Chronic estrogen depletion alters adenosine diphosphate-induced pial arteriolar dilation in female rats

We examined pial arteriolar reactivity to a partially endothelial nitric oxide synthase (eNOS)-dependent vasodilator ADP as a function of chronic estrogen status. The eNOS-dependent portion of the ADP response was ascertained by comparing ADP-induced pial arteriolar dilations before and after suffusion of a NOS inhibitor, N(omega)-nitro-L-arginine (L-NNA; 1 mM) in intact, ovariectomized (Ovx), and 17beta-estradiol (E2)-treated Ovx females. We also examined whether ovariectomy altered the participation of other factors in the ADP response. Those factors were the following: 1) the prostanoid indomethacin (Indo); 2) the Ca2+-dependent K+ (K(Ca)) channel, iberiotoxin (IbTX); 3) the ATP-regulated K+ (K(ATP)) channel glibenclamide (Glib); 4) the K(Ca)-regulating epoxygenase pathway miconazole (Mic); and 5) the adenosine receptor 8-sulfophenyltheophylline (8-SPT). In intact females, the eNOS-dependent (L-NNA sensitive) portion of the ADP response represented approximately 50% of the total. The ADP response was retained in the Ovx rats but L-NNA sensitivity disappeared. On E2 replacement, the initial pattern was restored. ADP reactivity was unaffected by Indo, Glib, Mic, and 8-SPT. IbTX was associated with 50-80% reductions in the response to ADP in the intact group that was nonadditive with L-NNA, and 60-100% reductions in the Ovx group. The present findings suggest that estrogen influences the mechanisms responsible for ADP-induced vasodilation. The continued sensitivity to IbTX in Ovx rats, despite the loss of a NO contribution, is suggestive of a conversion to a hyperpolarizing factor dependency in the absence of E2.     

Nuclear magnetic relaxation dispersion profiles of substantia nigra pars compacta in Parkinson's disease patients are consistent with protein aggregation

Nuclear Magnetic Relaxation field-cycling relaxometry is a technique, able to report on water mobility in tissues. By means of this technique, post-mortem specimens from both controls and idiopathic Parkinson's disease patients have been investigated. Results show different relaxometric behavior between the groups, which is consistent with protein aggregation in Parkinson's disease specimens.     

Patterns of Annual Seed Production by Northern Hemisphere Trees: A Global Perspective

We tested whether annual seed production (masting or mast fruiting) in Northern Hemisphere trees is an evolved strategy or a consequence of resource tracking by comparing masting patterns with those of annual rainfall and mean summer temperatures, two environmental variables likely to correlate with available resources. There were generally significant negative autocorrelations between the seed crop in year x and year x+1 (year x+2 in species of Quercus requiring 2 yr to mature acorns), as expected if resources are depleted in mast years in part by switching resources from growth to reproduction. Spatial autocorrelation in annual seed production generally declined with distance but was statistically significant over large geographic areas. Variability in annual seed production was relatively high and inversely correlated with latitude and generally not bimodally distributed. Patterns of spatial autocorrelation in annual rainfall and summer temperatures are generally similar to those exhibited by annual seed production, and relative variability in annual rainfall is also inversely correlated with latitude. However, these environmental variables exhibit distinctly different patterns of temporal autocorrelation, are much less variable, and are more normally distributed than annual seed production. Combined with the inverse relationship between growth and reproduction previously documented, these results support the hypothesis that variability in annual seed production is an evolved strategy and that annual seed production is more or less normally distributed rather than an all-or-none phenomenon.     

Midregional-proAtrial Natriuretic Peptide and High Sensitive Troponin T Strongly Predict Adverse Outcome in Patients Undergoing Percutaneous Repair of Mitral Valve Regurgitation

Background

It is not known whether biomarkers of hemodynamic stress, myocardial necrosis, and renal function might predict adverse outcome in patients undergoing percutaneous repair of severe mitral valve insufficiency. Thus, we aimed to assess the predictive value of various established and emerging biomarkers for major adverse cardiovascular events (MACE) in these patients.

Methods

Thirty-four patients with symptomatic severe mitral valve insufficiency with a mean STS-Score for mortality of 12.6% and a mean logistic EuroSCORE of 19.7% undergoing MitraClip therapy were prospectively included in this study. Plasma concentrations of mid regional-proatrial natriuretic peptide (MR-proANP), Cystatin C, high-sensitive C-reactive protein (hsCRP), high-sensitive troponin T (hsTnT), N-terminal B-type natriuretic peptide (NT-proBNP), galectin-3, and soluble ST-2 (interleukin 1 receptor-like 1) were measured directly before procedure. MACE was defined as cardiovascular death and hospitalization for heart failure (HF).

Results

During a median follow-up of 211 days (interquartile range 133 to 333 days), 9 patients (26.5%) experienced MACE (death: 7 patients, rehospitalization for HF: 2 patients). Thirty day MACE-rate was 5.9% (death: 2 patients, no rehospitalization for HF). Baseline concentrations of hsTnT (Median 92.6 vs 25.2 ng/L), NT-proBNP (Median 11251 vs 1974 pg/mL) and MR-proANP (Median 755.6 vs 318.3 pmol/L, all p<0.001) were clearly higher in those experiencing an event vs event-free patients, while other clinical variables including STS-Score and logistic EuroSCORE did not differ significantly. In Kaplan-Meier analyses, NT-proBNP and in particular hsTnT and MR-proANP above the median discriminated between those experiencing an event vs event-free patients. This was further corroborated by C-statistics where areas under the ROC curve for prediction of MACE using the respective median values were 0.960 for MR-proANP, 0.907 for NT-proBNP, and 0.822 for hsTnT.

Conclusions

MR-proANP and hsTnT strongly predict cardiovascular death and rehospitalization for HF in patients undergoing percutaneous repair of mitral valve insufficiency. Both markers might be useful components in new scoring systems to better predict short- and potentially long-term mortality and morbidity after MitraClip procedure.     

A Second Look at the Association between Gender and Mortality on Antiretroviral Therapy

Objective

We assessed the association between gender and mortality on antiretroviral therapy (ART) using identical models with and without sex-specific categories for weight and hemoglobin.

Design

Cohort study of adult patients on ART.

Setting

GHESKIO Clinic in Port-au-Prince, Haiti.

Participants

4,717 ART-naïve adult patients consecutively enrolled on ART at GHESKIO from 2003 to 2008.

Main Outcome Measure

Mortality on ART; multivariable analyses were conducted with and without sex-specific categories for weight and hemoglobin.

Results

In Haiti, male gender was associated with mortality (OR 1.61; 95% CI: 1.30–2.00) in multivariable analyses with hemoglobin and weight included as control variables, but not when sex-specific interactions with hemoglobin and weight were used.

Conclusions

If sex-specific categories are omitted, multivariable analyses indicate a higher risk of mortality for males vs. females of the same weight and hemoglobin. However, because males have higher normal values for weight and hemoglobin, the males in this comparison would generally have poorer health status than the females. This may explain why gender differences in mortality are sometimes observed after controlling for differences in baseline variables when gender-specific interactions with weight and hemoglobin are omitted.     

Genotyping of Single Nucleotide Polymorphisms in DNA Isolated from Serum Using Sequenom MassARRAY Technology

Background

Large epidemiologic studies have the potential to make valuable contributions to the assessment of gene-environment interactions because they prospectively collected detailed exposure data. Some of these studies, however, have only serum or plasma samples as a low quantity source of DNA.

Methods

We examined whether DNA isolated from serum can be used to reliably and accurately genotype single nucleotide polymorphisms (SNPs) using Sequenom multiplex SNP genotyping technology. We genotyped 81 SNPs using samples from 158 participants in the NYU Women’s Health Study. Each participant had DNA from serum and at least one paired DNA sample isolated from a high quality source of DNA, i.e. clots and/or cell precipitates, for comparison.

Results

We observed that 60 of the 81 SNPs (74%) had high call frequencies (≥95%) using DNA from serum, only slightly lower than the 85% of SNPs with high call frequencies in DNA from clots or cell precipitates. Of the 57 SNPs with high call frequencies for serum, clot, and cell precipitate DNA, 54 (95%) had highly concordant (>98%) genotype calls across all three sample types. High purity was not a critical factor to successful genotyping.

Conclusions

Our results suggest that this multiplex SNP genotyping method can be used reliably on DNA from serum in large-scale epidemiologic studies.