Framework for policymaking on self-management of health by older adults using technologies.

Background: During the coronavirus disease 2019 (COVID-19) pandemic, the use of information and communication technologies (ICTs) to support care management exponentially increased. Governments around the world adapted existing programs to meet the needs of patients. The reactivity of governments, however, led to changes that were inequitable, undermining groups such as older adults living with chronic diseases and disability.

Effects of virtual reality guided meditation in older adults: the protocol of a pilot randomized controlled trial.

Background: Virtual reality (VR) based meditation has been shown to help increase relaxation and decrease anxiety and depression in younger adults. However, this has not been studied in Randomized Controlled Trials (RCT) in the older adult population. The aim of this RCT is to assess the feasibility and acceptability of a VR-guided meditation intervention for community-dwelling older adults and its effect on stress and mental health.

Policymaker perspectives on self-management of disease and disabilities using information and communication technologies.

Background: Policies that support health self-management are malleable and highly dependent on various factors that influence governments. Within a world that is shifting toward digitalization due to pressures such as the COVID-19 pandemic and labor shortages, policymaking on older adults' self-management of chronic diseases and disability using information and communication technologies (ICTs) needs to be better understood. Using the province of Ontario, in Canada, as a case study, the research question was What is the environment that policymakers must navigate through in development and implementation of policies related to older adults' self-management of disease and disability using information and communication technologies (ICTs)?

Methods: This study used a qualitative approach where public servants from 4 ministries within the government of Ontario were invited to participate in a 1-h, one-on-one, semi-structured interview.

Evolution of public health policy on healthcare self-management: the case of Ontario, Canada.

Background: As people live longer, they are at increased risk for chronic diseases and disability. Self-management is a strategy to improve health outcomes and quality of life of those who engage in it. This study sought to gain a better understanding of the factors, including digital technology, that affect public health policy on self-management through an analysis of government policy in the most populous and multicultural province in Canada: Ontario.

Isolating together during COVID-19: Results from the Telehealth Intervention Program for older adults.

Background: A pressing challenge during the COVID-19 pandemic and beyond is to provide accessible and scalable mental health support to isolated older adults in the community. The Telehealth Intervention Program for Older Adults (TIP-OA) is a large-scale, volunteer-based, friendly telephone support program designed to address this unmet need.

Methods: A prospective cohort study of 112 TIP-OA participants aged ≥60 years old was conducted in Quebec, Canada (October 2020-June 2021).

Acute cardiovascular effects of inhaled ambient particulate matter: Chemical composition-related oxidative stress, endothelin-1, blood pressure, and ST-segment changes in Wistar rats.

Short-term increases in particulate matter (PM) are associated with heightened morbidity and mortality from cardiovascular causes. Inhalation of PM is known to increase endothelin (ET)-1 levels. Yet, less is known about particle composition-related changes at the molecular level including the endothelinergic system and relationship with cardiovascular function changes.

Towards triple vasopeptidase inhibitors for the treatment of cardiovascular diseases.

Cardiovascular diseases (CDs) are among the most encountered pathologies in western countries; with obesity reaching pandemic proportions, they are soon to become a worldwide problem. High blood pressure is the main risk factor for CDs, and its tight control is an imperative for the treatment of complications such as renal diseases, heart failure, and atherosclerosis. Blood homeostasis and vascular tone are regulated through at least 3 major closely interrelated pathways in which zinc metallopeptidases modulate the concentration of vasoactive mediators.

Inhibition of basal and stimulated release of endothelin-1 from guinea pig tracheal epithelial cells in culture by beta 2-adrenoceptor agonists and cyclic AMP enhancers.

The effects of cyclic AMP-related compounds and beta adrenoceptor agonists on the basal and lipopolysaccharide (LPS)-stimulated release of endothelin-1 (ET-1) from guinea-pig tracheal epithelial cells (GPTEpCs) in culture were studied. Forskolin (a potent activator of adenylyl cyclase), 8-bromo-cyclic AMP (a cyclic AMP analogue), salbutamol and salmeterol (two beta 2-adrenoceptor agonists), were used to increase cyclic AMP levels. Cultured GPTEpCs released ET-1 continuously over a 24 h incubation period.

Profile of past and current clinical trials involving endothelin receptor antagonists: the novel "-sentan" class of drug.

Since its initial characterization in 1988, over 18,236 papers, including 2,485 reviews, have been published in the endothelin (ET) field. Over this period, several generations of selective and mixed (dual) ET receptor antagonists (ERAs), from peptidic backbones to orally active potent (subnanomolar) small molecular compounds, have been developed. These agents have been studied in many experimental animal models of various pathological conditions (cardiovascular, respiratory, and neuro-immunological).

CGS 35601, a triple inhibitor of angiotensin converting enzyme, neutral endopeptidase and endothelin converting enzyme.

CGS 35601 (L-tryptophan, N-[[1-[[(2S)-2-mercapto-4-methyl-1-oxopentyl]amino]-cyclopentyl]carbonyl]) is one of a few single molecules capable of inhibiting the activities of angiotensin-converting enzyme (ACE), neutral endopeptidase (NEP) and endothelin converting enzyme (ECE) simultaneously, with IC(50) values of 22, 2, and 55 nM, respectively. Through the inhibition of ACE and ECE, it blocks the conversion of angiotensin I (AI) and big endothelin-1 (big ET-1) into the two most potent peptidic vasoconstrictors, angiotensin II (AII) and ET-1, respectively. By inhibiting NEP, CGS 35601 also prevents the degradation of peptidic vasodilators such as bradykinin (BK), natriuretic peptides (NPs) and adrenomedullin (ADM) and, hence, modulates the secondary release of other vasoactive mediators such as nitric oxide (NO) and prostaglandins.

The kinin system mediates hyperalgesia through the inducible bradykinin B1 receptor subtype: evidence in various experimental animal models of type 1 and type 2 diabetic neuropathy.

Both insulin-dependent (type 1) and insulin-independent (type 2) diabetes are complex disorders characterized by symptomatic glucose intolerance due to either defective insulin secretion, insulin action or both. Unchecked hyperglycemia leads to a series of complications among which is painful diabetic neuropathy, for which the kinin system has been implicated. Here, we review and compare the profile of several experimental models of type 1 and 2 diabetes (chemically induced versus gene-prone) and the incidence of diabetic neuropathy upon aging.

Triple vasopeptidase inhibition normalizes blood pressure in conscious, unrestrained, and spontaneously hypertensive rats.

Background: CGS 35601 is a potent triple vasopeptidase inhibitor (VPI) of angiotensin-converting enzyme (ACE), neutral endopeptidase (NEP), and endothelin-converting enzyme (ECE). The aim of the study was to determine the effects of this VPI on the hemodynamic profile of conscious, instrumented, unrestrained spontaneously hypertensive rats (SHR), in comparison to selective inhibitors of ACE and ACE + NEP, than +ECE combined. Circulating plasma concentrations of vasoactive mediators and reactive oxygen species were measured.

Integrated in vivo pharmacology using an instrumented, unrestrained and conscious rat platform: application to rat models of diabetes.

Introduction: We define the technical and methodological aspects that led to a practical and reproducible biological in vivo platform allowing the measurement of more than 65 physiobiochemical parameters on a daily basis in freely moving conscious animals. Such a platform presents the ability to unleash incremental information in the hands of modern-day pharmacologists and physiologists.

Methods: To validate this platform, we fully characterized three rat models of Type 1 and Type 2 diabetes and their respective controls.

Modulating effect of a selective endothelin A receptor antagonist on pulmonary endothelin system protein expression in experimental diaphragmatic hernia.

Background/purpose: Previously, we reported that perinatal administration of atrasentan, a selective endothelin A receptor (ETA) antagonist, provided a beneficial effect on the cardiopulmonary profile under short-term conditions in newborn lambs with surgically induced congenital diaphragmatic hernia (CDH). We hypothesized that changes in the hemodynamic profile that we observed at birth in treated animals could be influenced by pulmonary modulation of the endothelin (ET) system.

Methods: The effect of atrasentan on protein expression levels of ETs and ET receptors (ETA and ETB receptor) was investigated by immunohistochemistry in lung tissues of untreated control (n = 3), treated control (n = 6), untreated CDH (n = 6), and treated CDH newborn lambs (n = 8).

Inhibition of type 1 diabetic hyperalgesia in streptozotocin-induced Wistar versus spontaneous gene-prone BB/Worchester rats: efficacy of a selective bradykinin B1 receptor antagonist.

Insulin-dependent type 1 diabetes (T1D) is linked to a series of complications, including painful diabetic neuropathy (PDN). Several neurovascular systems are activated in T1D, including the inducible bradykinin (BK) B1 receptor (BKB1-R) subtype. We assessed and compared the efficacy profile of a selective BKB1-R antagonist on hyperalgesia in 2 models of T1D: streptozotocin (STZ) chemically induced diabetic Wistar rats and spontaneous BioBreeding/Worchester diabetic-prone (BB/Wor-DP) rats.

Effects of a selective bradykinin B1 receptor antagonist on increased plasma extravasation in streptozotocin-induced diabetic rats: distinct vasculopathic profile of major key organs.

Diffuse vasculopathy is a common feature of the morbidity and increased mortality associated with insulino-dependent type 1 diabetes. Increased vascular permeability leading to plasma extravasation occurs in surrounding tissues following endothelial dysfunction. Such micro- and macro-vascular complications develop over time and lead to oedema, hypertension, cardiomyopathy, renal failure (nephropathy) and other complications (neuropathy, retinopathy).

Triple vasopeptidase inhibition of angiotensin-converting enzyme/neutral endopeptidase/endothelin-converting enzyme activities on the hemodynamic profile of chronically instrumented unrestrained conscious spontaneously hypertensive rats.

Inhibition of the renin-angiotensin system with an angiotensin-converting enzyme inhibitor (ACEi) is an effective therapy in hypertension. Vasopeptidase inhibition was initially proposed with compounds inhibiting both angiotensin-converting enzyme and neutral endopeptidase (omapatrilat), but clinical trials revealed that reducing angiotensin II while blocking the degradation of vasodilatory peptides was not without concerns. We have previously investigated the combination of an ACEi with an endothelin-converting enzyme inhibitor (ECEi); now we add a neutral endopeptidase inhibitor (NEPi) toward triple vasopeptidase inhibition.

Profile of endothelin isopeptides and markers of oxidative stress alongside the onset of streptozotocin-type I diabetes in rats.

Type I diabetes is associated with vascular endothelial abnormalities. Vasoactive mediators such as endothelins and reactive oxygen species are modulated in diabetic patients. We studied the hemodynamic profile and the release of mediators alongside the onset of streptozotocin-induced type I diabetes in rats.

Enhanced dermal and retinal vascular permeability in streptozotocin-induced type 1 diabetes in Wistar rats: blockade with a selective bradykinin B1 receptor antagonist.

The vascular complications associated with type 1 diabetes are to some extent related to the dysfunction of the endothelium leading to an increased vascular permeability and plasma extravasation in the surrounding tissues. The various micro- and macro-vascular complications of diabetes develop over time, leading to nephropathy, retinopathy and neuropathy and cardiomyopathy. In the present study, the effect of a novel selective bradykinin B1 receptor (BKB1-R) antagonist, R-954, was investigated on the changes of vascular permeability in the skin and retina of streptozotocin (STZ)-induced type 1 diabetic rats.

Early endothelial dysfunction in cholesterol-fed rabbits: a non-invasive in vivo ultrasound study.

Background: Endothelial function in hypercholesterolemic rabbits is usually evaluated ex vivo on isolated aortic rings. In vivo evaluation requires invasive imaging procedures that cannot be repeated serially.

Aim: We evaluated a non-invasive ultrasound technique to assess early endothelial function in rabbits and compare data with ex vivo measurements.

Plasma levels of endothelin-1, big endothelin-1 and thromboxane following acute pulmonary air embolism.

Acute pulmonary air embolism (APAE) was induced in nine piglets by repeated intravenous bolus injection of room air into a large bore central venous catheter at time=0 min so that the mean pulmonary artery pressure (MPAP) was maintained at two times the baseline value for 4 h. Another five animals served as controls. At time=0, 30, 60, 120, 240 min, circulating arterial plasma levels of endothelin-1 (ET-1), its precursor big ET-1, and thromboxane (Tx), were measured by RIA and EIA, respectively, along with hemodynamics and blood gases.

Modulation and roles of the endothelins in the pathophysiology of pulmonary embolism.

Recent research on the endothelins (ETs) and their pathways in acute pulmonary embolism (APE) has led to significant advances in the understanding of this disease. ETs are potent vasoconstrictors and bronchoconstrictors found abundantly in the lung and can be released by stimuli such as endothelial injury, hypoxia, or thrombin, a key product in the coagulation cascade. Many studies using different approaches and methods of inducing pulmonary embolization, both in vitro and in vivo in various species, have mostly shown that ETs play an important role in the pathophysiology of APE.

Long-term effects of ovariectomy and estrogen replacement treatment on endothelial function in mature rats.

Objectives: Estrogen replacement therapy (ERT) improves blood flow through various mechanisms including an augmented release of nitric oxide (NO). We report on the long-term effects of estrogen loss on vascular function and endothelial regulation.

Methods: Male, female, ovariectomized and ovariectomized+ERT treated rats were used.

The endothelin axis: emerging role in cancer.

Collectively, the endothelins and their receptors--referred to as the endothelin (ET) axis--have key physiological functions in normal tissue, acting as modulators of vasomotor tone, tissue differentiation, development, cell proliferation and hormone production. Based on new data, the ET axis also functions in the growth and progression of various tumours. Preliminary results from clinical trials, such as those with atrasentan--an ET(A)-receptor antagonist--in prostate cancer, are encouraging.

Effects of a selective endothelin A receptor antagonist, ABT-627, in healthy normotensive anaesthetized rats developing acute pulmonary air embolism.

Acute pulmonary air embolism (APAE) injures the vascular endothelium in the lung and results in pulmonary hypertension (PH). Endothelins (ETs), a family of potent vasoactive peptides, are known to be associated with PH of various aetiologies. We evaluated the effects of ABT-627, a selective ET(A) receptor (ET(A)-R) antagonist in a rat model of APAE over 3 h.