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ACE inhibitors Research

04:40 EST 21st January 2019 | BioPortfolio

Losartan treatment enhances chemotherapy efficacy and reduces ascites in ovarian cancer models by normalizing the tumor stroma.

In ovarian cancer patients, tumor fibrosis and angiotensin-driven fibrogenic signaling have been shown to inversely correlate with survival. We sought to enhance drug delivery and therapeutic efficacy by remodeling the dense extracellular matrix in two orthotopic human ovarian carcinoma xenograft models. We hypothesized that targeting the angiotensin signaling axis with losartan, an approved angio...

Trained immunity and diabetic vascular disease.

Trained immunity is a recently described phenomenon whereby innate immune cells undergo functional reprogramming in response to microbial products, vaccines, or other stimuli, leading them to mount a sensitized nonspecific response to subsequent stimulation. While it is essential for the host response to pathogens, many diseases are the product of excessive or chronic inflammation. Atherosclerosis...

Gut bacterial tyrosine decarboxylases restrict levels of levodopa in the treatment of Parkinson's disease.

Human gut microbiota senses its environment and responds by releasing metabolites, some of which are key regulators of human health and disease. In this study, we characterize gut-associated bacteria in their ability to decarboxylate levodopa to dopamine via tyrosine decarboxylases. Bacterial tyrosine decarboxylases efficiently convert levodopa to dopamine, even in the presence of tyrosine, a comp...

Lsd1 as a therapeutic target in Gfi1-activated medulloblastoma.

Drugs that modify the epigenome are powerful tools for treating cancer, but these drugs often have pleiotropic effects, and identifying patients who will benefit from them remains a major clinical challenge. Here we show that medulloblastomas driven by the transcription factor Gfi1 are exquisitely dependent on the enzyme lysine demethylase 1 (Kdm1a/Lsd1). We demonstrate that Lsd1 physically associ...

A selective inhibitor of mitofusin 1-βIIPKC association improves heart failure outcome in rats.

We previously demonstrated that beta II protein kinase C (βIIPKC) activity is elevated in failing hearts and contributes to this pathology. Here we report that βIIPKC accumulates on the mitochondrial outer membrane and phosphorylates mitofusin 1 (Mfn1) at serine 86. Mfn1 phosphorylation results in partial loss of its GTPase activity and in a buildup of fragmented and dysfunctional mitochondria i...

Clinical pathophysiology of thyroid eye disease: The Cone Model.

The clinical features of thyroid eye disease are dictated by the orbit's compartmentalisation; particularly, the muscle cone, which is delimited by the rectus muscles, their inter-muscular septa and the posterior sclera. The cone is anchored to the orbit apex and contains the posterior globe, the muscle bellies, a fat pad, and the blood circulation, optic nerve, and CSF sheath. It is surrounded by...

Diagnosis and management of glycogen storage diseases type VI and IX: a clinical practice resource of the American College of Medical Genetics and Genomics (ACMG).

Glycogen storage disease (GSD) types VI and IX are rare diseases of variable clinical severity affecting primarily the liver. GSD VI is caused by deficient activity of hepatic glycogen phosphorylase, an enzyme encoded by the PYGL gene. GSD IX is caused by deficient activity of phosphorylase kinase (PhK), the enzyme subunits of which are encoded by various genes: ɑ (PHKA1, PHKA2), β (PHKB), ɣ (P...

Cardioprotective apelin effects and the cardiac-renal axis: review of existing science and potential therapeutic applications of synthetic and native regulated apelin.

First described in 1998, apelin is one of the endogenous ligands of the apelinergic receptor. Since its discovery, its possible role in human physiology and disease has been intensively studied. Apelin is a native cardioprotective agent that the body synthesizes to create atheroprotective, antihypertensive, and regenerative effects in the body. By antagonizing the RAA system, apelin could play an ...

A genetic risk score for hypertension is associated with risk of thoracic aortic aneurysm.

A genetic risk score (GRS) based on 29 single nucleotide polymorpysms (SNPs) associated with high blood pressure (BP) was prospectively associated with development of hypertension, stroke and cardiovascular events. The aim of the present study was to evaluate the impact of this GRS on the incidence of aortic disease, including aortic dissection (AD), rupture or surgery of a thoracic (TAA) or abdom...

Difference in positive relation between cardio-ankle vascular index (CAVI) and each of four blood pressure indices in real-world Japanese population.

This study aimed to investigate the association of cardio-ankle vascular index (CAVI), an arterial stiffness parameter, with four blood pressure (BP) indices, systolic BP (SBP), diastolic BP (DBP), pulse pressure (PP) and mean BP (MBP), in real-world population including untreated hypertension. We analyzed the cross-sectional data from 23,257 Japanese subjects (12,729 men and 10,528 women, aged 47...

Prognostic factors for one-year mortality in patients with acute heart failure with and without chronic kidney disease: differential impact of beta-blocker and diuretic treatments.

The pathophysiology and treatment of acute decompensated heart failure (HF) in the presence of chronic kidney disease (CKD) remain ill defined. Here we compared the prognostic factors for 1-year mortality in patients with acute HF with and without CKD. We retrospectively studied 392 consecutive patients with acute decompensated HF. CKD as a comorbidity in these patients was defined by an estimated...

Comparison between cuff-based and radial tonometry exercise-induced central blood pressure.

Non-invasive central blood pressure assessed during exercise may provide better cardiovascular prognostic than measurements taken at rest. Radial tonometry is the only technique validated to perform this type of assessment; however, it relies on the experience of the tester. Cuff-based devices have been developed to avoid operator dependency, although these systems have yet to be validated during ...

Pericardial fluid: an underrated molecular library of heart conditions and a potential vehicle for cardiac therapy.

The remote but heart-encircling location of pericardial fluid confers this biofluid unique properties. Once past the limitation of the invasive collection, for instance, on occasion of heart surgery or pericardiocentesis, the scrutiny of pericardial fluid content can be of great interest in cardiovascular research. This liquid concentrates many heart-derived factors, thus enclosing several surroga...

Preventing Heart Failure by Treating Systolic Hypertension: What Does the SPRINT Add?

Previous trials definitively established that lowering systolic blood pressure (BP) to 140 mmHg prevented heart failure (HF) exacerbations, but the potential benefits and risks of further BP reduction remain unclear due to a paucity of trial-based data.

Unanswered Questions Regarding Blood Pressure Management for HF Prevention.

Evaluate the relevant new findings regarding hypertension treatment and heart failure prevention published in the past 3 years.

Angiotensin-(1-7) exerts a protective action in a rat model of ventilator-induced diaphragmatic dysfunction.

Ventilator-induced diaphragmatic dysfunction (VIDD) is a common event during mechanical ventilation (MV) leading to rapid muscular atrophy and contractile dysfunction. Recent data show that renin-angiotensin system is involved in diaphragmatic skeletal muscle atrophy after MV. In particular, angiotensin-II can induce marked diaphragm muscle wasting, whereas angiotensin-(1-7) (Ang-(1-7)) could coun...

Indoleamine Dioxygenase Inhibitors: Clinical Rationale and Current Development.

This review focuses on the recent clinical development of indolamine-2,3-dioxygenase-1 (IDO-1) inhibitors.

Management of "Hypertension" Based on Blood Pressure Level Versus an Absolute Cardiovascular Risk Approach.

To address the tension between guideline recommendations and the evidence from clinical trials supporting them and clinician concerns of overtreatment of elevated blood pressure.

Screening responsive or resistant biomarkers of immune checkpoint inhibitors based on online databases.

Immune checkpoint inhibitors are a promising strategy in the treatment of cancer, especially advanced types. However, not all patients are responsive to immune checkpoint inhibitors. The response rate depends on the immune microenvironment, tumor mutational burden (TMB), expression level of immune checkpoint proteins, and molecular subtypes of cancers. Along with the Cancer Genome Project, various...

Long-term management of chronic heart failure patients in internal medicine.

Chronic heart failure (CHF) is one of the main disabilities in elderly patients requiring frequent hospitalizations with high health care costs. We studied the outcome of CHF outpatient management in reducing hospitalization after discharge from a division of Internal Medicine at a large 3rd referral regional Hospital. 147 CHF inpatients (M:F: 63:84; mean age 76 ± 9.6 years) admitted for acut...

Examining the Relation Between Physiological and Psychological Components of Stress Reactivity and Recovery in Cigarette Smokers.

Cigarette smokers exhibit reduced physiological stress reactivity, yet it is unclear whether blunted reactivity predicts differences in subjective recovery and vice versa. The study examined whether basal heart rate and heart rate reactivity were related to recovery in anxiety following stress, and conversely, whether initial self-reported anxiety and anxiety reactivity were related to heart rate ...

A Mechanistic Analysis of Possible Blood Transfusion Failure to Increase Circulatory Oxygen Delivery in Anemic Patients.

The effects of changing hematocrit (Hct) on the rate of circulatory oxygen ([Formula: see text]) delivery were modeled analytically to describe transfusion of 0.5-3.0 units of packed red blood cells (pRBC, 300 mL/unit, 60% Hct) to anemic patients. In our model, Hct affects [Formula: see text] delivery to the microcirculation by changing blood [Formula: see text] carrying capacity and blood viscosi...

Frontal Fibrosing Alopecia: An Update on Pathogenesis, Diagnosis, and Treatment.

Frontal fibrosing alopecia (FFA), first described by Kossard in the early 1990s, is a form of primary lymphocytic cicatricial alopecia characterized by selective involvement of the frontotemporal hairline and eyebrows. Since the original description, an increasing number of cases have been reported worldwide and the clinical aspects of the disease have been better characterized. However, the path...

Healthcare Providers Underestimate Patients' Glucocorticoid Use in Crohn's Disease.

One of the therapy goals for Crohn's disease (CD) is glucocorticoid-free remission. Studies have shown care setting-specific variations in inflammatory bowel disease (IBD) management.

Di (2-ethylhexyl) phthalate induces cardiac disorders in BALB/c mice.

Because of the extensive use of phthalates for domestic, medical, and industrial applications, the evaluation of their toxic effects is of major concern to public health. The aim of the present study was to assess the propensity of di (2-ethylhexyl) phthalate (DEHP), one of the most used phthalates, to cause oxidative cardiac damage in mice. DEHP was administered intraperitoneally at doses of 5, 5...

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