Selenoprotein N is dynamically expressed during mouse development and detected early in muscle precursors

<p>Abstract</p> <p>Background</p> <p>In humans, mutations in the <it>SEPN1 </it>gene, encoding selenoprotein N (SelN), are involved in early onset recessive neuromuscular disorders, referred to as <it>SEPN1</it>-related-myopathies. The mechanisms behind these pathologies are poorly understood since the function of SelN remains elusive. However, previous results obtained in humans and more recently in zebrafish pointed to a potential role for SelN during embryogenesis. Using qRT-PCR, Western blot and whole mount <it>in situ </it>hybridization, we characterized in detail the spatio-temporal expression pattern of the murine <it>Sepn1 </it>gene during development, focusing particularly on skeletal muscles.</p> <p>Results</p> <p>In whole embryos, <it>Sepn1 </it>transcripts were detected as early as E5.5, with expression levels peaking at E12.5, and then strongly decreasing until birth. In isolated tissues, only mild transcriptional variations were observed during development, whereas a striking reduction of the protein expression was detected during the perinatal period. Furthermore, we demonstrated that <it>Sepn1 </it>is expressed early in somites and restricted to the myotome, the sub-ectodermal mesenchyme and the dorsal root ganglia at mid-gestation stages. Interestingly, <it>Sepn1 </it>deficiency did not alter somitogenesis in embryos, suggesting that SelN is dispensable for these processes in mouse.</p> <p>Conclusion</p> <p>We characterized for the first time the expression pattern of <it>Sepn1 </it>during mammalian embryogenesis and we demonstrated that its differential expression is most likely dependent on major post-transcriptional regulations. Overall, our data strongly suggest a potential role for selenoprotein N from mid-gestation stages to the perinatal period. Interestingly, its specific expression pattern could be related to the current hypothesis that selenoprotein N may regulate the activity of the ryanodine receptors.</p

Increased Muscle Stress-Sensitivity Induced by Selenoprotein N Inactivation in Mouse: A Mammalian Model for SEPN1-Related Myopathy

Selenium is an essential trace element and selenoprotein N (SelN) was the first selenium-containing protein shown to be directly involved in human inherited diseases. Mutations in the SEPN1 gene, encoding SelN, cause a group of muscular disorders characterized by predominant affection of axial muscles. SelN has been shown to participate in calcium and redox homeostasis, but its pathophysiological role in skeletal muscle remains largely unknown. To address SelN function in vivo, we generated a Sepn1-null mouse model by gene targeting. The Sepn1−/− mice had normal growth and lifespan, and were macroscopically indistinguishable from wild-type littermates. Only minor defects were observed in muscle morphology and contractile properties in SelN-deficient mice in basal conditions. However, when subjected to challenging physical exercise and stress conditions (forced swimming test), Sepn1−/− mice developed an obvious phenotype, characterized by limited motility and body rigidity during the swimming session, as well as a progressive curvature of the spine and predominant alteration of paravertebral muscles. This induced phenotype recapitulates the distribution of muscle involvement in patients with SEPN1-Related Myopathy, hence positioning this new animal model as a valuable tool to dissect the role of SelN in muscle function and to characterize the pathophysiological process

Connaissance et impact de la PMSA dans le suivi des patients âgés (enquête auprès des médecins généralistes du Calvados)

CAEN-BU Médecine pharmacie (141182102) / SudocSudocFranceF

Evaluation et prise en charge de la dénutrition du sujet âgé par les médecins généralistes du Calvados

CAEN-BU Médecine pharmacie (141182102) / SudocSudocFranceF

Création d'un support éducatif sur les AVK adapté aux personnes âgées et évaluation dans deux services de gériatrie et en ambulatoire

PARIS7-Xavier Bichat (751182101) / SudocSudocFranceF

Crise d'épilepsie de novo chez le sujet âgé de plus de 65 ans dans un service de soins de suite et réadaptation

L épilepsie est une affection plus fréquente chez le sujet âgé que chez l enfant ou l adulte jeune, avec une incidence supérieure à 100/100000 après 60 ans. C est pourquoi nous avons voulu effectuer un travail rétrospectif sur une période de 5 ans. Ce travail a porté sur 33 patients (13 hommes et 20 femmes, d âge moyen : 81,6 ans), ayant présenté une première crise d épilepsie survenue après l âge de 65 ans. Tous les patients ont bénéficié d un examen clinique, d un bilan biologique, d un électroencéphalogramme et d une imagerie cérébrale. Les crises étaient généralisées dans 55 % des cas, et partielles dans 30 %. Les 15 % restant étaient représentés par la confusion. 60,6 % des cas sont des crises symptomatiques aigues contre 39,4 % de crises non provoquées. La pathologie vasculaire cérébrale a été l étiologie la plus fréquente avec 48,5 % des cas. Dans 39,4 % des cas, les crises sont survenues dans un contexte de démence dégénérative ; 18 % des crises sont liées à des causes métaboliques et/ou toxiques ; 12 % des crises à des tumeurs cérébrales, 12 % à un bas débit cérébral, 9 % à des infections générales. Au décours de la première crise, un traitement antiépileptique a été introduit dans 88 % des cas, avec une préférence pour le valproate de sodium (48 % des cas en première intention). Notre étude a permis de mettre en évidence que l épilepsie du sujet âgé est d origine plurifactorielle avec une part non négligeable de la iatrogénicité chez ces personnes, âgées, polypathologiques et donc polymédiquées. Ce constat nous montre donc bien la complexité de la prise en charge d une personne âgée. Les médecins généralistes doivent donc être sensibilisés à l épilepsie du sujet âgé et à ses atypiesEpilepsy is a more frequent affection in the elderly people than in the child or the young adult, with an incidence higher than 100/10000 afters 60 years.This is why we wanted to carry out a retrospective work over 5 years period. This work concerned 33 patients (13 men and 20 women, of average age 81,6 years), having presented a first epileptic seizure after the 65 years age. All the patients had a clinical examination, a biological assessment, an electroencephalogram and a cerebral imagery. The seizures were generalized in 55% of the cases and partial in 30%. The 15% remainder were represented by confusion. 60,6% of the cases are acute symptomatic seizures against 39,4% of unprovoked seizures. Cerebrovascular disease was the most frequent etiology with 48,5% of the cases. In 39,4%, the seizures occured in a context degenerative dementia; 18% of seizures are related to metabolic causes and/or toxic; 12% of seizures to cerebral tumors, 12% to an anoxic brain injury, 9% to infective disturbances. After the first seizure, an antiepileptic treatment was introduced into 88% of cases, with a preference for sodium valproate (48% in first intention). Our study showed that the epilepsy of elderly people is of plurifactoriel origin with a considerable share of the iatrogenicity at these old people, polypathologic and thus polymedicated. This report thus shows us well to the complexity of the assumption of responsibility of old person. The general practitionners must be sensitived with the epilepsy of elderly people and its atypies.PARIS12-CRETEIL BU Médecine (940282101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Crise d'épilepsie de novo chez le sujet âgé de plus de 65 ans dans un service de soins de suite et réadaptation

L épilepsie est une affection plus fréquente chez le sujet âgé que chez l enfant ou l adulte jeune, avec une incidence supérieure à 100/100000 après 60 ans. C est pourquoi nous avons voulu effectuer un travail rétrospectif sur une période de 5 ans. Ce travail a porté sur 33 patients (13 hommes et 20 femmes, d âge moyen : 81,6 ans), ayant présenté une première crise d épilepsie survenue après l âge de 65 ans. Tous les patients ont bénéficié d un examen clinique, d un bilan biologique, d un électroencéphalogramme et d une imagerie cérébrale. Les crises étaient généralisées dans 55 % des cas, et partielles dans 30 %. Les 15 % restant étaient représentés par la confusion. 60,6 % des cas sont des crises symptomatiques aigues contre 39,4 % de crises non provoquées. La pathologie vasculaire cérébrale a été l étiologie la plus fréquente avec 48,5 % des cas. Dans 39,4 % des cas, les crises sont survenues dans un contexte de démence dégénérative ; 18 % des crises sont liées à des causes métaboliques et/ou toxiques ; 12 % des crises à des tumeurs cérébrales, 12 % à un bas débit cérébral, 9 % à des infections générales. Au décours de la première crise, un traitement antiépileptique a été introduit dans 88 % des cas, avec une préférence pour le valproate de sodium (48 % des cas en première intention). Notre étude a permis de mettre en évidence que l épilepsie du sujet âgé est d origine plurifactorielle avec une part non négligeable de la iatrogénicité chez ces personnes, âgées, polypathologiques et donc polymédiquées. Ce constat nous montre donc bien la complexité de la prise en charge d une personne âgée. Les médecins généralistes doivent donc être sensibilisés à l épilepsie du sujet âgé et à ses atypiesEpilepsy is a more frequent affection in the elderly people than in the child or the young adult, with an incidence higher than 100/10000 afters 60 years.This is why we wanted to carry out a retrospective work over 5 years period. This work concerned 33 patients (13 men and 20 women, of average age 81,6 years), having presented a first epileptic seizure after the 65 years age. All the patients had a clinical examination, a biological assessment, an electroencephalogram and a cerebral imagery. The seizures were generalized in 55% of the cases and partial in 30%. The 15% remainder were represented by confusion. 60,6% of the cases are acute symptomatic seizures against 39,4% of unprovoked seizures. Cerebrovascular disease was the most frequent etiology with 48,5% of the cases. In 39,4%, the seizures occured in a context degenerative dementia; 18% of seizures are related to metabolic causes and/or toxic; 12% of seizures to cerebral tumors, 12% to an anoxic brain injury, 9% to infective disturbances. After the first seizure, an antiepileptic treatment was introduced into 88% of cases, with a preference for sodium valproate (48% in first intention). Our study showed that the epilepsy of elderly people is of plurifactoriel origin with a considerable share of the iatrogenicity at these old people, polypathologic and thus polymedicated. This report thus shows us well to the complexity of the assumption of responsibility of old person. The general practitionners must be sensitived with the epilepsy of elderly people and its atypies.PARIS12-CRETEIL BU Médecine (940282101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Evaluation du score de probabilité clinique et de facteurs prédictifs de thrombose veineuse profonde chez le sujet âgé hospitalisé (à propos d'une étude prospective menée en court séjour gériatrique)

CAEN-BU Médecine pharmacie (141182102) / SudocSudocFranceF

Development and interpretation of activity test for microbial transformation of inorganic arsenic

International audienceArsenic is one of the more widespread toxic trace elements, whose presence in environment is linked either to geological background or human activities. The fate of arsenic in environmental compartments is closely linked to the microbial transformations of the inorganic species AsIII and AsV. In order to monitor the evolution of microbial As-related global activities, a simple batch test has been designed and applied. The principle of the test is based on the monitoring of oxidation of 1 mM AsIII in a basal medium inoculated with environmental samples. Results are interpreted considering of oxidation rate or rate constant, and lapse time. Several phenomena are likely to influence the global oxidation rate, such as the relative activity of diverse oxidizing microbes and the competition between oxidizing and reducing processes, in relation to organic matter bioavailability. AsIII oxidizing activities of microorganisms in eight surface soils from polluted sites were quantified with and without addition of organic substrates to the basal medium. Results suggested that AsIII oxidation rate constant was limited by the low concentration of organic substrate, this limitation being removed by supplying 0.08 g/L of organic carbon. Higher organic carbon input negatively affected AsIII oxidation rate constant. Then, the AsIII oxidizing test was applied to a soil highly polluted by the destruction of chemical weapons, simultaneously with the enumeration of AsIII-oxidizing microbes using the Most Probable Number method. Results suggested that the concentration of AsIII-oxidizing microbes was correlated with the lapse time and not with the oxidation rate. Experiments performed with a pure AsIII oxidizing bacterium confirmed a correlation between the lapse time and initial concentration of active cells, AsIII oxidation being detected when the bacterial concentration was close to 107 cells ml-1. In these conditions, the oxidation rate was independent from bacterial concentration. In a next step, the influence of microbial AsV reduction parameters will be considered