85 research outputs found

    Solid Lipid Particles for Lung Metastasis Treatment

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    Solid lipid particles (SLPs) can sustainably encapsulate and release therapeutic agents over long periods, modifying their biodistribution, toxicity, and side effects. To date, no studies have been reported using SLPs loaded with doxorubicin chemotherapy for the treatment of metastatic cancer. This study characterizes the effect of doxorubicin-loaded carnauba wax particles in the treatment of lung metastatic malignant melanoma in vivo. Compared with the free drug, intravenously administrated doxorubicin-loaded SLPs significantly reduce the number of pulmonary metastatic foci in mice. In vitro kinetic studies show two distinctive drug release profiles. A first chemotherapy burst-release wave occurs during the first 5 h, which accounts for approximately 30% of the entrapped drug rapidly providing therapeutic concentrations. The second wave occurs after the arrival of the particles to the final destination in the lung. This release is sustained for long periods (>40 days), providing constant levels of chemotherapy in situ that trigger the inhibition of metastatic growth. Our findings suggest that the use of chemotherapy with loaded SLPs could substantially improve the effectiveness of the drug locally, reducing side effects while improving overall survival.This research was funded by the European Regional Development Fund (ERDF) and the Spanish MINECO Refs. PI16/00496 (AES 2016), PI19/00349 (AES 2019), and DTS19/00033; IDIVAL Refs. INNVAL17/11 and INNVAL19/12. J.G. and M.B.-L. also acknowledge financial support from the Fundação para a Ciência e a Tecnologia and the ERDF through NORTE2020 (2014–2020 North Portugal Regional Operational Program) through the projects UTAP-EXPL/NTec/0038/2017 (NANOTHER) and NORTE-01-0145-FEDER-031142 (MAGTARGETON). Nano2clinics COST Action CA17140

    La Plataforma de Tortosa (Cuenca catalana) durante el Jurásico Medio: unidades litoestratigráficas, paleogeografía y ciclos ambientales

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    El presente trabajo constituye una guía de campo de un transecto de la Plataforma de Tortosa, en dirección SW-NE, desde el Estrecho de Beceite hacia las proximidades del Alto de Tarragona. Los afloramientos situados en las proximidades de Alfara, Tivenys, Llaberia y Cap Salou permiten reconocer las sucesivas unidades litoestratigráficas, así como las variaciones de espesor y facies en los distintos sectores, facilitando la reconstrucción paleogeográfica y secuencial de la Cuenca Catalana para este intervalo temporal, entre el Toarciense y el Oxfordiense. Los materiales del Jurásico Medio en la Cuenca Catalana forman una potente sucesión carbonática que sobrepasa los 350 m de potencia, y muestran una fuerte reducción de espesor hacia el norte (área de Llaberia) y el nordeste (el llamado Alto de Tarragona). Estos materiales han sido estudiados a partir de los datos de superficie (más de 30 perfiles estratigráficos) y de subsuelo (más de 30 sondeos petrolíferos). Se han reconocido tres formaciones que habían sido previamente definidas: la Fm. Sant Blai, preferentemente carbonatada (Toarciense inferior a Bajociense inferior), la Fm. Cardó, preferentemente margosa (Bajociense inferior a Bajociense superior), y la Fm. La Tossa, formada por calizas y dolomías (Bajociense superior a Calloviense medio). En la Fm. Sant Blai se distingue a su vez cinco miembros estratigráficamente sucesivos. Por encima de la Fm. La Tossa se desarrolla la Fm. Serra de la Creu, formada por calizas bioclásticas y peloidales (Oxfordiense medio a superior). Las variaciones de facies y de espesor son indicativas de que la sedimentación estuvo controlada por fracturas de basamento, que condicionaron el desarrollo de diversas plataformas carbonáticas así como sucesivos cambios relativos del nivel del mar. No obstante, las discontinuidades de mayor amplitud, localizadas en el Aaleniense (Biozona Murchisonae), en el límite Batboniense - Calloviense (Biozona Discus) y en el límite Calloviense - Oxfordiense, se encuentran también en la Cuenca Ibérica y fueron debidas a factores alocíclicos. Las profundidades relativas de estas áreas de plataforma epicontinental alcanzaron valores mínimos durante el desarrollo de estas tres discontinuidades mencionadas, que localmente pudieron corresponder a episodios prolongados de exposición subaérea. Los máximos valores batimétricos se alcanzaron durante el Bajociense superior (Biocrón Niortense) y durante el Oxfordiense medio (biocronos Schilli y Rotoides). Durante estos intervalos de máxima profundización relativa se registraron las únicas evidencias de colonización generalizada de la Cuenca Catalana por poblaciones de ammonites

    Effect of Size, Shape, and Composition on the Interaction of Different Nanomaterials with HeLa Cells

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    The application of nanomaterials in the fields of medicine and biotechnology is of enormous interest, particularly in the areas where traditional solutions have failed. Unfortunately, there is very little information on how to optimize the preparation of nanomaterials for their use in cell culture and on the effects that these can trigger on standard cellular systems. These data are pivotal in nanobiotechnology for the development of different applications and to evaluate/compare the cytotoxicity among the different nanomaterials or studies. The lack of information drives many laboratories to waste resources performing redundant comparative tests that often lead to partial answers due to differences in (i) the nature of the start-up material, (ii) the preparation, (iii) functionalization, (iv) resuspension, (v) the stability/dose of the nanomaterial, etc. These variations in addition to the different analytical systems contribute to the artefactual interpretation of the effects of nanomaterials and to inconsistent conclusions between different laboratories. Here, we present a brief review of a wide range of nanomaterials (nanotubes, various nanoparticles, graphene oxide, and liposomes) with HeLa cells as a reference cellular system. These human cells, widely used as cellular models for many studies, represent a reference system for comparative studies between different nanomaterials or conditions and, in the last term, between different laboratories.This work has been supported by the Spanish MINECO and European FEDER under Project ref. PI16/000496, the NanoBioApp Network Ref. MINECO-17-MAT2016-81955-REDT. We thank IDIVAL for INNVAL15/16, INNVAL 17/11, PREVAL 16/03, 16/02, 17/04, and the Raman4clinics BMBS COST Actions BM1401 and TD1402. We also thank Débora Muñoz for her technical assistance. We are grateful to the Nikon A1R Laser Microscopy Unit and the TEM Unit of the IDIVAL Institute

    La terapia interpersonal de la depresión y las psicoterapias en el fin del milenio.

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    En este trabajo presentamos los fundamentos teóricos y clínicos de la Terapia Interpersonal de la depresión y analizamos los motivos que la han consolidado como una alternativa eficaz y frecuentemente practicada de psicoterapia en los Estados Unidos de América. Exponemos la situación en España y en Europa. Discutimos algunas implicaciones de esto para la práctica de la psicoterapia en los próximos años

    La terapia interpersonal de la depresión y las psicoterapias en el fin del milenio.

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    En este trabajo presentamos los fundamentos teóricos y clínicos de la Terapia Interpersonal de la depresión y analizamos los motivos que la han consolidado como una alternativa eficaz y frecuentemente practicada de psicoterapia en los Estados Unidos de América. Exponemos la situación en España y en Europa. Discutimos algunas implicaciones de esto para la práctica de la psicoterapia en los próximos años

    In-depth in vitro Evaluation of the Activity and Mechanisms of Action of Organic Acids and Essential Oils Against Swine Enteropathogenic Bacteria

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    P. 1-13Alternative antimicrobials require a deep understanding of their action mechanisms by in vitro assays which support science-based field use. This study focuses on the characterization of bactericidal mechanisms of potential antimicrobial compounds, two organic acids and three single essential oil (EO) compounds against swine enteropathogenic bacteria Escherichia coli, Salmonella enterica subsp. enterica serovar Typhimurium, and Clostridium perfringens. Target concentrations of the compounds were evaluated using the inhibitory potential of the vapor phase and bacterial viability after short-term exposure, while cell targets were disclosed using flow cytometry (FC), Fourier-transform infrared (FTIR) spectroscopy, and scanning electron microscopy (SEM). All tested compounds exhibited vapor phase activity against the three bacterial species, except sodium salt of coconut fatty acid distillates against C. perfringens. Survival test results evidenced that effects on bacterial viability were concentration dependent and higher in single EO compounds than in organic acids. In detail, thymol and its isomer carvacrol were the most effective compounds. Further characterization of thymol and cinnamaldehyde activity revealed that thymol main target was the cell membrane, since it caused striking damages in the membrane permeability, integrity and composition evidenced by FC and FTIR in the three enteric pathogens. In contrast, cinnamaldehyde was more effective against enterobacteria than against C. perfringens and only caused slightly damages at the highest concentration tested. Its target at the molecular level differed between enterobacteria and C. perfringens isolates. The SEM micrographs allowed us to confirm the results previously obtained for both EO compounds by other techniques. Altogether, the study showed the straight effect of these antimicrobials, which could constitute relevant information to optimize their feed inclusion rates in field studies or field use.S

    Allergic patients with long-term asthma display low levels of bifidobacterium adolescentis

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    Accumulated evidence suggests a relationship between specific allergic processes, such as atopic eczema in children, and an aberrant fecal microbiota. However, little is known about the complete microbiota profile of adult individuals suffering from asthma. We determined the fecal microbiota in 21 adult patients suffering allergic asthma (age 39.43 ± 10.98 years old) and compare it with the fecal microbiota of 22 healthy controls (age 39.29 ± 9.21 years old) using culture independent techniques. An Ion-Torrent 16S rRNA gene-based amplification and sequencing protocol was used to determine the fecal microbiota profile of the individuals. Sequence microbiota analysis showed that the microbial alpha-diversity was not significantly different between healthy and allergic individuals and no clear clustering of the samples was obtained using an unsupervised principal component analysis. However, the analysis of specific bacterial groups allowed us to detect significantly lower levels of bifidobacteria in patients with long-term asthma. Also, in allergic individuals the Bifidobacterium adolescentis species prevailed within the bifidobacterial population. The reduction in the levels on bifidobacteria in patients with long-term asthma suggests a new target in allergy research and opens possibilities for the therapeutic modulation of the gut microbiota in this group of patients
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