, (ii) développement d’un modèle numérique d’anévrisme, (iii) stratégie de simulation du déploiement des SG. La méthode numérique employée est celle des éléments finis. Dans un premier temps, une vérification du modèle éléments finis (MEF) des SG est realisée par comparaison des différents cas de charge avec leur pendant expérimental. Ensuite, le MEF vasculaire (AAA) est lui aussi vérifié lors d’une comparaison des niveaux de contraintes maximales principales dans la paroi avec des valeurs de la littérature. Enfin, le déploiement est abordé tout en intégrant les cathéters. Les tests mécaniques menés sur les SG ont été simulés avec une différence maximale de 5,93%, tout en tenant compte de la pré-charge des stents. Le MEF de la structure vasculaire a montré des contraintes maximales principales éloignées de 4,41% par rapport à un modèle similaire précédemment publié. Quant à la simulation du déploiement, un jeu complet de SG a pu être déployé avec un bon contrôle de la position relative et globale, dans un AAA spécifique pré-déformé, sans toutefois inclure de thrombus intra-luminal (TIL). La paroi du AAA a été modélisée avec une loi de comportement isotropique hyperélastique. Étant donné que la différence maximale tolérée en milieu clinique entre réalité et simulation est de 5%, notre approche semble acceptable et pourrait donner suite à de futurs développements. Cela dit, le petit nombre de SG testés justifie pleinement une vaste campagne de tests mécaniques et simulations supplémentaires à des fins de validation. / This thesis work is concerned with the simulation of the deployment of stent-graft (SG) vascular prostheses in abdominal aortic aneurysms (AAA) during endovascular repair (EVAR). This study is composed of three main parts: (i) mechanical tests in bending and compression of frequently used SG (body and leg from Cook) as well as the numerical simulation of these tests, (ii) development of a numerical AAA model, (iii) strategy of simulation of SG deployment. The finite element method is used. In a first step, a verification of the finite element model (FEM) of SG is performed by comparison of the different load cases with their experimental counterparts. Subsequently, the vascular FEM is also verified in terms of maximal principal constraints in the wall against values available in the literature. Finally, the deployment is investigated while taking the catheters into account. The mechanical tests performed on the SG were simulated with a maximal difference of 5.93%, while accounting for the pre-load in stents. The FEM of the vascular structure showed maximal principal stresses that were 4.41% far from the ones found in the literature for a similar model. Regarding the simulation of SG deployment, a complete set of SG could be deployed with a good control of the relative and global position into a specific and pre-deformed AAA, however, no intra-luminal thrombus (ILT) was included. The AAA wall was modeled with an isotropic hyperelastic constitutive law. In the clinical setting, the maximum tolerated difference between reality and simulation is 5%, therefore, our approach seems acceptable, and could give rise to further developments. However, the small amount of tested SG justifies a wide campaign of additional mechanical tests and simulations for the sake of validation.

Implantation and the care of vascular reconstructions and accesses for haemodialysis is one of areas of cardiovascular surgery. Both vascular reconstructions, known as bypasses, and prosthetic haemodialytic accesses, known as grafts, are used only if conventional therapies are unsuccessful. Thus effectivity of these operations is critically important for patient survival. The aim of this thesis is development of software system for evidence data obtained during vascular operations and following checkups. Important is also support for basic analytical and statistical processing of collected data. Another goal is to transform collected data into knowledge useful for increasing effectivity of vascular operations.

Bone grafts and titanium implants are commonly used for surgical/prosthetic rehabilitation of the atrophic edentulous maxilla. The factors which influence bone graft healing and implant integration are not sufficiently understood. The aim of this dissertation was to evaluate autogenous bone grafting and delayed placement of titanium endosteal implants for reconstruction of the atrophic maxilla, including the effects of different patient factors on bone graft healing and integration of titanium implants into grafted bone. A total of 46 patients with severe maxillary atrophy received onlay- (n=35) or interpositional bone grafts (n=11) and 6 mo. later received 341 titanium endosteal implants. All bone grafts were harvested from the iliac crest. All patients received fixed dental bridges and were followed clinically and with radiographical examinations for 3 yr. In Papers I and II, a total of 68 titanium microimplants were placed and retrieved from the bone grafts at various time points for histological analysis of the bone graft-implant interface. Integration was better after 6 mo. healing than placement in conjunction with bone grafting. Implant integration was similar for the two bone-grafting techniques. In Papers III and IV, originally including 29 patients and 222 implants, implant stability was measured with resonance frequency analysis (RFA) at placement, abutment connection, after 6 mo. of loading (III) and after 3 yr. of loading (IV). Ten non-grafted patients measured at the same time points were used as controls (III). RFA showed equal implant stability in grafted bone vs. non-grafted bone (III). Stability did not change from the 6-mo. to the 3-yr. control. Cumulative survival was 90% after 3 yr. (21 implants failed). Thirteen implants were lost prior to loading and 8 during functional loading. The group of failed implants showed a lower primary RFA stability than those that remained stable for 3 yr. All patients received and maintained a fixed dental bridge throughout the study. In Paper V, the graft volume changes (GVC) during the 6-mo. healing period prior to implant placement were studied in 30 patients using computerized tomography. Blood samples were taken from 25 patients in conjunction with bone grafting and were analysed for 13 haematological factors. Bone mineral density (BMD) was measured in 21 patients. Biopsies of the bone grafts were analysed for bone volume fraction (BVF). GVC (loss) was correlated with decreased BMD of the lumbar vertebrae L2-L4. There was no correlation between the haematological factors and GVC. Implant failure was not correlated with BMD, BVF or GVC. This dissertation shows that surgical/prosthetic rehabilitation of the atrophic edentulous maxilla with autogenous iliac crest bone grafts and delayed placement of titanium implants after 6 mo. of graft healing is effective, reproducible and functional. RFA at placement may be able to predict later implant failure.

Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 4 uppsatser.

Thesis (doctoral)--Katholieke Universiteit te Nijmegen.

NASCIMENTO, Joyce Kelly Melo. Membranas de quitosana-graft-acrilato de sódio incorporadas com nanopartículas de prata para o desenvolvimento de curativos. 2012. 77 f. Dissertação (Mestrado em química)- Universidade Federal do Ceará, Fortaleza-CE, 2012. / Submitted by Elineudson Ribeiro (elineudsonr@gmail.com) on 2016-06-02T18:19:16Z No. of bitstreams: 1 2012_dis_jkmnascimento.pdf: 1875159 bytes, checksum: 3b7fcf890b841321d324440bd2b45087 (MD5) / Approved for entry into archive by José Jairo Viana de Sousa (jairo@ufc.br) on 2016-06-21T23:21:39Z (GMT) No. of bitstreams: 1 2012_dis_jkmnascimento.pdf: 1875159 bytes, checksum: 3b7fcf890b841321d324440bd2b45087 (MD5) / Made available in DSpace on 2016-06-21T23:21:39Z (GMT). No. of bitstreams: 1 2012_dis_jkmnascimento.pdf: 1875159 bytes, checksum: 3b7fcf890b841321d324440bd2b45087 (MD5) Previous issue date: 2012 / Silver nanoparticles (NPsAg) can be obtained by chemical, physical and biological methods. One of the most used methods is based on chemical reduction with sodium borohydride in the presence of stabilizers. Chitosan can act as NPsAg stabilizer. The grafting of acrylic monomers in the side chain of chitosan gives copolymers with improved physical roperties. Type graft copolymer based on chitosan and sodium acrylate was obtained by copolymerizing a system solution using free radical initiation, and from this membrane were prepared. NPsAg membranes were synthesized by the method of reduction with borohydride. The copolymer was characterized by proton absorption in the infrared (FTIR), thermogravimetric analysis, differential scanning calorimetry, elemental analysis, absorption capacity in water and scanning electron microscopy. The reason monomer / polysaccharide used in the reaction was 1/2. The grafting percentage was 49%. FTIR and elemental analysis confirmed the formation of the copolymer. Observed absorption capacity water membrane of the copolymer 13% higher compared to chitosan membrane, confirming the efficiency of grafting of the sodium acrylate in increasing hydrophilicity of the material. Nanocomposite chitosan-graft-sodium acrylate / Ag were obtained by varying the concentrations of silver nitrate (2, 5 and 10 mmol.L-1) and sodium borohydride (40, 100 and 200 mmol.L-1) added to the membranes. The nanocomposites were characterized by spectrophotometry in the UV-Vis region. The Color changes in the membranes from light yellow to dark brown shows the formation of silver nanoparticles. The analysis showed UV-Vis absorption bands in the region of 430 nm, confirming the formation of silver nanoparticles in the membranes of the copolymer. The displacement of the plasmon band of the samples 2/40, 5/100 and 10/200 mmol.L-1, respectively, for shorter wavelengths demonstrate that decreased particle diameter with increasing concentration of silver ions. The bacteriological test showed that the nanocomposite membranes exhibit antibacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa species. studies Preliminary indicate that the nanocomposite has potential for the study with potential application as dermatological dressing. / Nanopartículas de prata (NPsAg) podem ser obtidas por métodos químicos, físicos e biológicos. Um dos métodos mais utilizados baseia-se na redução química com boroidreto de sódio, na presença de estabilizantes. Quitosana pode agir como estabilizante de NPsAg. A enxertia de monômeros acrílicos na cadeia lateral da quitosana origina copolímeros com ropriedades físicas melhoradas. Copolímero do tipo enxertado à base de quitosana e acrilato de sódio foi obtido por copolimerização em solução utilizando um sistema de iniciação via radical livre e a partir deste foram preparadas membranas. NPsAg foram sintetizadas nas membranas por método de redução com boroidreto. O copolímero foi caracterizado por espectroscopia de absorção na região do infravermelho (FTIR), análise termogravimétrica, calorimetria exploratória diferencial, análise elementar, capacidade de absorção em água e microscopia eletrônica de varredura. A razão monômero/polissacarídeo utilizada na reação foi de 1/2. A porcentagem de enxertia foi de 49%. FTIR e análise elementar confirmaram a formação do copolímero. Observou-se uma capacidade de absorção de água da membrana do copolímero 13% maior em relação à membrana de quitosana, confirmando a eficiência da enxertia do acrilato de sódio no aumento da hidrofilicidade do material. Nanocompósitos quitosana-graft-acrilato de sódio/Ag foram obtidos variando-se as concentrações de nitrato de prata (2, 5 e 10 mmol.L-1) e boroidreto de sódio (40, 100 e 200 mmol.L-1) adicionados às membranas. Os nanocompósitos foram caracterizados por espectrofotometria na região do UV-Vis. A mudança nas cores das membranas de amarelo claro para marrom escuro evidencia a formação das nanopartículas de prata. A análise por UV-Vis mostrou bandas de absorção na região de 430 nm, confirmando a formação das nanopartículas de prata nas membranas do copolímero. O deslocamento da banda plasmônica das amostras 2/40, 5/100 e 10/200 mmol.L-1, respectivamente, para menores comprimentos de onda demonstra que houve diminuição do diâmetro das partículas à medida que aumenta a concentração do íons prata. O teste bacteriológico mostrou que as membranas dos nanocompósitos apresentam atividade antibacteriana contra as espécies Staphylococcus aureus e Pseudomonas aeruginosa. Os estudos preliminares indicam que o nanocompósito apresenta potencial para o estudo com potencial aplicação como curativo dermatológico.

Made available in DSpace on 2014-06-11T19:35:03Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-06-06Bitstream added on 2014-06-13T21:07:04Z : No. of bitstreams: 1 macedo_lgs_dr_sjc.pdf: 1328056 bytes, checksum: 2dc22b18ce2b29898eeed7a8c9f63b1d (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / A utilização de enxerto ósseo autógeno previamente à instalação de implantes osseointegráveis tem apresentado bons resultados, entretanto, a necessidade de uma segunda área cirúrgica como fonte doadora e o grau de morbidade da técnica têm direcionado a busca por alternativas seguras para a reconstrução óssea. O propósito desta pesquisa foi avaliar o efeito do enxerto de osso alógeno fresco congelado, oriundo de Banco de Tecido, em comparação ao autógeno no processo de reparação de enxertos na calvária de coelhos. Foram utilizados 15 coelhos adultos, nos quais foram realizados 2 enxertos em blocos nos ossos parietais, divididos aleatoriamente nos seguintes grupos de acordo com o tratamento: autógeno (A – enxerto com osso autógeno) e alógeno (B – enxerto com osso alógeno processado em Banco). Decorridos 15, 30 e 60 dias, 5 animais foram sacrificados por período, sendo as peças contendo os enxertos processadas para análises histológica e histomorfométrica. Os resultados foram submetidos ao teste RM ANOVA e de comparação múltipla de Tukey, demonstrando diferenças estatisticamente significantes entre os grupos e entre os tempos estudados. Concluímos que o enxerto alógeno promove formação óssea, porém em menor quantidade e de forma mais lenta em comparação ao enxerto autógeno / The use of autogenous bone graft prior to installation of dental implants has shown good results, however, the need for a second surgical site and donor source and degree of morbidity of the technique have led the search for safe alternatives to bone reconstruction. The purpose of this study was to evaluate the effect of allogeneic bone graft, fresh frozen from Bank of tissue, as compared to autograft in the repair of calvarial grafts in rabbits. A total of 15 adult rabbits, in which grafts were performed in two blocks in the parietal bone were divided randomly into four groups according to treatment: autogenous (A - with autogenous bone graft) and allogeneic (B - allogeneic bone graft processed in Bank Bone). After 15, 30 and 60 days, five animals were sacrificed by period, and the pieces containing the grafts were processed for histology and histomorphometry. The results were submitted to the RM ANOVA and Tukey's multiple comparison, statistically significant differences between groups and between time points. We conclude that allograft promotes bone formation, but fewer and more slowly compared to autografts

Orientador: Marco Antonio Bottino / Banca: Lafayette Nogueira Jr. / Banca: Wilson Roberto Sendyk / Banca: Márcia Carneiro Valera Garakis / Banca: Renata Faria / Resumo: A utilização de enxerto ósseo autógeno previamente à instalação de implantes osseointegráveis tem apresentado bons resultados, entretanto, a necessidade de uma segunda área cirúrgica como fonte doadora e o grau de morbidade da técnica têm direcionado a busca por alternativas seguras para a reconstrução óssea. O propósito desta pesquisa foi avaliar o efeito do enxerto de osso alógeno fresco congelado, oriundo de Banco de Tecido, em comparação ao autógeno no processo de reparação de enxertos na calvária de coelhos. Foram utilizados 15 coelhos adultos, nos quais foram realizados 2 enxertos em blocos nos ossos parietais, divididos aleatoriamente nos seguintes grupos de acordo com o tratamento: autógeno (A - enxerto com osso autógeno) e alógeno (B - enxerto com osso alógeno processado em Banco). Decorridos 15, 30 e 60 dias, 5 animais foram sacrificados por período, sendo as peças contendo os enxertos processadas para análises histológica e histomorfométrica. Os resultados foram submetidos ao teste RM ANOVA e de comparação múltipla de Tukey, demonstrando diferenças estatisticamente significantes entre os grupos e entre os tempos estudados. Concluímos que o enxerto alógeno promove formação óssea, porém em menor quantidade e de forma mais lenta em comparação ao enxerto autógeno / Abstract: The use of autogenous bone graft prior to installation of dental implants has shown good results, however, the need for a second surgical site and donor source and degree of morbidity of the technique have led the search for safe alternatives to bone reconstruction. The purpose of this study was to evaluate the effect of allogeneic bone graft, fresh frozen from Bank of tissue, as compared to autograft in the repair of calvarial grafts in rabbits. A total of 15 adult rabbits, in which grafts were performed in two blocks in the parietal bone were divided randomly into four groups according to treatment: autogenous (A - with autogenous bone graft) and allogeneic (B - allogeneic bone graft processed in Bank Bone). After 15, 30 and 60 days, five animals were sacrificed by period, and the pieces containing the grafts were processed for histology and histomorphometry. The results were submitted to the RM ANOVA and Tukey's multiple comparison, statistically significant differences between groups and between time points. We conclude that allograft promotes bone formation, but fewer and more slowly compared to autografts / Doutor

NanopartÃculas de prata (NPsAg) podem ser obtidas por mÃtodos quÃmicos, fÃsicos e biolÃgicos. Um dos mÃtodos mais utilizados baseia-se na reduÃÃo quÃmica com boroidreto de sÃdio, na presenÃa de estabilizantes. Quitosana pode agir como estabilizante de NPsAg. A enxertia de monÃmeros acrÃlicos na cadeia lateral da quitosana origina copolÃmeros com ropriedades fÃsicas melhoradas. CopolÃmero do tipo enxertado à base de quitosana e acrilato de sÃdio foi obtido por copolimerizaÃÃo em soluÃÃo utilizando um sistema de iniciaÃÃo via radical livre e a partir deste foram preparadas membranas. NPsAg foram sintetizadas nas membranas por mÃtodo de reduÃÃo com boroidreto. O copolÃmero foi caracterizado por espectroscopia de absorÃÃo na regiÃo do infravermelho (FTIR), anÃlise termogravimÃtrica, calorimetria exploratÃria diferencial, anÃlise elementar, capacidade de absorÃÃo em Ãgua e microscopia eletrÃnica de varredura. A razÃo monÃmero/polissacarÃdeo utilizada na reaÃÃo foi de 1/2. A porcentagem de enxertia foi de 49%. FTIR e anÃlise elementar confirmaram a formaÃÃo do copolÃmero. Observou-se uma capacidade de absorÃÃo de Ãgua da membrana do copolÃmero 13% maior em relaÃÃo à membrana de quitosana, confirmando a eficiÃncia da enxertia do acrilato de sÃdio no aumento da hidrofilicidade do material. NanocompÃsitos quitosana-graft-acrilato de sÃdio/Ag foram obtidos variando-se as concentraÃÃes de nitrato de prata (2, 5 e 10 mmol.L-1) e boroidreto de sÃdio (40, 100 e 200 mmol.L-1) adicionados Ãs membranas. Os nanocompÃsitos foram caracterizados por espectrofotometria na regiÃo do UV-Vis. A mudanÃa nas cores das membranas de amarelo claro para marrom escuro evidencia a formaÃÃo das nanopartÃculas de prata. A anÃlise por UV-Vis mostrou bandas de absorÃÃo na regiÃo de 430 nm, confirmando a formaÃÃo das nanopartÃculas de prata nas membranas do copolÃmero. O deslocamento da banda plasmÃnica das amostras 2/40, 5/100 e 10/200 mmol.L-1, respectivamente, para menores comprimentos de onda demonstra que houve diminuiÃÃo do diÃmetro das partÃculas à medida que aumenta a concentraÃÃo do Ãons prata. O teste bacteriolÃgico mostrou que as membranas dos nanocompÃsitos apresentam atividade antibacteriana contra as espÃcies Staphylococcus aureus e Pseudomonas aeruginosa. Os estudos preliminares indicam que o nanocompÃsito apresenta potencial para o estudo com potencial aplicaÃÃo como curativo dermatolÃgico. / Silver nanoparticles (NPsAg) can be obtained by chemical, physical and biological methods. One of the most used methods is based on chemical reduction with sodium borohydride in the presence of stabilizers. Chitosan can act as NPsAg stabilizer. The grafting of acrylic monomers in the side chain of chitosan gives copolymers with improved physical roperties. Type graft copolymer based on chitosan and sodium acrylate was obtained by copolymerizing a system solution using free radical initiation, and from this membrane were prepared. NPsAg membranes were synthesized by the method of reduction with borohydride. The copolymer was characterized by proton absorption in the infrared (FTIR), thermogravimetric analysis, differential scanning calorimetry, elemental analysis, absorption capacity in water and scanning electron microscopy. The reason monomer / polysaccharide used in the reaction was 1/2. The grafting percentage was 49%. FTIR and elemental analysis confirmed the formation of the copolymer. Observed absorption capacity water membrane of the copolymer 13% higher compared to chitosan membrane, confirming the efficiency of grafting of the sodium acrylate in increasing hydrophilicity of the material. Nanocomposite chitosan-graft-sodium acrylate / Ag were obtained by varying the concentrations of silver nitrate (2, 5 and 10 mmol.L-1) and sodium borohydride (40, 100 and 200 mmol.L-1) added to the membranes. The nanocomposites were characterized by spectrophotometry in the UV-Vis region. The Color changes in the membranes from light yellow to dark brown shows the formation of silver nanoparticles. The analysis showed UV-Vis absorption bands in the region of 430 nm, confirming the formation of silver nanoparticles in the membranes of the copolymer. The displacement of the plasmon band of the samples 2/40, 5/100 and 10/200 mmol.L-1, respectively, for shorter wavelengths demonstrate that decreased particle diameter with increasing concentration of silver ions. The bacteriological test showed that the nanocomposite membranes exhibit antibacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa species. studies Preliminary indicate that the nanocomposite has potential for the study with potential application as dermatological dressing.