The Role of Nonpharmacologic Device Interventions in the Management of Drug-Resistant Hypertension

Resistant systemic hypertension in patients is defined as the inability to control blood pressure despite taking at least three antihypertensive drugs, one of which is a diuretic. Two nonpharmacologic approaches are being evaluated in resistant hypertensive patients. First, the Rheos® Baroreflex Hypertension Therapy system is an implantable device that activates the carotid baroreflex through electrical stimulation of the carotid sinus wall. Sustained and clinically lower blood pressure has been observed in patient clinical trials. The second approach is a catheter-based strategy which denervates the renal afferent and efferent autonomic nervous system. This strategy has also been shown to be effective in drug-resistant patients, and has also been shown to decrease renin production, preserve renal function, improve glucose tolerance, and reduce left ventricular hypertrophy. Both carotid sinus stimulation and renal denervation are now being evaluated in clinical trials for the long-term control of hypertension

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

International audienceIn 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field