Development of metformin HCl granules using brown flaxseed mucilage as a retardant polymer: effects of polymer and drug ratio

Flaxseed (Linum usitatissimum L.) is the seed of a multipurpose plant of pharmaceutical interest, as its mucilage can be used as a natural matrix to develop extended-release dosage forms and potentially replace synthetic polymers. In this study, a 3² factorial design with two replicates of the central point was applied to optimize the development of extended-release granules of metformin HCl. The total fiber content of the mucilage as well as the friability and dissolution of the formulations were evaluated. The lyophilized mucilage presented a high total fiber content (42.63%), which suggests a high efficiency extraction process. Higher concentrations of the mucilage and metformin HCl yielded less friable granules. In addition, lower concentrations of metformin HCl and higher concentrations of the mucilage resulted in slower drug release during the dissolution assays. The release kinetics for most formulations were better represented by the Hixson-Crowell model, while formulations containing a higher concentration of the mucilage were represented by the Korsmeyer-Peppas model. Nonetheless, five formulations showed a longer release than the reference HPMC formulation. More desirable results were obtained with a higher concentration of the mucilage (13-18%) and a lower concentration of metformin (40%)

Cytotoxic effects of the essential oil from leaves of Casearia sylvestris Sw. (Salicaceae) and its nanoemulsion on A549 tumor cell line

Extracts from leaves of C. sylvestris have cytotoxic effect in different tumor cell lines, possibly due to clerodane type diterpenes (casearins). On the other hand, there are few studies related to the antitumor activity of the essential oils from this species. This work evaluated for the first time the cytotoxicity effects of the pure essential oil and its nanoemulsion against A549 tumor cell line (human lung carcinoma). The essential oil was obtained from fresh leaves by hydrodistillation in a Clevenger-type apparatus and analyzed by GC/MS and GC/FID. Cytotoxicity evaluation was performed using the WST-1 test. The chemical analysis of the essential oil revealed a volatile fraction composed mainly of non-oxygenated sesquiterpenes (72.1%). The essential oil and its nanoemulsion exhibited cytotoxic activity against A549 tumor cells with EC50 of 4.0 μg/mL and EC50 of 1.0 μg/mL, respectively. Both samples displayed a dose dependent pattern (r = -0.79, p = 0.03) as determined by linear regression test

Influence of grape seed oil on sun protection factor in sunscreen formulations: a study using Central Composite Design approach

This study aimed to evaluate the influence of the grape seed oil (GSO) on the sun protection factor (SPF) of sunscreen emulsified formulations containing butyl methoxydibenzoylmethane (avobenzone (AVO)) and octyl methoxycinnamate (OMC) developed by phase inversion temperature (PIT) employing a Central Composite Design. Formulations were prepared by PIT emulsification process. Seventeen emulsions containing different amounts of GSO, AVO and OMC were obtained according to experimental design. In vitro SPF was determined using a spectrophotometric method. As expected, formulations with the highest concentrations of UV filters, AVO and OMC, resulted in the highest SPF values, while the lowest SPF values were obtained by formulations containing concentrations of these filters below the central point. In the tested concentrations, the variable OMC and its combination with GSO showed to influence the SPF linearly as a function of their concentrations in formulations. The combination of GSO with OMC contributed to increase in vitro SPF. The use of natural compounds with antioxidant activity, such as GSO, is a viable strategy to increase the effectiveness of sunscreens to protect the human skin against UV-induced damage

Foam mat drying of Tommy Atkins mango: Effects of air temperature and concentrations of soy lecithin and carboxymethylcellulose on phenolic composition, mangiferin, and antioxidant capacity

In this study, foam mat drying was applied to Tommy Atkins mango. Using a multifactorial design, the effect of soy lecithin (L) and carboxymethylcellulose (CMC) used as foam stabilizers (0–1.50 g/100 g), as well as temperature (T) (53–87 °C), on phenolic content and antioxidant capacity of mango were eval- uated. Mango pulp contains antioxidant, such as mangiferin, that can be utilized in foods to enhance their functional properties. Our results indicated that L and T had negative effects (p < 0.05) on the phenolic content and antioxidant capacity, whereas CMC had a positive effect (p < 0.05). Increasing the total amount of phenolic compounds present in dried mango contributed to the higher antioxidant capacity after the drying process. This study concluded that a drying T of 80 °C, and a concentration of 0.30 g/100 g of CMC and L are optimal for increased retention of phenolic compounds and antioxidant capacity.Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ)-E-26/111.710/201

Linear stability analysis of hypersonic boundary layers computed by a kinetic approach: a semi-infinite flat plate at 4.5 <= M-infinity <= 9

Linear stability analysis is performed using a combination of two-dimensional Direct Simulation Monte Carlo (DSMC) method for the computation of the basic state and solution of the pertinent eigenvalue problem, as applied to the canonical boundary layer on a semi-infinite flat plate. Three different gases are monitored, namely nitrogen, argon and air, the latter as a mixture of 79\% Nitrogen and 21\% Oxygen at a range of free-stream Mach numbers corresponding to flight at an altitude of 55km. A neural network has been utilised to predict and smooth the raw DSMC data; the steady laminar profiles obtained are in very good agreement with those computed by (self-similar) boundary layer theory, under isothermal or adiabatic wall conditions, subject to the appropriate slip corrections computed in the DSMC method. The leading eigenmode results pertaining to the unsmoothed DSMC profiles are compared against those of the classic boundary layer theory. Small quantitative, but no significant qualitative differences between the results of the two classes of steady base flows have been found at all parameters examined. The frequencies of the leading eigenmodes at all conditions examined are practically identical, while perturbations corresponding to the DSMC profiles are found to be systematically more damped than their counterparts arising in the boundary layer at the conditions examined, when the correct velocity slip and temperature jump boundary conditions are imposed in the base flow profiles; by contrast, when the classic no-slip boundary conditions are used, less damped/more unstable profiles are obtained, which would lead the flow to earlier transition. On the other hand, the DSMC profiles smoothed by the neural network are marginally more stable than their unsmoothed counterparts

Nanoemulsão aquosa, processo de produção de nanoemulsão aquosa e método de controle de pragas

DepositadaApresenta uma nanoemulsão com atividade bioinseticida, permite a incorporação de substâncias insolúveis em meio aquoso, através de uma formulação estável, fina e elegante. A possibilidade de solubilizar substâncias apolares em meio aquoso permite que a formulação seja utilizada na liberação de substâncias insolúveis bioativas, com potencial ação inseticida frente a pragas agrícolas e/ou aplicação em focos de proliferação de larvas de Aedes aegypti, importante vetor da dengue. Ainda, a presente invenção apresenta processo de produção de nanoemulsão aquosa e método de controle de pragas por nanoemulsão aquosa

Síndrome de Ehrlers-Danlos: Ehrlers-Danlos Syndrome

INTRODUÇÃO: A Síndrome de Ehlers-Danlos (SED) refere-se a distúrbios hereditários do tecido conjuntivo e da função do colágeno provocando como manifestações principais a hiperextensibilidade da pele, a hipermobilidade articular e a fragilidade de tecidos. De acordo com a Classificação Internacional de 2017, são reconhecidos 13 diferentes subtipos que caracterizam a sua extensa variabilidade clínica, por conseguinte, seu difícil diagnóstico. Embora apresente rara incidência, possui alta complexidade no tratamento multidisciplinar de suas complicações clínicas, o que motiva maior produção de literatura científica, ainda escassa, principalmente em território nacional. APRESENTAÇÃO DO CASO: M.M.V.R., 30 anos, sexo feminino, raça branca, G2P2, com história familiar positiva para hipermobilidade articular com queixa de dor crônica que piorou há cerca de 15 anos, associado a sintomas gastrointestinais, dermatológicos e vasculares. DISCUSSÃO: Realizou-se o diagnóstico de SED, com base na história clínica e no exame físico, utilizando-se os critérios de Beighton, a paciente foi encaminhada para acompanhamento multidisciplinar, com adesão ao tratamento observou-se melhora na qualidade de vida da paciente. CONCLUSÃO: É de se notar, portanto, que a SED é extremamente complexa desde o diagnóstico ao manejo, porém, este relato evidenciou que o diagnóstico precoce associado a um projeto terapêutico multidisciplinar pode trazer resultados impactantes

Laceração esplênica: AAST grau IV: Splenic laceration: AAST grade IV

Introdução: Em vítimas de trauma abdominal fechado, cerca de 13% das lesões são esplênicas. Devido a importância dessas lesões, algumas mudanças quanto ao tratamento foram realizadas ao longo dos anos. Foi criada uma escala de pontuação que reflete lesões por ordem de gravidade, impactando na conduta terapêutica de escolha, restringindo atuações cirúrgicas apenas a quadros mais severos. Apresentação do caso: Sexo masculino, 29 anos, com relato de trauma contuso em hipocôndrio esquerdo, orientado, verbalizando, palidez cutaneo-mucosa, hipotensão, taquipneia, abdome globoso, rígido e sinal de Kehr positivo. Observada lesão esplênica grau IV em laparotomia exploradora, evoluindo para esplenectomia total e lavagem da cavidade abdominal. Discussão: As lesões esplênicas mais frequentes são as de classificação grau IV. Atualmente o padrão-ouro para trauma esplênico é o tratamento não-operatório, devendo ser realizado junto à angioembolização da artéria esplênica em lesões graves e paciente hemodinamicamente estável. Mas em casos de instabilidade hemodinâmica, adota-se a laparotomia imediata e a esplenectomia. Conclusão: O baço é um órgão com importância significativa no sistema imune e hematopoiético, e por isso foi criada uma escala de pontuação pela Associação Americana de Cirurgia do Trauma (AAST) com a finalidade de determinar a gravidade das lesões esplênicas e evitar condutas cirúrgicas desnecessárias

Étude de la composition chimique de Calceolaria chelidonioides Humb. Bonpl. & Kunth. (de l'ethnopharmacologie à l'élaboration de formulations topiques contre Herpes simplex)

L espèce Calceolaria chelidonioides, inconnue scientifiquement jusqu à présent, a été choisie pour la réalisation de ce travail à partir des résultats obtenus au cours une étude ethnopharmacologique avec la communauté agricole de Alto de Macabú (RJ). Cette communauté est composée par des agriculteurs descendants, dans la plus grande partie, des italiens et allemands. Ils ont été interviewés dans le but de connaitre des espèces utilisées par la population dans des traitements dermatologiques. En effet, les interviews ont été structurées à partir d un questionnaire préalablement élaboré envisageant exclusivement des pathologies dermatologiques. Ce travail a rendu quelques espèces dont Calceolaria chelidonioides, utilisées par la population pour le traitement des problèmes cutanées et différents types des cancers. Notre objectif a été d isoler et caractériser les substances métabolisés par cette espèce, d évaluer la toxicité et les propriétés pharmacologiques de l extrait obtenu, jusqu au développement de formulations galéniques topiques avec l extrait comme actif, assurant sa sécurité et son efficacité. La partie phytochimie a été évaluée la composition de l huile essentielle en montrant la présence de 5 substances: un sesquiterpène, hexahydrofarnesilone (I); un stéroïde, androstan-17b-ol-3-one (II) and trois diterpènes, biformene (III) le composant majoritaire, rimuene (IV) et 8-acetoxi-9-epi-ent-pimara-15-ene (V). C est la première fois qu on a été évaluée l huile essentielle d une espèce du genre Calceolaria. Cette composition, considérée un peu bizarre au début à cause du grand temps de rétention obtenu pour les substances, a été réévaluée sur les mêmes conditions, en assurant l identité des métabolites. On a pu donc suggérer que l espèce Calceolaria chelidonioides synthétise un type d huile dans ses feuilles et ses tiges avec très bas volatilité et qu il possède quelque activité de protection à cause de son aspect collant et la forte odeur, n étant pas rare trouver quelques petits insectes attachés au végétal. La présence de biformene comme constitutif majoritaire est d accord avec ça. Cette substance huileuse, synthétisé normalement par quelques espèces végétaux des familles Araucariaceae et Leguminoseae, est trouvé comme une résine responsable pour la protection des ces espèces contre différents pathogènes et animaux. Cette activité peut encore être reliée à l huile présente dans les fleurs des espèces du genre Calceolaria que développent importante fonction d attraction des abeilles pour la pollinisation. De toute fois, la composition riche en diterpènes est d accord avec la phytochimie connue pour les espèces du genre. Il faut remarquer l inexistence dans la littérature scientifique un travaille d évaluation de la composition chimique d huile essentielle des espèces du genre Calceolaria. En utilisant différentes techniques chromatographiques il a été possible d isoler et d identifier le calceolarioside B (VI), le calceolarioside A (VII) et l apigenine (VIII) de la fraction acétate d éthyle des tiges; rutine (IX) et verbascoside (X) de la fraction acétate d éthyle des fleurs; et isorhamnetine 3-O-glucoside (XI) de la fraction butanolique des feuilles et des fleurs. L extrait éthanolique des feuilles et fleurs a été évalué sur le potentiel cytotoxique in vitro et en modèles in vivo d irritation oculaire et cutanée primaire sans mettre en évidence quelque type des toxicités dans les méthodes employées. Des études d évaluation toxicologique in vitro et in vivo de l extrait éthanolique des fleurs ont été aussi réalisées sans mettre en évidence de potentiel cytotoxique, phototoxique, mutagénique ou irritant, ceci indiquant la sécurité de son usage. Dans le but de mettre en évidence une activité pharmacologique, des essais d activité antioxydante ont été réalisés en modèle in vitro par la méthode du DPPH et in vivo avec Saccharomyces cereviseae. Dans le modèle in vitro tous les extraits éthanoliques ont été évalués. Les meilleurs résultats ont été démontrés pour l extrait de feuilles et fleurs. Dans la méthode in vivo employée, seulement l extrait des fleurs a été évalué, mettant en évidence une spécificité pour les radicaux peroxyde sans démontrer activité contre les radicaux superoxyde.Tous les extraits éthanoliques de Calceolaria chelidonioides ont été aussi evalués par rapport à des activités antimicrobiennes, montrant des résultats assez intéressants contre la souche MRSA surtout pour les extraits de fleurs et ceux de feuilles; Une activité antivirale contre le vírus Herpes simplex types 1 et 2, a aussi été demontrée, avec en général une plus grande specificité pour le type 2. La fraction acetate d ethyle des fleurs a montré la meilleure activité antivirale contre les deux types de virus. De plus, il a été possible d attribuer au verbascoside l activité anti HSV-2 observée pour l extrait brut de fleurs. Basé sur les résultats du screening toxicologique et pharmacologique, et également sur la plus grande viabilité économique, l extrait éthanolique de fleurs a été choisi comme celui présentant le plus grand intérêt pour le développement des formulations galéniques topiques. Deux formulations ont été mises au point, une nanoémulsion et une microémulsion avec 5% d extrait normalisé en 14,5% du verbascoside, visant la prophylaxie d'infections primaires ou récurrentes à l Herpes simplex type 2. Le pouvoir promoteur d absorption des formulations a été évalué en utilisant le verbascoside comme marqueur de l extrait. Parmi les produits testés, la microémulsion fut la formulation montrant les effets recherchés, c'est-à-dire l effet réservoir du verbascoside dans l épiderme. Grâce à ces résultats nous avons pu conclure que la microémulsion répondait aux conditions de la formulation désirée. Seront nécessaires de futures études de développement d'une méthodologie capable d'évaluer l'activité antivirale de la formulation finie, dont la réalisation n'a pas été possible dans ce travail.MONTPELLIER-BU Pharmacie (341722105) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

Effects of the Q80K Polymorphism on the Physicochemical Properties of Hepatitis C Virus Subtype 1a NS3 Protease

Hepatitis C virus genotype 1a (HCV-1a) comprises clades I and II. The Q80K polymorphism is found predominantly in clade I but rarely in clade II. Here, we investigated whether natural polymorphisms in HCV-1a clade II entailed structural protein changes when occurrence of the Q80K variant was simulated. Based on HCV-1a clade I and II protein sequences, the structure of the HCV-1a Q80K mutant NS3-4A was obtained by comparative modeling. Its physicochemical properties were studied by molecular dynamics simulations and network analysis. Results demonstrate that, in the presence of the K80 variant, clade II protease polymorphisms A91 and S/G174 led to variations in hydrogen bond occupancies. Structural analyses revealed differences in (i) flexibility of the H57 catalytic residue on the NS3 protease and (ii) correlations between amino acids on the NS3 protease and the NS4A cofactor. The latter indicated possible destabilization of interactions, resulting in increased separation of these proteins. The present findings describe how the relationships between different HCV-1a NS3 protease amino acid residues could affect the appearance of viral variants and the existence of distinct genetic barriers to HCV-1a isolates