Síntese e caracterização de nanopartículas de ouro conjugadas com curcumina e seus efeitos na osteoartrite experimental induzida / Synthesis and characterization of gold nanoparticles combined with curcumin and its effects on experimentally induced osteoarthritis

RESUMO: A Osteoartrite (OA) é uma denominação clínica para uma combinação de condições patológicas que envolvem a degeneração progressiva da cartilagem articular e remodelação de osso subcondral. A curcumina, um potente agente anti-inflamatório, têm sido extensivamente estudada, no entanto não oferece boa biodisponibilidade sistêmica. Nanopartículas de ouro (AuNPs) apresentam aplicações potenciais na administração de substâncias terapêuticas aumentando a eficiência do transporte de fármacos. O objetivo deste estudo foi realizar a síntese e caracterização de um sistema conjugando as AuNPs à curcumina e avaliar seu potencial terapêutico em um modelo experimental de OA em camundongos por desestabilização do menisco medial (DMM). As AuNPs foram conjugadas com curcumina e os sistemas foram caracterizados por espectroscopia no UV-VIS, espalhamento de luz dinâmico (DLS) e determinação do potencial zeta. Formou-se 4 grupos de oito animais cada, denominados A, B, C, D que receberam injeção intra-articular de AuNPs, curcumina, AuNP-curcumina e solução fisiológica, respectivamente. Após 7 semanas, a cartilagem da articulação-femoro- tibio-patelar (AFTP) foi avaliada em uma variação de escore de 0 a 24. A conjugação de AuNP-curcumina mostrou boa estabilidade e aplicação terapêutica, mas não diferiu significativamente (P>0,05) dos grupos A e B, no entanto, mostrou menor valor de escore e significância (P<0,001) em relação ao grupo controle. Os resultados deste trabalho mostram a importância do desenvolvimento de novos nanofármacos. Neste caso a conjugação de AuNPs com a curcumina permitiu a obtenção de um nanofármaco com sugestivo potencial para aplicação no tratamento da OA.

ABSTRACT: Osteoarthritis (OA) is the clinical term for a combination of pathological conditions that involve the progressive degeneration of articular cartilage and subchondral bone remodelling. Curcumin, a potent anti-inflammatory agent, has been extensively studied; however, it does not provide good systemic bioavailability. Gold nanoparticles (AuNPs) have potential applications in the administration of therapeutic substances in order to increase the transport efficiency of drugs. The objectives of this study were to explore the synthesis and characterization of a system combining AuNPs with curcumin and evaluate its therapeutic potential in an experimental model of OA in mice by the destabilization of the medial meniscus (DMM). The AuNPs were conjugated with curcumin and the systems were characterized by UV-VIS spectroscopy, dynamic light scattering (DLS), and zeta potential. Four groups of eight animals each were formed and labelled A, B, C, and D, which received intra-articular injections of AuNPs, curcumin, AuNP-curcumin, and physiologic solution, respectively. After seven weeks, the cartilage of the stifle joint (SJ) was rated on a scale ranging from 0 to 24. Combination of AuNP-curcumin demonstrated good stability and therapeutic applications, but it did not differ significantly (P>0.05) from groups A and B. However, the control group had a significantly lower score (P<0.001). Results of this study demonstrated the importance of developing new nanodrugs. In this case, the combination of AuNPs and curcumin yielded the nanodrug effects suggestive of a potential for application in the treatment of OA.

Effects of dorzolamide/timolol and tafluprost on intraocular pressure and pupil diameter in healthy dogs / Efeitos da dorzolamida/timolol e da tafluprosta sobre a pressão intraocular e o diâmetro pupilar em cães saudáveis

ABSTRACT: This study aimed to evaluate and compare the effects of the fixed combination of dorzolamide/timolol with those of tafluprost on intraocular pressure (IOP) and pupil diameter (PD) in healthy dogs (n=10). Two experiments were conducted with an interval of 30 days. In both, IOP and PD were assessed at 8, 11, 14, 17, and 20h. Parameters were evaluated during baseline, treatment period of four days, and one day of post-treatment. During treatment phase, IOP decreased by 0.74 (P<0.05), 1.88 (P<0.01), 2.94 (P<0.001), and 3.10mmHg (P<0.01), in dorzolamide/timolol-treated eyes; and by 1.50, 2.18, 2.14, and 2.18mmHg (P<0.001), in tafluprost-treated eyes. PD decreased by 0.24 (P<0.01), 0.32 (P<0.01), 0.49 (P<0.001), and 0.40mm (P<0.001), in dorzolamide/timolol treated eyes; and by 2.31, 2.55, 2.43, and 2.70mm (P<0.001), in tafluprost-treated eyes. Dorzolamide/timolol and tafluprost were able to decrease IOP and PD in healthy dogs. However, a cumulative effect of the fixed combination of dorzolamide/timolol was more effective in reducing IOP, than tafluprost. Comparisons between treatments showed that tafluprost was more effective in reducing PD throughout the treatment phase.

RESUMO: O estudo objetivou avaliar e comparar os efeitos da combinação fixa da dorzolamida/timolol com os da tafluprosta sobre a pressão intraocular (PIO) e o diâmetro pupilar (DP) em cães saudáveis (n=10). Dois experimentos com intervalo de 30 dias foram conduzidos. Em ambos, a PIO e o DP foram avaliados às 8, 11, 14, 17 e às 20h. Os parâmetros foram avaliados durante a fases basal, um período de tratamento de quatro dias, e um dia de pós-tratamento. Durante a fase de tratamento, a PIO dos olhos tratados com dorzolamida/timolol reduziram em 0.74 (P<0.05), 1.88 (P<0.01), 2.94 (P<0.001), e 3.10mmHg (P<0.01); e dos olhos tratados com tafluprosta em 1.50, 2.18, 2.14 e 2.18mmHg (P<0.001). O DP dos olhos tratados com dorzolamida/timolol reduziram em 0.24 (P<0.01), 0.32 (P<0.01), 0.49 (P<0.001) e 0.40mm (P<0.001); e dos olhos tratados com tafluprosta em 2.31, 2.55, 2.43 e 2.70mm (P<0.001). A dorzolamida/timol e a tafluprosta foram capazes de reduzir a PIO e o DP em cães saudáveis. Porém, efeito cumulativo do tratamento com dorzolamida/timolol foi observado, decorridos três dias de tratamento. Por essa razão, a dorzolamida/timolol foi mais efetiva que a tafluprosta na redução da PIO. Comparações entre os tratamentos demonstraram que a tafluprosta foi mais efetiva em reduzir o DP, durante toda a fase de tratamento.

Evaluation of intraluminal pressure in cystorrhaphies with and without intestinal serosal patch supplementation from canine cadavers

PURPOSE:To evaluate the maximal intraluminal pressure (MIP) supported by canine cadaveric urinary bladders that underwent cystotomy followed by cystorraphy, with and without serosal patching-supplementation.METHODS:Two groups (n=8 each) were formed, and in one (conventional) the cystotomy was closed with cushing pattern. In the other group (serosal), the same procedure was performed, and a piece of jejunum was used for the construction of the serosal patching over the cystorraphy. MIP was measured by means of an invasive blood pressure transducer with closed stopcock attached to a multiparameter monitor. At the end of each measurement, the bladder body circumference was assessed.RESULTS:Mean±SD MIP sustained for the conventional and serosal groups were 28.88±5.08 and 65.38±10.99 mmHg, respectively (p<0.0001). Bladder circumference did not change significantly between groups (p=0.35) and did not correlate with MIP assessed in conventional (p=0.27; r=0.4379) and serosal groups (p=0.37; r=-0.3637).CONCLUSION:Serosal patch-supplemented cystorraphies were able to sustain intraluminal pressures 55.8% higher, than nonsupplemented cystorraphies in specimens from canine cadavers.