Dodecyl creatine ester, a promising treatment to deliver creatine to neurons, achieves pharmacology efficacy in creatine transporter deficiency.

Dodecyl creatine ester (DCE) is a creatine prodrug currently developed for brain diseases, including creatine transporter deficiency (CTD), an incurable rare genetic disease. A dual strategy combining a prodrug to bypass the non-functional creatine transporter and its delivery via the nose-to-brain pathway has been proposed to replenish creatine levels in cerebral cells, particularly in neurons of CTD patients. In vitro and in vivo studies in various animal models, including wild-type non-human primates and creatine transporter deficient mice, show that formulated DCE, when administered intranasally, achieves significant cerebral distribution up to the target cells, the neurons, and modulates the expression of neuronal markers related to cognitive function at doses intended for patients.

Impaired brain glucose metabolism as a biomarker for evaluation of dodecyl creatine ester in creatine transporter deficiency: Insights from patient brain-derived organoids and in vivo [18F]FDG PET imaging in a mouse model.

Creatine transporter deficiency (CTD) is an inborn error of creatine (Cr) metabolism in which Cr is not properly distributed to the brain due to a mutation in the Cr transporter (CrT) SLC6A8 gene. CTD is associated with developmental delays and with neurological disability in children. Dodecyl creatine ester (DCE), as a Cr prodrug, is a promising drug to treat CTD after administration by the nasal route, taking advantage of the nose-to-brain pathway.

Dodecyl creatine ester improves cognitive function and identifies key protein drivers including KIF1A and PLCB1 in a mouse model of creatine transporter deficiency.

Creatine transporter deficiency (CTD), a leading cause of intellectual disability is a result of the mutation in the gene encoding the creatine transporter SLC6A8, which prevents creatine uptake into the brain, causing mental retardation, expressive speech and language delay, autistic-like behavior and epilepsy. Preclinical and data indicate that dodecyl creatine ester (DCE) which increases the creatine brain content, might be a therapeutic option for CTD patients. To gain a better understanding of the pathophysiology and DCE treatment efficacy in CTD, this study focuses on the identification of biomarkers related to cognitive improvement in a Slc6a8 knockout mouse model (Slc6a8-/y) engineered to mimic the clinical features of CTD patients which have low brain creatine content.

The papillary muscle sling for ischemic mitral regurgitation.

Objective: Our objective was to evaluate long-term stability of mitral repair and reverse remodeling in patients with severe ischemic left ventricular dysfunction and functional mitral regurgitation.

Methods: Since June 2000, a total of 37 patients with ischemic functional mitral regurgitation have benefited from a double-level mitral repair that comprises an intraventricular peripapillary muscle sling completed by a classic intra-atrial mitral annuloplasty ring (mean age, 56 years; left ventricular end-diastolic diameter, 70 +/- 0 mm; left ventricular end-systolic diameter, 55 +/- 5.6 mm; ejection fraction, 15% to 45%; pulmonary hypertension > 60 in all patients; all were in New York Heart Association class III-IV).

In vitro study of percutaneous aortic valve replacement: selection of a tissue valve.

Background: Selection of the best tissue valve is an essential step before percutaneous aortic valve replacement (PAVR) becomes a clinical reality. The aim of this study was to evaluate in vitro three different tissue valves mounted within the same endovascular stent.

Methods: Thirty stented valves (10 aortic porcine, 10 pulmonary porcine, and 10 pericardial tubular) were sutured within a 32-mm long by 23-mm diameter cobalt-nickel stent.

Redo aortic root surgery for failure of an aortic homograft is a major technical challenge.

Objective: Aortic homografts offer many advantages over prosthetic valves. However, homograft dysfunction due to degeneration or infection may lead to reoperation. Aortic valve replacement in patients who have undergone previous aortic root replacement with an aortic homograft remains a technical challenge.

A lesional classification to standardize surgical management of aortic insufficiency towards valve repair.

Objective: Aortic valve repair is an alternative to valve replacement for treatment of chronic aortic insufficiency (AI). In order to standardize surgical management, we suggest a classification based on echocardiographic and operative analysis of valvular lesions.

Methods: Classification was based on the retrospective analysis of chronic AI mechanisms of 781 adults operated on electively between 1997 and 2003.

[Evolution of the surgical strategy in hypertrophic cardiomyopathy: case studies of eight patients].

Introduction: Hypertrophic cardiomyopathy is an inherited disease characterized by a left ventricular hypertrophy, a diastolic dysfunction and rhythm troubles with risk of sudden death. There was an evolution in the surgical strategy to treat the patients who present a left ventricular outflow tract gradient.

Materials And Methods: A retrospective study was conducted: We selected eight cases who presented an hypertrophic cardiomyopathy and operated on.

Dimensional ratios of normal mitral valve structures: a tool for determining the degree of geometric distortion in individual patients.

Background And Aim Of The Study: One objective of mitral valve repair is to restore the distorted mitral apparatus geometry to its normal dimensions specific for each patient. Because all dimensions of the normal aortic and mitral valves should be related, it was hypothesized that, in the presence of a normal aortic annulus, it would be possible to determine the dimensions of the structures needed for mitral valve repair.

Methods: In seven sheep, sonometric ultrasound crystals were implanted at the left and right trigones (T1, T2), lateral annulus (P1, P2), and the tips of the anterior and posterior papillary muscles (Ml, M2).

Coronary flow obstruction in percutaneous aortic valve replacement. An in vitro study.

Objective: Coronary flow obstruction is a serious complication reported in percutaneous aortic valve replacement. In an in vitro study of porcine hearts, the effects of valved stent implantation on coronary artery flow were studied with the native valve's leaflets intact and excised.

Methods: The right and left main coronary arteries of porcine hearts were dissected 20mm distal to the aortic root and directed into lengths of latex tubing leading to collection flasks.

The papillary muscles as shock absorbers of the mitral valve complex. An experimental study.

Objective: Although it is known that the papillary muscles ensure the continuity between the left ventricle (LV) and the mitral apparatus, their precise mechanism needs further study. We hypothesize that the papillary muscles function as shock absorbers to maintain a constant distance between their tips and the mitral annulus during the entire cardiac cycle.

Materials And Methods: Sonomicrometry crystals were implanted in five sheep in the mitral annulus at the trigones (T1 and T2), mid anterior annulus (AA) mid posterior annulus (PA), base of the posterior lateral scallops (P1 and P2), tips of papillary muscles (M1 and M2), and LV apex.

Sutureless stented aortic valve implantation under direct vision: lessons from a negative experience in sheep.

Background And Aim Of The Study: Percutaneous aortic valve replacement has been proposed as a valid alternative to surgery in selected cases; however, it still has many problems. As a less radical preliminary step, we implanted a balloon-expandable stented aortic valve under direct vision in sheep.

Methods: Under cardiopulmonary bypass (CPB) and through a transverse aortotomy, an aortic valve mounted in a long tubular balloon-expandable stent was implanted in six acute sheep.

Evidence of mitigated calcification of the Mosaic versus Hancock Standard valve xenograft in the mitral position of young sheep.

Objectives: Durability remains the main problem of all bioprosthetic valves, and calcification is the major cause of failure. New tissue treatment processes are expected to reduce mineralization. A comparative animal study was undertaken to evaluate the behavior of a new-generation porcine bioprosthesis in contrast with a first-generation porcine bioprosthesis.

Functional terminology for the tricuspid valve.

Background And Aim Of The Study: Advances in echocardiography have awoken new interest in the tricuspid valve, which otherwise has been largely ignored by cardiologists and surgeons. These advances demand a precise terminology for the description of the tricuspid valve's different anatomic structures in health and disease. While simple nomenclatures have been developed for the mitral valve, no such system has been described for the tricuspid valve.