Potential role of the endocannabinoid receptor antagonist rimonabant in the management of cardiometabolic risk: a narrative review of available data

The endocannabinoid system (ECS) is an endogenous physiological system composed of two cannabinoid receptors and several endogenous ligands. The ECS is intimately involved in appetite regulation and energy homeostasis, which makes it an intriguing target for pharmacological treatment of obesity, diabetes, and the metabolic syndrome. Rimonabant is the first cannabinoid receptor (CB-1) antagonist being studied and utilized to treat obesity (it is approved in Europe but is currently under review in the United States). Large randomized trials with rimonabant have demonstrated efficacy in treatment of overweight and obese individuals with weight loss significantly greater than a reduced calorie diet alone. In addition, multiple other cardiometabolic parameters were improved in the treatment groups including increased levels of high density lipoprotein cholesterol, reduced triglycerides, reduced waist circumference, improved insulin sensitivity, decreased insulin levels, and in diabetic patients improvement in glycosylated hemoglobin percentage. There was an increase in the adverse effects of depression, anxiety, irritability, and nausea in rimonabant-treated groups. This novel medication may become an important therapeutic option in the fight to reduce cardiovascular disease worldwide through its unique action on cardiometabolic risk

Immunocompetent murine models for the study of glioblastoma immunotherapy.

Glioblastoma remains a lethal diagnosis with a 5-year survival rate of less than 10%. (NEJM 352:987-96, 2005) Although immunotherapy-based approaches are capable of inducing detectable immune responses against tumor-specific antigens, improvements in clinical outcomes are modest, in no small part due to tumor-induced immunosuppressive mechanisms that promote immune escape and immuno-resistance. Immunotherapeutic strategies aimed at bolstering the immune response while neutralizing immunosuppression will play a critical role in improving treatment outcomes for glioblastoma patients. In vivo murine models of glioma provide an invaluable resource to achieving that end, and their use is an essential part of the preclinical workup for novel therapeutics that need to be tested in animal models prior to testing experimental therapies in patients. In this article, we review five contemporary immunocompetent mouse models, GL261 (C57BL/6), GL26 (C57BL/6) CT-2A (C57BL/6), SMA-560 (VM/Dk), and 4C8 (B6D2F1), each of which offer a suitable platform for testing novel immunotherapeutic approaches

Relationship of Dropout and Psychopathology in a High School Sample in Mexico

School dropout has significant consequences for both individuals and societies. Only 21% of adults in Mexico achieve the equivalent of a high school education. We examined the relationship between school dropout and self-reported psychiatric symptoms in a middle school in a suburb of Mexico City. We used binomial logistic regression to examine the odds ratio (OR) of school dropout associated with students’ self-reported psychopathology. Two-hundred thirty-seven students participated in the study. Psychosis [OR = 8.0 (95% confidence interval, CI: 1.7–37.2)], depression [OR = 4.7 (95% CI: 2.2–9.7)], tic disorders [OR = 3.7 (95% CI: 1.4–9.5)], ADHD [OR = 3.2 (95% CI: 1.5–6.4)], and social phobia [OR = 2.6 (95% CI: 1.2–5.8)] were associated with increased risk of school dropout after controlling for age and gender as covariates. Our study suggested that students’ self-reported psychopathology is associated with increased school dropout in Mexico. ADHD and depression may be particularly useful childhood psychiatric disorders to target with public health interventions because they explain the greatest amount of the variance in school dropout of child psychiatric disorders

Measuring the temporal coherence of an atom laser beam

We report on the measurement of the temporal coherence of an atom laser beam extracted from a $^{87}$Rb Bose-Einstein condensate. Reflecting the beam from a potential barrier creates a standing matter wave structure. From the contrast of this interference pattern, observed by magnetic resonance imaging, we have deduced an energy width of the atom laser beam which is Fourier limited by the duration of output coupling. This gives an upper limit for temporal phase fluctuations in the Bose-Einstein condensate.Comment: 4 pages, 3 figure

Optics with an Atom Laser Beam

We report on the atom optical manipulation of an atom laser beam. Reflection, focusing and its storage in a resonator are demonstrated. Precise and versatile mechanical control over an atom laser beam propagating in an inhomogeneous magnetic field is achieved by optically inducing spin-flips between atomic ground states with different magnetic moment. The magnetic force acting on the atoms can thereby be effectively switched on and off. The surface of the atom optical element is determined by the resonance condition for the spin-flip in the inhomogeneous magnetic field. A mirror reflectivity of more than 98% is measured

Shear Stress Ameliorates Superoxide Impairment to Erythrocyte Deformability With Concurrent Nitric Oxide Synthase Activation

The cellular deformability of red blood cells (RBC) is exceptional among mammalian cells and facilitates nutrient delivery throughout the microcirculation; however, this physical property is negatively impacted by oxidative stress. It remains unresolved whether the molecular determinants of cellular deformability – which in the contemporary model of RBC are increasingly recognized – are sensitive to free radicals. Moreover, given cellular deformability has recently been demonstrated to increase following exposure to specific doses of mechanical stimulation, the potential for using shear “conditioning” as a novel method to reverse free-radical induced impairment of cell mechanics is of interest. We thus designed a series of experiments that explored the effects of intracellular superoxide (O2-) generation on the deformability of RBC and also activation of pivotal molecular pathways known to regulate cell mechanics – i.e., PI3K/Akt kinase and RBC nitric oxide synthase (NOS). In addition, RBC exposed to O2- were conditioned with specific shear stresses, prior to evaluation of cellular deformability and activation of PI3K/Akt kinase and RBC-NOS. Intracellular generation of O2- decreased phosphorylation of RBC-NOS at its primary activation site (Ser1177) (p < 0.001), while phosphorylation of Akt kinase at its active residue (Ser473) was also diminished (p < 0.001). Inactivation of these enzymes following O2- exposure occurred in tandem with decreased RBC deformability. Shear conditioning significantly improved cellular deformability, even in RBC previously exposed to O2-. The improvement in cellular deformability may have been the result of enhanced molecular signaling, given RBC-NOS phosphorylation in RBC exposed to O2- was restored following shear conditioning. Impaired RBC deformability induced by intracellular O2- may be due, in part, to impaired activation of PI3K/Akt, and downstream signaling with RBC-NOS. These findings may shed light on improved circulatory health with targeted promotion of blood flow (e.g., exercise training), and may prove fruitful in future development of blood-contacting devices

Experimental decoupling of canopy opening and debris addition on tropical gastropod populations and communities

a b s t r a c t Climate-induced disturbances such as hurricanes affect the structure and functioning of many ecosystems, especially those in the Caribbean Basin, where effects are well documented with regard to biodiversity and biogeochemical dynamics. Because climate change will likely alter the frequency or intensity of such storms, it is increasingly important to understand the mechanistic bases for ecosystem responses. However, this is particularly difficult to do in the absence of manipulative experiments that decouple confounded factors such as canopy opening and debris deposition. To address this issue, we exploited a replicated factorial design to experimentally distinguish the effects of canopy opening and debris deposition on population-and community-level characteristics of gastropods in the Luquillo Experimental Forest of Puerto Rico. Despite considerable spatial variation, abundances of all gastropods (combined) as well as abundances of each of 3 species (i.e., Alcadia striata, Platysuccinea portoricensis, and Polydontes acutangula) responded significantly to canopy opening while abundances of each of 2 species (i.e., Pl. portoricensis, and Po. acutangula) responded significantly to debris deposition within two years of experimental manipulation. In contrast, two species (i.e., Gaeotis nigrolineata and Nenia tridens) did not respond to any experimental manipulations in the short term. Moreover, species composition did not differ between pre-and post-manipulation periods, in part because of considerable variation among replicated blocks. In contrast, canopy removal consistently affected species richness, Shannon diversity, and rarity, while debris deposition consistently affected species richness and Shannon diversity. Neither treatment affected species dominance or evenness. Longer-term responses of the gastropod fauna were more complex. Although considerable interspecific heterogeneity characterized responses of the gastropod fauna, temporal variation in mean abundance for each of the three manipulative treatments was similar to that of the non-manipulated treatment when abundances were combined for all species. In contrast, temporal variation in each of the manipulative treatments was unrelated to temporal variation in the non-manipulated treatment for species richness, evenness, dominance, and rarity. Moreover, temporal variation in abundance generally differed between at least two of the manipulative treatments for most species and temporal variation in components of taxonomic biodiversity generally differed between manipulative treatments as well. Temporal variation in species composition was considerable and comparable for each of the four treatment combinations. Species composition within each treatment combination varied over time in ways unrelated to temporal variation in the other treatment combinations, including the reference treatment (i.e., no canopy trimming and no debris addition). Manipulated treatments were surrounded by large areas of intact forest, and tabonuco forest generally exhibits appreciable spatial and temporal variation. Natural spatiotemporal variation in the study system likely overwhelmed many of the effects of experimental manipulations on gastropod populations or communities via edge effects and recruitment of individuals from nearby less disturbed portions of the landscape