Progesterone activates fatty acid amide hydrolase (FAAH) promoter in human T lymphocytes through the transcription factor Ikaros. Evidence for a synergistic effect of leptin.

Physiological concentrations of progesterone stimulate the activity of the endocannabinoid-degrading enzyme fatty acid amide hydrolase (FAAH) in human T lymphocytes, up to a ∼270% over the untreated controls. Stimulation of FAAH occurred through up-regulation of gene expression at transcriptional and translational level and was specific. Indeed, neither the activity of the anandamide-synthesizing N-acyltransferase and phospholipase D, nor the activity of the anandamide transporter, nor the binding to cannabinoid receptors were affected by progesterone under the same experimental conditions. The activation of FAAH by progesterone was paralleled by a decrease (down to 60%) of the cellular levels of anandamide and involved increased nuclear levels of the transcription factor Ikaros. Analysis of the FAAH promoter showed an Ikaros binding site, and mutation of this site prevented FAAH activation by progesterone in transient expression assays. Electrophoretic mobility shift and supershift assays further corroborated the promoter activity data. Furthermore, the effect of progesterone on FAAH promoter was additive to that of physiological amounts of leptin, which binds to a cAMP response element-like site in the promoter region. Taken together, these results suggest that progesterone and leptin, by up-regulating the FAAH promoter at different sites, enhance FAAH expression, thus tuning the immunomodulatory effects of anandamide. These findings might also have critical implications for human fertility

Recognition of Cherenkov patterns in high multiplicity environments

An algorithm for the recognition of Cherenkov patterns based on the Hough Transform Method (HTM), modified for signals with intrinsic width in presence of background, is presented. The method basically consists in a mapping of the pad coordinate space directly to the Cherenkov angle parameter space with a crucial increase of performance in the treatment of different pattern shapes and amount of background. The method has been developed in the framework of the ALICE experiment at CERN for the analysis of data taken in the HMPID (High Momentum Particle IDentification) RICH detector prototype test beam

Anandamide Uptake by Human Endothelial Cells and Its Regulation by Nitric Oxide

Anandamide (AEA) has vasodilator activity, which can be terminated by cellular re-uptake and degradation. Here we investigated the presence and regulation of the AEA transporter in human umbelical vein endothelial cells (HUVECs). HUVECs take up AEA by facilitated transport (apparent K(m) = 190 +/- 10 nm and V(max) = 45 +/- 3 pmol. min(-1).mg(-1) protein), which is inhibited by alpha-linolenoyl-vanillyl-amide and N-(4-hydroxyphenyl)-arachidonoylamide, and stimulated up to 2.2-fold by nitric oxide (NO) donors. The NO scavenger hydroxocobalamin abolishes the latter effect, which is instead enhanced by superoxide anions but inhibited by superoxide dismutase and N-acetylcysteine, a precursor of glutathione synthesis. Peroxynitrite (ONOO(-)) causes a 4-fold activation of AEA transport into cells. The HUVEC AEA transporter contributes to the termination of a typical type 1 cannabinoid receptor (CB(1)) -mediated action of AEA, i.e. the inhibition of forskolin-stimulated adenylyl cyclase, because NO/ONOO(-) donors and alpha-linolenoyl-vanillyl-amide/N-(4-hydroxyphenyl)-arachidonoylamide were found to attenuate and enhance, respectively, this effect of AEA. Consistently, activation of CB(1) cannabinoid receptors by either AEA or the cannabinoid HU-210 caused a stimulation of HUVEC inducible NO synthase activity and expression up to 2.9- and 2. 6-fold, respectively. Also these effects are regulated by the AEA transporter. HU-210 enhanced AEA uptake by HUVECs in a fashion sensitive to the NO synthase inhibitor Nomega-nitro-l-arginine methyl ester. These findings suggest a NO-mediated regulatory loop between CB(1) cannabinoid receptors and AEA transporter

The complex issue of medication management in older persons: a challenge for nurses

With increasing life expectancy, the share of older persons with coexisting multiple chronic degenerative diseases (comorbidity / multimorbidity) is expanding. These conditions require the use of multiple drugs, leading to polypharmacy, which plays a central role in making the therapeutic approach to the elderly particularly complex, together with age-related changes in pharmacokinetics and pharmacodynamics. Physicians and nurses both are challenged by polypharmacy and by the other drug-related issues involving older patients, in all care settings. In particular, nurses should be aware of the main issues of pharmacotherapy in older persons, because they are often the frontline for older patients care, especially in nursing homes. This review addresses the main issues related to pharmacotherapy in late life, such as pharmacokinetics and pharmacodynamics changes, limitations of evidence-based medicine, polypharmacy, drug interactions, adverse drug reactions, and lack of adherence. Focus will be on how these problems may impact on nursing, and on what nurses should know and do to improve drug treatment of older patients. In the last decade, the role and responsibilities of nurses in the management of drug therapy have significantly changed in most countries. There is consensus in educational programs and legislation that the preparation and administration of medications are essential aspects of nursing practice. These are considered as collaborative tasks with physicians and not purely mechanistic tasks. The nurse must intervene in the event of a perceived error, and he/she must report doubts about congruity or relevance of the therapy. Although nursing students gain knowledge and develop skills on drug therapy during their education, these are often perceived as insufficient. The need for post-graduation continuing education should be also emphasized. Thus, graduate and post-graduate educational programs should be developed, in order to offer adequate answers to the increasing and challenging share of older patients seen in clinical practice

A pattern recognition method for the RICH-based HMPID detector in ALICE

A pattern recognition method developed for the High Momentum Particle IDentification (HMPID) detector in the ALICE experiment at CERN is presented. The algorithm is based on the Hough transform with a mapping of the pad coordinate space directly to the Cherenkov angle parameter space. Cherenkov angle reconstruction has been studied as a function of different particle densities in the photodetector using real data taken in the ALICE tests at the CERN SPS: a satisfactory resolution can be achieved even in events where the occupancy reaches more than 12, which is the situation we may be confronted with in central Pb-Pb interactions at LHC. (9 refs)

DAPT plus anticoagulant therapy: The difficult coexistence post-ACS in older patients with atrial fibrillation

Atrial fibrillation (AF) and coronary artery disease requiring percutaneous coronary intervention (PCI) and stenting often coexist in older patients. This poses the difficult problem of concurrent anticoagulant and double antiplatelet therapy (triple therapy). Current treatment guidelines do recommend triple therapy, especially in the course of acute coronary syndrome (ACS), with limitations due to an excessive risk of bleeding associated with this therapeutic regimen. This review summarizes randomized clinical trials and observational studies that compared triple therapy with a variety of different therapeutic options. Although the available evidence is not completely satisfactory and other studies are urgently needed, alternative regimens to triple therapy in AF patients undergoing PCI and stenting are promising, at least in terms of safety