The phase III trial reported here was conducted to assess the immunogenicity, tolerability and safety of a new DTwP vaccine manufactured using semi-synthetic medium for both tetanus and diphtheria toxoids in comparison with the routinely manufactured DTwP vaccine.\n\nMethods: In all, 331 infants aged 6-8 weeks were enrolled, out of which 308 completed the study. The vaccination was done at 6-10-14 weeks following EPI/WHO recommended immunization schedule. Blood samples were collected prior to the administration of first dose and one month after the third dose.\n\nResults: Postvaccination, geometric mean titres for each

component did not differ significantly amongst the two study groups. Though, the immunogenicity results were comparable between the two vaccines, the incidence of adverse events was comparatively low in semi-synthetic vaccine as against the routine vaccine LDK378 group for all the three doses.\n\nConclusions: The semi-synthetic DTwP vaccine was immunogenic and showed a significant lower incidence

of local adverse events in comparison to the routine vaccine. This vaccine is now being used in the routine vaccination programme both as a triple antigen (DTwP alone) as well as a combination with Hepatitis B and/or Haemophilus influenzae type b vaccine. (C) 2012 Elsevier Ltd. All rights reserved.”
“Background and aims: Hepatitis B virus (HBV) infection is a public health problem and affects nearly 350 million people worldwide. The present study was conducted in order to investigate the role of circulating angiotensin-converting enzyme AC220 concentration selleck chemicals (ACE) in the context of renin-angiotensin-aldosterone in newly diagnosed chronic hepatitis B infection. Moreover the association between liver fibrosis and serum ACE levels was also investigated.\n\nMaterials and methods: The study was performed on 50 chronic hepatitis B (CHB) patients (24 males, 26 females; median age 39.4 years, range 18-63) and 20 healthy controls. The clinical features

of CHB patients including demographics, laboratory and liver biopsy findings were summarized. Serum ACE levels were measured by using commercially available kits.\n\nResults: Serum median ACE levels were 48.4 (14-83) U/L and 26.2 (12-48) U/L for the CHB patients and controls, respectively. Serum ACE levels were significantly higher in patients with CHB compared with the control group (p<0.001). Twenty-two patients (44%) had advanced liver fibrosis (Ishak score >2) and 28 patients (56%) had mild liver fibrosis (Ishak score <= 2). Mean serum levels of ACE were significantly higher among patients with advanced fibrosis as compared with those without advanced fibrosis (60.3 +/- 14.2 U/L vs. 39.0 +/- 10.5 U/L, p<0.001). Receiver operating characteristic (ROC) curve analysis suggested that the optimum ACE level cut-off point for advanced fibrosis was 52.5 U/L (sensitivity: 81.8%, specificity: 82.1%, PPV 78.

All rights reserved.”
“There are few alternatives to glucocorticosteroids for treatment of asthma. We assessed the activity of a novel protein drug designated ISU201, the extracellular domain

of the human cell surface protein BST2, stabilised by fusion with the Fc region of IgG, in mouse models of mild chronic asthma and an acute exacerbation of asthma. The ability of ISU201 to suppress airway inflammation and remodelling was compared with that of dexamethasone. Female BALB/c mice were systemically sensitised with ovalbumin, then received controlled low-level challenge with aerosolised ovalbumin for 6 weeks, which induced lesions of mild chronic asthma, and were treated with drugs during the final 2 weeks. Alternatively, sensitised mice received 4 weeks of chronic low-level challenge and were treated 24 and 2 hours before a final single moderate-level challenge, which triggered acute airway inflammation GSK461364 simulating an asthmatic exacerbation. Inflammation and remodelling were quantified, as was the S3I-201 clinical trial expression of pro-inflammatory cytokines in bronchoalveolar lavage fluid and tissues. To identify cellular targets of ISU201, we assessed the effects of the drug on activated lymphocytes, macrophages and airway epithelial cells. In the model of mild chronic asthma, ISU201 was as effective as dexamethasone in suppressing airway inflammation and most

changes of remodelling. In the model of an allergen-induced acute exacerbation of chronic asthma, ISU201 was also an effective anti-inflammatory agent, although it was less active than dexamethasone. The drug acted on multiple cellular targets, suppressing production of pro-inflammatory cytokines by lymphocytes and macrophages. ISU201 significantly reduced acetylation selleck kinase inhibitor of histone H4 in airway epithelial cells, suggesting at least one potential mechanism of action. We conclude that in these models of asthma, ISU201 is a broad-spectrum inhibitor of both airway inflammation and remodelling. Thus, unlike drugs which target specific mediators, it could potentially be an alternative or an adjunct to glucocorticoids for the treatment of asthma.”
“We have performed surface acoustic wave (SAW) measurements

to examine vacancies in a surface layer of a borondoped silicon wafer currently used in semiconductor industry. A SAW with a frequency of f(s) = 517MHz was optimally generated by an interdigital transducer with a comb gap of w = 2: 5 mu m on a piezoelectric ZnO film deposited on the (001) silicon surface. The SAW propagating along the [100] axis with a velocity of v(s) = 4: 967 km/s is in agreement with the Rayleigh wave, which shows an ellipsoidal trajectory motion in the displacement components u(x) and u(z) within a penetration depth of lambda(p) = 3.5 mu m. The elastic constant C-s of the SAW revealed the softening of Delta C-s/C-s = 1.9 x 10(-4) below 2K down to 23 mK. Applied magnetic fields of up to 2 T completely suppress the softening.

Bioinformatics training programs that solely rely on traditional didactic methods are being superseded by these newer resources. Yet such face-to-face instruction is still invaluable in the learning continuum. Bioinformatics.ca, which hosts the Canadian Bioinformatics Workshops, has blended more traditional learning

styles with current online and social learning styles. Here we share our growing experiences over the past 12 years and look toward what the future holds for bioinformatics training programs.”
“In many parts of the world there are extensive landscapes Ferroptosis inhibitor where forests and people strongly intermingle, notably in the suburbs and exurbs of cities. This landscape of transitional forest generally receives limited attention from policy makers and researchers who tend to be rooted in traditions centered on either urban planning or management of natural resources in rural areas. The transitional forest is on the periphery of both perspectives, but it is a large area that provides numerous important values (biodiversity, ecosystem function, forest products, and amenities) to the people that live in them and their neighboring cities. Here we argue for increased attention to transitional forests, identify major challenges, and suggest changes

to planning and management practices needed to ensure that the values of these forests are sustained.”
“A standardized echocardiographic selleck chemical technique was recently established for the Florida manatee (Trichechus manatus latirostris). There are no available published data on normal echocardiographic parameters in any Sirenian species. The purpose of this study was to report reference parameters for various echocardiographic measurements. These parameters are intended to serve as a comparison for future research into the prevalence of cardiac diseases in the manatee and to aid in diagnosing animals with suspected cardiac disease in rehabilitation facilities. Annual health assessments of Dactolisib nmr free-ranging

manatees in Crystal River National Wildlife Refuge, Florida, and pre-release health assessments of rehabilitated manatees at Tampa’s Lowry Park Zoo permitted comparison of echocardiographic measurements in adult (n = 14), subadult (n = 7), and calf (n = 8) animals under manual restraint.”
“Background: Reduced consumption of inhalation anesthetics can be safely achieved by reducing excess fresh gas flow (FGF). In this study the authors describe the use of a real-time decision support tool to reduce excess FGF to lower, less wasteful levels.\n\nMethod: The authors applied a decision support tool called the Smart Anesthesia Manager T (University of Washington, Seattle, WA) that analyzes real-time data from an Anesthesia Information Management System to notify the anesthesia team if FGF exceeds 1 l/min.

As the control

of FA metabolism is essential for maintaining cardiac function, we investigated whether lipin-1 deficiency affects cardiac metabolism and performance. Cardiac PAP activity in lipin-1 deficient [fatty liver dystrophy (fld)] mice was decreased by >80% compared with controls. Surprisingly, oleate oxidation and incorporation in triacylglycerol (TG), as well as glucose oxidation, were not significantly different in perfused working fld hearts. Despite this, [H-3] oleate accumulation in phosphatidate and phosphatidylinositol was increased in fld hearts, reflecting the decreased PAP activity. Phosphatidate accumulation was linked to increased cardiac mammalian target of rapamycin complex 1 (mTORC1) signaling and endoplasmic reticulum (ER) stress. Transthoracic echocardiography showed decreased cardiac function in fld mice; however, cardiac dysfunction was not observed in ex vivo perfused working fld hearts. AG-014699 research buy This showed that changes Selleck JAK inhibitor in systemic factors due to the global absence of lipin-1 could contribute to the decreased cardiac function in vivo.

Collectively, this study shows that fld hearts exhibit unchanged oleate esterification, as well as oleate and glucose oxidation, despite the absence of lipin-1. However, lipin-1 deficiency increases the accumulation of newly synthesized phosphatidate and induces aberrant cell signaling.-Kok, B.P.C., P.C. Kienesberger, J.R.B. Dyck, and D.N. Brindley. Relationship of glucose and oleate metabolism to cardiac function in lipin-1 deficient (fld) mice. J. Lipid Res. 2012. 53: 105-118.”
“The question of molecular heterogeneity and of tumoral phenotype in cancer remains

unresolved. To understand the underlying molecular basis of this phenomenon, we analyzed QNZ genome-wide expression data of colon cancer metastasis samples, as these tumors are the most advanced and hence would be anticipated to be the most likely heterogeneous group of tumors, potentially exhibiting the maximum amount of genetic heterogeneity. Casting a statistical net around such a complex problem proves difficult because of the high dimensionality and multicollinearity of the gene expression space, combined with the fact that genes act in concert with one another and that not all genes surveyed might be involved. We devise a strategy to identify distinct subgroups of samples and determine the genetic/molecular signature that defines them. This involves use of the local sparse bump hunting algorithm, which provides a much more optimal and biologically faithful transformed space within which to search for bumps. In addition, thanks to the variable selection feature of the algorithm, we derived a novel sparse gene expression signature, which appears to divide all colon cancer patients into two populations: a population whose expression pattern can be molecularly encompassed within the bump and an outlier population that cannot be.

(C) 2014 AACR.”
“Spatial neglect is a devastating disorder in 50-70% of right-brain stroke survivors, who have problems attending to, or making movements towards, left-sided stimuli, and experience a high risk of chronic dependence. Prism adaptation is a promising treatment for neglect that involves brief, daily visuo-motor Navitoclax cell line training sessions while wearing optical prisms. Its benefits extend to functional behaviors such as dressing, with effects lasting 6 months or longer. Because one to two sessions

of prism adaptation induce adaptive changes in both spatial motor behavior (Fortis et al., 2011) and brain function (Saj et al., 2013), it is possible stroke patients may benefit from treatment periods shorter than the standard, intensive protocol of ten sessions over two weeks a protocol that is impractical for either US inpatient or outpatient rehabilitation. Demonstrating the effectiveness of a lower dose will maximize the availability of neglect treatment. We present preliminary data suggesting that four to six sessions of prism treatment may induce a large treatment effect, maintained three to four weeks post-treatment. We call for a systematic, randomized clinical trial to establish the minimal effective dose suitable for stroke intervention.”
“The tumor suppressor gene PTEN (phosphatase and tensin homolog deleted on chromosome 10) plays important roles in tumor development and progression. Among

www.selleckchem.com/products/shp099-dihydrochloride.html many functions, PTEN negatively regulates the AKT anti- apoptotic signaling pathway, while nuclear PTEN affects the cell cycle by repressing the mitogen- activated protein kinase pathway. However, the regulation of PTEN expression is still not well understood. We previously reported that androgen receptor (AR) activates PTEN transcription in breast

cancer cells. Here, we found that the transcription factor GATA2 (GATA binding protein 2) is overexpressed in non- cultured human breast carcinomas INCB028050 and is negatively correlated with PTEN expression. We then showed GATA2 promotes breast cancer cell growth and stimulates AKT phosphorylation by inhibiting PTEN transcription. We mapped a GATA2- binding site in the PTEN promoter, whereby GATA2 not only blocks AR- induced PTEN expression by preventing AR nuclear translocation, but also directly represses PTEN transcription independent of AR. Most importantly, for the first time, we have discovered a novel reverse regulation within the traditional PTEN/ AKT signaling pathway, whereby AKT induces GATA2 with consequent decreased PTEN transcription, likely germane in tumor invasion and metastases but not initiation.”
“The mechanical response of the periodontal ligament (PDL) is complex. This tissue responds as a hyperelastic solid when pulled in tension while demonstrating a viscous behavior under compression. This intricacy is reflected in the tissue’s morphology, which comprises fibers, glycosaminoglycans, a jagged interface with the surrounding porous bone and an extensive vascular network.

Complications directly related to support therapy were not lethal; these included hemorrhage from a cannulation site (n = 1), accidental

removal of a cannula (n = 1), and pressure sores (n = 3). Deaths occurred owing to septic (n = 2) and cardiogenic shock (n = 1). Survival rates were 60% and 80% on ECMO and iLA, respectively. Follow-up of survivors detected no neurologic deterioration. CONCLUSION: ECMO/iLA therapy can be used as a rescue therapy in adult trauma patients with severe hypoxemic respiratory failure, BI2536 even in the presence of coagulopathy and/or brain injury. The benefits of rewarming, acid-base correction, oxygenation, and circulatory support must be weighed individually against the risk of hemorrhage. Further research should determine whether ECMO therapy also confers survival benefit. (J Trauma Acute Care Surg. 2013;75:907-912. Copyright (C) 2013 by Lippincott Williams & Wilkins)”
“Importance YH25448 purchase of the field: The understanding of pulmonary drug delivery and

thus its utilization for medical purposes has remarkably advanced over the last decades. It has been recognized that this route of administration offers many advantages and several drug delivery systems have been developed accordingly. Thereby, single-use disposable dry powder inhalers may be considered an economically and therapeutically valuable option for both local and systemic administration of drugs to treat a variety of different disease states.\n\nAreas learn more covered in this review/What the reader will gain: This review highlights the required characteristics and potential applications of single-use disposable dry powder inhalers considering advantages as well as limitations of these drug delivery devices. Until now, such drug delivery systems have not become widely accepted. Several devices are available or under development and a few products have reached or completed the clinical phase, but none of them have received market authorization as yet.\n\nTake home message: Recent advances in formulation and device design, however, can be considered encouraging and should eventually lead to a wider establishment of single-use disposable

dry powder inhalers in pulmonary drug delivery.”
“Purpose: Vogt-Koyanagi-Harada (VKH) disease is a serious ocular inflammatory autoimmune insult directed against antigens associated with melanocytes. The repertoire of killer cell immunoglobulin-like receptors (KIRs) is known to play a significant role in the pathogenesis of various autoimmune disorders. Accordingly, we sought to determine the incidence of KIR genes and KIR ligand (Human leukocytes antigen [HLA-C]) interaction in a cohort of Saudi VKH patients and to compare the findings to normal controls.\n\nMethods: A total of 30 patients with VKH and 125 control subjects were included. PCR using sequence-specific oligonucleotide primers were employed to determine the genotype of the KIR genes and HLA-C alleles.

\n\nDesign, setting, participants, & measurements: This was an observational study of 15,368 adult participants in the National Health and Nutrition Examination Survey 111; 5.9% had CKD (eGFR < 60 ml/min per 1.73 m(2)). Based on the frequency and intensity of leisure time physical activity obtained by a questionnaire, participants were divided into inactive, insufficiently active, and active groups. Time to mortality was examined in Cox models, taking into account the complex survey design.\n\nResults: Inactivity was present in 13.5% of the non-CKD and 28.0% of the CKD groups (P < 0.001). In two separate multivariable Cox models, compared with the physically inactive group, hazard ratios

(95% click here confidence intervals) of mortality for insufficiently active and active groups were 0.60 (0.45 to 0.81) and 0.59 (0.45 to 0.77) in the non-CKD subpopulation and 0.58 (0.42 to 0.79) and 0.44 (0.33 to 0.58) in the CKD subpopulation. These hazard ratios did not differ significantly between the CKD and non-CKD subpopulations (P > 0.3).\n\nConclusions: Physical inactivity

is associated with increased mortality in CKD and non-CKD populations. www.selleckchem.com/products/U0126.html As in the non-CKD population, increased physical activity might have a survival benefit in the CKD population. Clin J Ant Soc Nephrol 4 1901-1906, 2009 doi 10 2215/CJN 01970309″
“We studied the effect of systemic administration of multipotent stem cells on impaired neurological status in rats with brain injury. It was found that transplantation of multipotent mesenchymal stromal cells of the bone marrow or human neural stem and progenitor cells

to rats with local brain injury promoted recovery of the brain control over locomotor function and proprioceptive sensitivity of forelegs. The dynamics of neurological recovery was similar after transplantation of fetal neural stem and progenitor cells and multipotent mesenchymal stromal cells. Transplantation of cell cultures improved survival of experimental animals. It should be noted that administration of neural stem and progenitor cells prevented animal death not only in the acute traumatic period, but also in delayed periods.”
“Objective:The aim of this study was to evaluate the prevalence Pinometostat datasheet and risk factors of anemia among adolescents in Denizli where Mediterranean cuisine (fresh fruit and vegetables) is adopted.\n\nMethods: We accepted hemoglobin values below 12 g/dl for girls and 13 g/dl for boys as the criteria of anemia. We recorded a detailed history including nutritional habits, consumption of animal source foods especially red meat, consumption of fresh fruit and vegetables, presence of parasitic infestation, psychosocial status, school success and any materials consumed except ordinary food.\n\nFindings:We investigated the prevalence of anemia in 1120 children (672 girls and 448 boys), aged 12 to 16 years. We found that the overall prevalence of anemia was 5.6%. 8.3% of the girls and 1.

ORF1s have been classified into five types based on structural organization and the domains identified. Here we perform a large scale analysis of ORF1 domains of 448 elements from the Jockey superfamily using multiple alignments and Hidden Markov Model (HMM)-HMM comparisons. 4SC-202 molecular weight Results: Three major lineages, Chicken repeat 1 (CR1), LINE2 (L2) and Jockey, were identified. All Jockey lineage elements have the same

type of ORF1. In contrast, in the L2 and CR1 lineage elements, all five ORF1 types are found, with no one type of ORF1 predominating. A plant homeodomain (PHD) is much more prevalent than previously suspected. ORF1 type variations involving the PHD domain were found in many subgroups of the L2 and CR1 lineages. A Jockey lineage-like ORF1 with a PHD domain was found in both lineages. A phylogenetic analysis of this ORF1 suggests that

it has been horizontally transferred. Likewise, an esterase containing ORF1 type was only found in two exclusively vertebrate L2 and CR1 groups, indicating that it may have been acquired in a vertebrate common ancestor and then transferred between the lineages. Conclusions: The ORF1 of the CR1 and L2 lineages is very structurally diverse. The presence of a PHD domain in many ORF1s of the L2 and CR1 lineages is suggestive of domain shuffling. There is also evidence of possible horizontal transfer of entire ORF1s between lineages. In conclusion, while the structure of the ORF2 appears to be highly constrained and its evolution tree-like, the structure of the ORF1 within the CR1 and L2 lineages is much more variable and its evolution reticulate.”
“A porous imidazolium polymeric network was synthesized BEZ235 ic50 via alkylation of tetrakis-[4-(1H-imidazole-1-yl)phenyl]methane with 1,4-bis(bromomethyl)benzene. Its complexation with palladium yielded a Pd-NHC porous polymeric network, namely Pd-pNHC. Pd-pNHC showed selective uptake of CO2 over N-2 due

to its polar surface. Pd-pNHC has a BET specific Fer-1 price surface area of 308 m(2) g(-1) and a micropore volume of 0.190 cm(3) g(-1). Pd-pNHC showed ability to absorb both hydrophilic and aromatic guests (MeOH, EtOH and benzene). Pd(II) catalytically active centers within the porous polymeric network were readily accessible to substrates as demonstrated in Suzuki-Miyaura coupling reactions. High yields were achieved in the coupling reactions of various arylbromides under mild conditions. Additionally, Pd-pNHC catalyzed the reactions in a heterogeneous way and the catalyst could be used for at least ten times without loss of activity. (C) 2014 Elsevier B.V. All rights reserved.”
“Fetal exposure to the perfluoroalkyl acids, perfluorooctanesulfonate (PFOS) and perfluorooctanoate (PFOA), has been associated with lower birth weight and lower weight and body mass index (weight (kg)/height (m)(2)) in early infancy. It is, however, unclear if exposure to prenatal PFOS and PFOA has a lasting influence on growth.

“
“OBJECTIVE To assess the clinical and urodynamic results of sigmoidocolocystoplasty in patients with neurogenic bladder dysfunction.\n\nMETHODS We retrospectively reviewed 78 augmentation enterocystoplasty cases in our database from 2005 to 2011 to identify 47 patients who had undergone sigmoidocolocystoplasty alone or combined with ureter reimplantation. The indications for surgery and postoperative complications were evaluated.

Renal function preservation, increased postoperative bladder capacity, decreased maximal detrusor CP-456773 datasheet pressure, and overall patient satisfaction were deemed successful outcomes.\n\nRESULTS The mean follow-up period was 24 months. The mean bladder capacity increased

from 160.6 +/- 128.3 to 468.5 +/- 60.6 mL (P < .001) and the maximal detrusor pressure decreased from 31.1 +/- 26.4 to 10.9 +/- 4.5 cm H2O (P = .002). The serum creatinine level decreased from 270.3 +/- 113.6 to 174.4 +/- 81.3 mu mol/L (P Ro 61-8048 datasheet = .001). Most patients resolved the urinary incontinence using clean self-intermittent catheterization. The decrease in the mean number of incontinence episodes and pads used daily indicated a marked improvement in patients’ quality of life. Postoperative complications included bowel dysfunction in 5 patients (10.6%), adhesive intestinal obstruction in 4 (8.5%), deteriorating renal function in 3 (6.4%), and vesicoureteral reflux recurrence in 2 patients (4.3%). Nearly all patients expressed satisfaction with the urologic management.\n\nCONCLUSION Our results suggest that sigmoidocolocystoplasty

is safe and effective in treating patients with neurogenic bladder dysfunction. Concomitant ureter reimplantation will be beneficial for patients with a long history of illness. UROLOGY 80: 440-445, 2012. Crown Copyright (c) 2012 Published by Elsevier Inc.”
“Introduction The anatomic localization of reticular pseudodrusen (RPD) has been an important area of research study.\n\nMethods A multimodal imaging analysis was conducted of two patients who were classified as having presumed CDK inhibitor RPD.\n\nResults Analysis of case 1 lends credence to original histopathologic evidence suggesting a choroidal origin of RPD, and analysis of case 2 supports RPD as originating above the RPE.\n\nConclusion This case series demonstrates that RPD may represent a compilation of diseases rather than one distinct clinical entity.”
“Study Design. Combined prospective randomized controlled trial and observational cohort study of degenerative spondylolisthesis (DS) with an as-treated analysis.\n\nObjective. To determine modifiers of the treatment effect (TE) of surgery (the difference between surgical and nonoperative outcomes) for DS using subgroup analysis.\n\nSummary of Background Data.

“
“Periodontal disease is a localised learn more inflammatory response caused by the infection of a periodontal pocket arising from the accumulation of subgingival plaque. Periodontal disease has been considered as a possible risk factor for other systemic diseases such as cardiovascular diseases and pre-term low birth weight infants. Advances in understanding the aetiology, epidemiology and microbiology of periodontal pocket flora have revolutionised the therapeutic strategies for the management of periodontal disease progression. This review summarises the recent developments in

the field of intra-pocket drug delivery systems and identifies areas where further research may lead to a clinically effective intra-pocket delivery system.”
“In humans, dehydroepiandrosterone (DHEA), with its sulfate, is the most abundant adrenal steroid, whereas the rat adrenals are not capable of synthesizing this steroid. Circulating concentrations of DHEA sulfate lie in the millimolar range and those of DHEA in the subnanomolar

range. DHEA exerts protective potential during vascular remodeling, HCS assay although the underlying mechanisms of this protection are imperfectly defined. We hypothesized that physiological doses of DHEA alter signaling pathways that are of central importance for vascular integrity. We exposed human endothelial cells, vascular smooth muscle cells, and fibroblasts to DHEA (10(-6) to 10(-10) mol/L) and observed

a dose-and time-dependent increase of extracellular signal-regulated kinases 1 and 2 activation. Similar results were observed in rat vascular smooth muscle cells. In addition, in rat vascular smooth muscle cells, we found altered phosphorylation and cellular translocation of the transcription factor FoxO1. Pharmacological blockade of the mineralocorticoid receptor AG-881 (MR) with eplerenone or small interfering RNA-mediated MR-silencing prevented DHEA-induced extracellular signal-regulated kinase 1/2 phosphorylation and its effects on FoxO1. Of note, in a cell-based MR transactivation assay, we did not find any agonist effect of DHEA on MR activity. We conclude that DHEA induces early signaling events in vascular cells that might underlie the DHEA-mediated protection against vasculopathies. These effects are dependent on the MR, although the finding that DHEA fails to act as a direct MR agonist suggests that additional signaling proteins are involved. In this regard, DHEA may either interact with coeffectors to modify MR activity or serves as a ligand for a yet unknown receptor that might transactivate the MR. (Hypertension. 2011;58:471-478.) .