In Vitro and In Vivo Effects of Tamoxifen against Larval Stage Echinococcus granulosus

Cystic echinococcosis is a zoonotic infection caused by the larval stage of the cestode Echinococcus granulosus. Chemotherapy currently employs benzimidazoles; however, 40% of cases do not respond favorably. With regard to these difficulties, novel therapeutic tools are needed to optimize treatment in humans. The aim of this work was to explore the in vitro and in vivo effects of tamoxifen (TAM) against E. granulosus. In addition, possible mechanisms for the susceptibility of TAM are discussed in relation to calcium homeostasis, P-glycoprotein inhibition, and antagonist effects on a putative steroid receptor. After 24 h of treatment, TAM, at a low micromolar concentration range (10 to 50 μM), inhibited the survival of E. granulosus protoscoleces and metacestodes. Moreover, we demonstrated the chemotherapeutic and chemopreventive pharmacological effects of the drug. At a dose rate of 20 mg/kg of body weight, TAM induced protection against the infection in mice. In the clinical efficacy studies, a reduction in cyst weight was observed after the administration of 20 mg/kg in mice with cysts developed during 3 or 6 months, compared to that of those collected from control mice. Since the collateral effects of high TAM doses have been largely documented in clinical trials, the use of low doses of this drug as a short-term therapy may be a novel alternative approach for human cystic echinococcosis treatment.Fil: Nicolao, María Celeste. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Biologia. Laboratorio de Zoonosis Parasitarias; ArgentinaFil: Elissondo, María Celina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Biologia. Laboratorio de Zoonosis Parasitarias; ArgentinaFil: Denegri, Guillermo Maria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Biologia. Laboratorio de Zoonosis Parasitarias; ArgentinaFil: Goya, Alejandra Beatriz. Ministerio de Agricultura, Ganadería, Pesca y Alimento. Servicio Nacional de Sanidad y Calidad Agroalimentaria; ArgentinaFil: Cumino, Andrea Carina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Biologia. Laboratorio de Zoonosis Parasitarias; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Química; Argentin

Diseños de protocolos criptográficos: nuevas propuestas basadas en grafos

Se destaca el papel que la teoría de grafos puede jugar en el entorno de la criptografía moderna. Se introduce también una nueva metodología de diseño en el campo de los protocolos criptográficos. Entre los protocolos estudiados destacan as de transferencia inconsciente y compromiso de bits por se considerados primitivos esenciales para el diseño de esquemas criptográficos más complejos. También se presta especial atención a las demostraciones de conocimiento nulo aportando nuevos algoritmos orientados a resolver el problema de la identificación

Recomendaciones no farmacológicas para la prevención de la recurrencia de la litiasis urinaria

La litiasis urinaria es la formación de un cálculo de pequeños minerales en la vía urinaria, que ocasiona su obstrucción. La incidencia de esta patología ha aumentado estos últimos años en los países industrializados, con una elevada morbilidad y recurrencia. El diagnóstico de este trastorno debe ser precoz para poder instaurar las medidas terapéuticas adecuadas. Medidas entre las que se encuentran aquellas centradas en la alimentación y estilo de vida, educación para la salud, rol fundamental de la enfermería. A través de esta revisión narrativa, se pretende conocer la importancia del análisis del cálculo en la prevención de futuras recurrencias, profundizar en la efectividad de las recomendaciones no farmacológicas para la prevención de la urolitiasis de la European Association of Urology (EAU), para luego compararlas con las de la American Urological Association (AUA). Para ello, se realizó una búsqueda bibliográfica a través de diferentes bases de datos de ciencias de la salud. También, se consultó en bibliografía de diferentes centros y páginas web de diferentes organismos oficiales, para aportar mayor riqueza a esta obra. Tras el desarrollo del trabajo, se muestra la importancia del análisis del cálculo como primer paso para la prevención de recurrencias, como ha quedado expuesta la razón de ser de las recomendaciones de la EAU. Asimismo, se confirma el consenso internacional de las medidas no farmacológicas preventivas recomendadas conjuntamente por ambas asociaciones. Por todo ello, enfermería tiene un papel fundamental en conocer y actualizarse en dichas pautas, para poder ofrecer una buena educación en la prevención de la urolitiasis

Derivados de cromenopirazoles como ligandos de receptores de cannabinoides

Derivados de cromenopirazoles como ligandos de receptores de cannabinoides. Compuestos derivados de cromenopirazoles que son ligandos de receptores de cannabinoides, su uso para la fabricación de un medicamento, uso de este medicamento para el tratamiento y/o la prevención de trastornos asociados a los receptores de cannabinoides, uso de dicho compuesto como reactivo en ensayos biológicos relacionados con receptores de cannabinoides y procedimiento de obtención de los mismos.Peer reviewedConsejo Superior de Investigaciones Científicas (España), Universidad Complutense de MadridA1 Solicitud de patente con informe sobre el estado de la técnic

Probiotic<i> Bacillus subtilis</i> protects against α-synuclein aggregation in <i>C. elegans</i>

How the gut microbiome affects Parkinson's disease remains unclear. Goya et al. show that the probiotic B. subtilis strain PXN21 inhibits and clears α-synuclein aggregation in a C. elegans model. The bacterium acts via metabolites and biofilm formation to activate protective pathways in the host, including DAF-16/FOXO and sphingolipid metabolism.Fil: Goya, María Eugenia. University of Edinburgh; Reino UnidoFil: Xue, Feng. University of Edinburgh; Reino UnidoFil: Sampedro Torres Quevedo, Cristina. University of Edinburgh; Reino UnidoFil: Arnaouteli, Sofia. University Of Dundee; Reino UnidoFil: Riquelme Dominguez, Lourdes. University of Edinburgh; Reino UnidoFil: Romanowski, Andrés. University of Edinburgh; Reino Unido. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Brydon, Jack. University of Edinburgh; Reino UnidoFil: Ball, Kathryn L.. University of Edinburgh; Reino UnidoFil: Stanley-Wall, Nicola R.. University Of Dundee; Reino UnidoFil: Doitsidou, Maria. University of Edinburgh; Reino Unid

The use of functionalization applied to nanobiotechnology:Targeting cancer stem cells and regioselective functionalization of phages

This work, composed of two subprojects, has been developed within the framework of two independent research lines on the functionalization and application of nanoprobes to nanobiotechnology field, specifically in biomedicine or biotechnology. The multidisciplinary research proposal involves physicists, chemists, biochemists and medical doctors, and therefore a part of the student’s training work was performed at several centers abroad: The Hillman Cancer Center (UPCI), Pittsburgh, USA; the Centre de Recherche Paul Pascal (CRPP), Bordeaux and the Institut National de la Recherche Agronomique (BFP-IBVM), Villenave d’Ornon, France. Example 1. The Cancer Stem Cell (CSCs) concept says that only a small proportion of cells within the tumor have tumorigenic capacity. These cells are usually chemo and radio resistance that is why it is believed that are responsible for tumor relapse and recurrence of cancer patients. There is an urgent need to develop cancer therapies that are effective in killing these specific tumor cells. Magnetic nanoparticles (MNPs), functionalized with specific monoclonal antibodies, can be generated to recognize CSCs target molecules within the tumors. Hyperthermia is a new approach of using these MNPs positioned in an alternating magnetic field (AMF) to produce localized heat and kill CSCs. Magnetic nanoparticles-induced hyperthermia is under investigation in different clinical trials on cancer patients. However, there is no information available on whether hyperthermia can eliminate CSCs. Therefore, the final goal of this project involve the application of hyperthermia to destroy CSCs and study the effect of this treatment in reducing tumor growth, increased cell death and improving the response to conventional therapies as chemo-radio therapy. More particularly, this work has focused on the first steps of this strategy related to the preparation of antibody-functionalized MNPs (MNPs:anti-CDs) and their application to target CSCs for several tumor cell lines by fluorescence microscopy. It has also been supplemented with cytotoxicity studies by MTT assays and surface and intracellular distribution studies by scanning electron microscopy (SEM) technique. Example 2. It is known that elongated viruses in concentrated solution self-organize into liquid-crystalline structures (mesophases) which exhibit different intermediate states between disordered liquids and perfectly organized crystals. Therefore, the introduction of specific functions by molecule grafting or nanoparticle bonding on the viral particles with a precise positional control, combined with the self-assembly properties of these functionalized bioparticles, would give access to a wide range of applications in biosensing, memory devices, nanocircuits, light-harvesting systems, nanobatteries or MRI contrast agents. We used the mutant M13-C7C phage which presents a genetic mutation that allows the creation of unique binding sites on only one end of the filamentous virus through a pair of cysteine residues. The final goal of the project is to develop hybrid materials formed by the monitored assembly of these mutant M13-C7C phages with magnetic nanoparticles, with a 1:1 molar ratio, to induced highly sensitive nanorods by magnetic field, which are otherwise absent from the viral coat protein of the wild type phage. More specifically, this work has focused in the mass production, amplification and purification processes, of the mutant M13-C7C phage which is during its growth in competition with the wild type one. We have then specifically studied the functionalization of these mutant phages with maleimide fluorophores, followed by the self-organization properties in order to validate our scientific approach. • Keywords: Nanobiotechnology; Nanofunctionalization; Cancer stem cells (CSCs); Magnetic nanoparticles (MNPs); Monoclonal antibodies; Viral nanoparticles (VNPs); Liquid crystalline structures

Caenorhabditis elegans as a Promising Model Organism in Chronobiology

Circadian rhythms represent an adaptive feature, ubiquitously found in nature, which grants living beings the ability to anticipate daily variations in their environment. They have been found in a multitude of organisms, ranging from bacteria to fungi, plants, and animals. Circadian rhythms are generated by endogenous clocks that can be entrained daily by environmental cycles such as light and temperature. The molecular machinery of circadian clocks includes a transcriptional-translational feedback loop that takes approximately 24 h to complete. Drosophila melanogaster has been a model organism of choice to understand the molecular basis of circadian clocks. However, alternative animal models are also being adopted, each offering their respective experimental advantages. The nematode Caenorhabditis elegans provides an excellent model for genetics and neuro-behavioral studies, which thanks to its ease of use and manipulation, as well as availability of genetic data and mutant strains, is currently used as a novel model for circadian research. Here, we aim to evaluate C. elegans as a model for chronobiological studies, focusing on its strengths and weaknesses while reviewing the available literature. Possible zeitgebers (including light and temperature) are also discussed. Determining the molecular bases and the neural circuitry involved in the central pacemaker of the C. elegans’ clock will contribute to the understanding of its circadian system, becoming a novel model organism for the study of diseases due to alterations of the circadian cycle.</p

Stress-induced Gene Expression Sensing Intracellular Heating Triggered by Magnetic Hyperthermia

It is known that alternating magnetic field applications on eukaryotic cells loaded with single domain iron oxide nanoparticles result in high hyperthermic citotoxicity leading to cell dead. Although magnetic hyperthermia therapy for cancer tumours is being developed under this idea, some in vitro assays have shown controversial results indicating that alternating magnetic field triggers large apoptotic effect without significant culture-temperature increase. In agreement with these observations a huge lowering in nanoparticle specific heating rates, when going from the colloidal suspension to cell endosomes, together with cell death, has been reported. Here, we propose a new methodology to determine the occurrence of local heating in cells when alternating magnetic fields in the radiofrequency field range are applied to cell cultures holding very low iron oxide concentrations, being these concentrations insufficient to produce a global cell-culture temperature increase up to therapeutic values. To this end, human lung adenocarcinoma cells (A549 cell line) were transduced with a lentiviral vector encoding the expression of the enhanced green fluorescence protein, EGFP, under the action of the inducible human heat shock protein 70B promoter. This modified A549 cell line was incubated with aqueous suspensions of magnetite core nanoparticles (uncoated or covered with coating agents like citric acid or silicon oxide), and exposed to radiofrequency fields. The application of an alternating magnetic field to cell cultures loaded with nanoparticles resulted in no global temperature increase but EGFP expression. Stress-inducible gene expression scales with uptake and nanoparticle properties like saturation magnetization and heat dissipation efficiency. Our analysis demonstrates that EGFP expression is linked to a localized intracellular temperature increase.Fil: de Sousa, María Elisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física La Plata; ArgentinaFil: Carrea, Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); ArgentinaFil: Mendoza Zélis, Pedro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física La Plata; ArgentinaFil: Muraca, Diego. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidade Estadual de Campinas; BrasilFil: Mykhaylyk, Olga. Technische Universitat Munchen; AlemaniaFil: Sosa, Yolanda Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata ; ArgentinaFil: Goya, Rodolfo Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata ; ArgentinaFil: Sánchez, Francisco Homero. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física La Plata; ArgentinaFil: Dewey, Ricardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); ArgentinaFil: Fernández van Raap, Marcela Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física La Plata; Argentin

Hétérogénéité de la prolactine circulante chez la chienne

Different molecular forms of circulating prolactin (PRL) are known to occur in several species. As no such information was available in dogs, we assessed the molecular profile of circulating PRL in bitches. Pooled sera from covertly (CTRL) and overtly pseudopregnant (PSPT) diestrous bitches with high or low (> 10 or -1, respectively) serum PRL (measured by ELISA) were analyzed by Sephadex G-100 and Concanavalin A-Sepharose column chromatography. Four serum PRL fractions were identified and termed big-big, big (> 67 kDa), native (23 kDa) and fragmented ( 10 ou -1 respectivement; dosages effectués par Elisa). Les sérums ont été analysés sur colonne de Séphadex G-100 et par chromatographie d’affinité, sur colonne de Sépharose couplée à de la Concanavaline A. La chromatographie sur G-100 a identifié quatre fractions de PRL, qui ont été appelées big-big, big (PM < 67 kDa), native (23 kDa) et fragmentée (< 20 kDa). Les pourcentages relatifs de ces fractions sont identiques chez les CTRL et les PSPT, quel que soit le taux, élevé ou bas, de PRL sérique (plus haut chez les animaux CTRL). De plus, une proportion importante de PRL sérique (69 à 100 %) est sous fonne glycosylée. En conclusion, la PRL sérique se trouve, chez le chien, sous des tonnes moléculaires multiples, dont l’abondance relative est comparable chez la chienne normale et pseudogestante.Facultad de Ciencias VeterinariasInstituto de Investigaciones Bioquímicas de La PlataFacultad de Ciencias Exacta