RESUMO
BACKGROUND: The mechanism(s) responsible for breast capsular contracture (CC) remain unknown, but inflammatory pathways play a role. Various molecules have been attached to implant shells in the hope of modifying or preventing CC. The intrinsic antibacterial and antifungal activities of chitosan and related oligochitosan molecules lend themselves well to the study of the infectious hypothesis; chitosan's ability to bind to growth factors, its hemostatic action, and its ability to activate macrophages, cause cytokine stimulation, and increase the production of transforming growth factor (TGF)-ß1 allow study of the hypertrophic scar hypothesis. OBJECTIVE: The authors perform a comprehensive evaluation, in a rabbit model, of the relationship between CC and histological, microbiological, and immunological characteristics in the presence of a chitooligosaccharide (COS) mixture and a low molecular weight chitosan (LMWC). METHODS: Eleven adult New Zealand rabbits were each implanted with three silicone implants: a control implant, one impregnated with COS, and one impregnated with LMWC. At four-week sacrifice, microdialysates were obtained in the capsule-implant interfaces for tumor necrosis factor alpha (TNF-α) and interleukin-8 (IL-8) level assessment. Histological and microbiological analyses were performed. RESULTS: Baker grade III/IV contractures were observed in the LMWC group, with thick capsules, dense connective tissue, and decreased IL-8 levels (p < .05) compared to control and COS groups. Capsule tissue bacterial types and microdialysate TNF-α levels were similar among all groups. CONCLUSIONS: Chitosan-associated silicone implantation in a rabbit model resulted in Baker grade III/IV CC. This preclinical study may provide a model to test various mechanistic hypotheses of breast capsule formation and subsequent CC.
Assuntos
Implantes de Mama/efeitos adversos , Quitosana/farmacologia , Modelos Animais de Doenças , Contratura Capsular em Implantes/etiologia , Animais , Feminino , Contratura Capsular em Implantes/microbiologia , Contratura Capsular em Implantes/patologia , Interleucina-8/metabolismo , Microdiálise , Oligossacarídeos/química , Coelhos , Géis de Silicone , Fator de Crescimento Transformador beta1/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
An original, simple, specific, and rapid high-performance liquid chromatography assay for the determination of clofazimine in human plasma is presented. The procedure consists of extracting the drug and the internal standard (medazepam) from 0.5 mL plasma with dichloromethane/diisopropyl ether (1:1, v/v) at pH 3.0, after precipitating the proteins with methanol. The drugs were then quantitated on a reversed-phase C8 using a mobile phase consisting of a mixture of methanol/0.25 N sodium acetate buffer at pH 3.0 (74:26, v/v). The flow-rate and wavelength were set at 1 mL/min and 286 nm, respectively. The precision, linearity, and limit of quantitation of the method were within acceptable limits. The method was considered adequate and could be applied in studies involving blood level monitoring and pharmacokinetics in leprosy patients.
Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Clofazimina/farmacocinética , Monitoramento de Medicamentos/métodos , Hansenostáticos/farmacocinética , Hanseníase/metabolismo , Clofazimina/uso terapêutico , Feminino , Humanos , Hansenostáticos/uso terapêutico , Hanseníase/tratamento farmacológico , Masculino , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
An original, simple, specific, and rapid high-performance liquid chromatography assay for the determination of clofazimine in human plasma is presented. The procedure consists of extracting the drug and the internal standard (medazepam) from 0.5 mL plasma with dichloromethane/diisopropyl ether (1:1, v/v) at pH 3.0, after precipitating the proteins with methanol. The drugs were then quantitated on a reversed-phase C8 using a mobile phase consisting of a mixture of methanol/0.25 N sodium acetate buffer at pH 3.0 (74:26, v/v). The flow-rate and wavelength were set at 1 mL/min and 286 nm, respectively. The precision, linearity, and limit of quantitation of the method were within acceptable limits. The method was considered adequate and could be applied in studies involving blood level monitoring and pharmacokinetics in leprosy patients.
