BMP2 gene transfer induces pericardial effusion and inflammatory response in the ischemic porcine myocardium.

Pro-angiogenic gene therapy is being developed to treat coronary artery disease (CAD). We recently showed that bone morphogenetic protein 2 (BMP2) and vascular endothelial growth factor-A synergistically regulate endothelial cell sprouting in vitro. BMP2 was also shown to induce endocardial angiogenesis in neonatal mice post-myocardial infarction. In this study, we investigated the potential of BMP2 gene transfer to improve cardiomyocyte function and neovessel formation in a pig chronic myocardial infarction model. Ischemia was induced in domestic pigs by placing a bottleneck stent in the proximal part of the left anterior descending artery 14 days before gene transfer. Intramyocardial gene transfers with adenovirus vectors (1 × 1012 viral particles/pig) containing either human BMP2 (AdBMP2) or beta-galactosidase (AdLacZ) control gene were performed using a needle injection catheter. BMP2 transgene expression in the myocardium was detected with immunofluorescence staining in the gene transfer area 6 days after AdBMP2 administration. BMP2 gene transfer did not induce angiogenesis or cardiomyocyte proliferation in the ischemic pig myocardium as determined by the quantitations of CD31 or Ki-67 stainings, respectively. Accordingly, no changes in heart contractility were detected in left ventricular ejection fraction and strain measurements. However, BMP2 gene transfer induced pericardial effusion (AdBMP2: 9.41 ± 3.17 mm; AdLacZ: 3.07 ± 1.33 mm) that was measured by echocardiography. Furthermore, an increase in the number of immune cells and CD3+ T cells was found in the BMP2 gene transfer area. No changes were detected in the clinical chemistry analysis of pig serum or histology of the major organs, implicating that the gene transfer did not induce general toxicity, myocardial injury, or off-target effects. Finally, the levels of fibrosis and cardiomyocyte apoptosis detected by Sirius red or caspase 3 stainings, respectively, remained unaltered between the groups. Our results demonstrate that BMP2 gene transfer causes inflammatory changes and pericardial effusion in the adult ischemic myocardium, which thus does not support its therapeutic use in chronic CAD.

[Fighting against unexplained sudden death]. / Mort subite, en quête d'une explication.

Sudden cardiac death, mostly related to ventricular arrhythmia, is a major public health issue, with still very poor survival at hospital discharge. Although coronary artery disease remains the leading cause, other etiologies should be systematically investigated. Exhaustive and standardized exploration is required to eventually offer specific therapeutics and management to the patient as well as his/her family members in case of inherited cardiac disease. Identification and establishing direct causality of the detected cardiac anomaly may remain challenging, underlying the need for a multidisciplinary and experimented team.

Ability of Three Lactic Acid Bacteria to Grow in Sessile Mode and to Inhibit Biofilm Formation of Pathogenic Bacteria.

In this study, we explored the effect of three lactic acid bacteria (LAB), i.e. Enterococcus sp CM9, Enterococcus sp CM18 and Enterococcus faecium H3, and their supernatants, on seven biofilm-forming pathogenic strains isolated from human urinary tract or nose infections. By quantitative biofilm production assay, a strong adherence ability of Enterococcus sp CM9 and Enterococcus sp CM18 was revealed while E. faecium H3 resulted to be moderately adherent. Inhibition tests demonstrated an antimicrobial activity of LAB against pathogens.The presence of cell free supernatant (CFS) of CM9 and CM18 strains significantly decreased the adhesion of S. aureus 10,850, S. epidermidis 4,296 and E. coli FSL24. The CFS of H3 strain was effective against S. epidermidis 4,296 and P. aeruginosa PA1FSL biofilms only. Biofilm formation of K. pneumoniae Kp20FSL, A. baumannii AB8FSL and ESBL+ E. coli FS101570 have not been affected by any CSF while P. aeruginosa PA1FSL biofilm increase in presence of CM9 and CM18 CFS.Confocal Laser Scanning Microscopy revealed that K. pneumoniae Kp20FSL biofilm was inhibited by Enterococcus sp CM9, when grown together.Our results suggest that the LAB strains and/or their bacteriocins can be considered as potential tools to control biofilm formation of some bacterial pathogens.

[Percutaneous treatment of mitral regurgitation]. / Prise en charge interventionnelle de la fuite mitrale.

Mitral regurgitation (MR) is currently the most frequent valvular heart disease, and the second most operated valve in Europe. Around 50% of patients presenting severe MR are denied surgery, despite the adverse prognosis associated with the absence of treatment, due to comorbidities and/or advanced age. During the previous years, percutaneous treatment of MR, whether by replacement or, more frequently, by repair, has been developed, providing an alternative for those patients who are deemed at prohibitive, but also, high surgical risk. Percutaneous edge-to-edge repair is currently the most frequently used technique, and is the only one recommended by the European Guidelines for Valvular Heart Disease Management. In the current article, we review the different strategies for MR repair, as well as the indications and level of evidence for their use.

[Sudden cardiac death and coronary thrombus]. / Arrêt cardiaque et thrombose coronaire.

Out-of-hospital cardiac arrest is most often due to an acute coronary artery occlusion. The cause of coronary thrombosis in cardiac arrest is debated. Plaque erosion could be a trigger leading to immediate thrombus formation followed by ventricular fibrillation or rapid ventricular tachycardia. Coronary artery spasm is frequent: spasm provocation tests should be performed in survivors with normal coronary arteries. Use of drugs such as cocaine can lead to sudden death and blood sampling at arrival is recommended in survivors of out-of-hospital cardiac arrest. Delivery of immediate and effective basic life support remains the most important predictive factor for survival in out-of-hospital cardiac arrest.

[Sudden cardiac death and anomalous connections of the coronary arteries: What is known and what is unknown?] / Mort subite cardiaque et anomalies de connexion des artères coronaires : connaissances et questions.

Some anomalous connections of the coronary arteries may be associated with a risk of sudden cardiac death. In opposite with others cardiac diseases at risk of sudden cardiac death, the relationship between these congenital abnormalities and the risk of sudden cardiac death are not well understood. A correction of the anomaly is generally indicated after an aborted sudden cardiac death. Primary prevention strategy after the discovery of an anomaly at risk is debated. Even if the absolute risk of sudden death is very low, a pre-participation screening in young athletes may be discussed due to a non-rare incidence.

[Sudden cardiac death: A better understanting for a better prevention]. / Mort subite de l'adulte : une meilleure compréhension pour une meilleure prévention.

Sudden cardiac death is defined as a natural and unexpected death, in a previous apparently healthy individual. It represents a major public health issue, with up to 50% of the cardiovascular mortality. Using data from the Paris Sudden Death Expertise Centre registry, this article summarises the main cardiovascular abnormalities associated with sudden cardiac death, the different preventives approaches, and provides a systematic diagnostic approach.

[Sudden cardiac death: Are women different?] / Mort subite : y a-t-il une spécificité féminine ?

Sudden cardiac death is a major public health problem with around 40,000 cases per year in France. Epidemiological, clinical and prognostic differences according to gender have been described in most cardiovascular diseases, including sudden cardiac death. In this article, we will review gender differences in sudden cardiac death incidence, circumstance of occurrence, management, and prognosis.

Efficacy and safety of myocardial gene transfer of adenovirus, adeno-associated virus and lentivirus vectors in the mouse heart.

Gene therapy is a promising new treatment option for cardiac diseases. For finding the most suitable and safe vector for cardiac gene transfer, we delivered adenovirus (AdV), adeno-associated virus (AAV) and lentivirus (LeV) vectors into the mouse heart with sophisticated closed-chest echocardiography-guided intramyocardial injection method for comparing them with regards to transduction efficiency, myocardial damage, effects on the left ventricular function and electrocardiography (ECG). AdV had the highest transduction efficiency in cardiomyocytes followed by AAV2 and AAV9, and the lowest efficiency was seen with LeV. The local myocardial inflammation and fibrosis in the left ventricle (LV) was proportional to transduction efficiency. AdV caused LV dilatation and systolic dysfunction. Neither of the locally injected AAV serotypes impaired the LV systolic function, but AAV9 caused diastolic dysfunction to some extent. LeV did not affect the cardiac function. We also studied systemic delivery of AAV9, which led to transduction of cardiomyocytes throughout the myocardium. However, also diffuse fibrosis was present leading to significantly impaired LV systolic and diastolic function and pathological ECG changes. Compared with widely used AdV vector, AAV2, AAV9 and LeV were less effective in transducing cardiomyocytes but also less harmful. Local administration of AAV9 was safer and more efficient compared with systemic administration.

The oriental fruitfly Bactrocera dorsalis s.s. in East Asia: disentangling the different forces promoting the invasion and shaping the genetic make-up of populations.

The Oriental fruit fly, Bactrocera dorsalis sensu stricto, is one of the most economically destructive pests of fruits and vegetables especially in East Asia. Based on its phytophagous life style, this species dispersed with the diffusion and implementation of agriculture, while globalization allowed it to establish adventive populations in different tropical and subtropical areas of the world. We used nine SSR loci over twelve samples collected across East Asia, i.e. an area that, in relatively few years, has become a theatre of intensive agriculture and a lively fruit trade. Our aim is to disentangle the different forces that have affected the invasion pattern and shaped the genetic make-up of populations of this fruit fly. Our data suggest that the considered samples probably represent well established populations in terms of genetic variability and population structuring. The human influence on the genetic shape of populations and diffusion is evident, but factors such as breeding/habitat size and life history traits of the species may have determined the post introduction phases and expansion. In East Asia the origin of diffusion can most probably be allocated in the oriental coastal provinces of China, from where this fruit fly spread into Southeast Asia. The spread of this species deserves attention for the development and implementation of risk assessment and control measures.

Uncovering the tracks of a recent and rapid invasion: the case of the fruit fly pest Bactrocera invadens (Diptera: Tephritidae) in Africa.

Phytophagous insects of the genus Bactrocera are among the most economically important invasive fruit fly pests. In 2003, an unknown Bactrocera species was found in Kenya. First identified as an 'aberrant form' of the Asian B. dorsalis complex, it was later recognized as a new species, Bactrocera invadens. Within 2 years of its discovery, the species was recorded in several African countries, becoming an important quarantine pest. As this invasive fly was discovered only recently, no data are available on its invasion pattern in Africa. This pilot study attempts to infer from genetic data the dynamic aspects of the African invasion of this pest. Using microsatellite markers, we evaluated the level of genetic diversity and the extent of common ancestry among several African populations collected across the invaded areas. A sample from the Asian Sri Lankan population was analysed to confirm the Asian origin of this pest. Genetic data cast no doubt that Sri Lanka belongs to the native range, but only a small percentage of its genotypes can be found in Africa. African populations display relatively high levels of genetic diversity associated with limited geographical structure and no genetic footprints of bottlenecks. These features are indicative of processes of rapid population growth and expansion with possible multiple introductions. In the span of relatively few years, the African invasion registered the presence of at least two uncorrelated outbreaks, both starting from the East. The results of the analyses support that invasion started in East Africa, where B. invadens was initially isolated.

Isolation and characterization of microsatellite markers in the newly discovered invasive fruit fly pest in Africa, Bactrocera invadens (Diptera: Tephritidae).

We describe the isolation and characterization of 11 polymorphic microsatellite loci from the recently discovered fruit fly pest, Bactrocera invadens. The polymorphism of these loci was tested in individual flies from two natural populations (Sri Lanka and Democratic Republic of Congo). Allele number per locus ranged from three to 15 and eight loci displayed a polymorphic information content greater than 0.5. These microsatellite loci provide useful markers for studies of population dynamics and invasion history of this pest species.

Diagnosis and management of chronic pericardial effusions.

Chronic pericardial effusions are a major cause of morbidity in some clinical settings. Although the treatment of choice for acute symptomatic pericardial effusions (tamponade) is pericardiocentesis, the long-term management of symptomatic chronic pericardial effusions provides a greater challenge. The aim of this review is to provide insight into the presentation,diagnosis, and different treatment options available to patients with chronic symptomatic pericardial effusions,with emphasis on malignant pericardial effusions. Peri-cardiocentesis with sclerosing agents, radiation therapy,percutaneous, and surgical pericardiotomy and other surgical techniques are particularly efficacious, depend-ing on the underlying cause and the patient's prognosis.

Detection of polygalacturonases and pectin esterases in lactic acid bacteria.

Of 80 strains of lactic acid bacteria tested, only Lactobacillus casei strains HNK10 and L1-8, Lactobacillus plantarum Lc5 and Lactococcus lactis NN01 produced polygalacturonases (EC 3.2.1.) and/or pectin-esterases (EC 3.1.1.). Crude extracellular extracts of strain L1-8 were able to clarify pectin.

Rheumatoid nodulosis of the meninges.

Rheumatoid nodulosis of the brain and leptomeninges has been reported only rarely, usually in patients with severe rheumatoid arthritis (RA). We describe the occurrence of leptomeningeal rheumatoid nodulosis occurring in a patient with nondeforming RA occurring in the setting of methotrexate therapy.