RESUMO
This chapter provides a summary of the literature including results from large trials, meta-analyses, and recent major recommendations. Two well-accepted and recent recommendations include those from the Agency for Health Research and Quality on calcium and vitamin D supplementation and from the Institute of Medicine's dietary reference intakes for calcium and vitamin D. This review suggests that there is strong evidence for synergistic roles of calcium and vitamin D in maintaining bone health in postmenopausal women, but the correlation between vitamin D alone and bone health is overall inconclusive.
Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Cálcio da Dieta/uso terapêutico , Suplementos Nutricionais , Necessidades Nutricionais , Osteoporose Pós-Menopausa/prevenção & controle , Vitamina D/uso terapêutico , Vitaminas/uso terapêutico , Densidade Óssea/fisiologia , Feminino , Humanos , Osteoporose Pós-Menopausa/etiologia , Osteoporose Pós-Menopausa/fisiopatologia , Fraturas por Osteoporose/prevenção & controle , Guias de Prática Clínica como Assunto , Vitamina D/fisiologia , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/diagnóstico , Deficiência de Vitamina D/prevenção & controleRESUMO
The molecular mechanisms underlying slow inactivation in sodium channels are elusive. Our results suggest that EEDD, a highly conserved ring of charge in the external vestibule of mammalian voltage-gated sodium channels, undermines slow inactivation. By employing site-directed mutagenesis, we found that charge alterations in this asymmetric yet strong local electrostatic field of the EEDD ring significantly altered the kinetics of slow inactivation gating. Using a non-linear Poisson-Boltzmann equation, quantitative computations of the electrostatic field in a sodium channel structural model suggested a significant electrostatic repulsion between residues E403 and E758 at close proximity. Interestingly, when this electrostatic interaction was eliminated by the double mutation E403C + E758C, the kinetics of recovery from slow inactivation of the double-mutant channel was retarded by 2500% compared to control. These data suggest that the EEDD ring, located within the asymmetric electric field, is a molecular motif that critically modulates slow inactivation in sodium channels.