RESUMO
We have demonstrated that the activation of P2X3 receptor on peripheral afferent neurons is critical to development of inflammatory hyperalgesia in peripheral tissue, although pharmacological administration of prostaglandin E(2) or sympathomimetic amines is enough to sensitize primary afferent neurons by acting directly in neuronal receptors. Therefore, to clarify this ambiguity this study verifies whether P2X3 receptor activation on primary afferent neurons enables the sensitization induced by prostaglandin E(2) or sympathomimetic amine. Initially, this study confirmed that co-administration of A317491 (60 µg/paw), a selective P2X3 receptor antagonist, or pre-treatment with dexamethasone (1 mg/mL/kg) prevents the mechanical hyperalgesia induced by carrageenan (300 µg/paw) in the rat's hind paw. Sub-threshold doses of PGE(2) (4 ng/paw) or dopamine (0.4 µg/paw), that do not induce hyperalgesia by themselves, when injected just following αßmeATP or carrageenan in rats treated with dexamethasone induced hyperalgesia, which is prevented by A317491 or treatment with periganglionar (DRG-L5) injections of ODN-antisense, against P2X3 receptor. Furthermore, because PKCÉ translocation induces an increase of neuronal susceptibility to inflammatory mediators, this study demonstrates that αßmeATP in peripheral tissue increases the expression of PKCÉ in cell membranes of DRG-L5, and in contrast, the administration of PKCÉ translocation inhibitor (1 µg/paw) in peripheral tissue 45 min before αßmeATP, prevented the hyperalgesia induced by sub-threshold dose of PGE(2) (4 ng/paw). In conclusion, this study suggests that neuronal P2X3 receptor activation and the consequent PKCÉ translocation increase the susceptibility of nociceptor to inflammatory mediators allowing the development of inflammatory hyperalgesia.
Assuntos
Hiperalgesia/metabolismo , Mediadores da Inflamação/fisiologia , Neurônios/metabolismo , Prostaglandinas/metabolismo , Receptores Purinérgicos P2X3/fisiologia , Simpatomiméticos/metabolismo , Animais , Hiperalgesia/prevenção & controle , Inflamação/metabolismo , Inflamação/prevenção & controle , Masculino , Neurônios/efeitos dos fármacos , Medição da Dor/efeitos dos fármacos , Medição da Dor/métodos , Antagonistas do Receptor Purinérgico P2X/farmacologia , Antagonistas do Receptor Purinérgico P2X/uso terapêutico , Ratos , Ratos Wistar , Receptores Purinérgicos P2X3/metabolismoRESUMO
Studies were conducted to evaluate citric acid production by solid-state fermentation (SSF) using cassava bagasse as substrate employing a fungal culture of Aspergillus niger LPB 21 at laboratory and semipilot scale. Optimization of the process parameters temperature, pH, initial humidity, aeration, and nutritive composition was conducted in flasks and column fermentors. The results showed that thermal treatment of cassava bagasse enhanced fungal fermentation efficacy, resulting in 220 g of citric acid/kg of dry cassava bagasse with only treated cassava bagasse as substrate. The results obtained from the factorial experimental design in a column bioreactor showed that an aeration rate of 60 mL/min (3 mL/[g.min]) and 60% initial humidity were optimum, resulting in 265.7 g/kg of dry cassava bagasse citric acid production. This was almost 1.6 times higher than the quantities produced under unoptimized conditions (167.4 g of citric acid/kg of dry cassava bagasse). The defined parameters were transferred to semipilot scale, which showed high promise for large-scale citric acid production by SSF with cassava bagasse. Respirometry assays were carried out in order to follow indirectly the biomass evolution of the process. Citric acid production reached 220, 309, 263, and 269 g/kg of dry cassava bagasse in Erlenmeyer flasks, column fermentors, a tray bioreactor, and a horizontal drum bioreactor, respectively.