Repeated or even a single exposure to drugs of abuse can lead to persistent locomotor sensitization, which is the result of an abundance of neuroplastic changes occurring within the circuitry involved in motivational behavior and is thought to play a key role in certain aspects of drug addiction. There is substantial controversy about the addictive potential of modafinil, a wake-promoting drug used to treat narcolepsy that is increasingly being used as a cognitive enhancer and has been proposed as a pharmacotherapy for cocaine dependence. Male mice were used to investigate the ability of modafinil to induce locomotor sensitization after repeated or single administration in mice. Bidirectional cross-sensitization with cocaine and modafinil-induced conditioned place preference were also evaluated. Both repeated and single exposure to moderate and high doses of modafinil produced a pronounced locomotor sensitization that cross-sensitized in a bidirectional way with cocaine. Remarkably, when cocaine and modafinil were repeatedly administered sequentially, their behavioral sensitization was additive. Supporting these behavioral sensitization data, modafinil produced a pronounced conditioned place preference in the mouse. Taken together, the present findings provide pre-clinical evidence for the addictive potential of modafinil. Our data also strongly suggest that similar neural substrates are involved in the psychomotor/rewarding effects of modafinil and cocaine.

No abstract

No abstract

ABSTRACT. Five-year survival rates for oral squamous cell carcinoma (OSCC) are 30% and the mortality rate is 50%. Immunohistochemistry panels are used to evaluate proliferation, vascularization, apoptosis, HPV infection, and keratin expression, which are important markers of malignant progression. Keratins are a family of intermediate filaments predominantly expressed in epithelial cells and have an essential role in mechanical support and cytoskeleton formation, which is essential for the structural integrity and stability of the cell. In this study, we analyzed the expressions of keratins 17 and 19 (K17 and K19) by immunohistochemistry in tumoral and non-tumoral tissues from patients with OSCC. The results show that expression of these keratins is higher in tumor tissues compared to non-tumor tissues. Positive K17 expression correlates with lymph node metastasis and multivariate analysis confirmed this relationship, revealing a 6-fold increase in lymph node metastasis when K17 is expressed. We observed a correlation between K17 expression with disease-free survival and disease-specific death in patients who received surgery and radiotherapy. Multivariate analysis revealed that low expression of K17 was an independent marker for early disease relapse and disease-specific death in patients treated with surgery and radiotherapy, with an approximately 4-fold increased risk when compared to high K17 expression. Our results suggest a potential role for K17 and K19 expression profiles as tumor prognostic markers in OSCC patients.

Oral cancer squamous cell carcinoma (OCSCC) mainly affects individuals aged between 50 and 70 years who consume tobacco and alcohol. tobacco smoke contains hundreds of known toxic and carcinogenic molecules, and a few studies have sought to verify the relationship of such trace elements as risk or prognostic factors for head and neck cancer. We obtained 78 samples of tumor tissues from patients with ocScc, and performed a qualitative elemental characterization using the micro X-Ray fluorescence technique based on synchrotron radiation. We found the presence of magnesium, phosphorus, sulfur, chlorine, potassium, calcium, chromium, manganese, iron, zinc, cobalt, nickel, copper, arsenic and bromine in ocScc samples. Magnesium, chlorine, chromium, manganese, nickel, arsenic and bromine are associated with smoking. We observed a significant association between relapse and chlorine and chromium. the presence of chlorine in the samples was an independent protective factor against relapse (oR = 0.105, CI = 0.01-0.63) and for best disease-free survival (HR = 0.194, CI = 0.04-0.87). Reporting for the first time in oral cancer, these results suggest a key relationship between smoking and the presence of certain elements. in addition, chlorine proved to be important in the context of patient prognosis and survival. Squamous cell carcinoma (SCC) accounts for more than 90% of oral cancer cases 1,2 and mainly affects individuals aged between 50 and 70 years who consume tobacco and alcohol. It may also be associated with human papillomavirus infection, genetic susceptibility and passive smoking exposure 1-5. Tobacco smoke itself, which contains hundreds of known toxic and carcinogenic molecules 6,7 , can induce DNA damage 8. Among these substances are several inorganic compounds, such as arsenic, calcium, chlorine, cobalt, copper, chromium, iron, magnesium, manganese, nickel, potassium, zinc and others 9,10. The analysis of trace elements is quite uncommon in the head and neck cancer field. Over the past two decades, a few studies have sought to verify the identity of these and other trace elements as risk or prognostic factors for head and neck cancer. Some authors verified the differences in the profile of trace elements in the blood (plasma/serum) of patients with or without head and neck cancer 11-19. Differences were also found in the analyses performed on the hair and nails of patients with head and neck cancer 15,17,20,21. However, in studies carried out

The NR3C1 glucocorticoid receptor (GR) gene is a component of the stress response system, which can be regulated by epigenetic mechanisms. NR3C1 methylation has been associated with trauma and mental issues, including depression, post-traumatic stress, anxiety, and personality disorders. Previous studies have reported that stressful events are involved in NR3C1 gene methylation, suggesting that its regulation under environmental effects is complex. The present study aimed to analyze associations involving stressors such as socioeconomic status, health conditions, and lifestyle in relation to NR3C1 methylation in adults. This study included 386 individual users of the Brazilian Public Unified Health System (SUS), and evaluated socioeconomic and health conditions, body mass index, cortisol levels, and lifestyle. Data were correlated with NR3C1 methylation, determined using DNA pyrosequencing. The results showed that alcohol consumption, overweight, and high cortisol levels were related to NR3C1 demethylation, while depression was related to its methylation. Habits, lifestyle, and health status may influence NR3C1 gene regulation via methylation, revealing the complexity of environmental impacts on NR3C1 methylation.

ObjectiveTo assess the association between indicators of psychosocial stress and central adiposity in adult users of the Unified Health System (SUS) from Southeast of Brazil.MethodsThis cross-sectional study was conducted with 384 adults (20 to 59 years old) from the city of Alegre, Southeastern Brazil. The simple random sample represented the population using the public health system of the municipality. The prevalence of obesity was based on the Body Mass Index, and central adiposity (dependent variable) was measured by waist circumference in centimeters. The independent variables were the following indicators of psychosocial stress: food and nutrition insecurity (yes/no), serum cortisol (μg/dL), symptoms suggestive of depression using the Beck Depression Inventory-II ≥ 17 (yes/no), and altered blood pressure ≥ 130/85 mmHg (yes/no). Univariate linear regression was performed between central adiposity and each stress indicator, and later the models were adjusted for socioeconomic, health, and lifestyle variables. All analyses were made separately by rural and urban location.ResultsThe prevalence of weight excess, by the classification of the Body Mass Index ≥ 25.0 kg/m2, was 68.3% and, by waist circumference, 71.5% of individuals presented an increased risk for metabolic complications related to central adiposity. Mean waist circumference scores for the rural and urban population were 89.3 ± 12.7 cm and 92.9 ± 14.7 cm, respectively (p = 0.012). Indicators of stress that were associated with central adiposity were: cortisol in the rural population (β = -0.60; 95% CI = -1.09;-0.11) and altered blood pressure in the urban population (β = 6.66; 95% CI = 2.14;11.18). This occurred both in the raw analysis and in the models adjusted for confounding factors.ConclusionCentral adiposity was inversely associated with cortisol in the rural population and directly associated with higher arterial blood pressure in the urban population, suggesting a local influence on how individuals react to stress.

No abstract