Twenty-four healthy, mixed breed dogs were divided into four groups. Group I received a placebo PO BID, group II received an average 16.5 (range, 15.1-17.8) mg/kg buffered aspirin PO BID, group III received an average 2.2 (range, 2.0-2.4) mg/kg carprofen PO BID, and group IV received an average 12.8 (range, 11.7-13.8) mg/kg etodolac PO QD (with a placebo in the P.M.). All treatments continued for 28 consecutive days. Gastroduodenal endoscopy was performed on days – 9, 0, 5, 14 and 28. Multiple gastric biopsies were obtained endoscopically on day – 9 to determine each dog's Helicobacter spp. status. Five areas, consisting of four regions in the stomach and one in the proximal duodenum, were evaluated endoscopically, and each was assigned a score from 1 to 11 based on qualitative assessment of submucosal hemorrhage, erosion, or ulceration. These scores for each region were then summed to give a total score for each endoscopic evaluation. Erosions and submucosal hemorrhages were seen in all dogs receiving aspirin. Only minor gastric lesions were observed in the carprofen, etodolac, and control groups. No adverse clinical signs were noted in any dog given any treatment during the course of the study. There was no predilection site for lesion development in any group. Median total score on days 0, 5, 14, and 28 were as follows: group I, 5.0, 5.0, 5.0, 5.0; group II, 5.0, 27.0, 26.0, 27.5; group III, 5.0, 5.0, 6.0, 5.0; group IV, 5.0, 7.0, 5.0, 5.0, respectively. There was no significant difference between dogs receiving carprofen, etodolac, or placebo. The administration of carprofen, etodolac, or placebo to healthy dogs resulted in significantly less gastroduodenal lesion development than in dogs receiving buffered aspirin. Thirty healthy, random source, dogs were evaluated to determine the prevalence of Helicobacter spp., and to compare the ‘Campylobacter-like organism’ test (CLOtest®) to histopathologic identification of Helicobacter spp. organisms. Gastric mucosal biopsies from each of four gastric regions (cardia, pyloric antrum, greater curvature, and angularis incisura) were obtained endoscopically for use in the CLOtest® and for histopathologic evaluation. Twenty-seven of 30 dogs (90%) were positive for spiral bacteria suspected to be Helicobacter spp. by histopathologic evaluation in at least one of the four gastric regions. Three dogs (10%) were negative for Helicobacter spp. in all gastric regions by histopathologic evaluation. The CLOtest® was found to have a sensitivity, specificity, and positive predictive value of 84%, 81%, and 92%, respectively, when compared to histopathologic evaluation. When only the angularis incisura was evaluated, the sensitivity, specificity, and positive predictive value increased to 92%, 94%, and 96%, respectively. The angularis incisura had the highest, whereas the pyloric antrum had the lowest, prevalence of positive test results when compared to dogs determined to be overall Helicobacter spp. positive (histopathologic positive in at least one gastric region). The results of this study suggest the prevalence of Helicobacter spp. in apparently healthy dogs is high. For accurate and economical detection of Helicobacter spp. in a dog undergoing upper gastrointestinal endoscopy, a tissue sample should be taken from the angularis incisura for CLOtest® sampling. / Master of Science

Chronic inflammation is intimately linked with cancer development and progression and therefore reducing or eliminating inflammation represents a logical treatment and prevention strategy. Studies have shown that anti-inflammatory agents have anti-tumour effects in cancers, with reduced metastases and mortality. Current use of anti-inflammatory agents in the treatment and prevention of cancer is limited by their toxicity and side effects. The emerging field of nanotechnology allows the fundamental properties of a drug to be altered, creating a product with improved reactivity and bioavailability, leading to more targeted treatments and reduced dosage. In the present study, the genotoxic effects of three commonly used anti-inflammatory drugs; aspirin, ibuprofen and hydrocortisone, in their bulk and nano forms were evaluated on peripheral blood lymphocytes of healthy donors using the comet assay and the micronucleus assay. In order to determine any anti-cancer effects, these agents were also tested in peripheral blood lymphocytes in patients with haematological cancers. The glucocorticoid hydrocortisone was also evaluated for anti-oxidant capacity. Our results demonstrate that the nano versions of each drug produced a different response than the bulk counterpart, indicating that a reduction in particle size had an impact on the reactivity of the drug. Our results also indicate that the nano versions of each drug were less genotoxic than the bulk formulation, further emphasising the potential of nanoparticles as an improvement to current treatment options. We also found an anti-oxidant effect with hydrocortisone, with a more profound effect seen with the nano formulation.

Orientador: Marco Antonio Alvarenga / Resumo: A administração de antiinflamatórios não esteroides (AINEs) no momento da transferência de embrião em éguas é empregada usualmente para conter a inflamação uterina e produção de prostaglandina F2α (PGF2α), na tentativa de evitar a luteólise. No entanto, estes fármacos podem prejudicar a produção de prostaglandinas pelo concepto e alterar o mecanismo de mobilidade embrionária e reconhecimento materno fetal. Nesse estudo foi avaliada a ação do flunixin meglumine (FM) em um grande número de receptoras de embrião (n=409) em um centro comercial de reprodução equina, verificando estatisticamente a ação deste medicamento na taxa de prenhez e perda gestacional precoce. Os animais foram divididos em dois grupos (FM e controle), recebendo uma única aplicação de FM na dose de 1,1mg/kg imediatamente após a transferência de embrião em éguas alternadas para correta randomização. A taxa de prenhez aos 15 dias do grupo controle foi de 70,95% e a do grupo tratado 75,22%, sem diferença entre os grupos (p=0,3337). Aos 60 dias o grupo controle apresentou taxa de prenhez de 65,22% e o grupo tratado de 65,92%, sem diferença estatística (p>0,05). No entanto, foi observado que a perda embrionária até 60 dias do grupo controle foi 5,03% e no grupo tratado 10,0%, havendo tendência (p=0,0578) para perda gestacional precoce. Em um segundo experimento, AINEs de outras categorias como COX-2 seletivo: firocoxibe e COX-2 preferencial: Meloxicam foram determinados a fim de tentar estabelecer um tratamento an... (Resumo completo, clicar acesso eletrônico abaixo) / Mestre

Introduction: Nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the most used drugs in equine medicine, mainly used to treat inflammation, endotoxemia, pain or fever. NSAIDs inhibit cyclooxygenases which induce to synthesize prostanoids. But NSAIDs have side effects to renal functions too. Objectives: The current study was carried out to investigate the effects of the most common used NSAIDs on urinary parameters in horses. Materials and Methods: Thirty healthy horses were used as a control group and 20 horses with left dorsal displacement, left ventral impaction or lameness of using either flunixin meglumine (FM), metamizole (MZ) or phenylbutazone (PHZ) have been assigned to groups 1, 2 or 3, respectively. Creatinine, urea nitrogen, glucose, protein and electrolytes were measured in serum and urine including GGT using an automatic analyzer. Fractional excretions (FE) of sodium, chloride, potassium, calcium, magnesium and inorganic phosphate, in addition to urinary protein (U-Pro):U-Cr and urinary gamma glutamyl transferase (U-GGT):U-Cr ratios were calculated. Urinary mucus and IgA concentrations were measured and their ratios to the urinary creatinine were calculated. The data were statistically analyzed using Shapiro-Wilks test, descriptive statistics, Kruskal-Wallis one-way analysis of variance and Dunn’s test. Significance was set at P £ 0.05. Results: The FEMg was significantly higher in group 3 (P < 0.033) compared to the control group. The U-GGT:U-Cr ratio was also significantly higher in group 3 (P < 0.001) compared with the control group. The U-Pro:U-Cr ratio was significantly higher in groups 1 and 2 (P < 0.007 and P < 0.001, respectively) than in the control group. PHZ group had a significantly increase in mucus:U-Cr ratio (P < 0.005). Significant increases were observed regarding the IgA:U-Cr ratio in groups 1 (P < 0.007) and 2 (P < 0.014). Conclusions: Long-term use of PHZ has an influence on the renal ascending limb of the loop of Henle, and all these drugs could have effects on the proximal tubules. Phenylbutazone causes an increase in urinary mucus secretion, probably as a protective mechanism against the necrotic effect in renal pelvis of PHZ. Parameters such as U-Pro:U-Cr and U-GGT:U-Cr ratios and FEMg are helpful in detecting these renal abnormalities.

Chronic inflammation is intimately linked with cancer development and progression and therefore reducing or eliminating inflammation represents a logical treatment and prevention strategy. Studies have shown that anti-inflammatory agents have anti-tumour effects in cancers, with reduced metastases and mortality. Current use of anti-inflammatory agents in the treatment and prevention of cancer is limited by their toxicity and side effects. The emerging field of nanotechnology allows the fundamental properties of a drug to be altered, creating a product with improved reactivity and bioavailability, leading to more targeted treatments and reduced dosage. In the present study, the genotoxic effects of three commonly used anti-inflammatory drugs; aspirin, ibuprofen and hydrocortisone, in their bulk and nano forms were evaluated on peripheral blood lymphocytes of healthy donors using the comet assay and the micronucleus assay. In order to determine any anti-cancer effects, these agents were also tested in peripheral blood lymphocytes in patients with haematological cancers. The glucocorticoid hydrocortisone was also evaluated for anti-oxidant capacity. Our results demonstrate that the nano versions of each drug produced a different response than the bulk counterpart, indicating that a reduction in particle size had an impact on the reactivity of the drug. Our results also indicate that the nano versions of each drug were less genotoxic than the bulk formulation, further emphasising the potential of nanoparticles as an improvement to current treatment options. We also found an anti-oxidant effect with hydrocortisone, with a more profound effect seen with the nano formulation.

No description available.

<b>Background:</b> Comparative assessments of the vascular and upper gastrointestinal risks of different regimens of non-steroidal anti-inflammatory drugs (NSAIDs) are required. <b>Methods:</b> Meta-analyses were conducted, using individual participant data where possible, of placebo-controlled trials of a selective cyclo-oxygenase [COX]-2 inhibitor ('coxib') or traditional NSAID, or randomised trials of a coxib versus traditional NSAIDs. A prespecified subdivision of traditional NSAID regimens of those with antiplatelet activity (mainly naproxen) and those without (mainly diclofenac) was made. Primary outcomes were major vascular events (MVEs; nonfatal myocardial infarction, nonfatal stroke or vascular death) and upper gastrointestinal complications (UGICs; perforation, obstruction or bleed). <b>Findings:</b> Searches identified 788 trials: 200 comparisons of a coxib vs placebo (88,604 participants, mean follow-up 0.60 years), 206 comparisons of a traditional NSAID vs placebo (43,482 participants, 0.46 years) and 149 comparisons of a coxib vs traditional NSAID (137,466 participants, mean follow-up 0.95 years). Compared to placebo, allocation to a coxib increased the risk of MVEs (rate ratio 1.38, 95&percnt; CI 1.14-1.66), vascular mortality (1.58, 1.11-2.24) and UGICs (1.81, 1.17-2.81). Overall, in the population studied, coxibs were associated with three additional major vascular events (one fatal) and two (rarely fatal) upper gastrointestinal complications per 1000 person-years exposure. There was no evidence of heterogeneity by duration of follow-up, coxib type, dose (other than for celecoxib), or patient characteristics, for the primary outcomes. The risk of MVEs for traditional NSAIDs without antiplatelet activity (mostly diclofenac 75mg bd or ibuprofen 800mg tds) were comparable to coxibs (1.40, 1.15-1.72); but the risk of UGICs (1.98, 1.39-2.84) was significantly greater. For traditional NSAIDs with antiplatelet activity (mostly naproxen 500mg bd) there were no significant excess of MVEs (0.84, 0.66-1.08), but UGICs were substantially increased (4.06, 2.85-5.78). Both coxibs and traditional NSAIDs increased risk of hospitalisation for heart failure by about two-fold. <b>Interpretation:</b> The vascular and upper gastrointestinal risks of coxibs and high-dose tNSAID regimens can be predicted, allowing the choice of analgesia to be tailored for particular patients.

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal.

Orientador: José Carlos de Figueiredo Pantoja / Resumo: Objetivou-se avaliar a eficácia do cetoprofeno em casos de mastite clínica (MC) com ausência de isolamento microbiológico nas amostras de leite cultivadas no sistema de cultura na fazenda (SCF). Vacas de três rebanhos foram alocadas aleatoriamente em dois grupos experimentais. Grupo cetoprofeno (N = 65 quartos) foi tratado com cetoprofeno (3 mg/kg, via intramuscular, dose única) e grupo controle (N = 64 quartos) não recebeu terapia. Amostras de leite foram coletadas no momento do diagnóstico da MC e 14 (D14) e 21 (D21) dias após o caso. Os desfechos avaliados foram risco de cura clínica, recidiva e recorrência de MC, risco de nova infecção intramamária (IIM) em D14 e D21 e contagem de células somáticas em D14 e D21. A proporção de cura clínica, recidiva e recorrência de MC nos grupos cetoprofeno e controle foi de 83,08% e 85,94%, 18,52% e 18,18% e 16,67% e 16,36%, respectivamente. O risco relativo de todos os desfechos mencionados não foi diferente entre os grupos experimentais. Em ambas as análises as chances de nova IIM não foram diferentes entre os grupos experimentais. Não houve diferença na CCS entre os grupos entre os dias de amostragem ou grupos experimentais. Os resultados sugerem que o uso de cetoprofeno em casos de MC com cultura negativa não foi associado ao risco de cura clínica, recidiva e recorrência de MC, novas IIM e CCS. / Abstract: The objective of this study was to evaluate the efficacy of ketoprofen in culture-negative clinical mastitis (CM) cases. Cows from three commercial herds were randomly allocated into two experimental groups. The ketoprofen group (N = 65 quarters) received a single intramuscular injection of 3 mg/kg of ketoprofen. The control group (N = 64 quarters). Milk samples were collected at the time of CM diagnosis and at 14 (D14) and 21 (D21) days after the case. The outcomes evaluated were clinical cure, relapse and recurrence of CM, risk of new intramammary infection (IIM) at D14 and D21, and somatic cell count at D14 and D21. The proportion of clinical cure, relapse and recurrence of CM in the ketoprofen and control groups was 83.08%, 85.94%, 18.52% and 18,18%, 16,67% and 16,36%, respectively. The relative risk of all mentioned outcomes was not different between the experimental groups. For both analyses, the odds of new IIM were not different between the experimental groups. Mean SCC was not different between sampling days or experimental groups. Results suggest that the use of ketoprofen for culture-negative CM was not associated with the risk of clinical cure, relapse and recurrence of CM, new IIM and SCC. / Mestre

A palavra DOR é definida como uma percepção consciente do indivíduo de impulsos nociceptivos modulados que originam uma experiência emocional e sensitiva desagradável, associada à lesão tecidual real ou potencial, ou descrita em termos de tal lesão. Considerando-se que a dor é um dos motivos mais comuns que levam um paciente a procurar por atendimento em consultório odontológico, este estudo teve como objetivo quantificar e qualificar a analgesia da musculatura mastigatória e da articulação temporomandibular proporcionada por medicamentos antiinflamatórios não esteroidais, associados ou não a outros agentes terapêuticos. O estudo clínico foi desenvolvido em pacientes que sofriam de algias crônicas na musculatura mastigatória, decorrentes de disfunções temporomandibulares. Foram selecionados, após anamnese e avaliação com a ferramenta RDC/TMD traduzido para a língua Portuguesa (PEREIRA JUNIOR, 2007), 18 voluntários para avaliar o efeito terapêutico (entendendo-se como efeito terapêutico o alívio da sintomatologia dolorosa e do restabelecimento da amplitude dos movimentos bordejantes mandibulares), dos três tratamentos coadjuvantes abaixo-relacionados, sendo dois medicamentos e um placebo para eliminar o efeito psicológico. Os tratamentos avaliados foram: um antiinflamatório não-esteroidal (AINES) Flanaren® (diclofenaco sódico), uma panacéia Sedilax® composta por AINES, miorrelaxante e analgésicos (diclofenaco sódico + carisoprodol + paracetamol + cafeína), ambos produzidos pelo laboratório Teuto® ; e um placebo, que consistia de pílulas preenchidas com 110 g de amido de milho, produzidas pela Faculdade de Ciências Farmacêuticas de Ribeirão Preto - USP. A administração de cada medicamento consistia de 1 unidade a cada 12 horas, durante um período de 10 dias, precedido e sucedido por avaliações de dor dos pacientes. Foi estabelecido um período de washout de 11 dias entre cada troca de tratamento. A avaliação dos tratamentos medicamentosos foi desenvolvida com diferentes ferramentas, como o McGill Pain Questionnaire (VAROLI; PEDRAZZI, 2006), para qualificar e quantificar dor não provocada, a escala visual analógica para dor à palpação, escala numérica para a quantificação da dor durante o tratamento, além de mensurações de amplitude de movimentos excursivos mandibulares. Foram colhidas também informações sobre possíveis efeitos colaterais indesejáveis relacionados aos tratamentos. O projeto foi submetido e aprovado pelo Comitê de Ética em Pesquisa envolvendo Seres Humanos da Faculdade de Odontologia de Ribeirão Preto da USP, Processo n.2006.1.558.58.0, Caae n.0022.0.138.000-06. Os resultados mostraram que a analgesia para a dor em repouso foi melhor com a utilização do Flanaren® e para a dor à palpação, igual para ambos os tratamentos. Os medicamentos Sedilax® e Flanaren® reduziram significantemente a dor após três dias de tratamento, enquanto o placebo, após oito dias. Não foram observadas melhoras na amplitude dos movimentos limítrofes da mandíbula. Também não foram observados efeitos colaterais significantes estatisticamente. Concluiu-se que o tratamento utilizando o diclofenaco sódico como adjuvante reduziu a dor em repouso; todos os tratamentos promoveram analgesia à dor à palpação, mas tanto o diclofenaco isolado como associado agiram no terceiro dia e o placebo, apenas no oitavo. Nenhum efeito colateral observado foi estatisticamente significante. / The word PAIN is defined as a conscious perception of modulated nociceptive input from an unpleasant emotional and sensitive experience, associated to a real or potential, or described in terms of such lesion. Considering that pain is one of main reasons which motivate patients to search for dental treatment, the aim of this study was quantify and qualify analgesia in masticatory muscles and temporomandibular joints by administration of non steroidal anti-inflammatory drugs, isolated or associated to other therapeutic agents. This clinical trial has been developed treating patients who had been suffering with chronic pain in masticatory muscles due to temporomandibular disorders. Eighteen volunteers were selected after anamnesis exam and assessment using RDC/TMD translated to Portuguese (PEREIRA JUNIOR, 2007), to evaluate the therapeutics effect (pain relief and maximum eccentric jaw movement recovery) of three adjuvant treatment: two medicines and one placebo, to eliminate psychological effects. Assessed treatments were: a non steroidal anti-inflammatory Flanaren® (sodium diclofenac), a panacea composed by an anti-inflammatory, muscle relaxant and analgesics (sodium diclofenac + carisoprodol + acetaminophen + caffeine), both produced by pharmaceutical laboratory Teuto® ; and a placebo, that were pills filled by 110 g of corn starch, produced by Faculty of Pharmaceutical Sciences of Ribeirão Preto USP. The dosage of all medicines was one pill every 12 hours, during 10 days, preceded and succeeded by patients` pain assessment. An 11 days washout period among each therapy has been established. The assessment of drug therapies were done using distinct instruments, as McGill Pain Questionnaire (VAROLI; PEDRAZZI, 2006), to qualify and quantify unprovoked pain; visual analogue scale for pain on palpation, numerical scale to quantify pain during treatment, and measurement of range of motion during maximum eccentric jaw movements. It has been obtained information about side effects related to treatments. The research project was submitted and approved by Ethics in Research Committee of Faculty of Dentistry of Ribeirão Preto USP, Lawsuit n.2006.1.558.0, CAAE n. 0022.0.138.000-06. Data analysis has shown that relief of unprovoked pain was better using Flanaren® , and reduction of pain on palpation was equal in all treatments. Both, diclofenac alone, also diclofenac associate to other drugs, reduced significantly pain after three days of treatment, while placebo, after eight days. It has not been observed increase of range of motion during maximum jaw excursive movements, neither statistically significant side-effect. It has been concluded that treatment using diclofenac as an adjuvant reduced unprovoked pain; all therapies relief pain on palpation, but it was observed on third day for diclofenac and diclofenac associated and on eighth day for placebo. There was not any statistically significant side effect.