Nanosystems in nose-to-brain drug delivery: a review of non-clinical brain targeting studies

The treatment of neurodegenerative and psychiatric disorders remains a challenge in medical research. Several strategies have been developed over the years, either to overcome the blood-brain barrier or to achieve a safer or faster brain delivery, one of them being intranasal (IN) administration. The possibility of direct nose-to-brain transport offers enhanced targeting and reduced systemic side effects. Nevertheless, labile, low soluble, low permeant and/or less potent drugs might need a formulation other than the common solutions or suspensions. For that, the formulation of nanosystems is considered to be a promising approach, since it can protect drugs from chemical and/or metabolic degradation, enhance their solubility, or offer transport through biological membranes. However, the understanding of the factors promoting efficient brain targeting when using nanosystems through the nasal route is currently patchy and incomplete. The main purpose of the present review was to evaluate the association between brain delivery efficacy (in terms of brain targeting, brain bioavailability and time to reach the brain) and nanosystem type. For that, we performed a systematic bibliographic search and analysis. Furthermore, study designs, nanosystem properties, and reporting quality were also analyzed and discussed. It was found a high heterogeneity in how pre-clinical brain targeting studies have been conducted, analyzed and reported in scientific literature, which surely originates a significant degree of bias and data dispersion. This review attempts to provide some systematization recommendations, which may be useful for researchers entering the field, and assist in increasing the uniformity of future reports. The analysis of literature data confirmed that there is evidence of the advantage of the IN route (when compared to the intravenous route) and in using carrier nanosystems (when compared to IN solutions) for brain delivery of a large set of drugs. Among the most represented nanosystem classes, microemulsions had some of the lowest pharmacokinetic ratios values, while polymeric micelles had some of the best. Nevertheless, brain targeting efficacy comparisons between nanosystem groups had little statistical significance, and the superiority of the polymeric micelles group disappeared when nanosystems were compared to the respective IN drug solutions. In fact, some drugs reached the brain so efficiently, even as drug solutions, that further benefit from formulating them into nanosystems became less evident.info:eu-repo/semantics/publishedVersio

Portuguese validation of the Cognitive Emotion Regulation Questionnaire short version in youth: Validity, reliability and invariance across gender and age

The Cognitive Emotion Regulation Questionnaire (CERQ) is a multidimensional measure widely used to access nine cognitive emotion regulation strategies. In this study, we examined the psychometric properties of the CERQ-Short Portuguese version. A sample of 1052 adolescents (aged 10–25 years old, 60.53% females) completed the CERQ-Short form, the Positive and Negative Affect Schedule, the Generalized Anxiety Disorder Scale, and the Patient Health Questionnaire. Confirmatory factor analyses showed that the nine latent dimensions of CERQ-Short provided an acceptable fit to the data. Measurement invariance (for gender and three age-groups), reliability and construct validity were adequate. The adaptative strategies were positively associated with higher positive affect, and maladaptive strategies with higher negative affect, symptoms of generalized anxiety and depression. These results suggest that CERQ-Short is a valid and reliable measure for Portuguese-speaking samples. Moreover, CERQ-Short’s length makes it a cost-effective tool for both clinicians and researchers.Fundação para a Ciência e Tecnologia - FCTinfo:eu-repo/semantics/publishedVersio

Intranasal fosphenytoin: the promise of phosphate esters in nose-to-brain delivery of poorly soluble drugs

Intranasal administration could increase both safety and efficacy of drugs acting on the central nervous system, but low solubility severely limits administration through this route. Phenytoin’s prodrug, fosphenytoin, is hydrophilic and freely soluble in water, but less permeable since it is dianionic. We aimed to assess whether this phosphoester prodrug could be a suitable alternative to phenytoin in intranasal delivery. Secondly, we aimed to compare simple formulation strategies in fosphenytoin delivery. Fosphenytoin formulations containing thermosensitive and/or mucoadhesive (hydroxypropyl methylcellulose, HPMC) polymers were developed, guided by viscosity, gelling temperatures, osmolality, and in vitro drug release tests. Then, a pharmacokinetic study was performed, comparing an intravenous fosphenytoin solution, an intranasal fosphenytoin solution, and intranasal fosphenytoin mucoadhesive formulations with or without albumin. Formulations containing HPMC allowed high drug strengths, and had a relatively fast release profile, which was not changed by albumin. Intranasal administration of a formulation with HPMC and albumin prolonged drug concentration over time and led to complete or even increased absolute bioavailability. Moreover, phenytoin’s blood levels did not reach the high peak obtained with intravenous administration. In conclusion, the use of phosphate ester prodrugs could be an efficient and safe strategy to increase the intranasal bioavailability of poorly soluble drugs.European Regional Development funds through the Operational Programme “Centro 2020”, through the ICON project (Interdisciplinary Challenges On Neurodegeneration, reference CENTRO-01-0145-FEDER-000013).info:eu-repo/semantics/acceptedVersio

Do difficulties in emotion regulation impact self-esteem and adult attachment? – the role of trauma

Abstract in proceedings of the Fourth International Congress of CiiEM: Health, Well-Being and Ageing in the 21st Century, held at Egas Moniz’ University Campus in Monte de Caparica, Almada, from 3–5 June 2019.This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.info:eu-repo/semantics/publishedVersio

A pilot study on the efficacy of a single intra-articular administration of Triamcinolone Acetonide, Hyaluronan, and a combination of both for clinical management of osteoarthritis in Police Working Dogs

Research Areas: Veterinary SciencesObjectives: To describe and compare the use and effectiveness of a single intra-articular injection (IA) of triamcinolone acetonide (TA), hyaluronan (HA), and a combination of both (TA+HA) in police working dogs with natural occurring hip osteoarthritis (OA). Study Design: Prospective, randomized, single-blinded study. Sample Population: Thirty animals with naturally occurring hip OA. Methods: Animals were randomly divided in three groups: GT, treated with 20 mg of TA per hip joint; GH, treated with treated 20 mg of HA per hip joint; and GTH, treated with a combination of 20 mg of TA and 20 mg of HA per hip joint. Response to treatment, measured by the Canine Brief Pain Inventory (divided in Pain Interference Score-PIS and Pain Severity Score-PSS) and the Hudson Visual Analog Scale (HVAS), was evaluated in seven different time points: T0 (before treatment), T1 (after 15 days), T2, T3, T4, T5, and T6 (after 1, 2, 3, 4, and 5 months, respectively). Results were compared using a Kruskal-Wallis test or a Wilcoxon signed ranks test, and p < 0.05 was set. Results: Comparing results of the different time points considered with T0, significant differences were registered in GH at T1 for HVAS (p = 0.03) and PIS (p = 0.04); and in GTH at T1 (p = 0.05 for HVAS and p = 1 for PSS or >= 2 for PIS. In GTH, treatment was successful in four animals between T1 and T5 (40%, n = 10) and three at T6-T7 (30%, n = 10) for PSS and three animals of GTH at T1 (30%), two at T2 (20%), three between T3 and T4 (30%), and two between T5 and T7 (20%)info:eu-repo/semantics/publishedVersio

Salt-Related Knowledge, Attitudes and Behavior in an Intervention to Reduce Added Salt When Cooking in a Sample of Adults in Portugal

(1) Background: Excessive salt intake is associated with an increased risk of hypertension and cardiovascular disease, so reducing it is critical. The main objective of this study was to verify whether one intervention to reduce added salt during cooking changed knowledge, attitudes and behavior (KAB) towards salt, and to analyze changes in the main sources of salt. (2) Methods: The intervention study was an 8-week randomized controlled trial with 97 workers from a public university. KAB in relation to salt were obtained through the WHO STEPwise questionnaire, and the main sources of salt were obtained by 24-h food recall and 24 h urinary sodium excretion over two days. (3) Results: After the intervention, participants in the intervention group reported a decrease in the addition of salt when cooking (p = 0.037), an increase in the percentage of subjects who avoided the consumption of processed foods (from 54.2% to 83.3%, p = 0.001), who looked for salt on food labels (from 18.8% to 39.6%, p = 0.013), and who bought low-salt food alternatives (from 43.8% to 60.4%, p = 0.039). However, there were no significant differences between the intervention group and the control group at baseline and post-intervention assessments. In the intervention group, after the intervention, the added salt decreased by 5%; food sources of salt such as the snacks and pizza group decreased by 7%, and the meat, fish and eggs group increased by 4%, but without statistical significance. (4) Conclusions: With innovative equipment for dosing salt when cooking, it is possible to change some dimensions of consumer behavior in relation to salt

A arma neuromarketing nas campanhas publicitárias infantis

O objetivo desta pesquisa está na promoção da discussão ética das propagandas, principalmente televisivas, de comunicação direta às crianças e adolescentes. Como estratégia, buscou-se resgatar a base teórica da área de Comunicação Social e prosseguiu pelos estudos e pesquisas até chegar ao novo segmento de estudo da área de Publicidade e Propaganda, o neuromaketing. Os resultados dessa investigação, associados à teoria pertinente, possibilitaram a compreensão do neuromarketing e a análise apontando as estratégicas de neuromarketing de um comercial que teve sua veiculação em TV aberta e fechada no início do ano de 2008

Antioxidant activity of Moringa oleifera tissue extracts

Moringa oleifera is an important source of antioxidants, tools in nutritional biochemistry that could be beneficial for human health; the leaves and flowers are used by the population with great nutritional importance. This work investigates the antioxidant activity of M. oleifera ethanolic (E1) and saline (E2) extracts from flowers (a), inflorescence rachis (b), seeds (c), leaf tissue (d), leaf rachis (e) and fundamental tissues of stem (f). The radical scavenging capacity (RSC) of extracts was determined using dot-blots on thin layer chromatography stained with a 0.4 mm 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) solution; spectrophotometric assays were recorded (515 nm). Antioxidant components were detected in all E1 and E2 from a, b and d. The best RSC was obtained with E1d; the antioxidants present in E2 reacted very slowly with DPPH. The chromatogram revealed by diphenylborinate-2-ethylamine methanolic solution showed that the ethanolic extract from the flowers, inflorescence rachis, fundamental tissue of stem and leaf tissue contained at least three flavonoids; the saline extract from the flowers and leaf tissue revealed at least two flavonoids. In conclusion, M. oleifera ethanolic and saline extracts contain antioxidants that support the use of the plant tissues as food sources.The authors acknowledge financial support from the Portuguese Fundacao para Ciencia e a Tecnologia (FCT) by the Post-doctoral grant SFRH/BPD/37349/2007. The Brazilian Programmes Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) for research grants and fellowships (PMGP and LCBBC) and the Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES) are acknowledged for financial support