Search Results (6)

Methadone is commonly used as an alternative to morphine in patients with pain associated with glioblastoma and other cancers. Although concomitant administration of methadone and cytostatics is relatively common, the effect of methadone on the efficacy of cytostatic drugs has not been well studied until recently. Moreover, the mechanism behind the effect of methadone on temozolomide efficacy has not been investigated in previous studies, or this effect has been automatically attributed to opioid receptors. Our findings indicate that methadone potentiates the effect of temozolomide on rat C6 glioblastoma cells and on human U251 and T98G glioblastoma cells and increases cell mortality by approximately 50% via a mechanism of action independent of opioid receptors. Our data suggest that methadone acts by affecting mitochondrial potential, the level of oxidative stress, intracellular Ca²⁺ concentration and possibly intracellular ATP levels. Significant effects were also observed on DNA integrity and on cleavage and expression of the DNA repair protein PARP-1. None of these effects were attributed to the activation of opioid receptors and Toll-like receptor 4. Our results provide an alternative perspective on the mechanism of action of methadone in combination with temozolomide and a potential strategy for the treatment of glioblastoma cell resistance to temozolomide. Full article

Opioids are known to have antioxidant effects and to modulate microglial function under certain conditions. It has been previously shown that opioid ligands can effectively inhibit the release of proinflammatory cytokines when stimulated with lipopolysaccharide (LPS) and convert microglia to an anti-inflammatory polarization state. Here, we used C8-B4 cells, the mouse microglial cell line activated by LPS as a model to investigate the anti-inflammatory/antioxidant potential of selected opioid receptor agonists (DAMGO, DADLE, and U-50488). We found that all of these ligands could exert cytoprotective effects through the mechanism affecting LPS-induced ROS production, NADPH synthesis, and glucose uptake. Interestingly, opioids elevated the level of reduced glutathione, increased ATP content, and enhanced mitochondrial respiration in microglial cells exposed to LPS. These beneficial effects were associated with the upregulation of the Nrf2/HO-1 pathway. The present results indicate that activation of opioid signaling supports the preservation of mitochondrial function with concomitant elimination of ROS in microglia and suggest that an Nrf2/HO-1 signaling pathway-dependent mechanism is involved in the antioxidant efficacy of opioids. Opioid receptor agonists may therefore be considered as agents to suppress oxidative stress and inflammatory responses of microglia. Full article

Some analyses state that buildings contribute to overall energy consumption by 20–40%, which, in the context of the recent geopolitical energy crisis, makes them a critical issue to study. Finding solutions for better energy management in buildings can have a significant impact on the energy sector, thus reducing EU energy dependencies and contributing to the fulfillment of the REPowerEU goals. This paper focuses on proposing a simplified model of a residential house considering the main appliances, heating and cooling, a photovoltaic system, and electric vehicle recharging. Weather and solar irradiance forecasts are taken into account. The model predicts the energy demands of a house based on online weather forecasts and the desired indoor temperature. The article also focuses on the analysis of how weather forecast uncertainty affects energy demand prediction. This model can be used to better understand and predict the energy demand of either a single house or a set of houses. A multi-objective optimization approach that takes into account the preferences of users/inhabitants is developed to provide a compromise between the price paid for the electricity and temperature comfort. The authors plan to apply the proposed model to a residential house’s real-time control system. The model will be tuned, its predictions will be tested, and it will be used for energy demand optimization. Full article

E-cigarettes, the most popular tobacco product among adolescents, vary widely in design and nicotine composition; thus, different devices may have different addictive potential. However, few studies examine levels of nicotine dependence across devices among adolescent and young adult (AYA) e-cigarette users. To assess the extent of nicotine dependence among US AYA (ages 13–24) by e-cigarette device type, we conducted a large, national, cross-sectional survey (n = 4351) and used the Hooked on Nicotine Checklist (HONC) to assess levels of nicotine dependence among those who had used disposable, pod-based, and/or mods/other e-cigarette devices in the past 30 days. We also examined HONC scores among those who had used combustible cigarettes in the past 30 days, whether with or without using e-cigarettes. Patterns of nicotine dependence were comparable across those who had used a combustible cigarette and/or e-cigarette in the past 30 days, with 91.4% of combustible cigarette users, 80.7% of disposable e-cigarette users, 83.1% of pod-based e-cigarette users, and 82.5% of mods/other e-cigarette users showing signs of nicotine dependence, as measured by endorsing at least one HONC symptom. This pattern persisted when analyses were restricted to e-cigarette only users, with more than 70% of all e-cigarette only past-30-day users endorsing at least one HONC symptom, across all types of devices. A thorough understanding of the extent and presentation of nicotine dependence among AYA will help researchers, public health officials, and clinicians recognize and manage AYA nicotine dependence. Full article

The prevalence of concurrent use of combustible and electronic cigarettes (dual-use) is on the rise among Malaysian adolescents. This study compares nicotine dependence among exclusive cigarette users, e-cigarette users, and dual adolescent users. A total of 227 adolescent smokers completed a self-administrated questionnaire with items based on Hooked on Nicotine Checklist (HONC) incorporated. Endorsement of at least one HONC item indicates nicotine dependence. Exhaled carbon monoxide readings and salivary cotinine data were also collected. Over half (52.9%) of the participants were exclusive e-cigarette users (EC). The prevalence of exclusive conventional cigarette smokers (CC) and dual users was 11.9% and 35.2%, respectively. Adolescents who have mothers with secondary school education were more likely to become addicted to nicotine (Adjusted Odd Ratio (aOR) = 2.72; 95% CI = 1.17–6.32). Adolescents’ “mother’s education” level predicted nicotine dependence. This highlighted the need to target families within the identified demography with a more supportive anti-tobacco program. Full article

Nicotine dependence is one of the main reasons for the continuation of smoking among adolescents. Loss of autonomy (LOA) is a measure of dependence. This study is the first to investigate LOA and its determinants among Greek adolescents. In 2013, 13-to-15-year-old middle-school students were selected by multi-stage clustered sampling. LOA was evaluated with the Hooked-on-Nicotine Checklist (HONC). Multiple univariate analysis was used to assess the association between adolescent demographics, smoking habits, and loss of autonomy. Three-hundred thirty-nine current smokers responded to the questionnaire (response rate: 82.3%). Of these respondents, 51.2% were male and 88.8% reported at least one LOA symptom. The mean HONC score was 4.13/10 (95% CI: 3.82–4.45). Higher scores were negatively associated with lower smoking frequency (cumulative odds ratio (cOR): 0.240, 95% CI: 0.144–0.400) and positively associated with lower age at first cigarette (cOR: 2.29, 95% CI: 1.38–3.82). Female gender was significantly associated with the prevalence but not the degree of LOA. Overall, the prevalence and the degree of nicotine dependence among adolescent smokers in Greece is similar to other countries. Frequent smoking and initiation of smoking at a younger age are linked to nicotine dependence, although it was not possible to make causal inferences. The relationship between nicotine dependence and gender remains unclear. Full article