Effects of the satiety signal oleoylethanolamide on binge-like food consumption in female rats

Several lines of evidence document the association between eating disorders and modern lifestyle, encompassing calorie-rich diets and psychological stress. Binge-eating disorder (BED) is a eating disorder characterized by excessive consumption of food in a short period of time, along with loss of control and psychological distress. Among the networks that partake in the neurobiological bases of BED a large body of evidence supports the activation of the hypothalamic-pituitary-adrenal stress (HPA) axis. Pharmacological treatments for BED are limited thus highlighting the need to identify novel targets that could lead to the development of more effective therapies. A large body of evidence has accumulated on the role played by the lipid signal oleoylethanolamide (OEA) as a pharmacological target for controlling aberrant eating disorders. As a drug, OEA reduces food intake and body weight gain in laboratory rodents by inducing a state of satiety. Additionaly, OEA dampens the hyperactivity of the HPA axis and ameliorates the effects of stress. On the bases of these premises, in the present study we investigated the effects of OEA on high palatable food (HPF) intake in a rat model of BED. Moreover, we assessed the impact of OEA on the corticotropin-releasing factor (CRF) system which plays a critical role in stress and on the oxytocinergic system which is crucial in mediating the pro-satiety effect of OEA. We used female rats with a history of intermittent food restriction which show binge-like palatable food consumption after the exposure to a “frustration stress”. On the test day, we either exposed or did not expose the rats to the sight of the palatable food (frustration stress) before assessing food consumption. OEA was administered at three different doses (2.5, 5, 10 mg/kg i.p.) and HPF intake was monitored over 2h. After the behavioural experiment brains were collected and in-situ hybridization experiment was performed to analyse CRF and oxytocin mRNA expression in selected brain areas. Our results demonstrate that OEA (10 mg/kg) was able to selectively prevent binge eating; the antibinge effect was accompained by a reduction of CRF mRNA within the central-amygdala. Finally, in keeping with our previous observations we found that the antibinge effect of OEA was accompanied by a significant increase of oxytocin mRNA at hypothalamic level. In the current study, we provide for the first time evidence to support that the endogenous fatty-gut lipid OEA exerts a selective inhibitory effects on binge-like eating behavior in female rats, supporting the hypothesis that OEA might represent a novel potential pharmacological target for the treatment of aberrant eating patterns

CDC in brief 2013

With the start of the 113th Congress, we\u2019d like to take an opportunity to (re)introduce the Centers for Disease Control and Prevention (CDC), and provide some helpful information about our agency and its work. This E-Brief contains links to useful information about CDC\u2019s science, budget, and presence on the ground. For quick access to additional information about CDC\u2019s work, please contact the CDC Washington Office at (202) 245-0600, and see below for information about how CDC Washington can help you.CS238048-6What CDC does -- Fast facts -- CDC on the ground -- How can CDC Washington help you?201

Olfactory receptor 984: a new target for obesity in rats and humans?

Aims: Obesity is a complex multifactorial and heterogeneous condition with an important genetic component matched with behavioral and environmental factors. Feeding behavior and body weight are controlled through complex interactions between the central nervous system (CNS) and peripheral organs. The aim of the present study was to identify and functionally characterize candidate gene/s involved in the development of resistance to diet-induced obesity (DIO) in rats. Methods: RNA Chip-Technology and genotype analysis was done in 10 visceral adipose tissue samples of DR (n=5) and DIO (n=5) rats. The most promising candidate gene, OR6C3 (orthologous with the rat Olr984 and mouse Olfr788) was measured by quantitative real-time PCR in adipocytes and stromal vascular fraction (SVF) from paired samples of human visceral and subcutaneous adipose tissue (AT) (n=225). Moreover, Olfr788 expression in 3T3-L1 adipocytes was measured after treatment with various hormones and cytokines. Results: Gene expression analyses showed Olr984 differently regulated in DIO-resistant rats. In the subcutaneous AT of human samples we found a down-regulation of OR6C3 compared to the visceral AT of the same population, independent of gender, glucose tolerance or type 2 diabetes. OR6C3 is more expressed in SVF than in adipocytes. Interestingly, treatment of 3T3-L1 cells with insulin decreased Olfr788 expression mRNA compared to untreated controls. Conclusions: Olr984 is a novel candidate gene related to diet-induced obesity in rats. Moreover, variation in human mRNA expression in AT is related to obesity parameters and glucose homeostasis, which might be attributed to the regulatory role of insulin on the Olr984

Deep Molecular Characterization of HIV-1 Dynamics under Suppressive HAART

In order to design strategies for eradication of HIV-1 from infected individuals, detailed insight into the HIV-1 reservoirs that persist in patients on suppressive antiretroviral therapy (ART) is required. In this regard, most studies have focused on integrated (proviral) HIV-1 DNA forms in cells circulating in blood. However, the majority of proviral DNA is replication-defective and archival, and as such, has limited ability to reveal the dynamics of the viral population that persists in patients on suppressive ART. In contrast, extrachromosomal (episomal) viral DNA is labile and as a consequence is a better surrogate for recent infection events and is able to inform on the extent to which residual replication contributes to viral reservoir maintenance. To gain insight into the diversity and compartmentalization of HIV-1 under suppressive ART, we extensively analyzed longitudinal peripheral blood mononuclear cells (PBMC) samples by deep sequencing of episomal and integrated HIV-1 DNA from patients undergoing raltegravir intensification. Reverse-transcriptase genes selectively amplified from episomal and proviral HIV-1 DNA were analyzed by deep sequencing 0, 2, 4, 12, 24 and 48 weeks after raltegravir intensification. We used maximum likelihood phylogenies and statistical tests (AMOVA and Slatkin-Maddison (SM)) in order to determine molecular compartmentalization. We observed low molecular variance (mean variability ≤0.042). Although phylogenies showed that both DNA forms were intermingled within the phylogenetic tree, we found a statistically significant compartmentalization between episomal and proviral DNA samples (P<10−6 AMOVA test; P = 0.001 SM test), suggesting that they belong to different viral populations. In addition, longitudinal analysis of episomal and proviral DNA by phylogeny and AMOVA showed signs of non-chronological temporal compartmentalization (all comparisons P<10−6) suggesting that episomal and proviral DNA forms originated from different anatomical compartments. Collectively, this suggests the presence of a chronic viral reservoir in which there is stochastic release of infectious virus and in which there are limited rounds of de novo infection. This could be explained by the existence of different reservoirs with unique pharmacological accessibility properties, which will require strategies that improve drug penetration/retention within these reservoirs in order to minimise maintenance of the viral reservoir by de novo infection

The influence of alkalosis on repeated high-intensity exercise performance and acid–base balance recovery in acute moderate hypoxic conditions

Purpose Exacerbated hydrogen cation (H⁺) production is suggested to be a key determinant of fatigue in acute hypoxic conditions. This study, therefore, investigated the effects of NaHCO3 ingestion on repeated 4 km TT cycling performance and post-exercise acid–base balance recovery in acute moderate hypoxic conditions. Methods Ten male trained cyclists completed four repeats of 2 × 4 km cycling time trials (TT1 and TT2) with 40 min passive recovery, each on different days. Each TT series was preceded by supplementation of one of the 0.2 g kg⁻¹ BM NaHCO3 (SBC2), 0.3 g kg⁻¹ BM NaHCO3 (SBC3), or a taste-matched placebo (0.07 g kg⁻¹ BM sodium chloride; PLA), administered in a randomized order. Supplements were administered at a pre-determined individual time to peak capillary blood bicarbonate concentration ([HCO3⁻]). Each TT series was also completed in a normobaric hypoxic chamber set at 14.5% FiO2 (~ 3000 m). Results Performance was improved following SBC3 in both TT1 (400.2 ± 24.1 vs. 405.9 ± 26.0 s; p = 0.03) and TT2 (407.2 ± 29.2 vs. 413.2 ± 30.8 s; p = 0.01) compared to PLA, displaying a very likely benefit in each bout. Compared to SBC2, a likely and possible benefit was also observed following SBC3 in TT1 (402.3 ± 26.5 s; p = 0.15) and TT2 (410.3 ± 30.8 s; p = 0.44), respectively. One participant displayed an ergolytic effect following SBC3, likely because of severe gastrointestinal discomfort, as SBC2 still provided ergogenic effects. Conclusion NaHCO3 ingestion improves repeated exercise performance in acute hypoxic conditions, although the optimal dose is likely to be 0.3 g kg⁻¹ BM

Critical review on biofilm methods

Biofilms are widespread in nature and constitute an important strategy implemented by microorganisms to survive in sometimes harsh environmental conditions. They can be beneficial or have a negative impact particularly when formed in industrial settings or on medical devices. As such, research into the formation and elimination of biofilms is important for many disciplines. Several new methodologies have been recently developed for, or adapted to, biofilm studies that have contributed to deeper knowledge on biofilm physiology, structure and composition. In this review, traditional and cutting-edge methods to study biofilm biomass, viability, structure, composition and physiology are addressed. Moreover, as there is a lack of consensus among the diversity of techniques used to grow and study biofilms. This review intends to remedy this, by giving a critical perspective, highlighting the advantages and limitations of several methods. Accordingly, this review aims at helping scientists in finding the most appropriate and up-to-date methods to study their biofilms.The authors would like to acknowledge the support from the EU COST Action BacFoodNet FA1202

Socio-demographic determinants of coinfections by HIV, hepatitis B and hepatitis C viruses in central Italian prisoners

BACKGROUND: The coinfections HIV/HCV/HBV are an important health issue in penitentiary communities. The aim of the study was to examine HIV, HBV and HCV coinfections determinants amongst prisoners in the jails of Southern Lazio (Central Italy), in the period 1995-2000. METHODS: Diagnosis of seropositivities for HIV, HBV and HCV was made using ELISA method. A multiple logistic regression analysis was conducted to verify the influence of socio-demographic factors on the HIV/HBV/HCV coinfections. RESULTS: HIV/HCV, HBV/HCV and HIV/HBV coinfections were detected in 42 (4%), 203 (17.9%) and 31 (2.9%) inmates, respectively. These coinfections are significantly associated with the status of drug addiction (OR = 16.02; p = 0.012; OR = 4.15; p &lt; 0.001; OR = 23.57; p = 0.002), smoking habits (OR = 3.73; p = 0.033; OR = 1.42; p = 0.088; OR = 4.25; p = 0.053) and Italian nationality (OR = 7.05; p = 0.009; OR = 2.31; p &lt; 0.001; OR = 4.61; p = 0.04). CONCLUSION: The prevalence of HIV, HBV and HCV seropositivity in jails suggests that information and education programs for inmates could be useful to reduce the spread of such infections

Cooperation in wild Barbary macaques: factors affecting free partner choice

A key aspect of cooperation is partner choice: choosing the best available partner improves the chances of a successful cooperative interaction and decreases the likelihood of being exploited. However, in studies on cooperation subjects are rarely allowed to freely choose their partners. Group-living animals live in a complex social environment where they can choose among several social partners differing in, for example, sex, age, temperament, or dominance status. Our study investigated whether wild Barbary macaques succeed to cooperate using an experimental apparatus, and whether individual and social factors affect their choice of partners and the degree of cooperation. We used the string pulling task that requires two monkeys to manipulate simultaneously a rope in order to receive a food reward. The monkeys were free to interact with the apparatus or not and to choose their partner. The results showed that Barbary macaques are able to pair up with a partner to cooperate using the apparatus. High level of tolerance between monkeys was necessary for the initiation of successful cooperation, while strong social bond positively affected the maintenance of cooperative interactions. Dominance status, sex, age, and temperament of the subjects also affected their choice and performance. These factors thus need to be taken into account in cooperative experiment on animals. Tolerance between social partners is likely to be a prerequisite for the evolution of cooperation

Carbon Monoxide Promotes Respiratory Hemoproteins Iron Reduction Using Peroxides as Electron Donors

The physiological role of the respiratory hemoproteins (RH), hemoglobin and myoglobin, is to deliver O2 via its binding to their ferrous (FeII) heme-iron. Under variety of pathological conditions RH proteins leak to blood plasma and oxidized to ferric (FeIII, met) forms becoming the source of oxidative vascular damage. However, recent studies have indicated that both metRH and peroxides induce Heme Oxygenase (HO) enzyme producing carbon monoxide (CO). The gas has an extremely high affinity for the ferrous heme-iron and is known to reduce ferric hemoproteins in the presence of suitable electron donors. We hypothesized that under in vivo plasma conditions, peroxides at low concentration can assist the reduction of metRH in presence of CO. The effect of CO on interaction of metRH with hydrophilic or hydrophobic peroxides was analyzed by following Soret and visible light absorption changes in reaction mixtures. It was found that under anaerobic conditions and low concentrations of RH and peroxides mimicking plasma conditions, peroxides served as electron donors and RH were reduced to their ferrous carboxy forms. The reaction rates were dependent on CO as well as peroxide concentrations. These results demonstrate that oxidative activity of acellular ferric RH and peroxides may be amended by CO turning on the reducing potential of peroxides and facilitating the formation of redox-inactive carboxyRH. Our data suggest the possible role of HO/CO in protection of vascular system from oxidative damage

Dopamine Receptor Activation Increases HIV Entry into Primary Human Macrophages

Macrophages are the primary cell type infected with HIV in the central nervous system, and infection of these cells is a major component in the development of neuropathogenesis and HIV-associated neurocognitive disorders. Within the brains of drug abusers, macrophages are exposed to increased levels of dopamine, a neurotransmitter that mediates the addictive and reinforcing effects of drugs of abuse such as cocaine and methamphetamine. In this study we examined the effects of dopamine on HIV entry into primary human macrophages. Exposure to dopamine during infection increased the entry of R5 tropic HIV into macrophages, irrespective of the concentration of the viral inoculum. The entry pathway affected was CCR5 dependent, as antagonizing CCR5 with the small molecule inhibitor TAK779 completely blocked entry. The effect was dose-dependent and had a steep threshold, only occurring above 108 M dopamine. The dopamine-mediated increase in entry required dopamine receptor activation, as it was abrogated by the pan-dopamine receptor antagonist flupenthixol, and could be mediated through both subtypes of dopamine receptors. These findings indicate that the effects of dopamine on macrophages may have a significant impact on HIV pathogenesis. They also suggest that drug-induced increases in CNS dopamine may be a common mechanism by which drugs of abuse with distinct modes of action exacerbate neuroinflammation and contribute to HIV-associated neurocognitive disorders in infected drug abusers