A novel dominant mutation of the Nav1.4 alpha-subunit domain I leading to sodium channel myotonia.

BACKGROUND: Mutations in SCN4A may lead to myotonia. METHODS: Presentation of a large family with myotonia, including molecular studies and patch clamp experiments using human embryonic kidney 293 cells expressing wild-type and mutated channels. RESULTS: In a large family with historic data on seven generations and a clear phenotype, including myotonia at movement onset, with worsening by cold temperature, pregnancy, mental stress, and especially after rest after intense physical activity, but without weakness, the phenotype was linked with the muscle sodium channel gene (SCN4A) locus, in which a novel p.I141V mutation was found. This modification is located within the first transmembrane segment of domain I of the Na(v)1.4 alpha subunit, a region where no mutation has been reported so far. Patch clamp experiments revealed a mutation-induced hyperpolarizing shift (-12.9 mV) of the voltage dependence of activation, leading to a significant increase (approximately twofold) of the window current amplitude. In addition, the mutation shifted the voltage dependence of slow inactivation by -8.7 mV and accelerated the entry to this state. CONCLUSIONS: We propose that the gain-of-function alteration in activation leads to the observed myotonic phenotype, whereas the enhanced slow inactivation may prevent depolarization-induced paralysis.

La protection des investissements suisses à l'étranger dans le cadre des accords de promotion et de protection des investissements

Dotée d'une économie traditionnellement ouverte vers l'extérieur, la Suisse dispose de l'un des plus vastes réseaux au monde d'accords bilatéraux de promotion et de protection des investissements (APPI). Instrument dont la faible notoriété est inversement proportionnelle au nombre élevé d'accords concernés et aux montants en jeu, les APPI visent à conférer aux entreprises suisses établies à l'étranger - et vice-versa - une large protection contre les risques non commerciaux. Le présent ouvrage s'attache à l'analyse du développement et du contenu des APPI conclus par la Suisse avec ses partenaires, essentiellement des pays en développement. S'appuyant sur la doctrine et la jurisprudence internationales, il traite de manière détaillée des droits matériels et procéduraux parfois contestés que ce type d'accords offrent aux investisseurs et met en évidence les particularités des APPI du réseau suisse.

Audit report on the Iowa Corn Promotion Board for the years ended August 31, 2009 and 2008

Audit report on the Iowa Corn Promotion Board for the years ended August 31, 2009 and 2008

Audit report on the Iowa Sheep and Wool Promotion Board for the years ended June 30, 2009 and 2008

Audit report on the Iowa Sheep and Wool Promotion Board for the years ended June 30, 2009 and 2008

Glomerular hyperfiltration and increased proximal sodium reabsorption in subjects with type 2 diabetes or impaired fasting glucose in a population of the African region.

BACKGROUND. Glomerular hyperfiltration (GHF) is a well-recognized early renal alteration in diabetic patients. As the prevalence of GHF is largely unknown in populations in the African region with respect to normal fasting glucose (NFG), impaired fasting glucose (IFG) and type 2 diabetes [diabetes mellitus (DM)], we conducted a cross-sectional study in the Seychelles islands among families including at least one member with hypertension. METHODS. The glomerular filtration rate (GFR), effective renal plasma flow (ERPF) and proximal tubular sodium reabsorption were measured using inulin, p-aminohippurate (PAH) and endogenous lithium clearance, respectively. Twenty-four-hour urine was collected on the preceding day. RESULTS. Of the 363 participants (mean age 44.7 years), 6.6% had IFG, 9.9% had DM and 63.3% had hypertension. The prevalence of GHF, defined as a GFR >140 ml/min, was 17.2%, 29.2% and 52.8% in NFG, IFG and DM, respectively (P trend <0.001). Compared to NFG, the adjusted odds ratio for GHF was 1.99 [95% confidence interval (CI) 0.73-5.44] for IFG and 5.88 (2.39-14.45) for DM. Lithium clearance and fractional excretion of lithium were lower in DM and IFG than NFG (P < 0.001). CONCLUSION. In this population of African descent, subjects with impaired fasting glucose or type 2 diabetes had a high prevalence of GHF and enhanced proximal sodium reabsorption. These findings provide further insight on the elevated incidence of nephropathy reported among African diabetic individuals.

Special investigation of the Iowa Department of Economic Development Film Office and the Film, Television and Video Production Promotion Program for the period May 17, 2007 through September 21, 2009

Special investigation of the Iowa Department of Economic Development Film Office and the Film, Television and Video Production Promotion Program for the period May 17, 2007 through September 21, 2009

Prévention des maladies et promotion de la santé: propositions pour une stratégie vaudoise

Ce document présente un plan de prévention pour le Canton de Vaud (version octobre 2007). Ce plan concentre ses efforts sur la prévention de quelques maladies (infarctus du myocarde, accident vasculaire cérébral, diabète, cancer colorectal, cancer du sein, cancer du poumon, dépression, fracture ostéoporotique), à l'aide d'un nombre restreint d'interventions (améliorer l'alimentation et augmenter l'activité physique, lutte contre le tabagisme, prévention primaire et secondaire de la maladie athéromateuse, prévention secondaire du cancer colorectal, prévention secondaire du cancer du sein, prévention secondaire de la dépression). Après la présentation de quelques enjeux de ce plan, le rapport conclut sur trois recommandations portant sur les structures de la prévention des maladies et de promotion de la santé, le monitorage des activités de prévention des maladies et de promotion de la santé et enfin sur le mandat et l'organisation de la Commission cantonale de prévention.

Report on the Local Public Health Services Grant administered by the Bureau of Local Public Health Services, a division of Health Promotion and Chronic Disease Prevention of the Iowa Department of Public Health for the period July 1, 2006 through June 30, 2008

Report on the Local Public Health Services Grant administered by the Bureau of Local Public Health Services, a division of Health Promotion and Chronic Disease Prevention of the Iowa Department of Public Health for the period July 1, 2006 through June 30, 2008

Audit report on the Iowa Corn Promotion Board for the years ended August 31, 2010 and 2009

Audit report on the Iowa Corn Promotion Board for the years ended August 31, 2010 and 2009

The PPARgamma agonist pioglitazone modifies the vascular sodium-angiotensin II relationship in insulin-resistant rats.

Glitazones are efficient insulin sensitizers that blunt the effects of angiotensin II (ANG II) in the rat. Sodium chloride is another important modulator of the systemic and renal effects of ANG II. Whether glitazones interfere with the interaction between sodium and the response to ANG II is not known. Therefore, we investigated the effects of pioglitazone on the relationship between sodium and the systemic and renal effects of ANG II in rats. Pioglitazone, or vehicle, was administered for 4 wk to 8-wk-old obese Zucker rats. Animals were fed a normal-sodium (NS) or a high-sodium (HS) diet. Intravenous glucose tolerance tests, systemic and renal hemodynamic responses to ANG II, and the renal ANG II binding and expression of ANG II type 1 (AT(1)) receptors were measured. The results of our study were that food intake and body weight increased, whereas blood pressure, heart rate, filtration fraction, and insulin levels decreased significantly with pioglitazone in obese rats on both diets. Pioglitazone blunted the systemic response to ANG II and abolished the increased responsiveness to ANG II induced by a HS diet. Pioglitazone modified the renal hemodynamic response to changes in salt intake while maintaining a lower filtration fraction with ANG II perfusion. These effects were associated with a decrease in the number and expression of the AT(1) receptor in the kidney. In conclusion, these data demonstrate that the peroxisome proliferator-activated receptor-gamma agonist pioglitazone modifies the physiological relationship between sodium chloride and the response to ANG II in insulin-resistant rats.