The goal of this thesis was to develop a new drug-delivering material to deliver anti-inflammatory protein for treating OA. Our central hypothesis for this work is that a controlled release/presentation system will more effectively deliver anti-inflammatory protein therapies to the OA joint. The primary goal of this work was to synthesize a block copolymer that could self-assemble into injectable, sub-micron-scale particles and would allow an anti-inflammatory protein, IL-1ra, to be tethered to its surface for efficient protein delivery. The block copolymer incorporated an oligo-ethylene monomer for tissue compatibility and non-fouling behavior, a 4-nitrophenol group for efficient protein tethering, and cyclohexyl methacrylate, a hydrophobic monomer, for particle stability. We engineered the copolymer and tested it in both in vitro culture experiments and an in vivo model to evaluate protein retention in the knee joint. The rationale for this project was that the rational design and synthesis of a new drug- and protein-delivering material can create a modular polymer particle that can deliver multi-faceted therapies to treat OA. This work characterizes the in vitro and in vivo behavior of our polymer particle system. The protein tethering strategy allows IL-1ra protein to be tethered to the surface of these particles. Once tethered, IL-1ra maintains its bioactivity and actively targets synoviocytes, cells crucial to the OA pathology. This binding happens in an IL-1-dependent manner. Furthermore, IL-1ra-tethered particles are able to inhibit IL-1beta-induced NF-kappaB activation. These studies show that this particle system has the potential to deliver IL-1ra to arthritic joints and that it has potential for localizing/targeting drugs to inflammatory cells of interest as a new way to target OA drug treatments.

Thesis--University of Oklahoma. / Bibliography: leaves 159-175.

Objective: To appraise whether adverse events following oral implant placement may be associated with peri-operative use of non-steroidal anti-inflammatory drugs (NSAIDs). Methods: All patients with recorded implant failures between 1979 and 2012 in the Implant Prosthodontics Unit were contacted to solicit additional information about potential peri-operative use of NSAIDs. Results: From a total of 168 patients with 292 implant failures between 1979 and 2012, 122 consented to participate and had intact records. Just over half (56.6%) reported no peri-operative NSAID usage. However, compared to patients who did not use peri-operative NSAIDs, four times as many had complicated medical histories and twice as many patients taking NSAIDs suffered multiple implant failures. Conclusions: Patients with a variety of systemic diseases may be adversely affected by the inhibitory effect of NSAIDs on bone healing. Further prospective clinical studies are warranted to clarify this potential causative relationship in humans.

Objective: To appraise whether adverse events following oral implant placement may be associated with peri-operative use of non-steroidal anti-inflammatory drugs (NSAIDs). Methods: All patients with recorded implant failures between 1979 and 2012 in the Implant Prosthodontics Unit were contacted to solicit additional information about potential peri-operative use of NSAIDs. Results: From a total of 168 patients with 292 implant failures between 1979 and 2012, 122 consented to participate and had intact records. Just over half (56.6%) reported no peri-operative NSAID usage. However, compared to patients who did not use peri-operative NSAIDs, four times as many had complicated medical histories and twice as many patients taking NSAIDs suffered multiple implant failures. Conclusions: Patients with a variety of systemic diseases may be adversely affected by the inhibitory effect of NSAIDs on bone healing. Further prospective clinical studies are warranted to clarify this potential causative relationship in humans.

Thesis (Ph.D. in Toxicology) -- University of Colorado Denver, 2007. / Typescript. Includes bibliographical references (leaves 156-176). Free to UCD affiliates. Online version available via ProQuest Digital Dissertations;

Thesis (M.Sc. (Pharmacology))--Mahidol University, 1986.

Despite the successful of tooth bleaching techniques performed in office, high incidence of trans- and post-operative sensitivity has been reported by patients. This is caused by pulp tissue inflammation, while using anti-inflammatories prior to procedure might be able to reduce the sensitivity. Thus, the aim of this study was evaluated, by a controlled, randomized, double-blinded, clinical trial with cross-over design; the effect of using the anti-inflammatory Naproxen prior to bleaching on tooth sensitivity. Fifty patients were submitted to two sessions of in-office tooth bleaching with 35% hydrogen peroxide used in a single application of 45 minutes with an interval of 7 days. One-hour prior of procedure, the patient randomly received a single dose of Naproxen (500 mg) or placebo in a double-blind, randomized, and crossover design. The sensitivity level was evaluated during and immediately after the bleaching using verbal and analogic visual analogue (VAS) scales; and after 24h using only the verbal scale. The bleaching effectiveness of procedures was evaluated with bleach guide scale. Relative risk to sensitivity was calculated and adjusted by session, while comparison of overall risk was performed by McNemar's Test. Data on the sensitivity level for both scales and shade were subjected to Friedman, Wilcoxon and Mann-Whitney tests (α = 0.05). The use of Naproxen only affected the risk and level of tooth sensitivity reported only at the second session, reducing the risk and level. The sequence of treatment did not affect the beaching effectiveness. Preventive use of Naproxen only reduced the tooth sensitivity reported by patients immediately after the second session of bleaching. / Apesar do sucesso das técnicas de clareamento dental realizada em consultório, alta incidência de sensibilidade trans- e pós-operatória ainda é relatada pelos pacientes. Esta é causada pela inflamação do tecido pulpar, sendo que o uso de anti-inflamatórios previamente ao procedimento pode reduzir a sensibilidade. Assim, o objetivo deste estudo foi avaliar, através de um ensaio clínico controlado, randomizado, duplo-cego e com desenho cross-over; o efeito do uso do anti-inflamatório Naproxeno previamente ao clareamento na sensibilidade dental. Cinquenta pacientes foram submetidos a duas sessões de clareamento dental com peróxido de hidrogênio a 35%, em uma única aplicação de 40 minutos, com intervalo de 7 dias entre sessões. Uma hora antes do procedimento, o paciente recebeu uma cápsula de Naproxeno (500 mg) ou placebo, de acordo com a randomização, sendo o tratamento invertido na segunda sessão. O nível de sensibilidade foi avaliado durante e imediatamente após o clareamento utilizando a escala visual analógica (EVA) e a escala verbal e após 24 horas utilizando apenas a escala verbal. A eficácia do clareamento foi avaliada com a escala bleach guide. O risco relativo de sensibilidade foi calculado e ajustado por sessão, enquanto a comparação do risco agrupado foi realizada pelo teste de McNemar. Os dados sobre o nível de sensibilidade para ambas às escalas e referente à avaliação de cor foram submetidos a Friedman, Wilcoxon e Mann-Whitney (α = 0,05). O uso de naproxeno apenas alterou o o risco e nível de sensibilidade dentária relatado na segunda sessão, reduzindo ambos. A sequência de tratamento não afetou a eficácia do clareamento. A administração preventiva de dose única do Naproxeno teve efeito limitado na prevenção de sensibilidade causada pelo clareamento.

Orientador: Ney Carter do Carmo Borges / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-18T22:09:06Z (GMT). No. of bitstreams: 1 Rigato_HamiltonModesto_D.pdf: 6113608 bytes, checksum: 50f727cd3e6ffa2e40c62a248f3e7fea (MD5) Previous issue date: 2011 / Resumo: Objetivo: O presente trabalho teve por objetivo avaliar o perfil farmacocinético do diclofenaco de colestiramina (cápsula de 140mg) e de duas apresentações farmacêuticas (comprimidos 100mg e suspensão oral 50mg/mL) de nimesulide realizado em voluntários sadios de ambos os sexos e relacioná-los aos desfechos clínicos em enzimas do painel hepático e da contagem de plaquetas. Materiais e métodos: Os estudos foram do tipo aberto, aleatório, cruzado, em dois períodos. As amostras de sangue foram analisadas em cromatografia líquida de alta eficiência acoplada, a um detector de ultravioleta (UV) para o primeiro fármaco, e a um espectrômetro de massa (EM/EM) para outro. Os valores séricos do painel hepático e contagem de plaquetas foram comparados pré e pós-medicação. Resultados: As razões geométricas e respectivos 90% do IC para a cápsula de diclofenado de colestiramina/Flotac® 140 mg foram 100.22% (84.99 - 118.19%) para a CMAX e 90,53% (82.86-98.91%) para a ASCULTIMO. Os valores para o comprimido de Nimesulide/Nisulid® 100mg foram 85.96% (77.54 - 95.30%) para a CMAX e 93.91% (84.42 - 104.46%) para a ASCULTIMO, e a formulação de suspensão oral de Nimesulide/Nisulid® 50mg/mL obteve 100.1% (91.05 - 110.15%) para CMAX e 107.7% (99.74 - 116.39%) para ASCULTIMO. Quanto ao desfecho clínico foi observada elevação significante no parâmetro de ALT para o diclofenaco de colestiramina e na formulação comprimido de nimesulide. A formulação de suspensão oral teve elevação significante para o parâmetro de ALP. Não foi observada diminuição na contagem de plaquetas. Conclusão: Considerando que 90% dos intervalos de confiança das razões de CMAX e ASCULTIMO, se encontram dentro de 80-125% do intervalo proposto pelo FDA e aceita pela ANVISA, concluiu-se que a formulação de cápsula de diclofenaco de colestiramina (140mg) e a formulação de suspensão oral (50mg/mL) de nimesulide são bioequivalentes em relação à taxa e extensão de absorção e que a formulação comprimido de nimesulide (100mg) não é bioequivalente ao Nisulid® com relação a taxa de absorção. Clinicamente os medicamentos se mostraram seguros mesmo apresentando alterações estatisticamente significantes nos parâmetros clínicos avaliados / Abstract: Objective: The present work aims to evaluation the pharmacokinetic profile of the diclofenac-cholestyramine (140mg capsule) and two pharmaceuticals formulations (100mg tablets and 50mg/m oral suspension) of nimesulide in healthy adult subjects related with clinic outcomes in the hepatic enzymes panel and platelet count. Method: The studies were open, randomized, simple crossover balanced with two periods. The blood samples were analyzed by high performance liquid chromatography coupled to ultraviolet detection in diclofenac formulations. For nimesulide a mass espectrometer was performed (MS/MS). Seric enzymes from liver panels and whole blood platelet count was compared with pre and post single dose treatment. Results: The geometric mean and 90% confidence intervals (CI) for the diclofenac-cholestyramine/Flotac® ratio were 100.22% (84.99 - 118.19%) for CMAX and 90,53% (82.86-98.91%) for AUCLAST. The geometric mean and 90% confidence intervals (CI) for the Nimesulide/Nisulid® 100mg tablet were 85.96% (77.54 - 95.30%) for CMAX and 93.91% (84.42 - 104.46%) for AUCLAST, and for the oral suspension 50mg/mL were 100.1% (91.05 - 110.15%) for CMAX and 107.7% (99.74 - 116.39%) for AUCLAST. For the hepatic enzyme panel was observed significant rise in the ALT for diclofenac-cholestyramine and nimesulide tablet. The oral suspension was significant rise in the ALP parameter (p<0.05). No platelet count decrease was observed. Conclusion: Since the 90% CI for CMAX and AUCLAST ratios were all inside the 80-125% interval proposed by the US Food and Drug Administration and accepted by ANVISA, it is concluded that the diclofenac-cholestyramine 140mg capsule and the nimesulide oral suspension formulation 50mg/mL are bioequivalent in regard to both extent and rate of absorption. The nimesulide 100mg tablet is not bioequivalent to Nisulid® 100mg tablet with respect to the rate of absorption. Clinically all the evaluated pharmaceuticals are safety despide the significant changes in the hepatic enzymes panel observed / Doutorado / Ciencias Basicas / Doutor em Clínica Médica

The non-steroidal anti-inflammatory drugs (NSAIDs) are widely used in Endodontics and when associated with some risk factors, such as concomitant use of other drugs, may develop undesirable and possibly serious effects. This cross-sectional study evaluated, through data collecting on dental records, potential interactions among the most commonly prescribed NSAIDs and medications used by patients treated in the Integrated Clinical Dentistry of UFSM, from 2007 to 2011. The data were processed on the EpiData and the statistical analysis was performed with SPSS Software. For analysis of interactions between drugs two tertiary bibliographic source were used: the book Drug Interaction Facts and computerized tool Drugdex in the Micromedex. Potential drug interactions with NSAIDs occurred with 20.2% of the drugs related by patients. The most common consequences in this context were gastrointestinal bleeding, decrease antihypertensive effect and renal failure. In relation to gravity and documentation of interaction, there was a higher frequency of the important gravity and well-documented in the issue of pharmacological interaction. Hence, special attention must be given to the elderly and other patients using several drugs at the same time alongside with educational initiatives focused on a more safe prescription method should be taught in educational institutions. / Os anti-inflamatórios não esteroides (AINEs) são fármacos amplamente utilizados em Endodontia e, quando associadas a alguns fatores de risco, como uso concomitante de outros medicamentos, podem desenvolver efeitos indesejados e possivelmente graves. Esse estudo transversal avaliou, por meio de uma coleta de dados nos prontuários odontológicos, as potenciais interações entre os AINEs mais comumente prescritos e os medicamentos em uso pelos pacientes atendidos nas Clínicas Integradas do Curso de Odontologia da UFSM, no período de 2007 a 2011. Os dados foram codificados no Programa EpiData e a análise estatística foi realizada com o Software SPSS. Para análise das interações entre os fármacos foram utilizadas duas fontes bibliográficas terciárias: o livro Drug Interaction Facts e a ferramenta informatizada Drugdex do Micromedex. As potenciais interações medicamentosas com AINEs ocorreram em 20,2% dos medicamentos relatados pelos pacientes. As consequências mais frequentes nesse contexto foram sangramento gastrointestinal, diminuição do efeito anti-hipertensivo e insuficiência renal. Em relação à gravidade e a documentação da interação, observou-se maior frequência de gravidade importante e bem documentada no quesito interação farmacológica. Então, atenção especial deve ser dada a pacientes idosos e outros pacientes que utilizem diversos medicamentos de forma paralela e iniciativas educacionais focadas em um método de prescrição mais seguro devem ser lecionadas em instituições de ensino.

Abstract Excessive pain after surgery causes many kinds of endocrine, metabolic and inflammatory responses, which may increase postoperative morbidity and mortality - especially among elderly patients. This study evaluated the effect of peripheral and central pain relief techniques after joint surgery. Intravenously administered doses of 100 mg, 200 mg and 300 mg of ketoprofen decreased the requirement for opioid (fentanyl) in a dose-dependent manner by 38%, 45% and 53%, respectively, compared with a placebo, without any noticeable ceiling-effect, when administered after hip and knee arthroplasty. Patients receiving a 300 mg dose of ketoprofen had significantly lower postoperative pain scores than those receiving a placebo. There were no significant differences in incidences of nausea and vomiting, or in the amount of bleeding between the ketoprofen and placebo groups. Intravenous doses of 200 mg of ketoprofen, 150 mg of diclofenac, and 120 mg of ketorolac produced similar postoperative pain scores and requirement for opioid (fentanyl) with no intergroup differences in the incidence of nausea and vomiting and in the amount of bleeding, when administered after hip arthroplasty. The addition of ropivacaine, 1 mg·ml-1, did not decrease the requirement for epidural fentanyl administered via a patient-controlled analgesia device for postoperative pain relief after hip arthroplasty. Both drug infusions provided effective pain relief. The most common adverse effect was pruritus, which occurred in a similar number of patients in both groups. An interscalene brachial plexus block with ropivacaine decreased the dose of PCA-delivered oxycodone by 78% after arthroscopic shoulder surgery while subacromial bursa blockade with ropivacaine decreased it by only 11 % compared to a placebo during the 20 hour study period. Postoperative pain scores were significantly lowest with a interscalene brachial plexus block.