Creation of pacemaker remote monitoring networks between hospital and pharmacies during Covid-19 outbreak.

INTRODUCTION: Remote Monitoring (RM) of Cardiac Implantable Electronic Devices (CIEDs) is proven to be safe and efficient. It has been adopted in our center since years. At the time of the recent Covid-19 outbreak, we introduced and tested a collaborative organizational model, through a new RM device (Totem), creating a network with the surrounding territory and limiting CIED patients' presence in hospital. METHODS: We involved 4 neighbor pharmacies where Totem devices were installed; we called and informed 64 patients with Totem compatible pacemaker (PM) about the possibility to perform their PM follow-up (FU) in-pharmacy; 58 gave their consent and their data were inserted into our RM database. RESULTS: During an 18-month FU period, a total of 70 RM transmissions have been received: one alert of high atrial burden triggering a pharmacological optimization, one alert of high ventricular impedance leading to a new ventricular lead implantation and four alerts of elective replacement indicator. Fulfilled questionnaires revealed complete patient satisfaction. CONCLUSIONS: A collaborative network between our hospital and the surrounding territory to perform RM FUs of CIEDs during Covid-19 pandemic was feasible, leading to patient compliance and satisfaction and revealing important technical and clinical alerts.

Hura crepitans L. Extract: Phytochemical Characterization, Antioxidant Activity, and Nanoformulation.

The purpose of this study was to improve the knowledge on Hura crepitans L., a plant belonging to the Euphorbiaceae family that, on the one hand, is known to be toxic, but on the other, is a source of polyphenols with health-promoting effects. Different green extraction methods were applied, varying solvent, temperature, and duration of extraction, which can influence the phytochemical profile and biological activity of plant extracts, and the extracts were fully characterized. Aqueous extracts exhibited a superior antioxidant activity, as indicated by different spectrophotometric tests, and were cytoprotective to HepG2 cells used as model cells. Liquid chromatography-mass spectrometry analyses were performed to identify the secondary metabolites involved in these effects and demonstrated that solvent, duration, and temperature indeed influenced the extraction of polyphenols. Furthermore, the most promising extract, in terms of antioxidant potential, was incorporated into liposomes with the aim of promoting cell interaction and enhancing the antioxidant activity.

Identification of Limonol Derivatives as Heat Shock Protein†90 (Hsp90) Inhibitors through a Multidisciplinary Approach.

The identification of inhibitors of Hsp90 is currently a primary goal in the development of more effective drugs for the treatment of various types of multidrug resistant malignancies. In an attempt to identify new small molecules modulating the activity of Hsp90, we screened a small library of tetranortriterpenes. A high-affinity interaction with Hsp90 inducible form was uncovered for eight of these compounds, five of which are described here for the first time. By monitoring the ATPase activity and the citrate synthase thermal induced aggregation, compound 1 (cedrelosin A), 3 (7α-limonylacetate), and 5 (cedrelosin B), containing a limonol moiety, were found to be the most effective in compromising the Hsp90α chaperone activity. Consistent with these findings, the three compounds caused a depletion of c-Raf and pAkt Hsp90 client proteins in HeLa and MCF/7 cell lines. Induced fit docking protocol and molecular dynamics were used to rationalize the structural basis of the biological activity of the limonol derivatives. Taken together, these results point to limonol-derivatives as promising scaffolds for the design of novel Hsp90α inhibitors.

A Novel Tirucallane-type Triterpene and Sesquiterpene from Trichilia maynasiana.

One new tirucallane-type triterpene {3ß, 24-dihydroxytirucallan-7,25-diene, 24-sulfate (1)}, one new sesquiterpene {7-epi-10-hydroxychabrol-1(2)-en-4,5-dione A (2)}, together with three known tirucallanes, and four aromadendranes were isolated from the leaves of Trichilia maynasiana C. DC.. Their structures were determined by means of NMR spectroscopy, mass spectrometric analysis, and chemical methods.

Bioactive limonoids from the leaves of Azaridachta indica (Neem).

Eight new limonoids (1-8) and one new phenol glycoside (9), along with six known compounds, were isolated from the leaves of Azaridachta indica. The structures of 1-9 were elucidated on the basis of spectroscopic data analysis. Compounds isolated were assayed for their cytotoxicity against different cancer cell lines. Moreover, their ability to interact with the molecular chaperone Hsp90, affecting its biological activity, was tested.

Actividad antibacteriana del Schinus molle l cultivado en Italia / Antibacterial activity of Schinus molle I grown in Italy

El objetivo de esta investigación fue determinar la actividad antibacteriana del extracto etanolico de las hojas y el extracto hexanoico obtenido de los frutos del Schinus molle L. (Anacardiaceae), cultivado en Italia, con un rendimiento de 32,42 % y 5,63 %, respectivamente. Independientemente del tipo de extracto y de la parte de la planta utilizada, el Schinus molle L., mostró una buena actividad antibacteriana contra bacterias Gram positivas (S. aureus ATCC 29213 y E. faecalis ATCC 29212) con una CMI 16 µg/mL. El rango de CBM de estas bacterias estuvo entre 32 y 64 mg/mL, respectivamente.

The aim of this research was to determine antibacterial activity of etanolic extract of the leaves and hexanoic extract obtained from fruits of Schinus molle L. (Anacardiaceae), grown in Italia. with a yield of 32,42 % and 5,63 %, respectively. Whatever type of extract and the plant part used, Schinus molle L., showed good antibacterial activity against Gram positive bacteria (S. aureus ATCC 29213 and E. faecalis ATCC 29212) with MIC 16 mg/mL. Range of MBC of these bacteria were between 32 and 64 mg/mL respectively.

Structural characterization of tetranortriterpenes from Pseudrocedrela kotschyi and Trichilia emetica and study of their activity towards the chaperone Hsp90.

Investigation of roots extracts Pseudrocedrela kotschyi and Trichilia emetica led to identification of 5 limonoid derivatives, Kotschyins D-H, and 11 known compounds. Their structures were elucidated by extensive 1D and 2D NMR experiments in conjunction with mass spectrometry. A surface plasmon resonance (SPR) approach was adopted to screen their Hsp90 binding capability and kotschyin D showed a significant affinity for the chaperone. Therefore, the characterization of the biological activity of kotschyin D by means of a panel of chemical and biological approaches, including limited proteolysis, molecular docking and biochemical and cellular assays, was performed. Our result indicated this compound as a type of client selective Hsp90 inhibitor, directly binding to the middle domain of the protein and possibly preventing its interaction with the activator of Hsp90 ATPase 1 (Aha1).

Anti-angiogenic activity evaluation of secondary metabolites from Calycolpus moritzianus leaves.

Angiogenesis is a crucial step in many pathological conditions like cancer, inflammation and metastasis formation; on these basis the search for antiangiogenic agents has widened. In order to identify new compounds able to interfere in the Vascular Endothelial Growth Factor Receptor-1 (VEGFR-1, also known as Flt-1) recognition by VEGFs family members, we screened Calycolpus moritzianus (O. Berg) Burret leaves extracts by a competitive ELISA-based assay. MeOH and CHCl3 extracts and several their fractions demonstrated to be able to prevent VEGF or PlGF interaction with Flt-1, with an inhibition about 50% at concentration of 100 microg/mL. Phytochemical and pharmacological investigation of the active fractions led to the isolation of flavonoids, and terpenes.

Isolation and structural characterization of glycosides from an anti-angiogenic extract of Monnina obtusifolia H.B.K.

Angiogenesis, the growth of new blood vessels from the pre-existing vasculature is of physiological and pathological importance. Substantial data over the last decade has implicated uncontrolled angiogenesis with various pathological states. Vascular endothelial growth factors (VEGFs) play a critical role in its regulation, and have become one of the most interesting anti-angiogenesis targets. We have investigated the anti-angiogenic potential of plant extracts in a preliminary ELISA screening. The n-BuOH extract obtained from the leaves of Monnina obtusifolia (Polygalaceae) demonstrated an inhibition of VEGF-A or Placental Growth Factor interaction with Flt-1 (VEGF receptor 1), with an inhibition over 50% in particular for VEGF-A/Flt-1 interaction at a concentration of 500 µg/mL. Successively fractionation of the bioactive n-BuOH extracts of M. obtusifolia aerial parts led to the isolation of six new compounds, 1-O-(4-hydroxy-2-methylene-butanoic acid)-6-O-ß-D-(4-hydroxy-2-methylene-butanoyl)-glucopyranose (1), 1-O-(isopentenyl)-6-O-ß-D-(4-hydroxy-2-methylene-butanoyl)-glucopyranose (2), 1-O-(4-hydroxy-2-methylene-butanoic acid)-6-O-ß-D-(isovaleroyl)-glucopyranose (3), 1-O-(3-methylbut-3enyl)-6-O-ß-D-(isovaleroyl)-glucopyranose (4), two new sucrose esters, 3,4-O-ß-D-di-feruloyl-fructofuranosyl-6-O-α-D-(p-coumaroyl)-glucopyranoside (5), and 3,4-O-ß-D-di-feruloyl-fructofuranosyl-6-O-α-D-(caffeoyl)-glucopyranoside (6), together with known flavonoids. Their structures were established on the basis of detailed spectral analysis. Since none of the isolated compounds showed a relevant inhibition of VEGFs, the biological activity observed for the butanolic extract might be due to the presence of a combination of compounds acting synergistically.

Quinic acids from Aster caucasicus and from transgenic callus expressing a beta-amyrin synthase.

Several different classes of secondary metabolites, including flavonoids, triterpenoid saponins and quinic acid derivatives, are found in Aster spp. (Fam. Asteraceae). Several Aster compounds revealed biological as well as pharmacological activities. In this work, a phytochemical investigation of A. caucasicus evidenced the presence of quinic acid derivatives, as well as the absence of triterpene saponins. To combine in one species the production of different phytochemicals, including triterpenes, an Agrobacterium-mediated transformation of A. caucasicus was set up to introduce A. sedifolius beta-amyrin synthase (AsOXA1)-encoding gene under the control of the constitutive promoter CaMV35S. The quali-quantitative analysis of transgenic calli with ectopic expression of AsOXA1 showed, in one sample, a negligible amount of triterpene saponins combined with higher amount of quinic acid derivatives as compared with the wild type callus.

Determinación del contenido de vitamina C en miel de abejas venezolanas por volumetría de óxido-reducción / Determination of the vitamin C content in honey of Venezuelan bees by oxide-reduction volumetry

En este trabajo se ha determinado el contenido de Vita mina C en mieles de abeja de la región andina venezolana. La Vitamina C pertenece junto con la Vitamina B al grupo de las hidrosolubles. Ayuda en el desarrollo de huesos, cartílagos, a la absorción del hierro, a la producción de colágeno (actuando como cofactor en la hidroxilación de los aminoácidos lisina y prolina). La propiedad química antioxidante es la más importante de la vitamina C; esto ayuda a prevenir la oxidación de las vitaminas A y E, y de algunas vitaminas del grupo B, tales como la riboflavina, tiamina, ácido fólico, y ácido pantoténico. Desarrolla acciones anti-infecciosas y actúa como un desintoxicante ya que puede reducir la toxicidad de metales pesados como el plomo, mercurio y arsénico. La Vitamina C no es sintetizada por el hombre, por esta razón debe ser ingerida en la dieta, los alimentos más ricos en Vitamina C son vegetales verdes, frutas cítricas y papas, entre otros. La Vitamina C esta presente en la miel en bajas concentraciones, el HPLC es la técnica más apropiada para su cuantificación, pero es una técnica costosa y de difícil acceso. Se propone una metodología más sencilla basada en volumetría de óxido-reducción, ya que la Vitamina C se oxida a ácido dehidroascórbico, por reacción con 2,6-diclorofenolindofenol el cual se reduce mediante una reacción redox a una solución incolora. Los valores encontrados, reportados en mg vit C/100 g miel, oscilan entre 12.74 y 40.13, con una media de 20.982 ± 2.8896.

This study has determined the content of Vitamin C in honey bee in the Andean Venezuelan region. The Vitamin C be - longs together with vitamin B to the group of water-soluble. Assists in the development of bones, cartilage, the absorption of iron, the production of collagen (acting as a cofactor in the hydroxylation of amino acids lysine and proline). The chemical antioxidant property is the most important of vitamin C. This helps prevent the oxidation of vitamins A and E, and some B vitamins such as riboflavin, thiamin, folic acid and pantothenic acid. Develops anti-infectious actions and acts as a detoxifying because it can reduce the toxicity of heavy metals like lead, mercury and arsenic. Vitamin C is not synthesized by man, for this reason should be eaten in the diet, foods rich in Vitamin C are green vegetables, citrus fruits and potatoes, among others. Vitamin C is present in honey in low concentrations, the HPLC technique is best suited to their quantification, but is a costly and difficult to access. It proposes a simpler method based on oxide-reduction volumetric, as the Vitamin C is oxidized to dehidroascorbic acid, a reaction with 2.6-dichlorophenolindophenol which is reduced by a redox reaction to a colourless solution. The values found, reported in mg vit C/100 g honey, ranging between 12.74 and 40.13, with an average of 20,982 ± 2.8896.

Actividad antibacteriana y antifúngica de extractos de algas marinas venezolanas / Antibacterial and antifungal activity from extracts of Venezuelan marine algae

En este trabajo se evaluaron las propiedades bioactivas antibacterianas y antimicóticas de 33 extractos (etanol, diclorometano, hexano) obtenidos de 11 especies de algas marinas recolectadas en las localidades de San Juan de Los Cayos y Chichiriviche, Estado Falcón, Venezuela. La actividad antibiótica y antimicótica de los extractos se evaluó mediante la aparición de halos de inhibición contra bacterias Gram positivas (Staphylococcus aureus), Gram negativas (Pseudomona aeruginosa, Klebsiella pneumoniae, Escherichia coli) y el hongo Candida albicans. De los 33 extractos ensayados sólo 17 presentaron actividad antibacteriana (5 con etanol, 6 con diclorometano y 6 con hexano), resultando activos 14 frente a las especies Gram(-) y 4 contra la especie Gram(+). Las especies algales que mostraron actividad antibacteriana fueron: Acanthophora sp., Bryothamnion triquetrum, Gracilaria sp., Gelidium sp., Caulerpa mexicana, Caulerpa sp., Caulerpa spp., Halimeda incrassata, Ulva sp., Codium decorticatum, Sargassum sp. Ninguno de los extractos de algas ensayados presentó actividad antimicótica sobre Cándida albicans. Los resultados obtenidos permiten concluir que las algas de la costa occidental de Venezuela, presentan compuestos bioactivos con actividad antibacteriana.

This study assessed the antibacterial and antifungal properties of 33 extracts (ethanol, dichloromethane, hexane) from 11 species of marine algae collected in the villages of San Juan de Los Cayos and Chichiriviche, Estado Falcon, Venezuela. The antibiotics and antifungal activity of extracts was evaluated by the appearance of halos of inhibition against gram-positive bacteria (Staphylococcus aureus), Gram negative (Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli) and the fungus Candida albicans. Of the 33 tested extracts showed antibacterial activity only 17 (5 with ethanol, 6 and 6 with dichloromethane-hexane), resulting assets compared to 14 species Gram(-) and 4 against the kind Gram(+). The algae species that showed antibacterial activity were: Acanthophora sp., Bryothamnion triquetrum, Gracilaria sp., Gelidium sp., Caulerpa mexicana, Caulerpa sp., Caulerpa spp., Halimeda incrassata, Ulva sp., Codium decorticatum, Sargassum sp.. None of the tested extracts from algae introduced antifungal activity on Candida albicans. The findings suggest that the algae on the west coast in Venezuela have bioactive compounds with antibacterial activity.

Determinación de la actividad antimicrobiana de los extractos de la azadirachta indica A. Juss (Neem) / Antimicrobiano activity determination of the extracts of Azadirachta A Juss (Neem)

Azadirachta indica A. juss, conocida como Neem, árbol sagrado, originaria de la India, utilizada en la medicina tradicional del Africa por sus propiedades bactericidas, antinflamatorias, antivirales, antipiréticas, insecticidas y fungicidas. Posee sustancias químicas activas capaces de combatir eficazmente numerosas enfermedades. En este estudio se realizó una evaluación de la actividad antimicrobiana de los extractos acuosos, etanólicos y cetónicos de las hojas sobre varios microorganismos como fueron: E. coli enteroinvasiva y E. coli enterotóxica, S aureus ATCC 25923, P. aeruginosa ATCC 27853, C. krusei ATCC 6258 y C. albicans ATCC 90028. Los resultados obtenidos en esta evaluación microbiológica muestran que dichos extractos, a la dosis de 0,02g/ml, presentaron una acción antibacteriana y antifúngica sobre los diferentes microorganismos de una maanera selectiva. Los extractos etanólicos y cetónicos mostraron actividad contra E. coli entroinvasiva y E. coli enterotóxica, S. aureus ATCC 25923, P. aeruginosa ATCC 27853 y C. krusei ATCC 6258. Los extractos acuosos no presentaron actividad contra ninguno de los microorganismos ensayados en la dosis empleada. Ninguno de los extractos evaluados fue activo contra la levadura C. albicans ATCC 90028

Producción de proteína unicelular de levaduras crecidas en desechos de harina de maíz precocida (Zea mays) / Unicell protein of production of grown yeasts in waste of precooked corn flour (zea mays)

En el presente trabajo se utilizaron desechos generados durante el empacado de harina de maíz precocida, para enriquecerlos en proteínas microbianas por procesos de fermentación líquida, los cuales poseen 78,55 por ciento de almidón y 7,8 por ciento de proteína cruda con el objeto de enriquecerlos en proteínas microbianas por procesos de fermentación líquida. El desecho fue sometido a hidrólisis por tratamientos químicos y enzimáticos. En la hidrólisis química, se utilizaron valores de 1:10 (p/v) para la relación desecho/ ácido sulfúrico al 2 por ciento, en la hidrólisis enzimática, se realizó con una levadura productora de &-amilasas y con una enzima comercial. Se determinaron, a nivel de fiolas y de fermentadores de 2.5 litros, las condiciones óptimas de crecimiento de Candida utilis, Saccharomyces cerevisiae y Schwannmyces. castelli. Las condiciones experimentales: pH 4;5 30°C. 1 vvm; 20 g/L del desecho, 1,25 g/L de (urea, sulfato de amonio, extracto de levadura y extracto de malta diastásico líquido). La fermentación de 250 litros se realizó en una fermentador PROYETSAN, la hidrólisis enzimática se realizó con Sch. castelli, y el consumo de azúcares con S. cerevisiae, obteniéndose 9 g de biomasa de peso seco/litro, y un incremento proteico de 7.8 a 41.13 por ciento. Se puede concluir que los desechos de harina de maíz precocida constituyen un substrato adecuado para obtener biomasa o proteína unicelular, que podría ser destinada como suplemento en formulaciones para alimentación animal

Producción de proteína unicelular a partir de desechos de vinaza / Unicell protein production to leave of waste vinaza

Las proteínas para consumo se obtienen principalmente de productos derivados animales y algunos vegetales como los cereales. Debido al crecimiento de la población mundial es necesario aumentar la calidad de los alimentos consumidos y los últimos estudios están orientados a encontrar nuevas fuentes proteicas. Por lo que se decidió estudiar la producción de proteína unicelular, específicamente de Candida utilis, a partir de un desecho agroindustrial; la vinaza. Para ello se realizaron una serie de fermentaciones con vinaza recolectada en la laguna de homogenización de una planta de tratamiento de una industria alcohólica, previamente esterilizada, e inoculada con cándida utilis, para encontrar las condiciones de crecimiento más apropiadas de esta levadura en la vinaza. El estudio se basó en agregar diferentes concentraciones de una mezcla de nutrientes conformada por sulfato de amonio, úrea y extracto de malta, para enriquecer la vinaza. Se experimentó con cuatro concentraciones de la mezcla de nutrientes: 0, 0.5, 1, y 1,5 g/L, resultando seleccionada la concentración de 1 g/L al presentar una alta concentración celular 2,2 x 10 al 8 células/ml, en un tiempo de fermentación de 5 h. La vinaza recolectada en la laguna, la proteína unicelular producida y el desecho líquido resultante de la fermentación fueron sometidos a una caracterización que incluyó los siguientes análisis: materia seca, proteína cruda, fibra cruda, extracto etéreo, ceniza y extracto libre de nitrógeno; encontrándose que la proteína unicelular obtenida presentó un 37 ± 4 por ciento de proteína cruda, con lo cual se demostró que se obtiene un producto de alto contenido proteico