Karlssonfox2849

All the metal-thiosemicarbazones have antitumor activity mediated by oxidative stress. The HPTSC*-Cu was the compound that showed the best antitumor and apoptotic characteristics for the cell line SW480, that is KRAS gene mutated. Vorinostat (suberoylanilide hydroxamic acid; SAHA) and Belinostat are two hydroxamate-based histone deacetylase inhibitors that are used clinically as potent anti-cancer agents. Their metabolic breakdown into inactive metabolites such as carboxylic acid and glucuronic derivatives results in them having short half-lives, which can negatively impact their pharmacokinetic profiles. Herein we report the potential of both Vorinostat and Belinostat to also act as nitric oxide donors under both chemical and biological ex vivo experimental conditions. More specifically, using ruthenium(III) as an effective NO scavenger, we were able to establish, in the first instance, that both Vorinostat and Belinostat had the capacity to release NO under chemical conditions. Both Vorinostat and Belinostat were then shown to cause vascular relaxation of rat aorta via NO-mediated activation of the haem-containing guanylate cyclase enzyme. A summary of our findings is reported herein. BACKGROUND Young adulthood has the highest rates of alcohol use and high-risk drinking behavior. This period is also a critical neurodevelopmental stage, with neural insults having a profound neurotoxic effect on the brain. Cortical gyrification is thought, in part, to reflect early brain maturation (e.g., hypogyrification in fetal alcohol syndrome). There is also evidence that cortical gyrification is sensitive to later-life events (e.g., fluctuations in malnutrition in young adults). However, no study has examined how alcohol use in young adulthood is associated with cortical gyrification. METHODS We examined the associations between cortical gyrification with lifetime alcohol use and past year hangover symptoms in young adults (N = 78). RESULTS Lifetime alcohol use was associated with hypogyria in multiple cortical regions (rs ≤ -.27, ps ≤ .0159; right orbitofrontal, right temporal pole, and left lateral occipital). Further, past year hangover symptoms were associated with hypogyria (rs ≤ -.27, ps ≤ .0034), overlapping with lifetime alcohol use (right orbitofrontal and left lateral occipital). Hangover symptoms were also uniquely associated with hypogyria of other cortical regions (rs ≤ -.30, ps ≤ .0002; right parahippocampal gyrus, left inferior temporal/parahippocampal gyrus and right anterior insula). CONCLUSIONS Thus, results suggest that young adulthood is a critical period for targeted prevention and intervention, especially for individuals exhibiting heavy alcohol consumption and high-risk drinking behavior. Hazardous drinking is prevalent among college students, yet few seek treatment. Anxiety sensitivity AS is one factor with relevance to drinking. Yet, there are no known estimates of the prevalence of elevated AS among hazardous drinkers. The current study sought to estimate the prevalence of elevated AS among hazardous drinking college students and to examine relations between AS and hazardous drinking. Data from 1257 students Mage = 22.08; 80.4 % female; 76.8 % racial/ethnic minorities was employed. Approximately one third (30.7 %) of the sample met criteria for hazardous drinking. TTK21 mouse Among hazardous drinkers, 77.5 % had clinically elevated AS; similar rates were evidenced across sex and race/ethnicity. Hazardous drinkers reported significantly greater AS scores than moderate drinkers and non-drinkers (p  less then  0.001; η2 = 0.09). Those with elevated AS were more than three times more likely to be hazardous drinkers (p  less then  0.001). Among hazardous drinkers, those with elevated AS had more severe drinking levels (p  less then  0.001; Cohen's d=0.07) as well as greater likelihood, number, and disturbance related to use of other substances (p's from less then 0.001-0.005; Cohen's d's from 0.01 to 0.02). Findings from this study suggest that most hazardous drinkers have elevated AS, and that elevated AS is associated with a substantially higher likelihood of being a hazardous drinker. Hazardous drinkers with elevated AS report more severe drinking and other substance use than those with normative AS. There may be practical clinical benefit of implementing focus on AS to reduce hazardous drinking in college settings. V.INTRODUCTION Despite the demonstrated benefit of methadone, the incidence opioid-related overdose, and its associated mortality continues to rise at an alarming rate. The impact of high prevalence comorbid features such as chronic liver disease (CLD) on methadone treatment response remain unclear. AIM To determine whether CLD is associated with poor response to methadone treatment. METHODS Using a well-established multi-center cohort from the Genetics of Opioid Addiction Study (GENOA), we evaluated if presence of CLD among 1234 eligible patients with opioid use disorder receiving methadone treatment impacted health and behavioural responses to treatment. CLD was classified as any liver disorder/dysfunction present for a minimum period of six months. Serial urine toxicology assessments were used to determine treatment response. The effect of CLD was determined using a multi-variable logistic regression model. RESULTS CLD was present in 25 % (n = 314) of the population. On average, patients with CLD were found these patients. V.BACKGROUND Disordered eating behaviors are associated with non-medical use of prescription stimulants for weight and appetite-related purposes. Yet, estimates of the prevalence and types of disordered eating associated with non-medical use vary. Additionally, little is known about the association between medical use of prescription stimulants and disordered eating. METHOD Data were collected from 87,296 college students at 127 institutions that participated in the Healthy Minds Study. We assessed the relationship between disordered eating, medical and nonmedical prescription stimulant use using multivariable logistic regression models adjusted for demographic characteristics, lifestyle and behavioral factors, and psychiatric comorbidity. RESULTS Non-medical use of prescription stimulants (NMUPS) was reported by 2.8 % n = 2435 of the sample. One-third of students using prescription stimulants non-medically reported two or more disordered eating attitudes and behaviors. Disordered eating was a significant predictor of non-medical, but not medical use of prescription stimulants.