Involvement and neuroplasticity of cholinergic interneurons of the nucleus accumbens in initiation and excessive alcohol drinking

Alcoholism is a complex disease that exists as a specific set of behaviors, such as the preoccupation with obtaining alcohol and compulsive alcohol drinking. Currently, more than 18 million adults in the United States suffer from alcohol abuse or alcoholism. This disease poses serious medical and economic consequences for society. Identifying the neurobiological mechanisms that underlie alcohol drinking, specifically the transition from initiation to binge drinking is critical for improved treatments for alcoholics and the vulnerability for relapse in those recovering. Many studies have identified brain regions and molecular mechanisms that underlie various stages of alcohol abuse; however few have investigated the role of specific cell types within these areas. The overarching hypothesis of the studies in this dissertation is that cholinergic interneurons of the nucleus accumbens (NAc) are key neural substrates that underlie alcohol drinking, and as drinking continues; neuroadaptations within these cells then facilitate such behaviors as compulsive alcohol drinking. More specifically, these studies tested whether 1) cholinergic cell ablation in the NAc causes a decrease in alcohol drinking in C57BL/6J mice, 2) neuroadaptive changes in dopamine (DA) D2 receptor and cyclin dependent kinase 5 (Cdk5) occur within these cells following initiation alcohol drinking, and to a greater extent following binge alcohol drinking in C57BL/6J mice, and 3) neuroadaptive changes in DA D2 receptor and Cdk5 also occur in brain regions that have been implicated in the rewarding and reinforcing effects of alcohol in inbred alcohol-preferring (iP) rats. The present findings report a causal role for accumbal cholinergic neurons in binge alcohol drinking and identify DA D2 receptor and Cdk5 neuroadaptations following initiation and binge alcohol drinking. These studies identify the involvement of cholinergic interneurons in binge drinking and reveal alcohol-induced region- and cell-specific receptor and molecular changes that occur with continued drinking. These findings contribute to the understanding of the neurobiological mechanisms that underlie alcohol drinking, and provide the basis for cholinergic targeted treatments designed to attenuate binge drinking. These data also provide the groundwork for future studies aimed to examine receptor and intracellular molecular changes that occur with compulsive alcohol drinking, craving, and relapse.Psycholog

Cell systems to investigate the impact of polyphenols on cardiovascular health

Polyphenols are a diverse group of micronutrients from plant origin that may serve as antioxidants and that contribute to human health in general. More specifically, many research groups have investigated their protective effect against cardiovascular diseases in several animal studies and human trials. Yet, because of the excessive processing of the polyphenol structure by human cells and the residing intestinal microbial community, which results in a large variability between the test subjects, the exact mechanisms of their protective effects are still under investigation. To this end, simplified cell culture systems have been used to decrease the inter-individual variability in mechanistic studies. In this review, we will discuss the different cell culture models that have been used so far for polyphenol research in the context of cardiovascular diseases. We will also review the current trends in cell culture research, including co-culture methodologies. Finally, we will discuss the potential of these advanced models to screen for cardiovascular effects of the large pool of bioactive polyphenols present in foods and their metabolites

Obesity and Vegetarianism in Seventh-day Adventist Women

This thesis describes a comparative study of 82 vegetarian and 21 non-vegetarian Seventh-day Adventist females ages 25 to 65 to discover if there is a possible correlation between diet and weight. The subjects were chosen by random sampling in the specified target population and were personally interviewed by the use of a questionnaire. The general linear hypothesis analysis shewed that present age and relative weight at age 25 were significant in terms of present relative weight; however, physical activity and socioeconomic stratum were not significant. Diet, defined as vegetarian or non-vegetarian, was only marginally significant. Conclusions of this study are that weight at age 25 and present age are important associated factors in present weight

Co-ingestion of black carrot and strawberry : effects on anthocyanin stability, bioaccessibility and uptake

Although the fate of anthocyanins along digestion has been a matter of research over the last decade, their bioaccessibility so far has been mainly assessed for single administered fruits or vegetables, which is far from the real scenario where they are co-ingested in a meal. Accordingly, the aim of this study was to evaluate the effect of simultaneous intake of fruit and vegetable on in vitro stability, bioaccessibility and uptake of anthocyanins. Black carrot and strawberry were used as food sources of anthocyanins. Anthocyanin identification and quantification were performed using HPLC-Qtof/HPLC-UV. Single matrices and mixtures thereof, were submitted to a standardized in vitro digestion procedure. Anthocyanin uptake was evaluated through an intestinal Caco-2 cell model. Our results showed an increased intestinal stability for specific anthocyanins as a consequence of co-digestion. The presence of the strawberry food matrix positively affected the bioaccessibility of the carrot associated cyanidin-based anthocyanins, whereas no reciprocal effect was observed for pelargonidin-based derivatives in the presence of the black carrot food matrix. Anthocyanin transport was maintained after co-administration. Overall, co-ingestion of black carrot and strawberry did not negatively affect the stability, bioaccessibility or uptake of cyanidin-based anthocyanins, although the effect on pelargonidin-based anthocyanins depended on the type of pelargonidin derivative

Resveratrol improves TNF-α-induced endothelial dysfunction in a coculture model of a Caco-2 with an endothelial cell line

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Seasonal temperature acclimatization in a semi-fossorial mammal and the role of burrows as thermal refuges.

Small mammals in habitats with strong seasonal variation in the thermal environment often exhibit physiological and behavioral adaptations for coping with thermal extremes and reducing thermoregulatory costs. Burrows are especially important for providing thermal refuge when above-ground temperatures require high regulatory costs (e.g., water or energy) or exceed the physiological tolerances of an organism. Our objective was to explore the role of burrows as thermal refuges for a small endotherm, the pygmy rabbit (Brachylagus idahoensis), during the summer and winter by quantifying energetic costs associated with resting above and below ground. We used indirect calorimetry to determine the relationship between energy expenditure and ambient temperature over a range of temperatures that pygmy rabbits experience in their natural habitat. We also measured the temperature of above- and below-ground rest sites used by pygmy rabbits in eastern Idaho, USA, during summer and winter and estimated the seasonal thermoregulatory costs of resting in the two microsites. Although pygmy rabbits demonstrated seasonal physiological acclimatization, the burrow was an important thermal refuge, especially in winter. Thermoregulatory costs were lower inside the burrow than in above-ground rest sites for more than 50% of the winter season. In contrast, thermal heterogeneity provided by above-ground rest sites during summer reduced the role of burrows as a thermal refuge during all but the hottest periods of the afternoon. Our findings contribute to an understanding of the ecology of small mammals in seasonal environments and demonstrate the importance of burrows as thermal refuge for pygmy rabbits

The impact of severe haemophilia and the presence of target joints on health-related quality-of-life

Background: Joint damage remains a major complication associated with haemophilia and is widely accepted as one of the most debilitating symptoms for persons with severe haemophilia. The aim of this study is to describe how complications of haemophilia such as target joints influence health-related quality of life (HRQOL). Methods: Data on hemophilia patients without inhibitors were drawn from the ‘Cost of Haemophilia across Europe – a Socioeconomic Survey’ (CHESS) study, a cost-of-illness assessment in severe haemophilia A and B across five European countries (France, Germany, Italy, Spain, and the UK). Physicians provided clinical and sociodemographic information for 1285 adult patients, 551 of whom completed corresponding questionnaires, including EQ-5D. A generalised linear model was developed to investigate the relationship between EQ-5D index score and target joint status (defined in the CHESS study as areas of chronic synovitis), adjusted for patient covariates including socio-demographic characteristics and comorbidities. Results: Five hundred and fifteen patients (42% of the sample) provided an EQ-5D response; a total of 692 target joints were recorded across the sample. Mean EQ-5D index score for patients with no target joints was 0.875 (standard deviation [SD] 0.179); for patients with one or more target joints, mean index score was 0.731 (SD 0.285). Compared to having no target joints, having one or more target joints was associated with lower index scores (average marginal effect (AME) -0.120; SD 0.0262; p < 0.000). Conclusions: This study found that the presence of chronic synovitis has a significant negative impact on HRQOL for adults with severe haemophilia. Prevention, early diagnosis and treatment of target joints should be an important consideration for clinicians and patients when managing haemophilia

Effect of processed meat related compounds on colon cells

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Synthesis of Novel Aza‐aromatic Curcuminoids with Improved Biological Activities towards Various Cancer Cell Lines

Curcumin, a natural compound extracted from the rhizomes of Curcuma longa, displays pronounced anticancer properties but lacks good bioavailability and stability. In a previous study, we initiated structure modification of the curcumin scaffold by imination of the labile -diketone moiety to produce novel -enaminone derivatives. These compounds showed promising properties for elaborate follow-up studies. In this work, we focused on another class of nitrogen-containing curcuminoids with a similar objective: to address the bioavailability and stability issues and to improve the biological activity of curcumin. This paper thus reports on the synthesis of new pyridine-, indole-, and pyrrole-based curcumin analogues (aza-aromatic curcuminoids) and discusses their water solubility, antioxidant activity, and antiproliferative properties. In addition, multivariate statistics, including hierarchical clustering analysis and principal component analysis, were performed on a broad set of nitrogen-containing curcuminoids. Compared to their respective mother structures, that is, curcumin and bisdemethoxycurcumin, all compounds, and especially the pyridin-3-yl -enaminone analogues, showed better water solubility profiles. Interestingly, the pyridine-, indole-, and pyrrole-based curcumin derivatives demonstrated improved biological effects in terms of mitochondrial activity impairment and protein content, in addition to comparable or decreased antioxidant properties. Overall, the biologically active N-alkyl -enaminone aza-aromatic curcuminoids were shown to offer a desirable balance between good solubility and significant bioactivity