Assuntos
Alérgenos/análise , Onicomicose/diagnóstico , Trichophyton/isolamento & purificação , Biomarcadores/análise , Estudos de Casos e Controles , Feminino , Proteínas Fúngicas/análise , Humanos , Masculino , Proteômica/métodos , Valores de Referência , Estudos de Amostragem , Sensibilidade e Especificidade , Trichophyton/metabolismoRESUMO
BACKGROUND: The facial erythema of rosacea is recognized as the most prevalent and most difficult manifestation of rosacea to treat. A recent approach in patients with rosacea has been to reduce this erythema through vasoconstriction of cutaneous blood vessels by selectively targeting α2-adrenergic receptors with brimonidine. OBJECTIVE: To further investigate the pharmacodynamic profile of brimonidine, its vasoconstrictive effects and its anti-inflammatory properties. METHODS: The potency for the α1A, α1B, α2A, α2B and α2C receptors of brimonidine was measured, as well as performing a large target profiling study in order to determine the target selectivity profile of brimonidine. The vasoconstrictive effects of brimonidine were measured using ex vivo wire myography and human skin biopsy neuroinflammation models. The anti-inflammatory properties of brimonidine were measured using two in vivo mice ear inflammation models. RESULTS: Brimonidine was found to be highly selective for the α2A adrenoreceptor (EC50 0.45nM) over the other α-adrenoreceptors. Additionally, the large target profiling study demonstrated the high selectivity of brimonidine with minimal off-target effects. The ex vivo wire myography model showed that brimonidine is a potent vasoconstrictor of human subcutaneous vessels with a diameter of less than 200µm (EC50 0.4nM). The ex vivo human skin biopsy neuroinflammation model demonstrated that brimonidine completely inhibited vasodilation induced by capsaicin. Both in vivo mouse ear inflammation models highlighted that brimonidine inhibited ear edema (up to 76%) when compared to vehicle. CONCLUSION: The selectivity, vasoconstrictive and anti-inflammatory properties of brimonidine that have been described in these studies are in agreement with the benefits observed with this compound in the treatment of facial erythema in rosacea.
Assuntos
Agonistas de Receptores Adrenérgicos alfa 2/farmacologia , Anti-Inflamatórios/farmacologia , Inflamação/prevenção & controle , Quinoxalinas/farmacologia , Receptores Adrenérgicos alfa 2/efeitos dos fármacos , Pele/irrigação sanguínea , Vasoconstritores/farmacologia , Vasodilatação/efeitos dos fármacos , Animais , Biópsia , Tartarato de Brimonidina , Modelos Animais de Doenças , Feminino , Humanos , Inflamação/induzido quimicamente , Inflamação/metabolismo , Camundongos Endogâmicos BALB C , Receptores Adrenérgicos alfa 2/metabolismo , Técnicas de Cultura de TecidosRESUMO
BACKGROUND: 5,11,14 20:3 is similar to 20:4n-6 but lacks the internal Delta8 double bond essential for prostaglandin and eicosanoid synthesis. When previously fed to laboratory animals as a gymnosperm seed oil component it has shown anti-inflammatory properties. RESULTS: Herein, topically applied Podocarpus nagi methyl esters (containing 26% 5,11,14 20:3) were incorporated into mouse ear phospholipids, reduced 20:4n-6, and reduced 20:4n-6- and TPA-induced mouse ear edema. Purified 5,11,14 20:3 was taken up by cultured human skin keratinocytes, reduced 20:4n-6, and reduced PGE2 levels dramatically. Purified 5,11,14 20:3 did not affect PPARalpha, PPARgamma, or PPARdelta transactivation. CONCLUSIONS: Topical application of 5,11,14 20:3 to skin surfaces can thus reduce inflammatory processes, most likely by displacing 20:4n-6 from phospholipid pools and reducing downstream inflammatory products derived from 20:4n-6 such as PGE2 and leukotrienes. It could have potential use in treating clinical skin disorders resulting from overproduction of 20:4n-6-derived eicosanoid products.