Effect of Calcium-Channel Blockade on the Aldosterone Response to Sodium Depletion and Potassium Loading in Man

Angiotensin II (Ang II) and potassium (K+) increase aldosterone (Aldo) production in vitro via Ca2+-dependent mechanisms. To determine the effects of Ca2+ antagonism in vivo, we examined the influence of nifedipine on the Aldo response to Na+ depletion and K+ loading in 11 healthy subjects. On the fifth day of a low-Na+/high-K+ diet (10 mmol Na+/100 mmol K+) the subjects were randomly given either nifedipine 30 mg po or placebo, and on the sixth day they received the alternative drug. KCl in 5% glucose was infused on days 5 and 6 from 10:00 to 12:00 AM(0.6 mmol/kg over 2 hours). Dexamethasone was given to suppress adrenal corticotrophic hormone. Plasma renin activity (PRA) and plasma Aldo were determined every 20 minutes. Nifedipine induced a rise in heart rate at 60 minutes but did not change blood pressure. During KCl/glucose infusions, plasma glucose increased significantly, but plasma K+ remained stable. PRA, but not baseline plasma Aldo, was stimulated by nifedipine. KCl provoked a significant and similar Aldo rise (P < .01) under placebo and nifedipine. Baseline Aldo/PRA ratio was reduced under nifedipine when compared to placebo (P < .01), whereas during KCl infusions this ratio was similarly elevated under placebo and nifedipine. We conclude that acute inhibition of slow Ca2+ channels does not interfere with K+-induced Aldo secretion in man, suggesting that adaptive mechanisms operate in vivo. Am J Hypertens 1988;1:245-24

Coordination of Emergency Medical Services for a Major Road Traffic Accident on a Swiss Suburban Highway

Abstract : On 9th April 2008 at 2:14 p.m., on the highway between Lausanne and Vevey in western Switzerland, there was a 72-car pileup including five trucks that caused one death and injured 26 others. The relatively light toll was attributed to reduced vehicular speeds on account of foggy weather, together with the quick actions and effectiveness of the first responders and the excellent collaboration between the various rescue groups (medical rescue services, fire and police departments). For the first time, we used an innovative on-site medical command and control system, based on a binomial team. Two hours after the accident, the last of the injured had been evacuated and first aid on the site had ended. This article describes how the Emergency Medical Services from the State of Vaud, Switzerland, handled the situation and how the binomial team is structure

Comment Darwin s’est transformé en singe.

Depuis la publication de L’origine des espèces au moyen de la sélection naturelle, ou La lutte pour l’existence dans la nature (raccourci plus loin en Origine ) en 1859, Charles Darwin personnifie à lui seul la théorie de la sélection naturelle, et l’évolution en général. Tout le monde connaît la face de l’homme mûr au crâne dégarni et à la grande barbe grise — le visage du naturaliste plusieurs années après la sortie de l’ Origine . L’impact de l’ouvrage fut ..

Postprandial hypotension and orthostatic blood pressure responses in elderly Parkinson's disease patients

OBJECTIVE: To investigate the change in systolic blood pressure (SBP) induced by meals and to compare their impact on the orthostatic SBP response in elderly Parkinson's disease with that in control patients. DESIGN: Ten elderly patients suffering from Parkinson's disease were compared with 10 age-matched elderly control patients. METHODS: The postprandial SBP change was measured by means of ambulatory blood pressure monitoring with the patient in the supine position. Orthostatic SBP responses were measured the next day by means of active standing and passive head-up tilting tests performed before and after the patients had their lunch. RESULTS: In Parkinson's disease patients, a postprandial SBP drop of 27 mmHg in the supine position was found compared with a drop of 8 mmHg in controls. In Parkinson's disease patients, that drop was moderately correlated to the orthostatic SBP responses and significantly correlated to the preprandial supine baseline SBP level. The orthostatic fall in SBP was greater with passive than with active standing and with both it was greater in Parkinson's disease patients than in the control subjects. The fall in orthostatic blood pressure was reduced by a previous meal. In contrast, there was no difference in orthostatic heart rate responses between the patients and the controls. CONCLUSIONS: Parkinson's disease patients demonstrated a significant postprandial drop in SBP and a tendency towards orthostatic hypotension, which was not worsened by the meal, probably owing to a stronger sympathetic activation. Postprandial supine SBP change and orthostatic SBP responses were only moderately associated in Parkinson's disease patients. In addition to autonomic dysfunction, an increased baseline SBP level might contribute to both phenomena

Human tissue engineering allows the identification of active miRNA regulators of glioblastoma aggressiveness

Glioblastoma multiforme (GBM) is among the most aggressive cancers associated with massive infiltration of peritumoral parenchyma by migrating tumor cells. The infiltrative nature of GBM cells, the intratumoral heterogeneity concomitant with redundant signaling pathways likely underlie the inability of conventional and targeted therapies to achieve long-term remissions. In this respect, microRNAs (miRNAs), which are endogenous small non-coding RNAs that play a role in cancer aggressiveness, emerge as possible relevant prognostic biomarkers or therapeutic targets for treatment of malignant gliomas. We previously described a tissue model of GBM developing into a stem cell-derived human Engineered Neural Tissue (ENT) that allows the study of tumor/host tissue interaction. Combined with high throughput sequencing analysis, we took advantage of this human and integrated tissue model to understand miRNAs regulation. Three miRNAs (miR-340, -494 and -1293) active on cell proliferation, adhesion to extracellular matrix and tumor cell invasion were identified in GBM cells developing within ENT, and also confirmed in GBM biopsies. The components of miRNAs regulatory network at the transcriptional and the protein level have been also revealed by whole transcriptome analysis and Tandem Mass Tag in transfected GBM cells. Notably, miR-340 has a clinical relevance and modulates the expression of miR-494 and -1293, emphasizing its biological significance. Altogether, these findings demonstrate that human tissue engineering modeling GBM development in neural host tissue is a suitable tool to identify active miRNAs. Collectively, our study identified miR-340 as a strong modulator of GBM aggressiveness which may constitute a therapeutic target for treatment of malignant gliomas