Nitric ocide mediates the blood pressure response to mental stress in humans

Objectif : Le monoxyde d'azote (NO) régule la pression artérielle en modulant le tonus vasculaire périphérique et l'activité sympathique vasoconstrictrice. La synthèse du NO est altérée dans plusieurs maladies cardiovasculaires importantes. La perte de l'effet vasodilatateur du NO et de son effet freinateur sur la décharge sympathique pourrait entraîner une réponse vasopressive exagérée au stress mental. Méthodes : Nous avons donc comparé les réponses sympathique (activité nerveuse musculaire sympathique) et hémodynamique au stress mental pendant une perfusion isotonique de NaCI et lors de l'administration d'un inhibiteur systémique de la NO- synthase (NG-monomethyl-L-arginine, L-NMMA). Résultats : Le résultat principal est que le stress mental qui pendant la perfusion saline augmente l'activité nerveuse sympathique d'environ 50% et la pression artérielle moyenne d'environ 15%, n'a eu aucun effet sympathoexcitateur et vasopresseur détectable lors de la perfusion de L-NMMA. Ces observations ne sont pas liées à une atteinte généralisée de la réponse hémodynamique et/ou sympathique lors de la perfusion de L-NMMA, car ces réponses étaient conservées lors de l'immersion de la main dans de l'eau glacée. Conclusions : Le stress mental induit des effets vasopresseurs et sympathoexcitateurs chez l'homme qui sont médiés par le NO. Ces résultats laissent penser que, contrairement à ce qui a été généralement supposé, le NO peut dans certaines circonstances augmenter la pression artérielle in vivo.

A user's guide to the encyclopedia of DNA elements (ENCODE).

The mission of the Encyclopedia of DNA Elements (ENCODE) Project is to enable the scientific and medical communities to interpret the human genome sequence and apply it to understand human biology and improve health. The ENCODE Consortium is integrating multiple technologies and approaches in a collective effort to discover and define the functional elements encoded in the human genome, including genes, transcripts, and transcriptional regulatory regions, together with their attendant chromatin states and DNA methylation patterns. In the process, standards to ensure high-quality data have been implemented, and novel algorithms have been developed to facilitate analysis. Data and derived results are made available through a freely accessible database. Here we provide an overview of the project and the resources it is generating and illustrate the application of ENCODE data to interpret the human genome.

Vaccine potentials of an intrinsically unstructured fragment derived from the blood stage-associated Plasmodium falciparum protein PFF0165c.

We have identified new malaria vaccine candidates through the combination of bioinformatics prediction of stable protein domains in the Plasmodium falciparum genome, chemical synthesis of polypeptides, in vitro biological functional assays, and association of an antigen-specific antibody response with protection against clinical malaria. Within the predicted open reading frame of P. falciparum hypothetical protein PFF0165c, several segments with low hydrophobic amino acid content, which are likely to be intrinsically unstructured, were identified. The synthetic peptide corresponding to one such segment (P27A) was well recognized by sera and peripheral blood mononuclear cells of adults living in different regions where malaria is endemic. High antibody titers were induced in different strains of mice and in rabbits immunized with the polypeptide formulated with different adjuvants. These antibodies recognized native epitopes in P. falciparum-infected erythrocytes, formed distinct bands in Western blots, and were inhibitory in an in vitro antibody-dependent cellular inhibition parasite-growth assay. The immunological properties of P27A, together with its low polymorphism and association with clinical protection from malaria in humans, warrant its further development as a malaria vaccine candidate.

Beyond intracranial pressure: optimization of cerebral blood flow, oxygen, and substrate delivery after traumatic brain injury.

Monitoring and management of intracranial pressure (ICP) and cerebral perfusion pressure (CPP) is a standard of care after traumatic brain injury (TBI). However, the pathophysiology of so-called secondary brain injury, i.e., the cascade of potentially deleterious events that occur in the early phase following initial cerebral insult-after TBI, is complex, involving a subtle interplay between cerebral blood flow (CBF), oxygen delivery and utilization, and supply of main cerebral energy substrates (glucose) to the injured brain. Regulation of this interplay depends on the type of injury and may vary individually and over time. In this setting, patient management can be a challenging task, where standard ICP/CPP monitoring may become insufficient to prevent secondary brain injury. Growing clinical evidence demonstrates that so-called multimodal brain monitoring, including brain tissue oxygen (PbtO2), cerebral microdialysis and transcranial Doppler among others, might help to optimize CBF and the delivery of oxygen/energy substrate at the bedside, thereby improving the management of secondary brain injury. Looking beyond ICP and CPP, and applying a multimodal therapeutic approach for the optimization of CBF, oxygen delivery, and brain energy supply may eventually improve overall care of patients with head injury. This review summarizes some of the important pathophysiological determinants of secondary cerebral damage after TBI and discusses novel approaches to optimize CBF and provide adequate oxygen and energy supply to the injured brain using multimodal brain monitoring.