The Journal of clinical endocrinology and metabolism
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J. Clin. Endocrinol. Metab. · Apr 2011
Randomized Controlled Trial Multicenter StudyEffects of denosumab treatment and discontinuation on bone mineral density and bone turnover markers in postmenopausal women with low bone mass.
Denosumab treatment for 24 months increased bone mineral density (BMD) and reduced bone turnover markers (BTM) in postmenopausal women. ⋯ In postmenopausal women with low BMD, the effects of 60 mg denosumab treatment for 24 months on BMD and BTM are reversible upon discontinuation, reflecting its biological mechanism of action. Residual BMD measurements remained above those of the group previously treated with placebo.
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J. Clin. Endocrinol. Metab. · Apr 2011
Randomized Controlled TrialInsufficient activation of autophagy allows cellular damage to accumulate in critically ill patients.
Responses to critical illness, such as excessive inflammation and hyperglycemia, may trigger detrimental chain reactions that damage cellular proteins and organelles. Such responses to illness contribute to the risk of (nonresolving) multiple organ dysfunction and adverse outcome. ⋯ Insufficient autophagy in prolonged critical illness may cause inadequate removal of damaged proteins and mitochondria. Such incomplete clearance of cellular damage, inflicted by illness and aggravated by hyperglycemia, could explain lack of recovery from organ failure in prolonged critically ill patients. These data open perspectives for therapies that activate autophagy during critical illness.
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J. Clin. Endocrinol. Metab. · Apr 2011
Inhibition of the Ras/Raf/MEK/ERK and RET kinase pathways with the combination of the multikinase inhibitor sorafenib and the farnesyltransferase inhibitor tipifarnib in medullary and differentiated thyroid malignancies.
Ras/Raf/MAPK kinase/ERK and rearranged in transformation (RET) kinase pathways are important in thyroid cancer. We tested sorafenib, a B-Raf, RET, and vascular endothelial growth factor receptor kinase inhibitor, combined with tipifarnib, a farnesyltransferase inhibitor that inactivates Ras and other farnesylated proteins. ⋯ Inhibiting the Ras/Raf/MAPK kinase/ERK and RET kinase pathways with sorafenib and tipifarnib is well tolerated and active against thyroid cancer.
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J. Clin. Endocrinol. Metab. · Apr 2011
Randomized Controlled TrialDifferential acylated ghrelin, peptide YY3-36, appetite, and food intake responses to equivalent energy deficits created by exercise and food restriction.
Acute energy deficits imposed by food restriction increase appetite and energy intake; however, these outcomes remain unchanged when energy deficits are imposed by exercise. ⋯ These findings suggest a mediating role of acylated ghrelin and PYY(3-36) in determining divergent feeding responses to energy deficits imposed by food restriction and exercise.
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J. Clin. Endocrinol. Metab. · Apr 2011
Postnatal decrease in circulating insulin-like growth factor-I and low brain volumes in very preterm infants.
IGF-I and IGF binding protein-3 (IGFBP-3) are essential for growth and maturation of the developing brain. ⋯ Postnatal IGF-I and IGFBP-3 concentrations are positively associated with brain volumes at 40 GW in very preterm infants. Normalization of the IGF-I axis, directly or indirectly, may support normal brain development in very preterm infants.