Ligand Screening of Membrane Proteins Embedded in Nanodiscs: How to Manage Non-Specific Interactions in Weak Affinity Chromatography?

Miniaturized weak affinity chromatography is emerging as an interesting alternative to conventional biophysical tools for performing fragment-screening studies in the context of fragment-based drug discovery. In order to push back the analytical limits, it is necessary not only to control non-specific interactions with chromatographic support, but also to adapt this methodology by comparing the results obtained on an affinity column to a control column. The work presented in this study focused on fragment screening that targets a model membrane protein, the adenosine A2A receptor, embedded in nanodiscs (NDs) as biomimetic membranes.

Extending the Affinity Range of Weak Affinity Chromatography for the Identification of Weak Ligands Targeting Membrane Proteins.

The identification of weak-affinity ligands targeting membrane proteins is of great interest in Fragment-Based Drug Design (FBDD). Recently, miniaturized weak affinity chromatography (WAC) has been proposed as a valuable tool to study interactions between small ligands and wild-type membrane proteins embedded in so-called nanodisc biomimetic membranes immobilized on GMA-co-EDMA monoliths in situ-synthesized in capillary columns (less than one microliter in volume). In this proof-of-concept study, the achievable affinity range was limited to medium affinity (low micromolar range).

[Pediatric heart surgery in developing countries. Twenty years experience of La Chaine de L'espoir (Chain of Hope)].

Because of their high incidence, cardiac disorders in children are now a public health issue. These children require multidisciplinary management, but surgery is sometimes unavoidable. The two most frequent types of cardiac disorder in children are congenital defects and rheumatic valve disease.

Pericardial patch anterior leaflet extension in rheumatic mitral insufficiency.

This report describes a technique for anterior leaflet extension using an autologous pericardial patch in patients suffering from rheumatic mitral regurgitation. The technique has recently evolved and now enables us to correct both vertical and transversal fibrotic leaflet retraction.

[Acute poststreptoccocal chorea: an atypical postoperative reaction following cardiac surgery for mitral valvulopathy].

We report on a 12-year-old patient from Congo who presented acute chorea following cardiac surgery for poststreptococcal mitral valvulopathy. She showed severe and asymmetrical chorea, associated with motor impersistence and agitation. Biological investigations disclosed inflammatory signs and brain MRI was normal.

Reoperation for failure of mitral valve repair in degenerative disease: a single-center experience.

Background: The purpose of this study was to report our 19-year experience in redo surgery for failure of mitral valve repair (MVRep) in degenerative disease.

Methods: From 1987 to 2006, 43 consecutive patients (32 males) underwent either redo MVRep (n = 21) or redo mitral valve replacement (n = 22) for failure of MVRep. Age ranged from 10 to 78 years (median, 59 years).

Congenital mitral valve regurgitation in adult patients. A rare, often misdiagnosed but repairable, valve disease.

Objective: Congenital mitral valve regurgitation (MVR) is a rare disease occurring in infancy or childhood. Although congenital MVR has been described in adults, no surgical series has been reported so far. We describe here a 6-year surgical experience of congenital MVR in adults at a single institution.

Late posterior failure after mitral valve repair in degenerative disease.

Objectives: Little is known regarding the mechanisms, the feasibility and the long-term results of re-repair in 'posterior failure' of a previous mitral valve repair performed for severe degenerative mitral regurgitation. We report our 16-year experience in redo surgery for late posterior failure of mitral valve repair in degenerative disease.

Methods: From 1991 to 2004, 13 consecutive patients (10 males; median age: 65 years) were reoperated for late posterior failure of mitral valve repair.

Cardiac stem cells in the real world.

Objective: Cardiac stem cell transplantation as a potential means of regenerating infarcted myocardium is currently receiving a great deal of interest. However, data on these endogenous cardiac precursors are primarily derived from animal studies, and their clinical relevance still remains elusive.

Methods: We prospectively screened 32 endomyocardial biopsies harvested from heart transplant recipients (off rejection episodes) and 18 right appendage biopsies collected during coronary artery bypass surgery, and processed the tissue specimens for the immunohistochemical detection of markers of stemness (c-kit, MDR-1, Isl-1), hematopoietic origin (CD45), mast cells (tryptase), endothelial cells (CD105), and cardiac lineage (Nkx2.

Is it reasonable to treat all calcified stenotic aortic valves with a valved stent? Results from a human anatomic study in adults.

Objectives: This study was designed to study the behavior of a stent deployed inside human stenotic aortic valves.

Background: Endovascular valved stent (VS) implantation is a promising new therapy for patients with severe calcific aortic stenosis (AS). The precise characteristics of stent deployment in humans have been poorly studied so far.

Unilateral pulmonary edema after pulmonary embolism in a bilateral lung transplant patient.

We report a case of unilateral pulmonary edema due to the decompensation of an asymptomatic ipsilateral pulmonary venous stenosis by a contralateral pulmonary embolism. Emergency surgery included pulmonary embolectomy and refashioning of the stenotic pulmonary venous anastomosis.

Posterior leaflet extension with an autologous pericardial patch in rheumatic mitral insufficiency.

We describe our technique of posterior leaflet extension with an autologous pericardial patch in patients suffering from rheumatic mitral regurgitation. Several simple rules have allowed us to achieve satisfying long-term results.

[Systolic anterior motion (SAM): a rare cause of late failure in mitral valve repair].

Systolic anterior motion (SAM) of the mitral valve is a rare complication of mitral valve repair. The treatment of the large majority of cases is purely medical. Nevertheless, an early degradation may require reoperation (revision of the repair or valve replacement).

Management of commissural lesions in native mitral valve endocarditis: long-term results of valve repair and partial homograft replacement.

Background And Aim Of The Study: Commissural lesions in the context of native mitral valve endocarditis are a technically challenging condition for conservative surgery. Herein are reported the authors' 10-year results for mitral valve repair (MVRep) or partial homograft replacement (PHR) performed in this setting.

Methods: Data were reviewed from 19 consecutive patients who underwent MVRep using either Carpentier's technique (n = 14) or PHR (n = 5) for endocarditis at the authors' institution between 1989 and 1994.

[Five years experience with non-pulsatile flow].

Mechanical circulatory assistances now belong to the therapeutic stock in case of advanced heart failure. Their mainspring lays on the substitution of the failing left and/or right ventricle function with a pump. The goal being to maintain or restore the system main functions.