1,411 research outputs found

    Molecular and behavioral mechanisms mediating paclitaxel-induced changes in affect-like behavior in mice

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    The antineoplastic paclitaxel is associated with negative affective outcomes, such as depression, anxiety, and decreased quality of life during treatment and convalescence. With the Baby Boomer population approaching peak cancer age, it is dire that the mechanisms behind paclitaxel-induced changes in mood are uncovered. Cancer-free male and female C57BL/6J mice were treated with one set of four injections of vehicle or paclitaxel (32mg/kg cumulative), or two sets of four injections of vehicle or paclitaxel (64mg/kg cumulative), and periodically assessed for depression-like behaviors. Paclitaxel caused significant, time-dependent deficits in sucrose preference and operant responding for palatable food. Because there is growing evidence to support the role of kappa opioid receptors (KORs) in stress-mediated depression and reward dysfunction, we investigated KOR signaling as a putative mechanism of paclitaxel-induced depression-like behaviors. The selective KOR antagonist norbinaltorphimine (norBNI) reversed paclitaxel-induced attenuation of sucrose preference. At the molecular level, paclitaxel time-dependently induced an increase in the expression of Prodynorphin mRNA, the precursor for endogenous KOR agonists, in the nucleus accumbens (NAc). Using the [35S]GTPγS assay, we discovered that a history of paclitaxel time-dependently attenuated activation of dopamine D2 receptors (D2R) and KORs in the NAc but not caudate putamen. These data suggest that paclitaxel-induced changes in affect-like behavior may be due to time- and region-dependent dysregulation of KOR and D2R signaling. These observations help to establish the roles of KOR and D2R systems in paclitaxel-induced disruption of behavioral reward, thus revealing potential neurochemical targets for therapeutic intervention in cancer survivors with treatment-resistant depression.https://scholarscompass.vcu.edu/gradposters/1038/thumbnail.jp

    Does ovarian cystectomy pose a risk to ovarian reserve and fertility?

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    Key content The impact of benign ovarian cysts on a woman’s fertility is dependent on the nature, size, number, bilaterality and risk of recurrence of the cyst(s). Children and adolescents presenting with pathological ovarian cysts require a multidisciplinary team approach and, where possible, fertility sparing treatment should be offered. Laparoscopic detorsion has the potential to preserve ovarian reserve and should remain the optimal treatment for ovarian torsion in girls and premenopausal women. Surgery for bilateral endometriomas has been shown to increase the risk of developing premature ovarian insufficiency. It is important to consider performing ovarian reserve assessments before any ovarian surgery in women who have not completed their family. Learning objectives To understand what factors need to be considered before making a decision to perform an ovarian cystectomy. To be aware of different surgical techniques and their impact on fertility outcomes. To take anatomical considerations into account to minimise damage to healthy ovarian tissue. Ethical issues The UK’s National Health Service does not routinely fund oocyte freezing for benign conditions

    Alterations of consciousness and mystical-type experiences after acute LSD in humans

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    Lysergic acid diethylamide (LSD) is used recreationally and in clinical research. Acute mystical-type experiences that are acutely induced by hallucinogens are thought to contribute to their potential therapeutic effects. However, no data have been reported on LSD-induced mystical experiences and their relationship to alterations of consciousness. Additionally, LSD dose- and concentration-response functions with regard to alterations of consciousness are lacking.; We conducted two placebo-controlled, double-blind, cross-over studies using oral administration of 100 and 200 μg LSD in 24 and 16 subjects, respectively. Acute effects of LSD were assessed using the 5 Dimensions of Altered States of Consciousness (5D-ASC) scale after both doses and the Mystical Experience Questionnaire (MEQ) after 200 μg.; On the MEQ, 200 μg LSD induced mystical experiences that were comparable to those in patients who underwent LSD-assisted psychotherapy but were fewer than those reported for psilocybin in healthy subjects or patients. On the 5D-ASC scale, LSD produced higher ratings of blissful state, insightfulness, and changed meaning of percepts after 200 μg compared with 100 μg. Plasma levels of LSD were not positively correlated with its effects, with the exception of ego dissolution at 100 μg.; Mystical-type experiences were infrequent after LSD, possibly because of the set and setting used in the present study. LSD may produce greater or different alterations of consciousness at 200 μg (i.e., a dose that is currently used in psychotherapy in Switzerland) compared with 100 μg (i.e., a dose used in imaging studies). Ego dissolution may reflect plasma levels of LSD, whereas more robustly induced effects of LSD may not result in such associations

    Asymmetric Lewis acid-catalyzed 1,3-dipolar cycloadditions

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    Highly tuned, one-point binding chiral iron and ruthenium complexes selectively coordinate and activate α,β-unsaturated aldehydes and ketones toward asymmetric catalytic Diels-Alder cycloaddition reactions. Here we focus on the application of these transition-metal Lewis acids to asymmetric catalytic 1,3-dipolar cycloaddition reaction between enals and cyclic and acyclic nitrones as well as aryl nitrile oxides to give isoxazolidines and isoxazolines, respectivel

    Epidemiological and socio-legal overview

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    Pharmacogenetics of ecstasy: CYP1A2, CYP2C19, and CYP2B6 polymorphisms moderate pharmacokinetics of MDMA in healthy subjects

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    In vitro studies showed that CYP2C19, CYP2B6, and CYP1A2 contribute to the metabolism of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) to 3,4-methylenedioxyamphetamine (MDA). However, the role of genetic polymorphisms in CYP2C19, CYP2B6, and CYP1A2 in the metabolism of MDMA in humans is unknown. The effects of genetic variants in these CYP enzymes on the pharmacokinetics and pharmacodynamics of MDMA were characterized in 139 healthy subjects (69 male, 70 female) in a pooled analysis of eight double-blind, placebo-controlled studies. MDMA-MDA conversion was positively associated with genotypes known to convey higher CYP2C19 or CYP2B6 activities. Additionally, CYP2C19 poor metabolizers showed greater cardiovascular responses to MDMA compared with other CYP2C19 genotypes. Furthermore, the maximum concentration of MDA was higher in tobacco smokers that harbored the inducible CYP1A2 rs762551 A/A genotype compared with the non-inducible C-allele carriers. The findings indicate that CYP2C19, CYP2B6, and CYP1A2 contribute to the metabolism of MDMA to MDA in humans. Additionally, genetic polymorphisms in CYP2C19 may moderate the cardiovascular toxicity of MDMA

    Contributing Factors for Turkey Consumption: An Empirical Analysis from Mymensingh City in Bangladesh

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    The study examined the factors influencing yearly consumption of turkey meat in Mymensingh city area. Data were collected from 60 consumers of turkey meat through Purposive sampling technique and face to face interview. Dummy coding was applied to code independent variables which were categorical in nature and multiple linear regression was carried out to find out the factors influencing consumption of turkey meat. Result indicated that the majority of the consumers (more than 50%) favored taste, color and aroma of turkey meat. The findings also revealed that age (P<0.05) and monthly family income (P<0.01) were significantly influencing yearly consumption of turkey meat among consumers in Mymensingh city. The major difficulty faced by the turkey farmer recognized as unavailability of turkey feed in the market, high price of day-old chick, lack of access to agricultural credit, lack of training and marketing facility and un-availability of vaccines. Analyzing the factors affecting consumption of turkey meat would facilitate in marketing decision making process of the turkey farmers and also deliver information to policy makers of Government as well as Department of Livestock Services to take necessary initiatives and support this alternative meat source to rise as a popular consumer choice
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