Developed in 1992, the flow-mediated dilation test is now the most commonly used noninvasive assessment of vascular endothelial function in humans. Since its inception, scientists have refined their ...understanding of the physiology, analysis, and interpretation of this measurement. Recently, a significant growth of knowledge has added to our understanding and implementation of this clinically relevant research methodology. Therefore, this tutorial provides timely insight into recent advances and practical information related to the ultrasonic assessment of vascular endothelial function in humans.
Context:
Skeletal deterioration, leading to an increased risk of fracture, is a known complication of type 2 diabetes mellitus (T2D). Yet plausible mechanisms to account for skeletal fragility in T2D ...have not been clearly established.
Objective:
The objective of the study was to determine whether bone material properties, as measured by reference point indentation, and advanced glycation endproducts (AGEs), as determined by skin autofluorescence (SAF), are related in patients with T2D.
Design:
This was a cross-sectional study.
Setting:
The study was conducted at a tertiary medical center.
Patients:
Sixteen postmenopausal women with T2D and 19 matched controls participated in the study.
Main Outcome Measures:
Bone material strength index (BMSi) by in vivo reference point indentation, AGE accumulation by SAF, and circulating bone turnover markers were measured.
Results:
BMSi was reduced by 9.2% in T2D (P = .02) and was inversely associated with the duration of T2D (r = −0.68, P = .004). Increased SAF was associated with reduced BMSi (r = −0.65, P = .006) and lower bone formation marker procollagen type 1 amino-terminal propeptide (r = −0.63, P = .01) in T2D, whereas no associations were seen in controls. SAF accounted for 26% of the age-adjusted variance in BMSi in T2D (P = .03).
Conclusions:
Bone material properties are impaired in postmenopausal women with T2D as determined by reference point indentation. The results suggest a role for the accumulation of AGEs to account for inferior BMSi in T2D.
“Bone material strength is impaired in type 2 diabetes and is lowest in diabetic patients with increased advanced glycation endproducts as determined by skin autofluorescence.”
ABSTRACT
Chronic kidney disease (CKD) patients may have high rates of bone loss and fractures, but microarchitectural and biochemical mechanisms of bone loss in CKD patients have not been fully ...described. In this longitudinal study of 53 patients with CKD Stages 2 to 5D, we used dual‐energy X‐ray absorptiometry (DXA), high‐resolution peripheral quantitative computed tomography (HRpQCT), and biochemical markers of bone metabolism to elucidate effects of CKD on the skeleton. Median follow‐up was 1.5 years (range 0.9 to 4.3 years); bone changes were annualized and compared with baseline. By DXA, there were significant declines in areal bone mineral density (BMD) of the total hip and ultradistal radius: −1.3% (95% confidence interval CI −2.1 to −0.6) and −2.4% (95% CI −4.0 to −0.9), respectively. By HRpQCT at the distal radius, there were significant declines in cortical area, density, and thickness and increases in porosity: −2.9% (95% CI −3.7 to −2.2), −1.3% (95% CI −1.6 to −0.6), −2.8% (95% CI −3.6 to −1.9), and +4.2% (95% CI 2.0 to 6.4), respectively. Radius trabecular area increased significantly: +0.4% (95% CI 0.2 to 0.6), without significant changes in trabecular density or microarchitecture. Elevated time‐averaged levels of parathyroid hormone (PTH) and bone turnover markers predicted cortical deterioration. Higher levels of serum 25‐hydroxyvitamin D predicted decreases in trabecular network heterogeneity. These data suggest that significant cortical loss occurs with CKD, which is mediated by hyperparathyroidism and elevated turnover. Future investigations are required to determine whether these cortical losses can be attenuated by treatments that reduce PTH levels and remodeling rates.
Endothelin-1 (ET-1), a potent vasoconstrictor secreted by vascular endothelial cells, has been implicated in the pathophysiology of numerous cardiovascular diseases, yet the direct impact of ET-1 on ...vascular function remains unclear. Therefore, in seven young (23 ± 1 yr) healthy subjects, we investigated the effect of an intra-arterial infusion of ET-1 on reactive hyperemia (RH) and flow-mediated dilation (FMD) in the popliteal artery following 5 min of suprasystolic cuff occlusion. ET-1 infusion significantly attenuated basal leg blood flow (control: 62 ± 4 ml/min, ET-1: 47 ± 9 ml/min), RH area-under-curve (AUC); control: 162 ± 15 ml, ET-1: 104 ± 16 ml, and peak RH (control: 572 ± 51 ml/min, ET-1: 412 ± 32 ml/min) (
< 0.05). Administration of ET-1 also reduced FMD (control: 2.4 ± 0.3%, ET-1: 0.5 ± 0.5%) and FMD normalized for shear rate (control: 10.5 × 10
± 2.0 × 10
/s
, ET-1: 0.9 × 10
± 2.8 ×10
/s
). These findings reveal that elevated levels of ET-1 have a significant impact on vascular function, indicating that studies employing RH and FMD as markers of microvascular function and nitric oxide bioavailability, respectively, should exercise caution, as ET-1 can impact these assessments by tipping the balance between vasodilation and vasoconstriction, in favor of the latter.
Endothelin-1 (ET-1) is recognized as the body's most potent endogenous vasoconstrictor, but the impact of this peptide on vascular function is not well understood. The present study revealed that the intra-arterial administration of ET-1 impaired both microvascular and conduit vessel function of the leg in young, healthy, humans. Studies employing vascular testing in patient cohorts that experience a disease-related increase in ET-1 should thus exercise caution, as ET-1 clearly impairs vascular function.
The Andromeda Galaxy recurrent nova M31N 2008-12a has been caught in eruption nine times. Six observed eruptions in the seven years from 2008 to 2014 suggested a duty cycle of ~1 yr, which makes this ...the most rapidly recurring system known and the leading single-degenerate Type Ia Supernova progenitor candidate; but no 2010 eruption has been found so far. Here we present evidence supporting the recovery of the 2010 eruption, based on archival images taken at and around the time of eruption. We detect the 2010 eruption in a pair of images at 2010 Nov. 20.52 UT, with a magnitude of mR = 17.84 ± 0.19. The sequence of seven eruptions shows significant indications of a duty cycle slightly shorter than one year, which makes successive eruptions occur progressively earlier in the year. We compared three archival X-ray detections with the well-observed multi-wavelength light curve of the 2014 eruption to accurately constrain the time of their optical peaks. The results imply that M31N 2008-12a might actually have a recurrence period of ~6 months (175 ± 11 days), making it even more exceptional. If this is the case, then we predict that two eruptions per year will be observable soon. Furthermore, we predict that the next eruption will occur in late Sep. 2015. We encourage additional observations.
Abstract Finite element (FE) analysis based on quantitative computed tomography (QCT) images is an emerging tool to estimate bone strength in a specific patient or specimen; however, it is limited by ...the computational power required and the associated time required to generate and solve the models. Thus, our objective was to develop a fast, validated method to estimate whole bone structural stiffness and failure load in addition to a sensitivity analysis of varying boundary conditions. We performed QCT scans on twenty fresh-frozen proximal femurs (age: 77±13 years) and mechanically tested the femurs in a configuration that simulated a sideways fall on the hip. We used custom software to generate the FE models with boundary conditions corresponding to the mechanical tests and solved the linear models to estimate bone structural stiffness and estimated failure load. For the sensitivity analysis, we varied the internal rotation angle of the femoral neck from −30° to 45° at 15° intervals and estimated structural stiffness at each angle. We found both the FE estimates of structural stiffness ( R2 =0.89, p <0.01) and failure load ( R2 =0.81, p <0.01) to be in high agreement with the values found by mechanical testing. An important advantage of these methods was that the models of approximately 500,000 elements took less than 11 min to solve using a standard desktop workstation. In this study we developed and validated a method to quickly and accurately estimate proximal femur structural stiffness and failure load using QCT-driven FE methods.
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