Search results for "ICO"
showing 10 items of 30544 documents
The Novel Oral Anticoagulants for Acute Venous Thromboembolism: Is Warfarin Dead?
2017
The direct oral anticoagulants (DOACs) have been compared with parenteral anticoagulants and vitamin K antagonists (VKAs) for the treatment of venous thromboembolism (VTE) in several robust studies. DOACs have shown similar efficacy in preventing recurrent VTE and significant reductions in critical site (intracranial) bleeding, fatal bleeding, major and nonmajor bleeding. Warfarin and other VKAs are not dead as treatment modalities for VTE. A better way to describe the current situation is to use a boxing expression, “down but not out.” VKAs and parenteral anticoagulants still have a role to play in the management of VTE in several clinical settings. In indications where DOACs can be used, …
Modelos animales de adicción a las drogas
2017
El desarrollo de modelos animales de refuerzo y adicción a las drogas es imprescindible para el avance en el conocimiento de las bases biológicas de este trastorno y la identificación de nuevas dianas terapéuticas. En función del componente del refuerzo que deseemos estudiar podemos servirnos de un tipo de modelos animales u otros. Podemos utilizar modelos de refuerzo basados en el efecto hedónico primario que produce el consumo de la sustancia adictiva, como los modelos de autoadministración (AA) y autoestimulación eléctrica intracraneal (AEIC), o modelos basados en el componente relacionado con el aprendizaje asociativo y la capacidad cognitiva de realizar predicciones sobre la obtención …
Cabozantinib targets bone microenvironment modulating human osteoclast and osteoblast functions
2016
Cabozantinib, a c-MET and vascular endothelial growth factor receptor 2 inhibitor, demonstrated to prolong progression free survival and improve skeletal disease-related endpoints in castration-resistant prostate cancer and in metastatic renal carcinoma. Our purpose is to investigate the direct effect of cabozantinib on bone microenvironment using a total human model of primary osteoclasts and osteoblasts.Osteoclasts were differentiated from monocytes isolated from healthy donors; osteoblasts were derived from human mesenchymal stem cells obtained from bone fragments of orthopedic surgery patients. Osteoclast activity was evaluated by tartrate resistant acid phosphatase (TRAP) staining and …
Recent advances on CDK inhibitors: An insight by means of in silico methods
2017
The cyclin dependent kinases (CDKs) are a small family of serine/threonine protein kinases that can act as a potential therapeutic target in several proliferative diseases, including cancer. This short review is a survey on the more recent research progresses in the field achieved by using in silico methods. All the "armamentarium" available to the medicinal chemists (docking protocols and molecular dynamics, fragment-based, de novo design, virtual screening, and QSAR) has been employed to the discovery of new, potent, and selective inhibitors of cyclin dependent kinases. The results cited herein can be useful to understand the nature of the inhibitor-target interactions, and furnish an ins…
Molecular topology: A new strategy for antimicrobial resistance control
2017
The control of antimicrobial resistance (AMR) seems to have come to an impasse. The use and abuse of antibacterial drugs has had major consequences on the genetic mutability of both pathogenic and nonpathogenic microorganisms, leading to the development of new highly resistant strains. Because of the complexity of this situation, an in silico strategy based on QSAR molecular topology was devised to identify synthetic molecules as antimicrobial agents not susceptible to one or several mechanisms of resistance such as: biofilms formation (BF), ionophore (IA) activity, epimerase (EI) activity or SOS system (RecA inhibition). After selecting a group of 19 compounds, five of them showed signific…
Mode of Action Analyses of Neferine, a Bisbenzylisoquinoline Alkaloid of Lotus (Nelumbo nucifera) against Multidrug-Resistant Tumor Cells
2017
Neferine, a bisbenzylisoquinoline alkaloid isolated from the green seed embryos of Lotus (Nelumbo nucifera Gaertn), has been previously shown to have various anti-cancer effects. In the present study, we evaluated the effect of neferine in terms of P-glycoprotein (P-gp) inhibition via in vitro cytotoxicity assays, R123 uptake assays in drug-resistant cancer cells, in silico molecular docking analysis on human P-gp and in silico absorption, distribution, metabolism, and excretion (ADME), quantitative structure activity relationships (QSAR) and toxicity analyses. Lipinski rule of five were mainly considered for the ADME evaluation and the preset descriptors including number of hydrogen bond d…
Innovative Strategies to Develop Chemical Categories Using a Combination of Structural and Toxicological Properties.
2016
Interest is increasing in the development of non-animal methods for toxicological evaluations. These methods are however, particularly challenging for complex toxicological endpoints such as repeated dose toxicity. European Legislation, e.g., the European Union's Cosmetic Directive and REACH, demands the use of alternative methods. Frameworks, such as the Read-across Assessment Framework or the Adverse Outcome Pathway Knowledge Base, support the development of these methods. The aim of the project presented in this publication was to develop substance categories for a read-across with complex endpoints of toxicity based on existing databases. The basic conceptual approach was to combine str…
Estudio de los hábitos alimentarios, actividad física, nivel socioeconómico y sedentarismo en adolescentes de la ciudad de Valencia
2020
Introducción: Unos adecuados hábitos alimenticios, junto a la práctica regular de actividad física son importantes para adoptar un estilo de vida saludable. En la actualidad, existe un abandono generalizado de la actividad física y la adopción de comportamientos sedentarios durante la adolescencia, así como la pérdida de unos óptimos patrones alimenticios. Material y métodos: El presente estudio tiene como objetivo conocer los hábitos alimenticios de 170 adolescentes de la ciudad de Valencia y saber si este comportamiento nutricional guarda relación con variables como la actividad física, el nivel socioeconómico, el tiempo de actividad sedentaria o el perfil de peso. Resultados: El análisis…
New Insights into the Genome Organization of Yeast Killer Viruses Based on “Atypical” Killer Strains Characterized by High-Throughput Sequencing
2017
Viral M-dsRNAs encoding yeast killer toxins share similar genomic organization, but no overall sequence identity. The dsRNA full-length sequences of several known M-viruses either have yet to be completed, or they were shorter than estimated by agarose gel electrophoresis. High-throughput sequencing was used to analyze some M-dsRNAs previously sequenced by traditional techniques, and new dsRNAs from atypical killer strains of Saccharomyces cerevisiae and Torulaspora delbrueckii. All dsRNAs expected to be present in a given yeast strain were reliably detected and sequenced, and the previously-known sequences were confirmed. The few discrepancies between viral variants were mostly located aro…
Cosavirus, Salivirus and Bufavirus in Diarrheal Tunisian Infants
2016
International audience; Three newly discovered viruses have been recently described in diarrheal patients: Cosa-virus (CosV) and Salivirus (SalV), two picornaviruses, and Bufavirus (BuV), a parvovirus. The detection rate and the role of these viruses remain to be established in acute gastroen-teritis (AGE) in diarrheal Tunisian infants. From October 2010 through March 2012, stool samples were collected from 203 children <5 years-old suffering from AGE and attending the Children's Hospital in Monastir, Tunisia. All samples were screened for CosV, SalV and BuV as well as for norovirus (NoV) and group A rotavirus (RVA) by molecular biology. Positive samples for the three screened viruses were …