Preclinical evaluation of methotrexate-loaded polyelectrolyte complexes and thermosensitive hydrogels as treatment for rheumatoid arthritis.

This work proposes new methotrexate (MTX) loaded drug delivery systems (DDS) to treat rheumatoid arthritis via the intra-articular route: a poloxamer based thermosensitive hydrogel (MTX-HG), oligochitosan and hypromellose phthalate-based polyelectrolyte complexes (MTX-PEC) and their association (MTX-PEC-HG). MTX-PEC showed 470 ± 166 nm particle size, 0.298 ± 0.108 polydispersity index, +26 ± 2 mV and 74.3 ± 5.8% MTX efficiency entrapment and particle formation was confirmed by infrared spectroscopy and thermal analysis. MTX-HG and MTX-PEC-HG gelled at 36.7°C. MTX drug release profile was prolonged for MTX-HG and MTX-PEC-HG, and faster for MTX-PEC and free MTX. The in vivo effect of the MTX-DDSs systems was evaluated in induced arthritis rats as single intra-articular dose. The assessed parameters were the mechanical nociceptive threshold, the plasmatic IL-1ß level and histological analysis of the tibiofemoral joint. MTX-HG and MTX-PEC-HG performance were similar to free MTX and worse than oral MTX, used as positive control. All DDSs showed some irritative effect, for which further studies are required. MTX-PEC was the best treatment on recovering cartilage damage and decreasing allodynia. Thus, MTX-PEC demonstrated potential to treat rheumatoid arthritis, with the possibility of decreasing the systemic exposure to the drug.

Participation of CXCL1 in the glial cells during neuropathic pain.

Neuropathic pain is a chronic pain characterized by injury to the central or peripheral nervous system and that most often causes disability in individuals. Among the mechanisms involved in central sensitization during neuropathic pain are cytokines and chemokines released by spinal glial cells; however, these mechanisms are not well elucidated. Thus, the present study aimed to investigate the involvement of Chemokine (C-X-C motif) ligand 1 (CXCL1) and glial cells in this process. Male Wistar rats weighing 220-240 g were used and underwent a neuropathic pain model induced by chronic constriction injury (CCI). To investigate the involvement of CXCL1, chemokine receptor type 2 (CXCR2), mitogen-activated protein kinases (MAPK) p38, and microglia and astrocytes, the following drugs were used: SB225002, an CXCR2 antagonist; SML0543, a MAPK p38 inhibitor; minocycline, a microglia inhibitor; fluorocitrate, an astrocytes inhibitor; and recombinant CXCL1. The microglia, astrocytes, CXCL1, and MAPK p38 protein levels was evaluated by a Western blot assay. Furthermore, an immunofluorescence assay was performed to localize microglia and astrocytes immunoreactivity in the spinal cord. The results demonstrated that both CCI and CXCL1 induced nociception, and this effect was reversed by SB225002. In addition, minocycline, fluorocitrate, and SML0543 reversed the mechanical allodynia induced by CCI. Furthermore, there was an increase of spinal CXCL1 and microglial marker Iba1 protein levels , which was reversed by SB225002. This antagonist also reduced the Iba1 immunoreactivity in spinal cord. Thus, the present study suggests that the CXCL1 chemokine participates in neuropathic pain through CXCR2 activation in spinal microglia.

Benefí­cios da atividade fí­sica em idosos do projeto de extensão Vida Ativa/UNATI / Benefits of physical activity in the elderly of the extension project Active Life/UNATI

Objetivo: Verificar os efeitos da atividade física na força muscular respiratória, função motora, sintomas depressivos, qualidade de vida e imagem corporal em idosos do projeto de extensão Vida Ativa/UNATI. Métodos: Sete indivíduos, ambos os sexos, com idade média de 68,14 ± 4,38 foram submetidos a avaliações e reavaliações de força muscular respiratória (PiMáx e PeMáx), função motora (FPP-D/E, TUG, SPPB, EEB), sintomas depressivos (GDS-15), qualidade de vida (SF-36) e imagem corporal (IPCg) após 10 intervenções com atividades físicas, duas vezes na semana, por uma hora. Resultados: Houve aumento significativo em SPPB (p = 0,01); aumento não significativo da média dos valores de PiMáx (p = 0,07) e diminuição de PeMáx (p = 0,65); manutenção em FPP-D/E (p = 1); diminuição em TUG (p = 0,48); aumento EEB (p = 0,08); diminuição em GDS-15 (p = 0,36); em SF-36, obteve-se aumento em alguns domínios, como Capacidade Funcional (p = 0,79), Estado Geral de Saúde (p = 0,20), Vitalidade (p = 0,25) e Saúde Mental (p = 0,36), manutenção em Aspectos Emocionais (p = -), e diminuição em Aspectos Físicos (p = 0,66), Dor (p = 0,28) e Aspectos Sociais (p = 0,14); aumento em IPCg (p = 0,61). Conclusão: Foi observada manutenção ou melhora de quase todos os aspectos analisados. (AU)

Aim: To verify the effects of physical activity on respiratory muscle strength, motor function, depression symptoms, quality of life and body image in the aging process in elderly participants of Active Life/UNATI extension project. Methods: Seven individuals of both sexes, mean age 68.14 ± 4.38 years, were included in the study. Initially, evaluations were performed and then reassessments of respiratory muscle strength (Pimax and Pemax), motor function (FPP-D/E, TUG, SPPB, BSE), depressive symptoms (GDS-15), quality of life and body image (IPCg) were performed after 10 interventions with physical activities, twice a week, lasting one hour. Results: We observed a significant increase in SPPB (p=0.01); non-significant increase of mean values of Pimax (p = 0.07) and decrease of Pemax (p = 0.65); maintenance in FPP-D/E (p = 1); decrease in TUG (p = 0.48); increase in EEB (p = 0.08); decrease in GDS-15 (p = 0.36); in SF36, an increase was obtained in some areas, such as Functional Capacity (p = 0.79), General Health Status (p = 0.20), Vitality (p = 0.25) and Mental Health (p = 0.36), maintenance in Emotional Aspects (p= -), and decrease in Physical Aspects (0.66), Pain (p = 0.28) and Social Aspects (p = 0.14); increase in IPCg (p = 0.61). Conclusion: The proposed protocol of physical activity promoted maintenance or improvement of almost all aspects analyzed. (AU)