Thesis (M. Med. Sc.)--University of Hong Kong, 2001. / Includes bibliographical references (leaves 44-57).

Thesis (M.S.)--Ohio State University, 2009. / Title from first page of PDF file. Includes vita. Includes bibliographical references (p. 68-76).

As implant survival extends into the second and third decades focal osteolysis around cemented femoral components in total hip replacement is emerging as an important failure mechanism. Whilst the problem of focal osteolysis is well recognised, there are many aspects of its development which are poorly understood. The broad aim of this thesis is to try to provide some insights into how, why and where focal osteolysis develops around the cemented femoral component. There are broadly two sections to this thesis, chapters 2-5 present clinical and geometrical studies and chapters 6-10 a series of experimental studies. The aim of the first section was to establish what is observed in clinical practice, the aim of the second to try to explain these findings. A mid-term clinical study showed that focal osteolysis is more common with rough than polished stems that differed in no aspect other than their surface finish. Further studies established that focal osteolysis is probably always associated with defects in the cement mantle. These defects occur anteriorly at the mid-stem of the prosthesis and posteriorly at the component tip. The distribution of focal osteolysis and its strong association with cement mantle defects suggests the importance of the stemcement interface as a pathway for fluid and debris to reach the distal femur. However, at 15-25 years, osteolysis rarely develops with the polished Exeter stem even in the presence of confirmed defects in the cement mantle, suggesting that the stem seals the stem-cement interface against fluid and debris. In an attempt to explain the clinical findings a series of bench top experiments were undertaken. These studies showed that the behaviour of fluid and dye at the stemcement interface was significantly influenced by component surface finish. Bonded and debonded stem-cement interfaces of rough stems provided an incomplete barrier to fluid movement along this interface. In contrast, polished stems both bonded and debonded were able to provide a seal at the stem-cement interface. The seal at this interface was improved with component subsidence in the presence of rotational stability. It is believed that this thesis provides a rationale explanation for why focal osteolysis rarely develops around the Exeter stem in clinical practice. It also explains how, where, and why osteolysis develops around certain designs of cemented femoral components used in total hip replacement.

Diss. (sammanfattning) Umeå : Umeå universitet, 2005. / Härtill 4 uppsatser.

Thesis (M.S.)--California Polytechnic State University, 2009. / Title from PDF title page; viewed on September 25, 2009. Major professor: Scott Hazelwood, Ph.D. "Presented to the faculty of California Polytechnic State University, San Luis Obispo." "In partial fulfillment of the requirements for the degree [of] Master of Science in Engineering with a specialization in Biomedical Engineering." "September 2009." Includes bibliographical references (p. 72-74). Also available on microfiche.

Thesis (M.S.)--Oregon State University, 2010. / Printout. Includes bibliographical references (leaves 46-50). Also available on the World Wide Web.

Thesis (M.Med.Sc.)--University of Hong Kong, 2001. / Includes bibliographical references (leaves 44-57). Also available in print.

Thesis (Ph.D.) - University of Queensland, 2003. / Includes bibliography.

Made available in DSpace on 2014-08-13T14:50:38Z (GMT). No. of bitstreams: 0 Previous issue date: 2013-07-30Bitstream added on 2014-08-13T18:01:36Z : No. of bitstreams: 1 000741596_20151231.pdf: 128176 bytes, checksum: bb8faabce5cb612e7108f388c4069a92 (MD5) Bitstreams deleted on 2016-01-04T10:26:44Z: 000741596_20151231.pdf,. Added 1 bitstream(s) on 2016-01-04T10:28:35Z : No. of bitstreams: 1 000741596.pdf: 1788749 bytes, checksum: 850a2b026a9bca705e9c6bb1c2600555 (MD5) / As interações microrganismo-hospedeiro se iniciam pela detecção de padrões moleculares associados a microrganismos (MAMPs) por receptores semelhantes à Toll (TLR) e por proteínas com domínio de ligação à nucleotídeos e oligomerização (Nod) na resposta imune inata. No entanto, como a cavidade bucal saudável é continuamente colonizada por microrganismos não patogênicos que também apresentam MAMPs, deve haver um mecanismo endógeno de regulação negativa da resposta do hospedeiro para evitar uma resposta exagerada e desnecessária com consequências negativas ao hospedeiro. Os mecanismos associados à distinção de microrganismos comensais e patogênicos na mucosa bucal são ainda pouco compreendidos. As proteínas Nod foram inicialmente descritas como ‘TLRs intracelulares’ capazes de reconhecer MAMPs no citosol; no entanto, estudos in vitro indicam que Nod têm papel relevante na regulação da expressão de RANKL e OPG induzidas por antígenos microbianos, bem como na modulação da atividade de vias de sinalização intracelular associadas à expressão de citocinas diretamente relacionadas à regulação do turnover do tecido ósseo. Devido à escassez de informações sobre o papel das proteínas Nod na modulação das interações microrganismo-hospedeiro na mucosa oral e com base nestas informações, nossa hipótese é que as proteínas Nod tem um papel relevante na modulação da reação inflamatória e suas consequências, incluindo a reabsorção do osso alveolar. Para testar esta hipótese, os objetivos específicos propostos foram: avaliar em camundongos knockout para Nod1, Nod2 ou Rip2, através de microtomografia computadorizada e avaliações histológicas descritivas, estereométricas e imunohistoquímicas (TRAP), o papel das proteínas Nod na inflamação e reabsorção óssea associadas à doença periodontal experimental induzida por bactérias inativadas por calor... / Recognition of pathogenic bacteria by the host is initially mediated by the innate immune response through detection of microbe-associated molecular pattern (MAMPs) by Toll-like receptors (TLR) and Nucleotide-oligomerization domain (Nod) proteins. Since the oral cavity, as well as other mucosal surfaces, is continuously colonized with non-pathogenic bacteria that also present MAMPs, there has to be an endogenous negative regulatory mechanism in place to prevent an overt host response with deleterious consequences. Specifically in the oral mucosa, it is not clear how the immune system is able to quickly distinguish between commensal and pathogenic bacteria and tailor the host response. Nod proteins were initially described as ‘intracellular TLRs’ that recognize MAMPs associated with bacteria invading the cytosol; however these proteins have been shown to modulate the activation of various signaling pathways involved in the expression of inflammatory genes, including p38 MAPK and NF-κB in concert with TLR stimulation. There is paucity of information on the in vivo role of Nod proteins in the modulation of host-microbe interactions in the oral mucosa. Based on this information, our hypothesis is that Nod proteins play an important role in the modulation of the inflammatory reaction associated with periodontal diseases and its consequences, including alveolar bone resorption. To test this hypothesis, we propose the following specific aims: Assess the role of Nod proteins in the inflammation and bone resorption in experimentally-induced periodontal disease Describe the influence of Nod proteins on the cytokine and signaling networks associated with periodontal disease.

Submitted by DAYANE DE ALMEIDA BRANDÃO null (dayaneabrandao@hotmail.com) on 2016-05-16T01:24:28Z No. of bitstreams: 1 Dayane de Almeida Brandão-FINAL.pdf: 3147709 bytes, checksum: 4a2e64ad8796eb690412408acd162ec3 (MD5) / Approved for entry into archive by Juliano Benedito Ferreira (julianoferreira@reitoria.unesp.br) on 2016-05-17T14:19:23Z (GMT) No. of bitstreams: 1 brandao_da_me_arafo.pdf: 3147709 bytes, checksum: 4a2e64ad8796eb690412408acd162ec3 (MD5) / Made available in DSpace on 2016-05-17T14:19:23Z (GMT). No. of bitstreams: 1 brandao_da_me_arafo.pdf: 3147709 bytes, checksum: 4a2e64ad8796eb690412408acd162ec3 (MD5) Previous issue date: 2016-03-18 / Curcumin é um polifenol amarelo extraído do rizoma de uma planta tropical, do tipo herbácea. Possui ações anti-inflamatória, antioxidante, antiangiogênica, imunomodulatória, citotóxica, antimicrobiana e antiapoptótica. A aplicação terapêutica do curcumin vem sendo avaliada em modelos pré-clínicos e estudos de várias doenças. As limitações da eficácia do curcumin in vivo são atribuídas à sua má solubilidade em veículos aquosos e baixa taxa de absorção no trato gastrointestinal. O objetivo desse trabalho foi avaliar o efeito dose-resposta do composto sintético análogo ao curcumin (CMC2.24) em diferentes doses (1 mg, 3 mg, 10 mg, 30 mg) sobre o processo inflamatório e osteoclastogênese em modelo de doença periodontal in vivo e in vitro, para analisar qual é a dose mínima necessária para que o composto tenha o efeito biológico. A doença periodontal foi induzida em ratos por meio de injeção de 30 µg de LPS de Escherichia coli, realizadas 3x/semana durante 4 semanas. Os controles receberam injeções do mesmo volume do veículo de diluição do LPS (PBS). A administração de CMC2.24 (1, 3, 10 e 30mg/kg) foi feita por via intragástrica (gavagem oral) diariamente, durante 29 dias (um dia antes da primeira injeção de LPS/PBS). A expressão de fosfatase ácido tartarato resistente (TRAP), indicativa de diferenciação osteoclástica, foi avaliada por meio de imunohistoquímica, a proporção de células inflamatórias, em cortes corados com H/E, por estereometria, a presença de citocinas através do PCR em tecido gengival e a reabsorção óssea por análise de coloração por azul de metileno e microtomografia computadorizada. Nos experimentos in vitro, macrófagos foram estimulados com microrganismos e tratados com CMC2.24 em concentração de 1, 3, 10 e 30 µM. A expressão gênica foi avaliada através de PCR e ELISA, enquanto fagocitose e quantificação de espécies reativas de oxigênio foram avaliadas por atividade fagocitária e produção de ROS, respectivamente. De acordo com os resultados, CMC2.24 reduziu significativamente o infiltrado inflamatório. Além disso, CMC diminuiu significativamente a quantidade de células TRAP positiva a partir de 3 mg/kg e a perda óssea alveolar, a partir de 1 mg/kg. In vitro, experimentos utilizando macrófagos demonstraram que o CMC inibe a produção de TNF e IL-10 após estímulos microbianos. Além disso, CMC2.24 também inibiu atividade fagocitária e estimulou a produção de ROS. CMC2.24 em diferentes doses demonstrou potencial terapêutico para aplicação em doença periodontal, devido à inibição da resposta inflamatória e também foi efetivo na redução da reabsorção óssea inflamatória. / Curcumin is a yellowish polyphenol extracted from the rizome of a herbaceous tropical plant. It has multiple biological activities described, including anti-inflammatory, antioxidant, antiangiogenic, immunomodulatory, cytotoxic, antimicrobial and pro- and antiapoptotic activities. Its therapeutic application is actively evaluated in preclinical models and clinical studies of various diseases. In vivo use of curcumin is limited by its pharmacodynamic propereties, such as poor solubility in aqueous vehicles, low absorption rate in the gastrointestinal tract and short half-life in the peripheral circulation. The aim of this study was to evaluate the dose-response effect of a synthetic compound that is structurally to natural curcumin (CMC2.24) in a model of experimental periodontal disease that mimics the host-microbial interaction and the resultant inflammation and bone resorption that are hallmarks of this conditions in humans. Periodontal disease was induced in mice by injection of 30 ug LPS of Escherichia coli, carried out 3x / week for 4 weeks. Controls received injections of the same volume of vehicle (PBS). Administration of CMC2.24 (1, 3, 10 and 30mg / kg) was performed daily (starting the day before the first LPS/PBS injection) by oral gavage (1, 3, 10 and 30 mg/Kg) during the whole experimental period. Immunohistochemical detection of tartrate-resistant acid phosphatase (TRAP) was used to identify osteoclasts in the area of interest; the inflammatory infiltrate was assessed by stereometric/morphological analysis in H/E-stained sections; expression of candidate inflammatory cytokines in the gingival tissue determined by RT-PCR and the extent of inflammatory bone resorption quantitated macroscopic analysis of the area of exposed root surface and also by computed microtomography. In in vitro experiments, murine macrophages were stimulated with periodontal diseaseassociated microorganisms in the presence and absence of CMC2.24 (1, 3, 10 and 30 uM). Gene expression was assessed by RT-PCR and ELISA; phagocytic activity was studied by immunocytofluorescence and production of reactive oxygen species was determined by a biochemical assay using a ROS-substrate that emit fluorescence upon cleavage. In vivo, administration of CMC2.24 significantly reduced the inflammatory infiltrate, and the number of osteoclasts starting at the 3 mg/Kg dosage; whereas inflammatory bone resorption was significantly inhibited already at the 1 mg/Kg dosage. In vitro, pre-treatment of macrophages with CMC2.24 markedly inhibited the production of TNF and IL-10 after microbial stimuli. CMC2.24 also inhibited phagocytic activity and stimulated production of ROS. We conclude that CMC2.24 at low doses (3 mg/Kg) has therapeutic potential for application in periodontal disease, due to inhibition of microbial-related inflammation.