Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Effets des champs électromagnétiques sur la membrane cellulaire et applications biomédicales potentielles

Le travail de la thèse concerne les impulsions de téléphonie mobile GSM (900MHz, 217Hz, 576 s) de DAS (débit d'absorption spécifique) jusqu'à 4.6W/kg, agissant sur l'endocytose et la mitose cellulaires. Les résultats montrent que l'endocytose en phase fluide des cellules en culture est stimulée de 1.4 fois environ sous GSM, pour des DAS moyens au-dessus de valeurs seuil entre 1.3 et 2.6W/kg, sans augmentation de température du milieu, dans deux systèmes d'exposition: une cellule fil-plaque et une cellule TEM, à 30C. L'endocytose dépendante de la clathrine est la voie d'incorporation endocytaire stimulée par les GSM. La composante électrique des GSM est à l'origine de cette stimulation. La durée totale de la mitose cellulaire et les durées des différentes phases mitotiques, aussi bien que la cinétique de succession de ces étapes ne sont pas modifiées par l'exposition pendant 1h aux GSM à DAS local de 2.2W/kg.This thesis reports the effects of electromagnetic GSM mobile phones pulses (900MHz, 217Hs, 576 s) with SAR (specific absorption rate) up to 4.6 W/kg on cellular endocytosis and mitosis. The results here presented report that the fluid phase endocytosis of different cells in culture is stimulated 1.4 fold under GSM exposure to average SARs above treshold values from 1.3 to 2.6W/kg without any bulk temperature increase. The effect was revealed using two exposure setups: a wire patch cell and a TEM cell, at 30C. The clathrin-mediated endocytosis is the endocytotic pathway perturbed by the GSM exposure. A similar stimulation was observed under exposure to electrical pulses comparable to GSM electrical component suggesting that this electrical component is at the origin of endocytosis perturbation. The GSM exposure of 2.2W/kg local SAR applied for 1h did not affect the mitosis progression, the total mitosis duration or each mitotic phase duration in our experimental conditions.CHATENAY M.-PARIS 11-BU Pharma. (920192101) / SudocSudocFranceF

Changes of cell electrical parameters induced by electroporation. A dielectrophoresis study

AbstractDielectrophoresis was employed to distinguish the electroporated from non-electroporated cells. It was found that the electric field frequency at which cells change the direction of their movement (the crossover frequency fCO) is higher when cells are electroporated. The contribution to the cell dielectrophoretic behavior of four electric and geometrical cell parameters was analyzed using a single shell model. fCO measurements were performed in media with conductivities of 0.001–0.09S/m, on B16F10 cells which were electroporated in a Mannitol solution (0.001S/m), using rectangular or exponential pulses. The control cells' fCO was found in a domain of 2 to 105kHz, while the electroporated cells' fCO was in a domain of 5 to 350kHz, depending on the external media conductivities. At exterior conductivities above ~0.02S/m, fCO of electroporated cells became significantly higher compared to controls. Even though the possible contribution of membrane permittivity to explain the observed fCO shift toward higher values cannot be excluded, the computations highlight the fact that the variation of cytosol conductivity might be the major contributor to the dielectrophoretic behavior change. Our experimental observations can be described by considering a linear dependence of electroporated cells' cytosol conductivity against external conductivity

900 MHz Modulated Electromagnetic Fields Accelerate the Clathrin-Mediated Endocytosis Pathway

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Microscopic observation of living cells during their exposure to modulated electromagnetic fields

Studying cell behaviour under irradiation with radiofrequency electromagnetic fields (RF-EMF) is often impeded by the difficulty to monitor cell characteristics during irradiation. Here we report the design and the application of a complete device for continuous microscopic observation of cells exposed to modulated EMF similar to mobile phones signals. The system allows the follow up of cell progression into mitosis under controlled temperature and CO(2) environment. Protocols are proposed in which the same cells are the controls before and after the EMF exposure and we demonstrate the interest of the "before exposure" controls. The exposure system was validated by cell endocytosis measurements. While the endocytosis rate was increased, no alteration of mitosis progression and mitosis duration was observed in cells exposed to 900 MHz modulated EMF for 1 h, at 30 degrees C and at a Specific Absorption Rate of 2.2 W/kg