L’épilepsie chez les personnes âgées

For a long time it was thought that epilepsy is a disease that mainly affects younger population. Epidemiological studies indicate that epilepsy is most frequently in the elderly. So we can say that epilepsy is a disease of old people because it is the most common disease affecting the brain tissue of the elderly, after a stroke and dementia. With all of this, if we consider that the quality of life, availability of medical services, reduce birth rates etc. all lead to more rapid growth in the number of people in this age group, we must pay great attention to this problem. Unfortunately there are a very small number of the conducted studies and guidelines on this topic. Since September 2008 in the literature can be found only 102 publications, of which only 50 original articles. Seizures are very often not clinically observed because the aura and secondary generalization of tonic-clonic seizures is rare in elderly patients. Besides the sudden loss of consciousness is a condition that is with age increasingly occurring for different reasons, so differential diagnosis is more challenging.Pendant longtemps, on a pensé que l'épilepsie est une maladie qui touche principalement les plus jeunes. Des études épidémiologiques indiquent que l'épilepsie est le plus fréquemment chez les personnes âgées. On peut donc dire que l'épilepsie est une maladie des personnes âgées, car il est la maladie la plus commune affectant le tissu cérébral des personnes âgées, après un accident vasculaire cérébral et la démence. Avec tout cela, si l'on considère que la qualité de la vie, de la disponibilité des services médicaux, de réduire les taux de natalité, etc conduisent tous à une croissance plus rapide du nombre de personnes dans ce groupe d'âge, nous devons prêter une grande attention à ce problème. Malheureusement, il ya un très petit nombre des études réalisées et des lignes directrices à ce sujet. Depuis Septembre 2008, dans la littérature peuvent être trouvées seulement 102 publications, dont seulement 50 articles originaux. Les convulsions sont très souvent pas observée en clinique parce que l'aura et la généralisation secondaire des crises tonico-cloniques est rare chez les personnes âgées. Outre la perte soudaine de conscience est une condition qui est de plus en plus avec l'âge se produisent pour des raisons différentes, de sorte diagnostic différentiel est plus difficile

NSAIDs and Cardiovascular Diseases: Role of Reactive Oxygen Species

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most commonly used drugs worldwide. NSAIDs are used for a variety of conditions including pain, rheumatoid arthritis, and musculoskeletal disorders. The beneficial effects of NSAIDs in reducing or relieving pain are well established, and other benefits such as reducing inflammation and anticancer effects are also documented. The undesirable side effects of NSAIDs include ulcers, internal bleeding, kidney failure, and increased risk of heart attack and stroke. Some of these side effects may be due to the oxidative stress induced by NSAIDs in different tissues. NSAIDs have been shown to induce reactive oxygen species (ROS) in different cell types including cardiac and cardiovascular related cells. Increases in ROS result in increased levels of oxidized proteins which alters key intracellular signaling pathways. One of these key pathways is apoptosis which causes cell death when significantly activated. This review discusses the relationship between NSAIDs and cardiovascular diseases (CVD) and the role of NSAID-induced ROS in CVD

Regulation of microRNA expression in vascular smooth muscle by MRTF-A and actin polymerization

Producción CientíficaThe dynamic properties of the actin cytoskeleton in smooth muscle cells play an important role in a number of cardiovascular disease states. The state of actin does not only mediate mechanical stability and contractile function but can also regulate gene expression via myocardin related transcription factors (MRTFs). These transcriptional co-activators regulate genes encoding contractile and cytoskeletal proteins in smooth muscle. Regulation of small non-coding microRNAs (miRNAs) by actin polymerization may mediate some of these effects. MiRNAs are short non-coding RNAs that modulate gene expression by post-transcriptional regulation of target messenger RNA. In this study we aimed to determine a profile of miRNAs that were 1) regulated by actin/MRTF-A, 2) associated with the contractile smooth muscle phenotype and 3) enriched in muscle cells.The Swedish Research Council (grant 2012-2197)The Crafoord Foundation (grant 20150629)Instituto de Salud Carlos III (grant RD12/0042/0006)Ministerio de Economía, Industria y Competitividad (grant BFU2013-45867-R

Transcriptional and post-transcriptional regulation of vascular smooth muscle cell phenotype - Implications for vascular disease states

As the world population is pushing toward 8 billion, cardiovascular diseases (CVD) remain the leading cause of death worldwide, representing 30% of all global deaths. A large body of work has recognized that smooth muscle cells (SMCs) surrounding the blood vessels play a prominent role in the development and progression of cardiovascular diseases. SMCs are highly specialized cells with the main function to maintain vascular tension and thereby regulate blood pressure and blood flow. SMCs retain remarkable plasticity. In response to changes in external cues, SMCs can modulate their phenotype from a highly mature contractile phenotype to a synthetic, proliferative phenotype. Although beneficial during key physiological processes such as wound healing, phenotypic modulation can contribute to the development and progression of several vascular disease states. Despite extensive studies on the transcriptional programs that define smooth muscle phenotype, the endogenous regulators that control smooth muscle specificity are still far from understood. The aim of this thesis was to gain further insight into the transcriptional and post-transcriptional regulation of gene expression that occurs during disease development and how these changes affect the function of the vascular wall.The work in the following papers has identified previously unknown mechanisms by which small non-coding RNAs (miRNAs), actin polymerization and transcriptional regulators MRTFA and GATA6 can contribute to the changes in vascular smooth muscle observed in vascular disease states. In summary, we show that actin polymerization and MRTFA regulate a profile of miRNAs that are downregulated in patients with mildly dilated aorta. Moreover, we demonstrate a novel role for MRTFA in lipid accumulation and foam cell formation. We further demonstrate the importance of miRNA-143 and miRNA-145 for vascular function and for adaptation to hypertension. Lastly, we show that GATA6 regulates migration of SMCs. A deeper understanding into the underlying molecular mechanisms is crucial in order to develop new efficient therapeutic approaches against cardiovascular disease states

Molecular regulation of arterial aneurysms : Role of actin dynamics and microRNAs in vascular smooth muscle

Aortic aneurysms are defined as an irreversible increase in arterial diameter by morethan 50% relative to the normal vessel diameter. The incidence of aneurysm rupture isabout 10 in 100,000 persons per year and ruptured arterial aneurysms inevitably resultsin serious complications, which are fatal in about 40% of cases. There is also a hereditarycomponent of the disease and dilation of the ascending thoracic aorta is often associatedwith congenital heart disease such as bicuspid aortic valves (BAV). Furthermore, specificmutations that have been linked to aneurysm affect polymerization of actin filaments.Polymerization of actin is important to maintain a contractile phenotype of smooth musclecells enabling these cells to resist mechanical stress on the vascular wall caused by theblood pressure according to the law of Laplace. Interestingly, polymerization of actin alsopromotes smooth muscle specific gene expression via the transcriptional co-activatorMRTF, which is translocated to the nucleus when released from monomeric actin. Inaddition to genes encoding for proteins involved in the contractile machinery, recentstudies have revealed that several non-coding microRNAs (miRNAs) are regulated bythis mechanism. The importance of these miRNAs for aneurysm development is onlybeginning to be understood. This review will summarize our current understanding aboutthe influence of smooth muscle miRNAs and actin polymerization for the developmentof arterial aneurysms

NSAIDs and Cardiovascular Diseases: Role of Reactive Oxygen Species.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most commonly used drugs worldwide. NSAIDs are used for a variety of conditions including pain, rheumatoid arthritis, and musculoskeletal disorders. The beneficial effects of NSAIDs in reducing or relieving pain are well established, and other benefits such as reducing inflammation and anticancer effects are also documented. The undesirable side effects of NSAIDs include ulcers, internal bleeding, kidney failure, and increased risk of heart attack and stroke. Some of these side effects may be due to the oxidative stress induced by NSAIDs in different tissues. NSAIDs have been shown to induce reactive oxygen species (ROS) in different cell types including cardiac and cardiovascular related cells. Increases in ROS result in increased levels of oxidized proteins which alters key intracellular signaling pathways. One of these key pathways is apoptosis which causes cell death when significantly activated. This review discusses the relationship between NSAIDs and cardiovascular diseases (CVD) and the role of NSAID-induced ROS in CVD

Regulation of microRNA expression in vascular smooth muscle by MRTF-A and actin polymerization

et al.The dynamic properties of the actin cytoskeleton in smooth muscle cells play an important role in a number of cardiovascular disease states. The state of actin does not only mediate mechanical stability and contractile function but can also regulate gene expression via myocardin related transcription factors (MRTFs). These transcriptional co-activators regulate genes encoding contractile and cytoskeletal proteins in smooth muscle. Regulation of small non-coding microRNAs (miRNAs) by actin polymerization may mediate some of these effects. MiRNAs are short non-coding RNAs that modulate gene expression by post-transcriptional regulation of target messenger RNA. In this study we aimed to determine a profile of miRNAs that were 1) regulated by actin/MRTF-A, 2) associated with the contractile smooth muscle phenotype and 3) enriched in muscle cells. This analysis was performed using cardiovascular disease-focused miRNA arrays in both mouse and human cells. The potential clinical importance of actin polymerization in aortic aneurysm was evaluated using biopsies from mildly dilated human thoracic aorta in patients with stenotic tricuspid or bicuspid aortic valve. By integrating information from multiple qPCR based miRNA arrays we identified a group of five miRNAs (miR-1, miR-22, miR-143, miR-145 and miR-378a) that were sensitive to actin polymerization and MRTF-A overexpression in both mouse and human vascular smooth muscle. With the exception of miR-22, these miRNAs were also relatively enriched in striated and/or smooth muscle containing tissues. Actin polymerization was found to be dramatically reduced in the aorta from patients with mild aortic dilations. This was associated with a decrease in actin/MRTF-regulated miRNAs. In conclusion, the transcriptional co-activator MRTF-A and actin polymerization regulated a subset of miRNAs in vascular smooth muscle. Identification of novel miRNAs regulated by actin/MRTF-A may provide further insight into the mechanisms underlying vascular disease states, such as aortic aneurysm, as well as novel ideas regarding therapeutic strategies. This article is part of a Special Issue entitled: ECS Meeting edited by Claus Heizmann, Joachim Krebs and Jacques Haiech.This work was supported by grants from the Swedish Research Council (2012-2197), the Crafoord Foundation (20150629), the Swedish Heart and Lung Foundation(20150664), the Royal Physiographic Society, the Per-Eric and Ulla Schyberg Foundation, the Magnus Bergvall foundation, the Spanish Instituto de Salud Carlos III (ISCIII-FEDER RD12/0042/0006, Heracles Program) and MINECO (BFU2013-45867-R). K.M.T. was supported by the European Union FP7 Marie Curie Initial Training Network on Small Artery Remodeling (SmArt).Peer Reviewe