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Ondrej Benek, Lukas Hroch, Laura Aitken, Frank Gunn-Moore, Lucie Vinklarova, Kamil Kuca, Daniel I Perez, Concepcion Perez, Ana Martinez, Zdenek Fisar, Kamil Musilek
Several neurodegenerative disorders including Alzheimer's disease (AD) have been connected with deregulation of casein kinase 1 (CK1) activity. Inhibition of CK1 therefore presents a potential therapeutic strategy against such pathologies. Recently, novel class of CK1-specific inhibitors with N-(benzo[d]thiazol-2-yl)-2-phenylacetamide structural scaffold has been discovered. 1-(benzo[d]thiazol-2-yl)-3-phenylureas, on the other hand, are known inhibitors amyloid-beta binding alcohol dehydrogenase (ABAD), an enzyme also involved in pathophysiology of AD...
December 2018: Journal of Enzyme Inhibition and Medicinal Chemistry
Enrique Gómez-Barrena, Norma G Padilla-Eguiluz, Cristina Avendaño-Solá, Concepción Payares-Herrera, Ana Velasco-Iglesias, Ferran Torres, Philippe Rosset, Florian Gebhard, Nicola Baldini, Juan C Rubio-Suarez, Eduardo García-Rey, José Cordero-Ampuero, Javier Vaquero-Martin, Francisco Chana, Fernando Marco, Javier García-Coiradas, Pedro Caba-Dessoux, Pablo de la Cuadra, Philippe Hernigou, Charles-Henri Flouzat-Lachaniette, François Gouin, Didier Mainard, Jean Michel Laffosse, Miriam Kalbitz, Ingo Marzi, Norbert Südkamp, Ulrich Stöckle, Gabriela Ciapetti, Davide Maria Donati, Luigi Zagra, Ugo Pazzaglia, Guido Zarattini, Rodolfo Capanna, Fabio Catani
ORTHOUNION is a multicentre, open, comparative, three-arm, randomized clinical trial (EudraCT number 2015-000431-32) to compare the efficacy, at one and two years, of autologous human bone marrow-derived expanded mesenchymal stromal cell (hBM-MSC) treatments versus iliac crest autograft (ICA) to enhance bone healing in patients with diaphyseal and/or metaphysodiaphyseal fracture (femur, tibia, and humerus) status of atrophic or oligotrophic nonunion (more than 9 months after the acute fracture, including recalcitrant cases after failed treatments)...
2018: Stem Cells International
Juan García de la Concepción, Martín Ávalos, Pedro Cintas, José Luis Jiménez
Computational strategies have gained increasing impact in the de novo design of large molecular sets targeted to a desired application. Here, we show that DFT-assisted theoretical analyses of cycloadditions involving mesoionic dipoles and strained cycloalkynes unveil a series of unexplored mesomeric betaines as vastly superior candidates for orthogonal applications. Thus, isosydnones, thiosydnones, and a six-membered homolog in particular, 6-oxo-1,3-oxazinium-4-olate, do exhibit enhanced reactivity with respect to sydnones, the archetypal mesoionic ring employed so far in orthogonal chemistry...
March 13, 2018: Chemistry: a European Journal
Joaquín M González-Cabrera, María Fernández-Prada, Concepción Iribar, Rogelio Molina-Ruano, María Salinero-Bachiller, José M Peinado
The objectives of this longitudinal study were to compare salivary cortisol release patterns in medical residents and their self-perceived anxiety levels between a regular working day and a day when on call in the emergency department (ED-duty day) and to determine any differences in cortisol release pattern as a function of years of residency or sex. The study included 35 residents (physicians-in-training) of the Granada University Hospital, Granada, Spain. Acute stress was measured on a regular working day and an ED-duty day, evaluating anxiety-state with the Spanish version of the State-Trait Anxiety Inventory...
March 13, 2018: International Journal of Environmental Research and Public Health
David de la Rosa Carrillo, Rodrigo Athanazio, Rosa Maria Girón Moreno, Luis Máiz Carro, Casilda Olveira, Javier de Gracia, Montserrat Vendrell, Concepción Prados Sánchez, Georgina Gramblicka, Monica Corso Pereira, Fernando Lundgren, Mara Fernandes De Figueiredo, Francisco Arancibia, Samia Rached, Miguel-Angel Martínez-Garcia
Both FACED and E-FACED scores have shown good short-term prognostic value for predicting mortality in bronchiectasis
January 2018: ERJ Open Research
M Montero, Brian D VanScoy, Carla López-Causapé, Haley Conde, Jonathan Adams, Concepción Segura, Laura Zamorano, Antonio Oliver, Juan P Horcajada, Paul G Ambrose
The aim of this study was to investigate the efficacy of ceftolozane-tazobactam in combination with meropenem against an extensively drug-resistant (XDR) Pseudomonas aeruginosa high-risk clone, ST175, isolated in a Spanish university hospital. A 14-day hollow-fiber infection model was used to simulate clinical exposure of the 2 drug regimens alone and in combination, and serial samples were collected to determine drug concentrations and colony-forming unit (CFU) counts. The untreated control failed, as did each study regimen when administered alone...
March 12, 2018: Antimicrobial Agents and Chemotherapy
E Quintero-Troconis, N Buelvas, C Carrasco-López, M R Domingo-Sananes, L González-González, R Ramírez-Molina, L Osorio, A Lobo-Rojas, A J Cáceres, P A Michels, H Acosta, W Quiñones, J L Concepción
Purification of enolase (ENO) from the cytosol of Trypanosoma cruzi indicated that it may interact with at least five other proteins. Two of them were identified as metallocarboxypeptidase-1 (TcMCP-1) and a putative acireductone dioxygenase (ARDp). Subcellular localization studies confirmed the presence of ARDp in the cytosol, as is the case for ENO and TcMCP-1. Analysis of the ARDp sequence showed that this protein has two domains, an N-terminal ARD and a C-terminal TRP14 (thioredoxin-related protein) domain...
March 9, 2018: Biochimica et Biophysica Acta
Pedro García, Concepción Romero, Manuel Brenes
BACKGROUND: The oxidation and polymerization of the phenolic compounds present in black ripe olives give rise to their black shiny colour which is fixed by the addition of ferrous salts such as ferrous gluconate. Among the many variables that can affect the successful of this fixation step, the influence of the pH on this process was assessed on fruits of the Hojiblanca cultivar processed at pilot plant scale. Hence, the aim of this work was to gain knowledge on the development of this fixation step, in particular on olives that were oxidized with a single alkaline treatment...
March 12, 2018: Journal of the Science of Food and Agriculture
O Villafraz, R Rondón-Mercado, A J Cáceres, J L Concepción, W Quiñones
T. rangeli epimastigotes contain only a single detectable phosphoglycerate kinase (PGK) enzyme in their cytosol. However, analysis of this parasite's recently sequenced genome showed a gene predicted to code for a PGK with the same molecular mass as the natural enzyme, and with a cytosolic localization as well. In this work, we have partially purified the natural PGK from T. rangeli epimastigotes. Furthermore, we cloned the predicted PGK gene and expressed it as a recombinant active enzyme. Both purified enzymes were kinetically characterized and displayed similar substrate affinities, with KmATP values of 0...
March 8, 2018: Experimental Parasitology
O Fernández-Concepción, M López Jiménez, C Valencia-Calderón, A Calderón-Valdivieso, A Recasén-Linares, L Reyes-Haro, C Vásquez-Ham
INTRODUCTION: There is sufficient evidence on the usefulness of surgery as a therapeutic alternative for patients with drug-resistant epilepsy; however this treatment is underutilized, especially in developing countries. METHODS: We describe the outcomes of epilepsy surgery in 27 paediatric patients at Hospital Baca Ortiz in Quito, Ecuador. Our analysis considered the following variables: reduction in seizure frequency, surgery outcome according to the Engel classification, improvement in quality of life, and serious complications due to surgery...
March 7, 2018: Neurología: Publicación Oficial de la Sociedad Española de Neurología
María Del Mar Roca-Rodríguez, María Carmen Ayala-Ortega, Ana Isabel Jiménez-Millán, María Concepción García Calzado, María Soledad Ruiz de Adana, Florentino Carral-San Laureano
INTRODUCTION: MODY diabetes encompasses heterogeneous group of monogenic forms of diabetes with low prevalence. It is not easily diagnosed because of the increase in obesity and family history of diabetes in the general population. PATIENTS AND METHODS: We present a clinical case with cardinal symptoms, diabetes,renal insufficiency with no acidosis and with a family history of diabetes and renal agenesis. RESULTS: Distinguishing MODY diabetes from DM1 and DM2 is very important to ensure optimal treatment, and because the risk of complications depends on each genetic defect...
March 7, 2018: Medicina Clínica
Alma L Saucedo-Yanez, Marlene M Perales-Quintana, David Paniagua-Vega, Concepcion Sanchez-Martinez, Paula Cordero-Perez, Noemi Waskman Minsky
Chronic kidney disease (CKD) is a progressive condition characterized by a permanent and irreversible loss of renal function. In accordance to international guidelines, CKD clinical diagnosis methods are based on creatinine and albumin levels and glomerular filtration rate. Unfortunately, these parameters are scarcely affected in early stages, and its inherent intrinsic variability only allows for the identification of intermediate and advanced stages, when life expectancy has become shorter and treatment poses a significant financial investment...
March 6, 2018: Current Medicinal Chemistry
Adriana Lopez-Pineda, Alberto Cordero, Concepción Carratala-Munuera, Domingo Orozco-Beltran, Jose A Quesada, Vicente Bertomeu-Gonzalez, Vicente F Gil-Guillen, Vicente Bertomeu-Martinez
These data are linked to the research article, entitled Hyperuricemia as a prognostic factor after acute coronary syndrome published in Atherosclerosis. Data from patients admitted for acute coronary syndrome between 2008 and 2013 were collected during the hospitalization, and a follow-up until endpoint or end of study was carried out. Multivariate analysis of variables associated with long term mortality after acute coronary syndrome in patients stratified by the presence of diabetes, hypertension or kidney failure is provided in this article...
April 2018: Data in Brief
Francisco Javier Manzano-Moreno, Javier Ramos-Torrecillas, Lucia Melguizo-Rodríguez, Rebeca Illescas-Montes, Concepción Ruiz, Olga García-Martínez
The aim of the present study was to elucidate the role of osteoblasts in bisphosphonates-related osteonecrosis of the jaw (BRONJ). The specific objective was to evaluate the effect on osteoblasts of two nitrogen-containing BPs (zoledronate and alendronate) and one non-nitrogen-containing BP (clodronate) by analyzing modulations in their expression of genes essential for osteoblast physiology. Real-time polymerase chain reaction (RT-PCR) was used to study the effects of zoledronate, alendronate, and clodronate at doses of 10-5 , 10-7 , or 10-9 M on the expression of Runx-2, OSX, ALP, OSC, OPG, RANKL, Col-I, BMP-2, BMP-7, TGF-β1, VEGF, TGF-βR1, TGF-βR2, and TGF-βR3 by primary human osteoblasts (HOBs) and MG-63 osteosarcoma cells...
2018: International Journal of Medical Sciences
Concepción Alonso, María Fuertes, Endika Martín-Encinas, Asier Selas, Gloria Rubiales, Cinzia Tesauro, Birgitta K Knudssen, Francisco Palacios
This work describes the synthesis of 1,2,3,4-tetrahydroquinolinylphosphine oxides, phosphanes and phosphine sulfides as well as that of quinolinylphosphine oxides and phosphine sulfides, which were synthesized in good to high overall yield. The synthetic route involves a multicomponent reaction of (2-phosphine-oxide)-, 2-phosphine- or (2-phosphine-sulfide)-aniline, aldehydes and olefins and allows the selective generation of two stereogenic centres in a short, efficient and reliable synthesis. The selective dehydrogenation of 1,2,3,4-tetrahydroquinolinylphosphine oxides and phosphine sulfides leads to the formation of corresponding phosphorus substituted quinolines...
February 22, 2018: European Journal of Medicinal Chemistry
Nerea G Ventades, Imanol M Laza, Montserrat Hervella, Concepción de-la-Rúa
The present study is focused on a group of arthropathies that may have very similar bone manifestations (rheumatoid arthritis, ankylosing spondylitis, reactive arthritis, psoriatic arthritis, osteoarthritis and diffuse idiopathic skeletal hyperostosis), which makes it more difficult to diagnose them in human remains from archaeological contexts. A stepwise recording form was designed in order to improve the identification and differential diagnosis of these pathological conditions in bone remains, particularly in joint manifestations of the spine, pelvis, hands, feet and other limb joints...
March 2018: International Journal of Paleopathology
Patricia Rosales-Cruz, Mayra Domínguez-Pérez, Elizabeth Reyes-Zárate, Oscar Bello-Monroy, Cristina Enríquez-Cortina, Roxana Miranda-Labra, Leticia Bucio, Luis Enrique Gómez-Quiroz, Emilio Rojas-Del Castillo, María Concepción Gutiérrez-Ruíz, Verónica Souza-Arroyo
Metabolic factors are the major risk of non-alcoholic fatty liver disease, although other factors may contribute steatosis. Cadmium exposure produces histopathological and molecular changes in liver, which are consistent with steatosis. In the present study, we describe the effect of low cadmium acute treatment on hepatocytes obtained from mice fed with a high cholesterol diet. Our data suggest that hepatocytes with cholesterol overload promote an adaptive response against cadmium-induced acute toxicity by up-regulating anti-apoptotic proteins, managing ROS overproduction, increasing GSH synthesis and MT-II content to avoid protein oxidation...
February 24, 2018: Toxicology
Miguel Angel Ortiz, Laura Espino-Paisan, Concepcion Nunez, Roberto Alvarez-Lafuente, Elena Urcelay
In the 1990s, the betainterferons and glatiramer acetate were introduced for treating relapsing-remitting multiple sclerosis. These medications have a demonstrated record of efficacy and safety, although they require frequent administration via injection and are only partially effective. The optimization of treatment in patients who do not respond adequately to this first-line therapy is essential for attaining the best long-term outcomes. Switching to the recently approved emergent therapies is a strategy to consider for treatment of patients with a suboptimal response...
February 25, 2018: Current Medicinal Chemistry
Rocío Aller de la Fuente, Natalia Mora Cuadrado, Carla Tafur, Juan Jose López Gómez, Sara Gómez de la Cuesta, María Concepción García Sánchez, Beatriz Antolin Melero, Daniel Antonio de Luis Román
BACKGROUND AND AIMS: Prevalence of non-alcoholic fatty liver disease (NAFLD) in developed countries is 30% in the general population and 50% in patients with type 2 diabetes mellitus (T2DM). The aim of this study was to compare the severity of NAFLD, as assessed by liver biopsy and using the non-invasive index NAFLD Fibrosis Score (NFS), in subjects with and without T2DM. PATIENTS AND METHODS: The study sample consisted of 217 patients with biopsy-proven NAFLD. Anthropometric assessments, laboratory tests, histological criteria established by the Non-alcoholic Steatohepatitis Clinical Research Network (NASH CRN), and the NFS were recorded...
February 21, 2018: Endocrinología, Diabetes y Nutrición
Antonio I Arroyo, Yolanda Pueyo, M Luz Giner, Ana Foronda, Pedro Sanchez-Navarrete, Hugo Saiz, Concepción L Alados
Many studies have reported the phytotoxicity of allelopathic compounds under controlled conditions. However, more field studies are required to provide realistic evidences for the significance of allelopathic interference in natural communities. We conducted a 2-years field experiment in a semiarid plant community (NE Spain). Specifically, we planted juvenile individuals and sowed seeds of Salsola vermiculata L., Lygeum spartum L. and Artemisia herba-alba Asso. (three co-dominant species in the community) beneath adult individuals of the allelopathic shrub A...
2018: PloS One
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