Early-life stress affects drug abuse susceptibility in adolescent rat model independently of depression vulnerability

The development of substance abuse problems occurs due to a diverse combination of risk factors. Among these risks, studies have reported depression and early-life stress as of importance. These two factors often occur simultaneously, however, there is a lack of understanding of how their combined effect may impact vulnerability to drug abuse in adolescence. The present study used rats with different vulnerability to depression (Wistar and Wistar-Kyoto) to investigate the impact of maternal separation (MS) on emotional state and drug addiction vulnerability during the adolescence period. Mothers and their litters were subjected to MS (180 min/day) from postnatal day 2 to 14. The offspring emotional state was assessed by observing their exploratory behavior. Drug abuse vulnerability was assessed through conditioning to cocaine. MS impacted the emotional state in both strains. Wistar responded with increased exploration, while Wistar-Kyoto increased anxiety-like behaviours. Despite the different coping strategies displayed by the two strains when challenged with the behavioural tests, drug conditioning was equally impacted by MS in both strains. Early-life stress appears to affect drug abuse vulnerability in adolescence independently of a depression background, suggesting emotional state as the main driving risk factor.info:eu-repo/semantics/publishedVersio

Maternal stress and vulnerability to depression: coping and maternal care strategies and its consequences on adolescent offspring

Depressive mothers often find mother-child interaction to be challenging. Maternal stress may further impair mother-child attachment, which may increase the risk of negative developmental consequences. We used rats with different vulnerability to depressive-like behavior (Wistar and Kyoto) to investigate the impact of stress (maternal separation-MS) on maternal behavior and adolescent offspring cognition. MS in Kyoto dams increased pup-contact, resulting in higher oxytocin levels and lower anxiety-like behavior after weaning, while worsening their adolescent offspring cognitive behavior. Whereas MS in Wistar dams elicited higher quality of pup-directed behavior, increasing brain-derived neurotrophic factor (BDNF) in the offspring, which seems to have prevented a negative impact on cognition. Hypothalamic oxytocin seems to affect the salience of the social environment cues (negatively for Kyoto) leading to different coping strategies. Our findings highlight the importance of contextual and individual factors in the understanding of the oxytocin role in modulating maternal behavior and stress regulatory processes.info:eu-repo/semantics/publishedVersio

Characterization of TiO2 nanoparticles in langmuir-blodgett films

In this work we have synthesized TiO2 nanoparticles, using either a sol–gel base catalysed process in the interior of CTAB reversed micelles (TiO2 CTAB sol), or the neutralization of a TiO2/H2SO4 solution in the interior of AOT reversed micelles. From the absorption and emission data of the TiO2 nanoparticles it is possible to conclude that in the sol–gel route there remains alkoxide groups in the structure, originating transitions lower than the energy gap of TiO2 semiconductor. These transitions disappear in the neutralization procedure, where the alkoxide groups are absent in the structure. We have assigned the observed indirect and direct optical transitions according to the anatase band structure. TiO2 Langmuir-Blodgett (LB) films were prepared either by direct deposition of titanium isopropoxide or by deposition of the TiO2 CTAB sol. These films showed photoluminescence, which was attributed to band-gap emission and to surface recombination of defect states

Development of pH-Sensitive magnetoliposomes containing shape anisotropic nanoparticles for potential application in combined cancer therapy

Late diagnosis and systemic toxicity associated with conventional treatments make oncological therapy significantly difficult. In this context, nanomedicine emerges as a new approach in the prevention, diagnosis and treatment of cancer. In this work, pH-sensitive solid magnetoliposomes (SMLs) were developed for controlled release of the chemotherapeutic drug doxorubicin (DOX). Shape anisotropic magnetic nanoparticles of magnesium ferrite with partial substitution by calcium (Mg0.75Ca0.25Fe2O4) were synthesized, with and without calcination, and their structural, morphological and magnetic properties were investigated. Their superparamagnetic properties were evaluated and heating capabilities proven, either by exposure to an alternating magnetic field (AMF) (magnetic hyperthermia) or by irradiation with near-infrared (NIR) light (photothermia). The Mg0.75Ca0.25Fe2O4 calcined nanoparticles were selected to integrate the SMLs, surrounded by a lipid bilayer of DOPE:Ch:CHEMS (45:45:10). DOX was encapsulated in the nanosystems with an efficiency above 98%. DOX release assays showed a much more efficient release of the drug at pH = 5 compared to the release kinetics at physiological pH. By subjecting tumor cells to DOX-loaded SMLs, cell viability was significantly reduced, confirming that they can release the encapsulated drug. These results point to the development of efficient pH-sensitive nanocarriers, suitable for a synergistic action in cancer therapy with magnetic targeting, stimulus-controlled drug delivery and dual hyperthermia (magnetic and plasmonic) therapy.This work was funded by the Portuguese Foundation for Science and Technology (FCT) within the framework of the Strategic Funding of Research Units UIDB/04650/2020 (CF-UM-UP), UIDB/00319/2020 (ALGORITMI), UIDB/04077/2020 (MEtRICs), UIDB/04436/2020 (CMEMS) and UIDB/00511/2020 (LEPABE). FCT, POCI, FEDER and NORTE2020 are acknowledged for funding through research projects PTDC/QUI-QFI/28020/2017, EXPL/EMD-EMD/0650/2021, PTDC/EEI-EEE/2846/2021 and NORTE-01-0145-FEDER-000054. MINECO (Spain) is acknowledged for project MAT2016-76824-C3-2-R. B.D.C. and V.M.C. acknowledge FCT for PhD grants SFRH/BD/141936/2018 (B.D.C.) and UI/BD/151028/2021 (V.M.C.). R.O.R. thanks FCT for contract 2020.03975.CEECIND

Uso de plantas com finalidade medicinal por pessoas vivendo com HIV/ AIDS em terapia antirretroviral

Este foi um estudo observacional, transversal analítico realizado em ambulatório de referência do Estado do Maranhão-Brasil, no período de maio de 2009 a fevereiro de 2010, com o objetivo de estudar o uso de plantas com finalidade medicinal entre pessoas vivendo com HIV/AIDS, em uso de antirretrovirais. Um total de 339 pessoas respondeu um questionário abordando o uso de plantas e características demográficas, socioeconômicas, comportamentais, relacionadas à soropositividade e ao uso de antirretrovirais. A prevalência de utilização de plantas foi de 34,81%. As mais utilizadas foram: Turnera ulmifolia (12,09%); Melissa officinalis (10,62%); Plectranthus barbatus (7,67%); Cymbopogan citratus (capim limão) (4,72%) e Mentha spp. (hortelã) (2,36%). A maioria das pessoas (96,61%) referiu melhora após a utilização. Um percentual de 75,42% dos usuários de plantas não informou essa prática ao médico. Entre os que informaram o uso, 55,17% afirmaram que o médico estava de acordo e somente uma pessoa foi orientada a interromper o uso (3,45%). Apenas um médico (3,45%) indicou o uso de plantas. A análise ajustada evidenciou diferença para uso de plantas em relação ao sexo feminino (RP=1,58, 95% IC 1,15-2,15 p 0,004) e à orientação sexual do tipo homossexual (RP=0,63 IC 0,44-0,90 p 0,012). Este estudo aponta para a necessidade de melhor diálogo entre médico e pacientes sobre o uso de plantas com finalidade medicinal, alertando sobre possíveis perigos quando associados aos antirretrovirais, especialmente entre usuários do sexo feminino ou com prática do tipo homossexual.It is an observational, analytic study, developed at a hospital in Maranhao-Brazil, from May-2009 to February-2010. The objective was to study the use of plants with medicinal purpose in people living with HIV/AIDS and using retroviral therapy. A total of 339 (three hundred and thirty-nine) people answered a questionnaire about the use of plants and demographic, socioeconomic, behavioral characteristics, including those related to HIV status and use of antiretroviral therapy The prevalence of the use of plants with medicinal purpose was 34,81%. The most often used were: Turnera ulmifolia (chanana) (12,09%), Melissa officinalis (erva cidreira,) (10,62%), Plectranthus barbatus (boldo) (7,67%), Cymbopogan citratus (capim limão) (4,72%) and Mentha spp. (hortelã) (2,36%). Most people interviewed (96,61%) reported improvement after use. A rate of 75,42% of the plant users had not reported their practice to a medical doctor. Among respondents who reported use, 55.17% said their doctor agreed to it, and only one person was advised to discontinue the use (3,45%); only one doctor (3,45%) indicated the use of plants. Multivariate analysis showed differences for the use of plants in relation to gender (female PR= 1,58, 95% CI 1,15 - 2,15 p 0,004) and homosexual practices (PR= 0,63, CI 0,44 - 0,90 p 0,012). This study highlights the need for a better dialogue between doctors and patients about the use of plants with medicinal purposes, and warns about possible dangers when they are combined with antirretroviral therapy, particularly between female and homossexual users

A breakthrough on Amanita phalloides poisoning: an effective antidotal effect by polymyxin B

Amanita phalloides is responsible for more than 90 % of mushroom-related fatalities, and no effective antidote is available. a-Amanitin, the main toxin of A. phalloides, inhibits RNA polymerase II (RNAP II), causing hepatic and kidney failure. In silico studies included docking and molecular dynamics simulation coupled to molecular mechanics with generalized Born and surface area method energy decomposition on RNAP II. They were performed with a clinical drug that shares chemical similarities to a-amanitin, polymyxin B. The results show that polymyxin B potentially binds to RNAP II in the same interface of a-amanitin, preventing the toxin from binding to RNAP II. In vivo, the inhibition of the mRNA transcripts elicited by a-amanitin was efficiently reverted by polymyxin B in the kidneys. Moreover, polymyxin B significantly decreased the hepatic and renal a-amanitin-induced injury as seen by the histology and hepatic aminotransferases plasma data. In the survival assay, all animals exposed to a-amanitin died within 5 days, whereas 50 % survived up to 30 days when polymyxin B was administered 4, 8, and 12 h post-a-amanitin. Moreover, a single dose of polymyxin B administered concomitantly with a-amanitin was able to guarantee 100 % survival. Polymyxin B protects RNAP II from inactivation leading to an effective prevention of organ damage and increasing survival in a-amanitin-treated animals. The present use of clinically relevant concentrations of an already human-use-approved drug prompts the use of polymyxin B as an antidote for A. phalloides poisoning in humans.Juliana Garcia, Vera Marisa Costa, Ricardo Dinis-Oliveira and Ricardo Silvestre thank FCT-Foundation for Science and Technology-for their PhD grant (SFRH/BD/74979/2010), Post-doc grants (SFRH/BPD/63746/2009 and SFRH/BPD/110001/2015) and Investigator grants (IF/01147/2013) and (IF/00021/2014), respectively. This work was supported by the Fundacao para a Ciencia e Tecnologia (FCT) - project PTDC/DTPFTO/4973/2014 - and the European Union (FEDER funds through COMPETE) and National Funds (FCT, Fundacao para a Ciencia e Tecnologia) through project Pest-C/EQB/LA0006/2013