Ste Foy, Canada
Ste Foy, Canada
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PubMed | Johns Hopkins University, Justus Liebig University, CHU de Bicetre, CRIUCPQ and 3 more.
Type: | Journal: American journal of respiratory and critical care medicine | Year: 2016

Despite important advances in its therapeutic management, pulmonary arterial hypertension (PAH) remains an incurable disease. Although numerous drugs exhibited beneficial effects in preclinical settings, only few have reached clinical trial phases, highlighting the challenges of translating preclinical investigations into clinical trials. Potential reasons for delayed PAH drug development may include the inherent limitations of the currently available animal and in vitro models, potential lack of appropriate standardization of the experimental design, regulatory agencies requirements, competing clinical trials and insufficient funding. Although this is not unique to PAH, there is urgency for reducing the number of false positive signals in preclinical studies and optimizing the development of innovative therapeutic targets through performance of clinical trials based on more robust experimental data. The current review discusses the challenges and opportunities in preclinical research to foster drug development in PAH.

Lavoie J.,IRSST | Marchand G.,IRSST | Cloutier Y.,IRSST | Halle S.,ETS | And 3 more authors.
Environmental Sciences: Processes and Impacts | Year: 2015

During hospital bronchoscopy examinations, aerosols emitted from the patient's during coughing can be found suspended in the ambient air. The aerosols can contain pathogenic microorganisms. Depending on their size, these microorganisms can remain in the air for a long time. The objective of this study was to measure the sizes and concentrations of the biological and non-biological particles produced during bronchoscopy examinations, and to propose preventive or corrective measures. Two bronchoscopy rooms were studied. An aerodynamic particle sizer (UV-APS) was used to establish the concentrations of the particles present and their size distributions. This instrument determines the aerodynamic diameter of the aerosols and can distinguish fluorescent (bioaerosols) and non-fluorescent particles. Reference concentrations were measured before the start of the examinations (morning background concentrations). They were used as comparison levels for the concentrations measured during and at the end of the bronchoscopies. In parallel, computational fluid dynamics (CFD) made it possible to isolate and understand different factors that can affect the concentration levels in bronchoscopy rooms. The concentrations of the non-fluorescent and fluorescent particles (bioaerosols) were significantly higher (p ≤ 0.05) during the bronchoscopy examinations than the reference concentrations. For the investigated factors, the bioaerosol concentrations were significantly higher during bronchoscope insertion tasks. The time required at the end of the day for the bioaerosols to reach the morning reference concentrations was about fifteen minutes. The average particle sizes were 2.9 μm for the fluorescent particles (bioaerosols) and 0.9 μm for the non-fluorescent particles. Our models based on computational fluid dynamics (CFD) enabled us to observe the behaviour of aerosols for the different rooms. This journal is © The Royal Society of Chemistry 2015.

Gauvreau D.,CRIUCPQ | Gauvreau D.,Laval University | Villeneuve N.,CRIUCPQ | Deshaies Y.,CRIUCPQ | And 3 more authors.
Annales d'Endocrinologie | Year: 2011

Today, cardiovascular diseases (CVD) remain the principal cause of death in industrialized countries and are linked to obesity and metabolic syndrome. Metabolic syndrome is characterized by changes in arterial blood pressure, glucose metabolism, lipid and lipoprotein profiles in addition to inflammation. Adipose tissue produces many cytokines and secretory factors termed adipokines. Intra-abdominal (visceral) adipose tissue in particular, rather than peripheral, appears to be associated with global cardiometabolic risk. The present article summarizes information on five recently discovered adipokines: vaspin, visfatin, apelin, acylation stimulating protein (ASP) and retinol-binding protein 4 (RBP4) and their potential beneficial or deleterious roles in obesity and atherosclerosis. Vaspin may have antiatherogenic effects through its potential insulin-sensitizing properties. Similarly, visfatin has been suggested to enhance insulin sensitivity, but its potential role in plaque destabilization may counteract this. Apelin, via inhibition of food intake, and increases in physical activity and body temperature, may promote weight loss, resulting in a beneficial antiatherogenic effect. Further, favourable effects on vasodilatation and blood pressure add to this positive effect. Considering its increased levels in subjects with demonstrated atherosclerosis, RBP4 may constitute a biomarker. Lastly, ASP, often increased in obesity and metabolic disorders, may be contributing to efficient lipid storage, and decreasing or blocking ASP may provide a potential antiobesity target. Adipokines may further contribute to obesity-atherosclerosis relationships, the full understanding of which will require further research.

PubMed | Yale University, CRIUCPQ and University of Pittsburgh
Type: | Journal: American journal of respiratory and critical care medicine | Year: 2016

Pulmonary hypertension (PH) is an enigmatic vascular disease with complex molecular origins, leading to right ventricular failure and often death. Recent studies have implicated the pervasive actions of microRNAs in the pulmonary vasculature and the right ventricle as essential to the development of PH. MicroRNAs are small, non-protein coding RNA molecules that negative regulate gene expression. Because greater than 5,500 microRNA molecules have been predicted or verified to be encoded by the human genome, we are still at the inception of our mechanistic understanding of how all of these factors, either singly or in combination, control pulmonary vascular function in health and disease. As insights into the biology of these pleiotropic molecules grow, we move closer to applying this biology in novel clinical diagnostic and therapeutic strategies in PH. In this review, we will discuss the recent molecular data of specific microRNAs in the pulmonary vasculature and methods by which we can begin to understand the systems biology of these pleiotropic molecules on overall pulmonary vascular pathophenotypes. We will also discuss advancing applications of quantifying plasma-based circulating microRNAs for development of new biomarkers in PH. Finally, we will examine the principles of therapeutic targeting of microRNAs in PH as well as the specialized challenges in such drug development. As such, we plan to illustrate the promise, challenges, and current limitations of leveraging microRNA biology to understand and manage pulmonary vascular disease.

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