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1.
Diabetes ; 65(2): 503-9, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26470782

RESUMO

Platelet activation is persistently enhanced, and its inhibition by low-dose aspirin is impaired in type 2 diabetes mellitus. We investigated in vivo thromboxane (TX) and prostacyclin (PGI2) biosynthesis and their determinants, as well as aspirin responsiveness, in young adult subjects with type 1 diabetes mellitus (T1DM) without overt cardiovascular disease and stable glycemic control. The biosynthesis of TXA2 was persistently increased in subjects with T1DM versus matched healthy subjects, with females showing higher urinary TX metabolite (TXM) excretion than male subjects with T1DM. Microalbuminuria and urinary 8-iso-PGF2α, an index of in vivo oxidative stress, independently predicted TXM excretion in T1DM. No homeostatic increase in PGI2 biosynthesis was detected. Platelet COX-1 suppression by low-dose aspirin and the kinetics of its recovery after drug withdrawal were similar in patients and control subjects and were unaffected by glucose variability. We conclude that patients with T1DM and stable glycemic control display enhanced platelet activation correlating with female sex and microvascular and oxidative damages. Moreover, aspirin responsiveness is unimpaired in T1DM, suggesting that the metabolic disturbance per se is unrelated to altered pharmacodynamics. The efficacy and safety of low-dose aspirin in T1DM warrant further clinical investigation.


Assuntos
Aspirina/farmacologia , Diabetes Mellitus Tipo 1/tratamento farmacológico , Epoprostenol/biossíntese , Ativação Plaquetária/fisiologia , Inibidores da Agregação Plaquetária/farmacologia , Tromboxano A2/biossíntese , Adulto , Albuminúria/urina , Aspirina/administração & dosagem , Glicemia/análise , Estudos Transversais , Ciclo-Oxigenase 1/efeitos dos fármacos , Diabetes Mellitus Tipo 1/metabolismo , Dinoprosta/análogos & derivados , Dinoprosta/urina , Feminino , Humanos , Masculino , Análise por Pareamento , Microvasos/fisiopatologia , Pessoa de Meia-Idade , Estresse Oxidativo/fisiologia , Ativação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/administração & dosagem , Fatores Sexuais , Tromboxano A2/urina
2.
Biomacromolecules ; 15(5): 1634-43, 2014 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-24720505

RESUMO

Oil-filled microcapsules of kraft lignin were synthesized by first creating an oil in water emulsion followed by a high-intensity, ultrasound-assisted cross-linking of lignin at the water/oil interface. The rationale behind our approach is based on promoting documented lignin hydrophobic interactions within the oil phase, followed by locking the resulting spherical microsystems by covalent cross-linking using a high intensity ultrasound treatment. As further evidence in support of our rationale, confocal and optical microscopies demonstrated the uniformly spherical morphology of the created lignin microparticles. The detailed elucidation of the cross-linking processes was carried out using gel permeation chromatography (GPC) and quantitative (31)P NMR analyses. The ability of lignin microcapsules to incorporate and release Coumarin-6 was evaluated in detail. In vitro studies and confocal laser scanning microscopy analysis were carried out to assess the internalization of capsules into Chinese hamster ovary (CHO) cells. This part of our work demonstrated that the lignin microcapsules are not cytotoxic and readily incorporated in the CHO cells.


Assuntos
Cápsulas/química , Cápsulas/síntese química , Lignina/química , Sonicação , Animais , Células CHO , Cápsulas/administração & dosagem , Cápsulas/metabolismo , Cumarínicos/administração & dosagem , Cumarínicos/metabolismo , Cricetulus , Interações Hidrofóbicas e Hidrofílicas , Lignina/administração & dosagem , Lignina/síntese química , Lignina/metabolismo , Estrutura Molecular , Tamanho da Partícula , Propriedades de Superfície , Tiazóis/administração & dosagem , Tiazóis/metabolismo
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