Brain GABA and Glutamate Concentrations Following Chronic Gabapentin Administration: A Convenience Sample Studied During Early Abstinence From Alcohol.

Gabapentin (GBP), a GABA analog that may also affect glutamate (Glu) production, can normalize GABA and Glu tone during early abstinence from alcohol, effectively treating withdrawal symptoms and facilitating recovery. Using in vivo magnetic resonance spectroscopy, we tested the degree to which daily GBP alters regional brain GABA and Glu levels in short-term abstinent alcohol-dependent individuals. Regional metabolite levels were compared between 13 recently abstinent alcohol-dependent individuals who had received daily GBP for at least 1 week (GBP+) and 25 matched alcohol-dependent individuals who had not received GBP (GBP-). Magnetic resonance spectra from up to five different brain regions were analyzed to yield absolute GABA and Glu concentrations. GABA and Glu concentrations in the parieto-occipital cortex were not different between GBP- and GBP+. Glu levels in anterior cingulate cortex, dorsolateral prefrontal cortex, and basal ganglia did not differ between GBP- and GBP+. However, in a subgroup of individuals matched on age, sex, and abstinence duration, GBP+ had markedly lower Glu in the frontal white matter (WM) than GBP-, comparable to concentrations found in light/non-drinking controls. Furthermore, lower frontal WM Glu in GBP+ correlated with a higher daily GBP dose. Daily GBP treatment at an average of 1,600 mg/day for at least 1 week was not associated with altered cortical GABA and Glu concentrations during short-term abstinence from alcohol, but with lower Glu in frontal WM. GBP for the treatment of alcohol dependence may work through reducing Glu in WM rather than increasing cortical GABA

Measures of Learning, Memory and Processing Speed Accurately Predict Smoking Status in Short-term Abstinent Treatment-seeking Alcohol-dependent Individuals

Aim: Chronic cigarette smoking appears to adversely affect several domains of neurocognition in those with alcohol use disorders (AUDs). The primary goal of this study was to identify which measures commonly used to assess neurocognition in AUDs accurately predict smoking status of individuals seeking treatment of alcohol dependence. Methods: Treatment-seeking alcohol-dependent participants (ALC; n = 92) completed a comprehensive neuropsychological battery after 33 ± 9 days of abstinence. Measures significantly different between smoking and non-smoking ALC were entered as predictors in binary logistic regression and discriminant analysis models, with smoking status as the dependent variable. Results: Smoking ALC performed significantly worse than non-smoking ALC on measures assessing processing speed, auditory–verbal and visuospatial learning and memory. Using these measures as predictors, a logistic regression model accurately classified 91% of smokers and non-smokers into their respective groups overall and accounted for 68% of the variance in smoking status. The discriminant analysis confirmed the findings from the logistic regression. In smoking ALC, smoking chronicity was inversely related to performance on multiple measures after controlling for lifetime alcohol consumption. Conclusions: Measures of processing speed, learning and memory robustly predicted the smoking status of ALC with high sensitivity and specificity during early abstinence. The results identified specific measures within a comprehensive neurocognitive battery that discriminated smoking and non-smoking alcohol-dependent individuals with a high sensitivity and specificity. The association of greater smoking chronicity and poorer performance on multiple measures after control for alcohol consumption suggests that chronic smoking adds an additional burden to neurocognitive function in those with alcohol dependence

The Potential Health Benefits of Polyphenol-Rich Extracts from Cichorium intybus

Phytochemicals can exert their bioactivity without reaching the systemic circulation; scarcely absorbed antioxidants might reach the large bowel contributing to protection from oxidative damage-induced gastrointestinal diseases. In the present work, we aimed to study the relationship between potential activity of polyphenol-rich extracts from Cichorium intybus L. and changes in morphological characteristics on Caco-2 cells. Phytochemicals content (carotenoids and flavonoids) and total antioxidant activity of Red Chicory of Treviso and Variegated Chicory of Castelfranco were evaluated. The bioactivity of polyphenol-rich extracts from chicories was studied in in vitro Caco-2 cell monolayers model. Morphological characteristics changes to test the antioxidant and/or prooxidant effect were verified by histological analysis and observed by Electronic Scansion Microscopy (SEM). On Caco-2 cell model, the polyphenols fractions from chicories have indicated a moderate antioxidant behavior until 17 μM concentration, while 70 μM and 34 μM exert cytotoxic effects for Treviso’s and Castelfranco’s Chicory, respectively, highlighted by TEER decreasing, increased permeability, and alteration of epithelium. Our findings support the beneficial effects of these products in counteracting the oxidative stress and cellular damage, induced in vitro on Caco-2 cell model, through interaction with the mucopolysaccharide complexes in the glycocalyx, maintaining in vivo a healthy and effective intestinal barrier

New nanotechnologies for the treatment and repair of skin burns infections

Burn wounds are highly debilitating injuries, with significant morbidity and mortality rates worldwide. In association with the damage of the skin integrity, the risk of infection is increased, posing an obstacle to healing and potentially leading to sepsis. Another limitation against healing is associated with antibiotic resistance mainly due to the use of systemic antibiotics for the treatment of localized infections. Nanotechnology has been successful in finding strategies to incorporate antibiotics in nanoparticles for the treatment of local wounds, thereby avoiding the systemic exposure to the drug. This review focuses on the most recent advances on the use of nanoparticles in wound dressing formulations and in tissue engineering for the treatment of burn wound infections.The authors would like to thank the financial support received from Portuguese Science and Technology Foundation (FCT/MCT) and from European Funds (PRODER/COMPETE) under the project references M-ERA-NET/0004/2015-PAIRED and UIDB/04469/2020, co-financed by FEDER, under the Partnership Agreement PT2020.info:eu-repo/semantics/publishedVersio

Metal-based nanoparticles as antimicrobial agents: an overview

Metal-based nanoparticles have been extensively investigated for a set of biomedical applications. According to the World Health Organization, in addition to their reduced size and selectivity for bacteria, metal-based nanoparticles have also proved to be effective against pathogens listed as a priority. Metal-based nanoparticles are known to have non-specific bacterial toxicity mechanisms (they do not bind to a specific receptor in the bacterial cell) which not only makes the development of resistance by bacteria difficult, but also broadens the spectrum of antibacterial activity. As a result, a large majority of metal-based nanoparticles efficacy studies performed so far have shown promising results in both Gram-positive and Gram-negative bacteria. The aim of this review has been a comprehensive discussion of the state of the art on the use of the most relevant types of metal nanoparticles employed as antimicrobial agents. A special emphasis to silver nanoparticles is given, while others (e.g., gold, zinc oxide, copper, and copper oxide nanoparticles) commonly used in antibiotherapy are also reviewed. The novelty of this review relies on the comparative discussion of the different types of metal nanoparticles, their production methods, physicochemical characterization, and pharmacokinetics together with the toxicological risk encountered with the use of different types of nanoparticles as antimicrobial agents. Their added-value in the development of alternative, more effective antibiotics against multi-resistant Gram-negative bacteria has been highlighted.M.L.G., M.E. (Miren Ettcheto), A.C., and E.S.L. belong to 2017SGR-1477. E.S.-L., A.C., M.E. (Marta Espina), and M.L.G. acknowledge the support of Institute of Nanoscience and Nanotechnology (ART2018 project). E.B.S. wants to acknowledge the Portuguese Science and Technology Foundation (FCT/MCT) and European Funds (PRODER/COMPETE) for the projects M-ERA-NET-0004/2015-PAIRED and UIDB/04469/2020, co-funded by FEDER, under the partnership Agreement PT2020.info:eu-repo/semantics/publishedVersio

Genetic and behavioral determinants of hippocampal volume recovery during abstinence from alcohol

Alcohol-dependent individuals (ALC) have smaller hippocampi and poorer neurocognition than healthy controls. Results from studies on the association between alcohol consumption and hippocampal volume have been mixed, suggesting that comorbid or premorbid factors (i.e., those present prior to the initiation of alcohol dependence) determine hippocampal volume in ALC. We aimed to characterize the effects of select comorbid (i.e., cigarette smoking) and premorbid factors (brain-derived neurotrophic factor [BDNF] genotype [Val66Met rs6265]) on hippocampal volume in an ALC cohort followed longitudinally into extended abstinence. One hundred twenty-one adult ALC in treatment (76 smokers, 45 non-smokers) and 35 non-smoking light-drinking controls underwent quantitative magnetic resonance imaging, BDNF genotyping, and neurocognitive assessments. Representative subgroups were studied at 1 week, 1 month, and at an average of 7 months of abstinence. ALC had smaller hippocampi than healthy controls at all time points. Hippocampal volume at 1 month of abstinence correlated with lower visuospatial function. Smoking status did not influence hippocampal volume or hippocampal volume recovery during abstinence. However, only BDNF Val homozygotes tended to have hippocampal volume increases over 7 months of abstinence, and Val homozygotes had significantly larger hippocampi than Met carriers at 7 months of abstinence. These findings suggest that BDNF genotype, but not smoking status or measures of drinking severity, regulate functionally relevant hippocampal volume recovery in abstinent ALC. Future studies aimed at exploring genetic determinants of brain morphometry in ALC may need to evaluate individuals during extended abstinence after the acute environmental effects of chronic alcohol consumption have waned