吡格列酮与罗格酮对糖尿病患者心血管事件发生的影响

研究目的：比较使用吡格列酮与罗格列酮治疗2型糖尿病时急性心肌梗死,心力衰竭以及死亡的发生风险. 方法：本研究是一项回顾性队列分析.受试者为来自加拿大安大略省的门诊患者,年龄均在60岁以上,且于2002年4月1日～2008年3月31日之间使用吡格列酮或罗格列酮治疗2型糖尿病.     

Mapping human brain capillary water lifetime: high-resolution metabolic neuroimaging

Shutter-speed analysis of dynamic-contrast-agent (CA)-enhanced normal, multiple sclerosis (MS), and glioblastoma (GBM) human brain data gives the mean capillary water molecule lifetime (τ_b) and blood volume fraction (v_b; capillary density–volume product (ρ^†V)) in a high-resolution ¹H₂O MRI voxel (40 μL) or ROI. The equilibrium water extravasation rate constant, k_po (τ_b⁻¹), averages 3.2 and 2.9 s⁻¹ in resting-state normal white matter (NWM) and gray matter (NGM), respectively (n = 6). The results (italicized) lead to three major conclusions. (A) k_po differences are dominated by capillary water permeability (P_W^†), not size, differences. NWM and NGM voxel k_po and v_b values are independent. Quantitative analyses of concomitant population-averaged k_po, v_b variations in normal and normal-appearing MS brain ROIs confirm P_W^† dominance. (B) P_W^† is dominated (>95%) by a trans(endothelial)cellular pathway, not the P_CA^† paracellular route. In MS lesions and GBM tumors, P_CA^† increases but P_W^† decreases. (C) k_po tracks steady-state ATP production/consumption flux per capillary. In normal, MS, and GBM brain, regional k_po correlates with literature MRSI ATP (positively) and Na⁺ (negatively) tissue concentrations. This suggests that the P_W^† pathway is metabolically active. Excellent agreement of the relative NGM/NWM k_pov_b product ratio with the literature ³¹PMRSI-MT CMR_oxphos ratio confirms the flux property. We have previously shown that the cellular water molecule efflux rate constant (k_io) is proportional to plasma membrane P-type ATPase turnover, likely due to active trans-membrane water cycling. With synaptic proximities and synergistic metabolic cooperativities, polar brain endothelial, neuroglial, and neuronal cells form “gliovascular units.” We hypothesize that a chain of water cycling processes transmits brain metabolic activity to k_po, letting it report neurogliovascular unit Na⁺,K⁺-ATPase activity. Cerebral k_po maps represent metabolic (functional) neuroimages. The NGM 2.9 s⁻¹ k_po means an equilibrium unidirectional water efflux of ~10¹⁵ H₂O molecules s⁻¹ per capillary (in 1 μL tissue): consistent with the known ATP consumption rate and water co-transporting membrane symporter stoichiometries. © 2015 The Authors NMR in Biomedicine Published by John Wiley & Sons Ltd.