Effects of dietary protein and phosphorus restriction on the progression of early renal failure

Effects of dietary protein and phosphorus restriction on the progression of early renal failure. Three groups of patients with chronic renal failure were studied. Group 1 comprised 25 patients with a mean serum creatinine of 2.18mg/dl and a mean arterial pressure of 117mm Hg. Group 2 had 20 patients with a mean serum creatinine of 4.24mg/dl and a mean arterial pressure of 119mm Hg. All these patients were kept for 18 to 76 months on a diet containing about 40 kcal/kg, 0.6 g/kg of protein, 700mg of phosphorus, and 1,000 to 1,500mg of calcium (orally supplemented). Group 3 comprised 30 patients with a mean serum creatinine of 2.28mg/dl and a mean arterial pressure of 116mm Hg. They had followed no specific dietary regimen for 3 to 72 months, and their dietary calorie, protein, phosphorus, and calcium intakes averaged 35 kcal/kg, 70 g, 900mg, and 800mg, respectively. The plots of reciprocal creatinine against time gave slopes of -0.0008 and -0.0010 in patients in groups 1 and 2, and a slope of -0.020 in group 3 patients. The slopes of both groups 1 and 2 were statistically different (analysis of variance and “F” test, P < 0.01) from that of group 3. No evidence of progressive protein and phosphorus depletion was observed in groups 1 and 2 patients. We conclude that a moderate dietary restriction of protein and phosphorus is an acceptable and effective regimen for delaying progression of functional deterioration in early renal failure.Effet de la restriction protéique et phosphorée alimentaire sur la progression de l'insuffisance rénale débutante. Trois groupes de malades ayant une insuffisance rénale chronique ont été étudiés. Le groupe 1 comprenait 25 malades ayant une créatinine sérique moyenne de 2,18mg/dl et une pression artérielle moyenne de 117mm Hg. Le groupe 2 comportait 20 malades ayant une créatinine sérique moyenne de 4,24mg/dl et une pression artérielle moyenne de 119mm Hg. Tous ces malades ont été soumis pendant 18 à 76 mois à un régime contenant environ 40 kcal/kg, 0,6kg de protéines, 700mg de phosphore, et 1000 à 1500mg de calcium (par supplémentation orale). Le groupe 3 comprenait 30 malades ayant une créatinine sérique moyenne de 2,28mg/dl et une pression artérielle moyenne de 116mm Hg. Ils n'avaient pas suivi de régime alimentaire spécifique pendant 3 à 72 mois, et leurs apports alimentaires caloriques, protéiques, phosphorés et calciques étaient en moyenne de 35 kcal/kg, 70 g, 900mg, et 800mg, respectivement. Les courbes de créatinine en fonction du temps ont donné des pentes de -0,0008 et de -0,0010 chez les malades des groupes 1 et 2, et une pente de -0,020 chez ceux de groupe 3. Des pentes des groupes 1 et 2 différaient statistiquement (analyse de variance et test de “F”, P < 0,01) de ceux du groupe 3. Il n'a pas été observé de preuve de déplétion progressive en protéines et en phosphore chez les malades des groupes 1 et 2. Nous concluons qu'une restriction alimentaire modérée en protéines et en phosphore est un régime acceptable et efficace pour retarder la progression de la détérioration fonctionnelle au cours de l'insuffisance rénale précoce

Gain-of-function defects of astrocytic Kir4.1 channels in children with autism spectrum disorders and epilepsy

Dysfunction of the inwardly-rectifying potassium channels Kir4.1 (KCNJ10) represents a pathogenic mechanism contributing to Autism-Epilepsy comorbidity. To define the role of Kir4.1 variants in the disorder, we sequenced KCNJ10 in a sample of affected individuals, and performed genotype-phenotype correlations. The effects of mutations on channel activity, protein trafficking, and astrocyte function were investigated in Xenopus laevis oocytes, and in human astrocytoma cell lines. An in vivo model of the disorder was also explored through generation of kcnj10a morphant zebrafish overexpressing the mutated human KCNJ10. We detected germline heterozygous KCNJ10 variants in 19/175 affected children. Epileptic spasms with dysregulated sensory processing represented the main disease phenotype. When investigated on astrocyte-like cells, the p.R18Q mutation exerted a gain-of-function effect by enhancing Kir4.1 membrane expression and current density. Similarly, the p.R348H variant led to gain of channel function through hindrance of pH-dependent current inhibition. The frequent polymorphism p.R271C seemed, instead, to have no obvious functional effects. Our results confirm that variants in KCNJ10 deserve attention in autism-epilepsy, and provide insight into the molecular mechanisms of autism and seizures. Similar to neurons, astrocyte dysfunction may result in abnormal synaptic transmission and electrical discharge, and should be regarded as a possible pharmacological target in autism-epilepsy. Supplementary information accompanies this paper in the files section.peer-reviewe

Integrated Toolset for WSN Application Planning, Development, Commissioning and Maintenance: The WSN-DPCM ARTEMIS-JU Project

In this article we present the main results obtained in the ARTEMIS-JU WSN-DPCM project between October 2011 and September 2015. The first objective of the project was the development of an integrated toolset for Wireless sensor networks (WSN) application planning, development, commissioning and maintenance, which aims to support application domain experts, with limited WSN expertise, to efficiently develop WSN applications from planning to lifetime maintenance. The toolset is made of three main tools: one for planning, one for application development and simulation (which can include hardware nodes), and one for network commissioning and lifetime maintenance. The tools are integrated in a single platform which promotes software reuse by automatically selecting suitable library components for application synthesis and the abstraction of the underlying architecture through the use of a middleware layer. The second objective of the project was to test the effectiveness of the toolset for the development of two case studies in different domains, one for detecting the occupancy state of parking lots and one for monitoring air concentration of harmful gasses near an industrial site

Diuretics in hypertension.

Despite the consistent reduction in the incidence of stroke and coronary events demonstrated in numerous clinical trials in young and elderly hypertensive subjects, the use of diuretics has declined as a first-line therapy in hypertension. The metabolic dose-dependent side effects and the increasing availability of new drugs appear the two main reasons for the decline. Although the neutral metabolic effects and the perception of a more physiological approach to hypertension has been advocated with the newer agents, no definite proof has been reported on the long-term effects on cardiovascular end-points. Many of adverse effects of diuretics can be limited by the use of low doses. For this reason, as well as their efficacy, safety, and cost-effectiveness, diuretics should remain a first-line therapy for hypertensive patients