Endothelin-Dependent Vasoconstriction in Human Uterine Artery: Application to Preeclampsia

BACKGROUND: Reduced uteroplacental perfusion, the initiating event in preeclampsia, is associated with enhanced endothelin-1 (ET-1) production which feeds the vasoconstriction of uterine artery. Whether the treatments of preeclampsia were effective on ET-1 induced contraction and could reverse placental ischemia is the question addressed in this study. We investigated the effect of antihypertensive drugs used in preeclampsia and of ET receptor antagonists on the contractile response to ET-1 on human uterine arteries. METHODOLOGY/PRINCIPAL FINDINGS: Experiments were performed, ex vivo, on human uterine artery samples obtained after hysterectomy. We studied variations in isometric tension of arterial rings in response to the vasoconstrictor ET-1 and evaluated the effects of various vasodilators and ET-receptor antagonists on this response. Among antihypertensive drugs, only dihydropyridines were effective in blocking and reversing the ET-1 contractile response. Their efficiency, independent of the concentration of ET-1, was only partial. Hydralazine, alpha-methyldopa and labetalol had no effect on ET-1 induced contraction which is mediated by both ET(A) and ET(B) receptors in uterine artery. ET receptors antagonists, BQ-123 and BQ-788, slightly reduced the amplitude of the response to ET-1. Combination of both antagonists was more efficient, but it was not possible to reverse the maximal ET-1-induced contraction with antagonists used alone or in combination. CONCLUSION: Pharmacological drugs currently used in the context of preeclampsia, do not reverse ET-1 induced contraction. Only dihydropyridines, which partially relax uterine artery previously contracted with ET-1, might offer interesting perspectives to improve placental perfusion

Self-Reported Health Status in Primary Health Care: The Influence of Immigration and Other Associated Factors

OBJECTIVE: The aims of this study are to compare self-reported health status between Spanish-born and Latin American-born Spanish residents, adjusted by length of residence in the host country; and additionally, to analyse sociodemographic and psychosocial variables associated with a better health status. DESIGN: This is a cross-sectional population based study of Latin American-born (n = 691) and Spanish-born (n = 903) in 15 urban primary health care centres in Madrid (Spain), carried out between 2007 and 2009. The participants provided information, through an interview, about self-reported health status, socioeconomic characteristics, psychosocial factors and migration conditions. Descriptive and multiple logistic regression analyses were conducted. RESULTS: The Spanish-born participants reported a better health status than the Latin America-born participants (79.8% versus 69.3%, p<0.001). Different patterns of self-reported health status were observed depending on the length of residence in the host country. The proportion of immigrants with a better health status is greater in those who have been in Spain for less than five years compared to those who have stayed longer. Better health status is significantly associated with being men, under 34 years old, being Spanish-born, having a monthly incomes of over 1000 euros, and having considerable social support and low stress. CONCLUSIONS: Better self-reported health status is associated with being Spanish-born, men, under 34 years old, having an uppermiddle-socioeconomic status, adequate social support, and low stress. Additionally, length of residence in the host country is seen as a related factor in the self-reported health status of immigrants

Direct observation of Anderson localization of matter-waves in a controlled disorder

We report the observation of exponential localization of a Bose-Einstein condensate (BEC) released into a one-dimensional waveguide in the presence of a controlled disorder created by laser speckle . We operate in a regime allowing AL: i) weak disorder such that localization results from many quantum reflections of small amplitude; ii) atomic density small enough that interactions are negligible. We image directly the atomic density profiles vs time, and find that weak disorder can lead to the stopping of the expansion and to the formation of a stationary exponentially localized wave function, a direct signature of AL. Fitting the exponential wings, we extract the localization length, and compare it to theoretical calculations. Moreover we show that, in our one-dimensional speckle potentials whose noise spectrum has a high spatial frequency cut-off, exponential localization occurs only when the de Broglie wavelengths of the atoms in the expanding BEC are larger than an effective mobility edge corresponding to that cut-off. In the opposite case, we find that the density profiles decay algebraically, as predicted in [Phys. Rev. Lett. 98, 210401 (2007)]. The method presented here can be extended to localization of atomic quantum gases in higher dimensions, and with controlled interactions

The CD4+ T-cell transcriptome and serum IgE in asthma: IL17RB and the role of sex

<p>Abstract</p> <p>Background</p> <p>The relationships between total serum IgE levels and gene expression patterns in peripheral blood CD4+ T cells (in all subjects and within each sex specifically) are not known.</p> <p>Methods</p> <p>Peripheral blood CD4+ T cells from 223 participants from the Childhood Asthma Management Program (CAMP) with simultaneous measurement of IgE. Total RNA was isolated, and expression profiles were generated with Illumina HumanRef8 v2 BeadChip arrays. Modeling of the relationship between genome-wide gene transcript levels and IgE levels was performed in all subjects, and stratified by sex.</p> <p>Results</p> <p>Among all subjects, significant evidence for association between gene transcript abundance and IgE was identified for a single gene, the interleukin 17 receptor B (IL17RB), explaining 12% of the variance (r²) in IgE measurement (p value = 7 × 10^-7, 9 × 10^-3after adjustment for multiple testing). Sex stratified analyses revealed that the correlation between IL17RB and IgE was restricted to males only (r²= 0.19, p value = 8 × 10^-8; test for sex-interaction p < 0.05). Significant correlation between gene transcript abundance and IgE level was not found in females. Additionally we demonstrated substantial sex-specific differences in IgE when considering multi-gene models, and in canonical pathway analyses of IgE level.</p> <p>Conclusions</p> <p>Our results indicate that IL17RB may be the only gene expressed in CD4+ T cells whose transcript measurement is correlated with the variation in IgE level in asthmatics. These results provide further evidence sex may play a role in the genomic regulation of IgE.</p

Toll-like receptor 4 signaling in liver injury and hepatic fibrogenesis

Toll-like receptors (TLRs) are a family of transmembrane pattern recognition receptors (PRR) that play a key role in innate and adaptive immunity by recognizing structural components unique to bacteria, fungi and viruses. TLR4 is the most studied of the TLRs, and its primary exogenous ligand is lipopolysaccharide, a component of Gram-negative bacterial walls. In the absence of exogenous microbes, endogenous ligands including damage-associated molecular pattern molecules from damaged matrix and injured cells can also activate TLR4 signaling. In humans, single nucleotide polymorphisms of the TLR4 gene have an effect on its signal transduction and on associated risks of specific diseases, including cirrhosis. In liver, TLR4 is expressed by all parenchymal and non-parenchymal cell types, and contributes to tissue damage caused by a variety of etiologies. Intact TLR4 signaling was identified in hepatic stellate cells (HSCs), the major fibrogenic cell type in injured liver, and mediates key responses including an inflammatory phenotype, fibrogenesis and anti-apoptotic properties. Further clarification of the function and endogenous ligands of TLR4 signaling in HSCs and other liver cells could uncover novel mechanisms of fibrogenesis and facilitate the development of therapeutic strategies