New TP receptor antagonists

Researchers at CIRM have synthesized and evaluated new series of original 2-aryloxy/arylamino-5-cyanobenzenesulfonylureas as thromboxane A2 receptor (TP receptor) antagonists.

Based on functional pharmacological test, several compounds were found to be as potent as the 2-arylamino-5-nitrobenzenesulfonylurea reference compound BM-573, supporting the view that the bio-isosteric replacement of the nitro group by a cyano group was tolerated.

TP receptor antagonist activity of the most promising molecules was confirmed in a platelet aggregation assay using the TP receptor agonist U-46619 as a pro-aggregant.

Three compounds were identified as leads for further non-clinical pharmacological and toxicological studies.

Interested in these projects? Drop us an email [info@b2h.be]. We are looking forward collaborating with you!

Cardiac Markers

We study new necrosis and fibrosis cardiac biomarkers in athletes to show their specificity as well as to highlight a cardiac biomarker helpful to discover potential risk of cardiac event during exercise.

Interested in these projects? Drop us an email [info@b2h.be]. We are looking forward collaborating with you!

Abdominal aortic aneurysm

Teams at the CHU hospital and the ULg are on the trail of markers that can predict the instability of abdominal aneurysms.

They examined, among other things, the proteins in the extracellular matrix of the aortic walls and shown a correlation between the instability of an aneurysm and the presence of MMP-9 and -2, enzymes that participate in the deterioration of elastin and collagens.

Interested in these projects? Drop us an email [info@b2h.be]. We are looking forward collaborating with you!

New mechanisms of Platelet activation

In order to identify new mechanisms or candidate genes involved in platelet biology, our team generated a cohort of healthy individuals.

A genome-wide association study is ongoing to identify genetic loci associated with platelet reactivity.

Interested in these projects? Drop us an email [info@b2h.be]. We are looking forward collaborating with you!

In Silico Model-based therapeutics

By combining mathematical models and experimental and/or clinical data, we have built “virtual patients”. A virtual patient represents a specific patient in a particular state relative to the system modeled (e.g. metabolic, cardiovascular, pulmonary and musculoskeletal).

These virtual patients are useful to:

  • Implement bedside decision-support clinical systems
  • Safely and rapidly design, prototype and optimize treatment protocols
  • Analyze the effects of vasoactive/inotrope drugs or cardiorespiratory assistance
  • Optimize glycemic control and mechanical ventilation strategies in critically ill patients

Interested in these projects? Drop us an email [info@b2h.be]. We are looking forward collaborating with you!

A realistic computational model of the heart and circulation was created for identifying patient’s time varying hemodynamic state.

This model has been tested on a porcine model of pulmonary embolism. Importantly, only information typically available on existing Intensive Care Unit monitors is required.

The model can be used to infer information on the left and right ventricle pressure volume loops, which would be important when assessing cardiac status and the impact of inotropes or other drug therapies.

Role of P2X1 in thrombosis

In brief, our latest findings indicate that P2X1 receptors contribute to ATP-dependent thrombosis in mouse microcirculation by promoting early neutrophil and platelet recruitment and subsequent fibrin generation, locally, at the sites of endothelial injury.

Upon systemic inflammatory challenge, P2X1 receptors would act to dampen the activation of circulating neutrophils, thereby limiting oxidative tissue damage and disseminated intravascular coagulation.

Targeting P2X1 receptors will not only inhibit platelets but also alter neutrophil function, and may therefore represent an innovative therapeutic strategy to prevent local thrombo-inflammation, only if neutrophil regulatory homeostasis is preserved.

Interested in these projects? Drop us an email [info@b2h.be]. We are looking forward collaborating with you!

Cardiovascular & cardiopulmonary systems Modeling

To get a better understanding of the complex behavior of the cardiovascular and cardiopulmonary systems, our research have developed different mathematical models such as:

  • 3-D models allowing in-depth analyses of properties or behaviors of limited parts of the studied system
  • Lumped parameter models studying whole entities such as the cardiovascular or the cardiopulmonary system
  • Multiscale models allowing to integrate cellular level systems into global hemodynamic models like cardiovascular system

Interested in these projects? Drop us an email [info@b2h.be]. We are looking forward to collaborating with you!

 

A new closed-loop cardiovascular system (CVS) model including a description of the progressive opening and closing dynamic of the mitral valve has been developed.

This new CVS includes a mathematical description of the left atrium and enables the study of valve dysfunction in the appropriate clinical context of the overall cardiac and circulatory hemodynamics.