Peut-on améliorer la notification des effets indésirables dans les établissements hospitaliers ? Bilan de 5 ans d’activité du réseau PharmacoMIP

Background. Spontaneous reporting of adverse drug reactions (ADR) is fundamental to drug safety surveillance (pharmacovigilance) and assessment of benefit/risk ratio. However, under-reporting remains the limit of the system. Objective. The aim of this study was to assess the effect of regular visits of an Assistant in Clinical Research (CRA) on the improvement of ADR reporting in non-university hospitals. Methods. We set up an ADR report collecting system that involved regular visits in non-university hospitals, We began the visits in 2006 in 2 areas (Haute Garonne and Gers), extended to 4 other areas in 2009. We compared the reporting rate (number of reports/number of beds) of total ADRs reported by non-university hospitals in these areas before (one year) and after the start of CRA visits. Results. A total 2831 of reports were collected by the CRA: 40% were "serious" including two deaths. The results suggest an increase of 100% of the rate of reporting of ADRs. Conclusion. This study shows that regular visits increases the number of ADRs reported by non-university hospitals. Further assessment of this procedure is necessary for long term evaluation of its effectiveness.     

Astrocyte-neuron metabolic relationships: for better and for worse

In recent years, previously unsuspected roles of astrocytes have been revealed, largely owing to the development of new tools enabling their selective study in situ. These exciting findings add to the large body of evidence demonstrating that astrocytes play a central role in brain homeostasis, in particular via the numerous cooperative metabolic processes they establish with neurons, such as the supply of energy metabolites and neurotransmitter recycling functions. Furthermore, impairments in astrocytic function are increasingly being recognized as an important contributor to neuronal dysfunction and, in particular, neurodegenerative processes. In this review, we discuss recent evidence supporting important roles for astrocytes in neuropathological conditions such as neuroinflammation, amyotrophic lateral sclerosis and Alzheimer's disease. We also explore the potential for neuroprotective therapeutics based on the modulation of astrocytic functions.     

Treatment of Aortoiliac Occlusive Disease: Medical versus Endovascular versus Surgical Therapy

Aortoiliac occlusive disease (AIOD) is an insidious, progressive atherosclerotic process that can lead to claudication, rest pain, tissue loss, and eventual lower extremity amputation. The patient with AIOD is also at risk for both fatal and nonfatal cardiovascular events. Treatment of the disease includes both risk factor modification and efforts to improve blood flow to the lower extremity. For mild to moderate intermittent claudication, medical therapy as well as a supervised exercise program is advised. For debilitating claudication or critical limb ischemia, a number of recent studies support an endovascular approach for patients with AIOD, citing patency rates that compare favorably to open surgery. Surgical revascularization, however, should still be considered in selected patients.     

Banques de données de mutations : enjeux et perspectives pour les maladies génétiques orphelines

New technologies, which constantly become available for mutation detection and gene analysis, have contributed to an exponential rate of discovery of disease genes and variation in the human genome. The task of collecting and documenting this enormous amount of data in genetic databases represents a major challenge for the future of biological and medical science. The Locus Specific Databases (LSDBs) are so far the most efficient mutation databases. This review presents the main types of databases available for the analysis of mutations responsible for genetic disorders, as well as open perspectives for new therapeutic research or challenges for future medicine. Accurate and exhaustive collection of variations in human genomes will be crucial for research and personalized delivery of healthcare.     

Multiple effects of melatonin on rhythmic clock gene expression in the mammalian pars tuberalis

In mammals, changing day length modulates endocrine rhythms via nocturnal melatonin secretion. Studies of the pituitary pars tuberalis (PT) suggest that melatonin-regulated clock gene expression is critical to this process. Here, we considered whether clock gene rhythms continue in the PT in the absence of melatonin and whether the effects of melatonin on the expression of these genes are temporally gated. Soay sheep acclimated to long photoperiod (LP) were transferred to constant light for 24 h, suppressing endogenous melatonin secretion. Animals were infused with melatonin at 4-h intervals across the final 24 h, and killed 3 h after infusion. The expression of five clock genes (Per1, Per2, Cry1, Rev-erbalpha, and Bmal1) was measured by in situ hybridization. In sham-treated animals, PT expression of Per1, Per2, and Rev-erbalpha showed pronounced temporal variation despite the absence of melatonin, with peak times occurring earlier than predicted under LP. The time of peak Bmal1 expression remained LP-like, whereas Cry1 expression was continually low. Melatonin infusion induced Cry1 expression at all times and suppressed other genes, but only when they showed high expression in sham-treated animals. Hence, 3 h after melatonin treatment, clock gene profiles were driven to a similar state, irrespective of infusion time. In contrast to the PT, melatonin infusions had no clear effect on clock gene expression in the suprachiasmatic nuclei. Our results provide the first example of acute sensitivity of multiple clock genes to one endocrine stimulus and suggest that rising melatonin levels may reset circadian rhythms in the PT, independently of previous phase.