Nanoemulsions and thermosensitive nanoemulgels of phenytoin and fosphenytoin for intranasal administration: Formulation development and in vitro characterization

Phenytoin is a low solubility anticonvulsant drug. It has, nonetheless, other possible therapeutic indications, such as neuropathic pain, including trigeminal neuralgia, or wound healing. Its use has decreased due to side effects, but nasal/intranasal administration could significantly increase drug safety and efficacy. The aim of this work was to develop and study nanoemulsions and thermosensitive nanoemulgels of phenytoin and fosphenytoin, in combination, for intranasal administration, with immediate and sustained release profiles. Nanoemulsions were prepared by adding the aqueous phase, containing gelling polymers in the case of nanoemulgels, to emulsion preconcentrates, followed, in the optimized procedure, by premix membrane emulsification. Formulation design and optimization was guided by drug strength, rheological behavior, osmolality, mean droplet size and polydispersity. Fosphenytoin interfered significantly with Carbopol but not with Pluronic's gelation, and allowed to achieve drug strengths equivalent to 22 or 27 mg/g of phenytoin in lead nanoemulsions, and 16.7 mg/g of phenytoin in the lead nanoemulgel. The final selected low viscosity nanoemulsions had an immediate or prolonged fosphenytoin release profile, depending of anhydrous phase proportion (10% or 40%, respectively). The thermosensitive nanoemulgel, with 10% anhydrous phase, showed prolonged drug release. Future studies will establish whether they are more suited for topical effects or therapeutic brain delivery.info:eu-repo/semantics/publishedVersio

Heat treatment and wounding as abiotic stresses to enhance the bioactive composition of pineapple by-products

Abiotic stress, like heat treatment and wounding, applied to pineapple by-products induce the accumulation of new compounds and add value. In this work the effect of the individual or combined application of wounding and heat treatment stresses on total phenolic content, antioxidant activity through complementary methods (DPPH, FRAP, and ABTS) and enzymatic activity (bromelain, phenylalanine ammonia lyase (PAL) and polyphenol oxidase) were evaluated. Whole and wounded pineapple shell and core were dipped in a hot water bath at 30 ± 1 °C or 40 ± 1 °C for 10 min and stored under refrigeration conditions (4 ± 1 °C) for 24 h or 48 h. Results allowed that pineapple by-products reacted differently to the tested stresses. For the core, the application of wounding and heat treatment (40 °C) before storage (24 h) induced a synergistic effect on the accumulation of phenols (increased 17%) and antioxidant activity (422%). For the shell samples, the treatment that most increased the content of phenols (14%) and antioxidant activity (3845%) was heat treatment at 30 °C and storage for 48 h. Treatments that positively influenced the content of phenols and antioxidant activity of the samples did not affect the activity of bromelain or PAL. This study showed that proper abiotic stresses could increase the functional value of by-products.The first author acknowledges the financial support from Fundação para a Ciência e a Tecnologia (FCT), Portugal, through Doctoral fellowship (SFRH/BD/109124/2015). This work was supported by the national funding of FCT, under the scope of the strategic funding to the research units LEAF, Linking Landscape, Environment, Agriculture, and Food, School of Agriculture, University of Lisbon, 1349-017 Lisbon (UIDP/04129/2020), Associate Laboratory LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro (UIDB/50006/2020) and CEB, Centre of Biological Engineering, Department of Biological Engineering, University of Minho, 4710–057 Braga (UIDP/04469/2020) through national funds and where applicable co-financed by the FEDER, within the PT2020 Partnership Agreement.info:eu-repo/semantics/publishedVersio

The importance of lipid conjugation on anti-fusion peptides against Nipah virus

© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).Nipah virus (NiV) is a recently emerging zoonotic virus that belongs to the Paramyxoviridae family and the Henipavirus genus. It causes a range of conditions, from asymptomatic infection to acute respiratory illness and fatal encephalitis. The high mortality rate of 40 to 90% ranks these viruses among the deadliest viruses known to infect humans. Currently, there is no antiviral drug available for Nipah virus disease and treatment is only supportive. Thus, there is an urgent demand for efficient antiviral therapies. NiV F protein, which catalyzes fusion between the viral and host membranes, is a potential target for antiviral drugs, as it is a key protein in the initial stages of infection. Fusion inhibitor peptides derived from the HRC-domain of the F protein are known to bind to their complementary domain in the protein's transient intermediate state, preventing the formation of a six-helix bundle (6HB) thought to be responsible for driving the fusion of the viral and cell membranes. Here, we evaluated the biophysical and structural properties of four different C-terminal lipid-tagged peptides. Different compositions of the lipid tags were tested to search for properties that might promote efficacy and broad-spectrum activity. Fluorescence spectroscopy was used to study the interaction of the peptides with biomembrane model systems and human blood cells. In order to understand the structural properties of the peptides, circular dichroism measurements and molecular dynamics simulations were performed. Our results indicate a peptide preference for cholesterol-enriched membranes and a lipid conjugation-driven stabilization of the peptide α-helical secondary structure. This work may contribute for the development of highly effective viral fusion against NiV inhibitors.This work was financially supported by Fundação para a Ciência e a Tecnologia—Ministério da Ciência, Tecnologia e Ensino Superior (FCT-MCTES, Portugal), through projects PTDC/BBB-BQB/3494/2014, PTDC/QUI-BIQ/114774/2009, PTDC/CCI-BIO/28200/2017 and Pest-OE/EQB/LA0004/2011, and by National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), project R01AI114736, lead by Anne Moscona (Columbia University Medical Center, NY, USA). This work was also financially supported by Project LISBOA-01-0145-FEDER-007660 (Microbiologia Molecular, Estrutural e Celular) funded by FEDER funds through COMPETE2020-Programa Operacional Competitividade e Internacionalização (POCI) and by national funds through FCT-MCTES. MCM, PMS and DL were supported by FCT-MCTES fellowships SFRH/BPD/118731/2016, SFRH/BD/118413/2016 and SFRH/BPD/92537/2013, respectively.info:eu-repo/semantics/publishedVersio

Polymeric biomaterials for wound healing

Skin indicates a person’s state of health and is so important that it influences a person’s emotional and psychological behavior. In this context, the effective treatment of wounds is a major concern, since several conventional wound healing materials have not been able to provide adequate healing, often leading to scar formation. Hence, the development of innovative biomaterials for wound healing is essential. Natural and synthetic polymers are used extensively for wound dressings and scaffold production. Both natural and synthetic polymers have beneficial properties and limitations, so they are often used in combination to overcome overcome their individual limitations. The use of different polymers in the production of biomaterials has proven to be a promising alternative for the treatment of wounds, as their capacity to accelerate the healing process has been demonstrated in many studies. Thus, this work focuses on describing several currently commercially available solutions used for the management of skin wounds, such as polymeric biomaterials for skin substitutes. New directions, strategies, and innovative technologies for the design of polymeric biomaterials are also addressed, providing solutions for deep burns, personalized care and faster healing.This research was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UIDB/04469/2020 unit, and by LABBELS—Associate Laboratory in Biotechnology, Bioengineering and Microelectromechanical Systems, LA/P/0029/2020. This study was also funded by program Marie Skłodowska-Curie grant (MSCA-RISE; FODIAC; 778388), and by the European Regional Development Fund (ERDF) through the Competitiveness factors Operational program—Norte 2020, COMPETE and by National Funds through the FCT—under the project AgriFood XXI (NORTE- 01-0145-FEDER-000041)

Probing the relationship between late endogenous ERP components with fluid intelligence in healthy older adults

The world population is rapidly aging, bringing together the necessity to better understand the advancing age. This characterization may be used to aid early diagnosis and to guide individually-tailored interventions. While some event-related potential (ERP) components, such as the P300 and late positive complex (LPC), have been associated with fluid intelligence (Gf) in young population; little is known whether these associations hold for older people. Therefore, the main goal of this study was to assess whether these ERP components are associated with Gf in the elderly. Fifty-seven older adults performed a continuous performance task (CPT) and a visual oddball paradigm while EEG was recorded. Participants were divided into two groups, according to their performance in the Raven's Advanced Progressive Matrices test: high-performance (HP) and low-performance (LP). Results showed that the HP group, compared to the LP group, had higher LPC amplitudes in the CPT and shorter P300 latencies in the oddball task, highlighting the role of ERP components as a potential electrophysiological proxy of Gf abilities in the elderly.We thank Camara Municipal de Vila Nova de Famalicao (Dr. Rui Baptista and Bruno Gomes), Associacao Geracoes (Dr. Cristiana Oliveira, Clara and Daniela Silva), Santa Casa da Misericordia de Barcelos (Dr. Ricardo Vieira and Dr. Helder Longras), and Fundacao Bomfim (Dr. Raquel Polonia) for hosting the study; all the volunteers for their participation, as well as, Silvia Alves, Carla Barros, Anabela Fernandes and our colleagues from the Psychological Neuroscience Laboratory for all the help during data collection and recruitment. This work was supported by the Portuguese Foundation for Science and Technology (FCT) [Doctoral Grants No. SFRH/BD/80965/2011 (awarded to ACT) and No. PD/BD/105964/2014 (awarded to DRP)] and by the Bial Foundation (Grant Number #286/16). It was conducted at the Psychology Research Centre (PSI/01662), School of Psychology, University of Minho, and supported by the Portuguese Foundation for Science and Technology and the Portuguese Ministry of Science, Technology and Higher Education (Grant Number UID/PSI/01662/2019), through the national funds (PIDDAC). DP was supported by FCT (Grant Number SFRH/BPD/120111/2016). SC was funded by the FCT (Grant Number IF/00091/2015) and COMPETE 2020 (Grant Number PTDC/PSI-ESP/29701/2017)

Storage Stability and In Vitro Bioaccessibility of Microencapsulated Tomato (Solanum Lycopersicum L.) Pomace Extract

Tomato pomace is rich in carotenoids (mainly lycopene), which are related to important bioactive properties. In general, carotenoids are known to react easily under environmental conditions, which may create a barrier in producing stable functional components for food. This work intended to evaluate the storage stability and in vitro release of lycopene from encapsulated tomato pomace extract, and its bioaccessibility when encapsulates were incorporated in yogurt. Microencapsulation assays were carried out with tomato pomace extract as the core material and arabic gum or inulin (10 and 20 wt%) as wall materials by spray drying (160 and 200 C). The storage stability results indicate that lycopene degradation was highly influenced by the presence of oxygen and light, even when encapsulated. In vitro release studies revealed that 63% of encapsulated lycopene was released from the arabic gum particles in simulated gastric fluid, whereas for the inulin particles, the release was only around 13%. The feed composition with 20% inulin showed the best protective ability and the one that enabled releasing the bioactives preferentially in the intestine. The bioaccessibility of the microencapsulated lycopene added to yogurt increased during simulated gastrointestinal digestion as compared to the microencapsulated lycopene alone. We anticipate a high potential for the inulin microparticles containing lycopene to be used in functional food formulationsinfo:eu-repo/semantics/publishedVersio

Evaluation of Microbial Biomass in Agroforestry Systems Using Forage Cactus and \u3ci\u3eLeucaena leucocephala\u3c/i\u3e and \u3ci\u3eGliricidia sepium\u3c/i\u3e

Vegetation type can affect soil microbiology in agroforestry systems. Plants release different organic exudates in the rhizosphere, affecting microbial growth. This study evaluated the effect of forage cactus intercropped with different tree legumes on soil microbial biomass. The research was performed in a tropical semiarid Regosol at Caruaru Experimental Station, Agronomic Institute of Pernambuco, Northeast Brazil. Treatments included: i) Gliricidia sepium (Jacq.) Steud and forage cactus IPA-Sertânia (Nopalea cochenillifera Salm Dyck); and ii) Leucaena leucocephala [Lam.] de Wit.) and forage cactus IPA-Sertânia. Treatments were allocated in a randomized complete block design in a split-split-plot scheme, with four replications. Main plots consisted of agroforestry system, split-plot was the distance from tree rows, and split-split-plot soil depths. Organic fertilization with cattle manure was applied aiming a rate of 200 kg N ha-1. Tree legumes were planted in double rows spaced 9 x 1 x 0.5 m and cactus planted between double rows spaced by 1 x 0.25 m. Plot size measured 960 m2. Soil collection occurred in the rainy period (April 2019). Samples were collected at depths of 0-10 cm and 10-20 cm at 0, 1.5, 3.0, and 4.5 m away from legume rows. Response variables included soil basal respiration (SBR), microbial biomass C (C-mic), and metabolic quotient (qCO2). Data were subjected to analysis of variance using SAS. Means were compared by Tukey test at 5% significance. No significant difference was observed for SBR, MBC, and qCO2, with average values of 9.36, 202.98, and 0.05, and standard error 1.16, 10.90 and 0.01, respectively, in the different distances away from tree legumes. Introduction of arboreal legumes did not cause changes in microbial biomass. Microbial activity was similar in soils under forage cactus intercropped with Leucaena or Gliricidia

Biomechanical properties of breast tissue, a state-of-the-art review

This paper reviews the existing literature on the tests used to determine the mechanical properties of women breast tissues (fat, glandular and tumour tissue) as well as the different values of these properties. The knowledge of the mechanical properties of breast tissue is important for cancer detection, study and planning of surgical procedures such as surgical breast reconstruction using pre-surgical methods and improving the interpretation of clinical tests. Based on the data collected from the analysed studies, some important conclusions were achieved: (1) the Young’s modulus of breast tissues is highly dependent on the tissue preload compression level, and (2) the results of these studies clearly indicate a wide variation in moduli not only among different types of tissue but also within each type of tissue. These differences were most evident in normal fat and fibroglandular tissues

POPs’ effect on cardiometabolic and inflammatory profile in a sample of women with obesity and hypertension

Persistent organic pollutants (POPs) are man-made compounds with metabolic disruption impact. We investigated the effect of POP exposure in the cardiometabolic and inflammatory profile in a population of women with obesity and hypertension. In 43 premenopausal women (22 treated vs. 21 nontreated) undergoing bariatric surgery, blood and adipose tissue samples (visceral (vAT) and abdominal subcutaneous (scAT)) were collected. Median concentrations of ∑HCH and ∑POPs in vAT were significantly higher in treated women. VAT ∑HCH and scAT ∑HCH and ∑POPs concentrations were positively correlated with systolic blood pressure in the non-treated group. Our findings suggest that exposure to POPs and its accumulation in vAT and circulating in plasma may be associated to a higher cardiovascular risk in women with obesity and hypertension, with or without antihypertensive treatment.This work was supported by FCT (Fundo Social Europeu, Programa Operacional Potencial Humano da EU (POPH); PEst-OE/SAU/UI0038/2011; SFRH/BD/46640/2008, SFRH/BD/64691/2009), and Projetos de Investigação na Pré-graduação 2011, Universidade do Porto.info:eu-repo/semantics/publishedVersio

Effect of moderate hydrostatic pressures on the enzymatic activity and bioactive composition of pineapple by-products

Special Issue Original ArticleThe application of abiotic stresses by moderate hydrostatic pressures (MHP) is still underdeveloped. Abiotic stresses allow activating the enzymatic complexes inducing the synthesis of de novo bioactive compounds. Pineapple by-products are rich in bromelain and bioactive compounds that can be enhanced through abiotic stresses. The aim of this study was to evaluate the effect of MHP on the enzymatic activity of pineapple by-products. Pineapple by-products were submitted to MHP (50–400 MPa between 1 and 15 min) according to a central composite factorial design matrix. Samples were stored at 5 ± 1 C for 24 hr, to allow enzymatic activity to occur. Enzymatic and antioxidant activities and total phenolic compounds (TPC) were quantified. MHP promoted a 262% increase in the phenylalanine ammonia-lyase activity and 36% increase in TPC, in shell samples. In core the activity of bromelain increased 350%. These results pinpoint the potential to increase the value of pineapple by-products by enhancing the amounts of bioactive compounds through MHP applicationinfo:eu-repo/semantics/publishedVersio