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ACE inhibitors Research

22:49 EDT 25th May 2018 | BioPortfolio

Design, Synthesis and Investigation of New Diphenyl Substituted Pyridazinone Derivatives as Both Cholinesterase and Aβ-Aggregation Inhibitors.

Backround: With respect to the increase in the average life expectancy, Alzheimer Disease (AD), the most common form of age-related dementia, has become a major threat to the population over the age of 65 during the past several decades. The majority of AD treatments are focused on cholinergic and amyloid hypotheses.

Liddle's-like syndrome associated with nephrotic syndrome secondary to membranous nephropathy: the first case report.

Liddle's syndrome is a rare monogenic form of hypertension caused by truncating or missense mutations in the C termini of the epithelial sodium channel (ENaC) β or γ subunits. Patients with this syndrome present with early onset of hypertension, hypokalemia, metabolic alkalosis, hyporeninemia and hypoaldosteronism, and a potassium-sparing diuretics (triamterene or amiloride) can drastically impr...

The effects of a lifestyle-focused text-messaging intervention on adherence to dietary guideline recommendations in patients with coronary heart disease: an analysis of the TEXT ME study.

A healthy diet is an important component of secondary prevention of coronary heart disease (CHD). The TEXT ME study was a randomised clinical trial of people with CHD that were randomised into standard care or a text-message programme in addition to standard care. This analysis aimed to: 1) assess the effects of the intervention onadherence to the dietary guideline recommendations; 2) assess the c...

Adding left atrial appendage closure to open heart surgery provides protection from ischemic brain injury six years after surgery independently of atrial fibrillation history: the LAACS randomized study.

Open heart surgery is associated with high occurrence of atrial fibrillation (AF), subsequently increasing the risk of post-operative ischemic stroke. Concomitant with open heart surgery, a cardiac ablation procedure is commonly performed in patients with known AF, often followed by left atrial appendage closure with surgery (LAACS). However, the protective effect of LAACS on the risk of cerebral ...

PCSK9 inhibition: ready for prime time in CKD?

Lowering LDL cholesterol reduces the risk of atherosclerotic vascular disease in a wide range of patients with chronic kidney disease, with no evidence of a threshold below which further reductions no longer reduce risk. Statins safely lower LDL cholesterol, but novel inhibitors of proprotein convertase subtilisin kexin 9 (PCSK9) provide additional reductions which may reduce atherosclerotic vascu...

"Biomarking" the transition from genetic risk to kidney disease.

Only some individuals carrying the high-risk APOL1 genotype go on to develop kidney disease phenotypes. In this issue of Kidney International, Nadkarni and colleagues report the associations of several biomarkers with renal outcomes in individuals with high-risk APOL1 genotypes. In the era of precision medicine, these findings should translate into improved longitudinal risk assessment for this hi...

DNA methylation yields epigenetic clues into the diabetic nephropathy of Pima Indians.

Environmental factors drive epigenetic programming. DNA methylation is the best studied modification transmitting epigenetic information. A study by Qiu et al. examined potential epigenetic roots for the decline of renal function in Pima Indians. A genomewide survey of blood leukocytes uncovered differentially methylated DNA sites in regulatory regions of genes associated with chronic kidney dise...

A novel endoscopic grading system for prediction of disease-related outcomes in patients with diverticulosis.

We describe a simple endoscopic grading system of diverticular disease for the assessment of disease severity and prediction of outcomes.

Blood Pressure Patterns and Subsequent Coronary Artery Calcification in Women Who Delivered Preterm Births.

Women who delivered preterm infants have excess cardiovascular disease, but vascular pathways linking these conditions are not understood. We considered that higher blood pressure over 25 years among women with preterm delivery may be associated with coronary artery calcification (CAC). The CARDIA study (Coronary Artery Risk Development in Young Adults) enrolled 1049 black and white women with bir...

Identification of patients with hemoglobin SS/Sβ thalassemia disease and pain crises within electronic health records.

Electronic health records (EHRs) are a source of big data that provide opportunities for conducting population-based studies and creating learning health systems, especially for rare conditions such as sickle cell disease (SCD). The objective of our study is to validate algorithms for accurate identification of patients with hemoglobin (Hb) SS/Sβ thalassemia and acute care encounters for pain amo...

Cellular Beacons-mediated Counting for Ultrasensitive Detection of Ebola Virus on an Integrated Micromagnetic Platform.

Ebola virus (EBOV) disease is a complex zoonosis that is highly virulent in humans, and has caused many deaths. Highly sensitive detection of EBOV is of great importance to early-stage diagnosis for increasing the probability of survival. Herein, we established a cellular beacon-mediated counting strategy for ultrasensitive EBOV assay on a micromagnetic platform. The detection platform that was as...

Pulmonary hypertension in congenital heart disease.

Pulmonary hypertension is defined as a mean pulmonary arterial pressure ≥25 mmHg. We focus on its relevance in congenital heart disease, reviewing pathophysiology, diagnosis and management. Pulmonary hypertension is a relatively common complication of congenital heart disease, with adult prevalence between 5 and 10%. A multifactorial cause is recognized, relating to the size and nature of card...

Pulmonary endothelial permeability and tissue fluid balance depend on the viscosity of the perfusion solution.

Fluid filtration in the pulmonary microcirculation depends on the hydrostatic and oncotic pressure gradients across the endothelium, and the selective permeability of the endothelial barrier. Maintaining normal fluid balance depends both on specific properties of the endothelium and of the perfusing blood. Although some of the essential properties of blood needed to prevent excessive fluid leak ha...

Newer human inosine 5'-monophosphate dehydrogenase 2 (hIMPDH2) inhibitors as potential anticancer agents.

Human inosine 5'-monophosphate dehydrogenase 2 (hIMPDH2), being an age-old target, has attracted attention recently for anticancer drug development. Mycophenolic acid (MPA), a well-known immunosuppressant drug, was used a lead structure to design and develop modestly potent and selective analogues. The steep structure-activity relationship (SAR) requirements of the lead molecule left little scope ...

Somatic ACE regulates self-renewal of mouse spermatogonial stem cells via the MAPK signaling pathway.

Spermatogonial stem cell (SSC) self-renewal is an indispensable part of spermatogenesis. Angiotensin I-converting enzyme (ACE) is a zinc dipeptidyl carboxypeptidase that plays a critical role in regulation of the renin-angiotensin system. Here, we used RT-PCR and Western blot analysis to confirm that somatic ACE (sACE) but not testicular ACE (tACE) is highly expressed in mouse testis before postpa...

Disparate effects of Shb gene deficiency on disease characteristics in murine models of myeloid, B-cell, and T-cell leukemia.

The Src homology-2 domain protein B is an adaptor protein operating downstream of tyrosine kinases. The Shb gene knockout has been found to accelerate p210 Breakpoint cluster region-cAbl oncogene 1 tyrosine kinase-induced leukemia. In human myeloid leukemia were tumors with high Src homology-2 domain protein B mRNA content, tumors were, however, associated with decreased latency and myeloid leukem...

How are patients with heart failure treated in primary care?
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The aim of this study was to assess the adherence of general practitioners (GPs) to guidelines in patients with heart failure with reduced ejection fraction (HFrEF) and to describe GPs' prescribing behavior regarding patients with heart failure with preserved ejection fraction (HFpEF).

Phosphotriesterase-magnetic nanoparticles bioconjugates with improved enzyme activity in a biocatalytic membrane reactor.

The need to find alternative bioremediation solutions for organophosphate degradation pushed the research to develop technologies based on organophosphate degrading enzymes, such as phosphotriesterase. The use of free phosphotriesterase poses limits in terms of enzyme reuse, stability and process development. The heterogenization of enzyme on a support and their use in bioreactors implemented by m...

Roasted barley extract (mugi-cha) containing cyclo (D-Phe-L-Pro) prevents lowering of cutaneous blood flow and skin temperature under air-conditioning - A randomized, double-blind, placebo-controlled, crossover study.

Roasted barley extract (RBE), also known as mugi-cha, is a well-known healthy non-caffeinated beverage and its health functionality has been widely reported. Our previous clinical study showed that RBE affects cutaneous blood flow and skin temperature after cold water immersion, and that cyclo (D-Phe-L-Pro) is responsible for its effect. In this study, we investigated whether cyclo (D-Phe-L-Pro)-c...

Managing comorbid cardiovascular disease and sleep apnea with pharmacotherapy.

Highly prevalent sleep disordered breathing (SDB) has been recognized as an independent cardiovascular disease (CVD) risk factor. Although these two entities often coexist, there is a shortage of sufficiently-powered studies testing the interplay between the course of sleep apnea and CVD pharmacotherapy. The mutual relationship between treated/untreated obstructive sleep apnea (OSA) with ongoing c...

Neonatal intake of oleanolic acid attenuates the subsequent development of high fructose diet-induced non-alcoholic fatty liver disease in rats.

Dietary manipulations during the early postnatal period are associated with the development of metabolic disorders including non-alcoholic fatty liver disease (NAFLD) or long-term protection against metabolic dysfunction. We investigated the potential hepatoprotective effects of neonatal administration of oleanolic acid (OA), a phytochemical, on the subsequent development in adulthood, of dietary ...

A Nanozyme- and Ambient Light-Based Smartphone Platform for Simultaneous Detection of Dual Biomarkers from Exposure to Organophosphorus Pesticides.

A transparent, lateral-flow test strip coupled with a smartphone-based ambient light sensor was first proposed for detect-ing enzymatic inhibition and phosphorylation. The principle of the platform is based on the simultaneous measurement of the total amount of the enzyme and enzyme activity to biomonitor exposure to organophosphorus (OP) pesticides. In this study, butyrylcholinesterase (BChE) was...

Label-free optical marker for RBC phenotyping of inherited anaemias.

The gold standard methods for anaemia diagnosis are the complete blood count and the peripheral smear observation. However, they do not allow for a complete differential diagnosis, which requires biochemical assays, thus being label-dependent techniques. On the other hand, recent studies focus on label-free quantitative phase imaging (QPI) of blood samples to investigate blood diseases by using vi...

Selectivity Within a Family of Bacterial Phosphothreonine Lyases.

Phosphothreonine lyases are bacterial effector proteins secreted into host cells to facilitate the infection process. This enzyme family catalyzes an irreversible elimination reaction that converts phosphothreonine or phosphoserine to dehydrobutyrine or dehydroalanine, respectively. Herein we report a study of substrate selectivity for each of the four known phosphothreonine lyases. This was accom...

Docking screens for dual inhibitors of disparate drug targets for Parkinson's disease.

Modulation of multiple biological targets with a single drug can lead to synergistic therapeutic effects and has been demonstrated to be essential for efficient treatment of CNS disorders. However, rational design of compounds that interact with several targets is very challenging. Here, we demonstrate that structure-based virtual screening can guide the discovery of multi-target ligands of unrela...

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