Ensayos clínicos con fármacos hipolipemiantes

La resinas, los fibratos y estatinas constituyen los fármacos hipolipemiantes utilizados en España con ensayos clínicos que demuestran una reducción de la morbilidad y mortalidad cardiovascular. Durante el año 2004 han aparecido dos estudios que comparan dos estatinas a distintas dosis. Las características de los pacientes incluidos en los estudios abarcan desde la prevención primaria de la enfermedad cardiovascular, diabetes, hipertensión arterial y ancianos hasta la prevención secundaria con enfermos afectos de cardiopatía isquémica o enfermedad cardiovascular. La reducción del colesterol de las lipoproteínas de baja densidad (cLDL) conseguida con estatinas está entre un 14% hasta un 43%. Las resinas y fibratos obtienen descensos inferiores al 10%. Estos afectan a los otros componentes del perfil lipídico aumentando las lipoproteínas de alta densidad (cHDL) y reduciendo los triglicéridos. El cLDL más bajo en el grupo control es 113 mg/dl y el más alto 198 mg/dl; mientras en el grupo intervención el cLDL más bajo es 82 mg/dl y el más alto 175 mg/dl. Los estudios que comparan dos estatinas ha distinta dosis presentan reducciones del 34,7% y 18,5% entre el grupo control e intervención. La demostración de la reducción del infarto de miocardio es el resultado más consistente de las estatinas y de los otros fármacos hipolipemiantes. Los estudios de prevención primaria obtienen un número necesario de pacientes a tratar (NNT) superior a 20 y los de prevención secundaria inferior a esta cifra. Algunos de los estudios de prevención primaria y secundaria han demostrado la prevención del ictus. El riesgo de ictus de los estudios con fármacos hipolipemiantes es más bajo que el de infarto de miocardio. El NNT más obtenido es de 30. Sólo algunos estudios de prevención secundaria han demostrado una reducción de la mortalidad total Los ensayos que comparan dos estatinas no reducen significativamente el número de infartos de miocardio, ictus o mortalidad total. Sólo cuando se asocian las diferentes enfermedades cardiovasculares los resultados son significativos. La utilización de dosis altas de estatinas también aumenta el riesgo de hepatopatía y miopatía

Algunas cuestiones pendientes

Las cuestiones pendientes de resolver en el tratamiento y control de los factores de riesgo son innumerables. Sin embargo, he elegido tres temas que encuentro más pertinentes por su actualidad y repercusión práctica: el inicio del tratamiento con fármacos antihipertensivos, el objetivo de control del colesterol de las lipoproteínas de baja densidad (cLDL), ambos temas utilizando parte del material de este número de la revista, y, por último, analizar las consecuencias derivadas de las nuevas recomendaciones de las Sociedades Europeas. La elección del mejor fármacos para iniciar el tratamiento antihipertensivo no es una cuestión resuelta como se ha podido comprobar en la lectura del capítulo de esta revista titulado "Ensayos clínicos que comparan dos fármacos antihipertensivos". Así, los resultados prometedores de dos grupos terapéuticos, inhibidores de la enzima de conversión de la angiotensina y los antagonistas de los receptores de la angiotensina II, por su efecto protector de los órganos diana no se ha visto refrendado por los resultados de los ensayos clínicos. En términos generales, hemos comprobado que no existen diferencias relevantes entre los distintos grupos de fármacos si analizamos los datos de los ensayos clínicos sobre prevención del infarto de miocardio, ictus o mortalidad total

On the behaviour of Atrazine removal from water using fabrics as anodes and Cathodes

[EN] This study examines the degradation of atrazine (ATZ) with Pt-modified textile electrodes using an electrochemical method that is comparatively studied in two electrochemical cell configurations: cells with separated anodic and cathodic compartments (divided configuration); and without any separation (undivided configuration). The influence of the presence of chloride ions was studied. The best results were obtained when an undivided cell was used. The morphology and composition of the dispersed Pt coatings were analyzed using field emission scanning electron microscopy (FESEM) and Energy Dispersive X-Ray Analysis. The FESEM analyses confirmed that the textile surface was effectively modified by the electrocatalytic material. High performance liquid chromatography, gas chromatography mass spectrometry, and spectroscopic methods were used to follow the evolution of major oxidation products. Total organic carbon, chemical oxygen demand, and total nitrogen were used to evaluate the degradation efficiency of treated aqueous solutions. The experimental results obtained indicate that the efficiency of the electrochemical treatment was high with a low energy consumption when using electrodes based on textile materials, such as anodes or as cathodes (in particular, in electrolysis without compartment separation). All these can be produced at very competitive pricesSpanish Agencia Estatal de Investigacion (AEI) and European Union (FEDER funds) are acknowledged for the financial support (contracts MAT 2016-77742-C2-1-P and CTQ 2017-90659-RED). Chemviron Carbon who kindly donated the FlexzorbTM FM10 activated carbon fabrics and Funding for open access charge, CRUE-Universitat Politècnica de València, are acknowledged tooHamous, H.; Khenifi, A.; Orts Maiques, FJ.; Bonastre Cano, JA.; Cases, F. (2022). On the behaviour of Atrazine removal from water using fabrics as anodes and Cathodes. Chemosphere. 291(Part 1):1-8. https://doi.org/10.1016/j.chemosphere.2021.132738S18291Part

Study of the Reuse of Industrial Wastewater After Electrochemical Treatment of Textile Effluents without External Addition of Chloride

[EN] The interference of human beings in the environment is causing rapid intense environmental damage which is particularly evident in the depletion of natural resources. Research into powerful practical treatments to decolorize and degrade colored textile wastewater is an important challenge nowadays for the textile industry due to environmental considerations, along with the potential water saving. It has been verified, in previous studies, that electrochemical oxidation-reduction treatment with doped SnO2 anodes was effective. In particular, those belonging to a trychromy (mix of three reactive dyes) achieved a significant reduction in Chemical Oxygen Demand (COD) and Total Organic Carbon (TOC), as well as the decolorization of the treated solutions. Subsequently, the next step is to proceed to study and verify that these treated waters can be reused in subsequent dyes and that acceptable values of color equalization in the dyed fabrics can be achieved. The color differences obtained in the dyed fabrics in the four studied reuses are below the threshold of acceptance of color differences in the textile industry, which is one unit. The only electrolyte used was sodium sulphate. Chloride was not added externally in order to avoid as far as possible indirect oxidation. This allows a true test of the electrooxidantion power of the anodes. In these conditions, the Ti/SnO2-Sb-Pt DSA electrode is stable. The degree of mineralization is evaluated by measurements of TOC and COD. These data also allow the Average Oxidation State (AOS) at the end of each electrolysis, as well as information on the efficiency in each case through the Carbon Oxidation State (COS) and Average Current Efficiency (ACE) to be established. High Performance Liquid Chromatography (HPLC) was used to study the decolorization kinetics and the evolution of the generated intermediates. Comparison of the spectra obtained by UV-Visible Spectroscopy allows the decolorization from the initial state to the end of the electrolysis to be monitored.The authors wish to thank the Spanish Agencia Estatal de Investigación (AEI) and European Union (FEDER funds) for the financial support (contract MAT2016-77742-C2-1-P). The authors wish to acknowledge Tim Vickers for help with the English revision and Texcoy S.L. company (Spain) where the dyeing processes were done.Orts Maiques, FJ.; Del Río García, AI.; Molina Puerto, J.; Bonastre Cano, JA.; Cases, F. (2019). Study of the Reuse of Industrial Wastewater After Electrochemical Treatment of Textile Effluents without External Addition of Chloride. International Journal of Electrochemical Science. 14(2):1733-1750. https://doi.org/10.20964/2019.02.27S1733175014

Electrochemical treatment of real textile wastewater: Trichromy Procion HEXL

[EN] The electrochemical treatment of wastewaters from the textile industry is a promising technique for not easily biodegradable compounds. This work is aimed at studying the electrochemical degradation of bifunctional reactive dyes after a real dyeing process. These are: Procion Yellow HELX®, Procion Crimson HELX® and Procion Navy HELX®, which are widely used in dyeing processes of cellulose fibers. Their structure is mainly characterized by the presence of two azo groups as chromophore group and two monochlorotriazinic groups as reactive groups. Electrolyses were carried out under galvanostatic conditions in an undivided electrolytic cell. Ti/SnO2-Sb-Pt and stainless steel electrodes were used as anode and cathode, respectively. In all cases Na2SO4 was used as electrolyte without external addition of chloride. The degree of degradation was evaluated by means of Total Organic Carbon (TOC) and Chemical Oxygen Demand (COD) measurements. The decolourization kinetics and the presence of the intermediates generated due to of the electrochemical treatment were studied by High Performance Liquid Chromatography (HPLC) and these studies were also carried out with UV¿Visible and Fourier Transform Infrared (FTIR) Spectroscopies. In all cases, a decrease in TOC and COD, and a complete decolourization were obtained after the electrochemical treatment. AOS and COS data proved the presence of oxidised intermediates in solution after the electrolyses. These results suggest the possibility of reusing the treated water in several dyeing processes.The authors wish to thank the Spanish Agencia Estatal de Investigacion (AEI) and European Union (FEDER funds) for the financial support (contract MAT2016-77742-C2-1-P). A.I. del Rio is grateful to the Spanish Ministerio de Ciencia y Tecnologia for her FPI fellowship. J. Molina is grateful to the Conselleria d'Educacio, Formacio i Ocupacio (Generalitat Valenciana) for the Programa VALi + D Postdoctoral Fellowship (APOSTD/2013/056). The authors wish to acknowledge to the Texcoy S.L. company (Spain) where the dyeing processes were done and Tim Vickers for help with the English revision.Orts Maiques, FJ.; Del Río García, AI.; Molina Puerto, J.; Bonastre Cano, JA.; Cases, F. (2018). Electrochemical treatment of real textile wastewater: Trichromy Procion HEXL. Journal of Electroanalytical Chemistry. 808:387-394. doi:10.1016/j.jelechem.2017.06.051S38739480

Electrochemical treatment of bifunctional dyes in a filter press reactor

[EN] In the present work, the electrochemical treatment of reactive bifunctional dyes is investigated. The selected dyes correspond to the tricromy HEXL. These dyes present two azo groups as chromophore groups and two monochlorotriazinic groups as reactive groups. This study has been carried out in two parts: in the fi rst part, synthetic solutions containing just one of these dyes, Procion HEXL, were studied (Solution (1)). Previous investigations have demonstrated that the best process to carry out this study is the oxidoreduction at 125 mA cm-2. Following to this fi rst part, the same study in the same working conditions was performed with solutions containing the three dyes of the tricromy H-EXL (Procion Yellow HEXL, Procion Crimson HEXL and Procion Navy HEXL). In this last case, the concentrations were selected considering the concentrations found in real effluents. In order to evaluate the decoloration/mineralization obtained, Total Organic Carbon (TOC) and the Chemical Oxygen Demand (COD) were measured. These parameters allowed to know the Average Oxidation State (AOS) after each electrolysis and the effi ciency at which the process takes place by means of calculating the Carbon Oxidation State (COS) and The Average Current Effi ciency (ACE). The UV-Visible spectroscopy permitted to observe the decoloration differences between the initial and fi nal stage. Moreover, the High Performance Liquid Chromatography (HPLC) gave information about the intermediates generated as well as the decoloration kinetics.[ES] En el presente trabajo se ha investigado el comportamiento electroquímico de colorantes reactivos bifuncionales. Los colorantes seleccionados son los correspondientes a la tricromía HEXL. Estos colorantes presentan dos grupos azo como cromóforos y dos grupos monoclorotriazínico como grupos reactivos. El estudio consta de dos partes: inicialmente, se han estudiado disoluciones sintéticas que contienen únicamente uno de estos colorantes, el Procion Yellow HEXL (Disolución 1). Investigaciones anteriores han demostrado que el proceso de oxido-reducción a 125 mA cm-2 es el que presenta mejores resultados. Posteriormente, se trasladó este estudio, en las mismas condiciones de trabajo, a disoluciones que contienen una mezcla de los tres colorantes correspondientes a la tricromía HEXL (Procion Yellow HEXL , Procion Crimson HEXL y Procion Navy HEXL) adaptando las concentraciones a condiciones reales (Disolución 2). Esta investigación se ha centrado en evaluar el grado de decoloración/mineralización mediante medidas de Carbono Orgánico Total (COT) y Demanda Química de Oxígeno (DQO). Esto ha permitido conocer el Estado de Oxidación Promedio (EOP) tras cada electrólisis además de la eficiencia en cada caso mediante análisis del Estado de Oxidación del Carbono (EOC) y Eficiencia en Corriente Promedio (ECP). La Espectroscopía UV-Visible ha permitido observar las diferencias de decoloración entre el estado inicial y final en todos los casos. Además, la Cromatografía Líquida de Alta Resolución (HPLC) ha permitido conocer la evolución de los intermedios generados así como la cinética de decoloración.Los autores desean agradecer agradecimiento al Ministerio de Ciencia e Innovación y los Fondos de la Unión Europea (FEDER) la financiación proporcionada (CTM2010-18842-C02-02 y CTM 2011-23583).Del Río García, AI.; Orts Maiques, FJ.; Molina Puerto, J.; Bonastre Cano, JA.; Cases Iborra, FJ. (2012). Tratamiento electroquímico de colorantes bifuncionales tipo Hexl en una célula filtro prensa. DYNA: Ingeniería e Industria. 87(6):679-688. https://doi.org/10.6036/4682S67968887

Statement of the Spanish Interdisciplinary Cardiovascular Prevention Committee (CEIPC ) on the 2012 European Cardiovascular Prevention Guidelines

Las guías europeas de prevención cardiovascular contemplan dos sistemas de evaluación de la evidencia (SEC y GRADE) y recomiendan combinar las estrategias poblacional y de alto riesgo, interviniendo en todas las etapas de la vida, con la dieta como piedra angular de la prevención. La valoración del RCV incorpora los niveles de HDL y los factores psicosociales, una categoría de muy alto riesgo y el concepto edad-riesgo. Se recomienda e luso de métodos cognitivo-conductuales (entrevistamotivadora, intervenciones psicológicas), aplicados por profesionales sanitarios, con la participación de familiares de los pacientes, para contrarrestar el estrés psicosocial y reducir el RCV mediante dietas saludables, entrenamiento físico, abandono del tabaco y cumplimiento terapéutico. También se requieren medidas de salud pública, como la prohibición de fumar en lugares públicos o eliminar los ácidos grasos trans de la cadena alimentaria. Otras novedades consisten en desestimar el tratamiento antiagregante en prevención primaria y la recomendación de mantener la PA dentro del rango13-139/80-85 mmHg en pacientes diabéticos o con RCV alto. Se destaca el bajo cumplimiento terapéutico observado, porque influye en el pronóstico de los pacientes y en los costes sanitarios. Para mejorar la prevención cardiovascular se precisa una verdadera alianza entre políticos, administraciones, asociaciones científicas y profesionales de la salud, fundaciones de salud, asociaciones de consumidores, pacientes y sus familias, que impulse las estrategias poblacional e individual, mediante el uso de toda la evidencia científica disponible, desde ensayos clínicos hasta estudios observacionales y modelo matemáticos para evaluar intervenciones a nivel poblacional, incluyendo análisis de coste-efectividadBased on the two main frameworks for evaluating scientific evidence—SEC and GRADE—European cardiovascular prevention guidelines recommend interventions across all life stages using a combination of population-based and high-risk strategies with diet as the cornerstone of prevention. The evaluation of cardiovascular risk (CVR) incorporates HDL level and psycho-social factors, a very high risk category, and the concept of age-risk. They also recommend cognitive-behavioural methods (e.g.,motivational interviewing, psychological interventions, led by health professionals and with the participation of the patient’s family, to counterbalance psychosocial stress and reduce CVR through the institution of positive habits such as a healthy diet, physical activity, smoking cessation, and adherence to treatment. Additionally, public health interventions—such as smoking ban in public areas or the elimination of trans fatty acids from the food chain—are also essential. Other innovations include abandoning antiplatelet therapy in primary prevention and the recommendation of maintaining blood pressure (BP) within the1 30-139/80-85 mmHg range in diabetic patients and individuals with high CVR. Finally ,due to the significant impact on patient progress and medical costs, special emphasisis given to the low therapeutic adherence levels observed . In sum ,improving cardiovascular prevention requires a true partnership among the political class, public administrations, scientific and professional associations, health foundations, consumer associations, patients and their families. Such partnership would promote population-based and individual strategies by taking advantage o the broad spectrum of scientific evidence available, from clinical trials to observational studies and mathematical models to evaluate population-based interventions, including cost-effectiveness analyse

Microwave versus radiofrequency ablation for the treatment of liver malignancies: a randomized controlled phase 2 trial

[EN] Microwave (MWA) and radiofrequency ablation (RFA) are main ablative techniques for hepatocellular carcinoma (HCC) and colorectal liver metastasis (MT). This randomized phase 2 clinical trial compares the effectiveness of MWA and RFA as well as morphology of corresponding ablation zones. HCC and MT patients with 1.5-4 cm tumors, suitable for ablation, were randomized into MWA or RFA Groups. The primary endpoint was short-to-long diameter ratio of ablation zone (SLR). Primary technical success (TS) and a cumulative local tumor progression (LTP) after a median 2-year follow-up were compared. Between June 2015 and April 2020, 82 patients were randomly assigned (41 patients per group). For the per-protocol analysis, five patients were excluded. MWA created larger ablation zones than RFA (p = 0.036) although without differences in SLR (0.5 for both groups, p = 0.229). The TS was achieved in 98% (46/47) and 90% (45/50) (p = 0.108), and LTP was observed in 21% (10/47) vs. 12% (6/50) (OR 1.9 [95% CI 0.66-5.3], p = 0.238) of tumors in MWA vs. RFA Group, respectively. Major complications were found in 5 cases (11%) vs. 2 cases (4%), without statistical significance. MWA and RFA show similar SLR, effectiveness and safety in liver tumors between 1.5 and 4 cm.This work was supported by a grant for medical research from Spanish Government (FIS-PI12/00799) and by the Spanish Ministerio de Ciencia, Innovacion y Universidades under "Programa Estatal de I+D+i Orientada a los Retos de la Sociedad", Grant RTI2018-094357-B-C21.Radosevic, A.; Quesada, R.; Serlavos, C.; Sánchez, J.; Zugazaga, A.; Sierra, A.; Coll, S.... (2022). Microwave versus radiofrequency ablation for the treatment of liver malignancies: a randomized controlled phase 2 trial. Scientific Reports. 12(1):1-10. https://doi.org/10.1038/s41598-021-03802-xS11012

Use of an interactomics pipeline to assess the potential of new antivirals against SARS-CoV-2

(Póster 80) Background: In late 2019 SARS-CoV-2 infection appeared in China, becoming a pandemic in 2020. The scientific community reacted rapidly, characterizing the viral genome and its encoded proteins, aiming at interfering with viral spreading with vaccines and antivirals. The receptor binding domain (RBD) of the viral spike (S) protein plays a key role in cell entry of the virus. It interacts with the cellular receptor for SARS-CoV-2, the membrane-bound human Angiotensin Converting Ectoenzyme 2 (ACE2). With the goal of monitoring interference with this interaction by potential antiviral drugs, we have set up at the Institute for Biomedicine of Valencia (IBV-CSIC) an interactomics pipeline targeting the initial step of viral entry. Methods: For the production part of the pipeline (pure RBD/Spike variants and soluble ACE2), see parallel poster. These proteins allowed monitoring of the RBD/Spike-ACE2 interaction in presence or absence of potential inhibitors. Thermal shift assays (thermofluor) were used for initial detection of compound binding at different ligand/protein ratios and media conditions (pH, buffers, chaotropic agents). Next, binding affinity and on/off kinetics were characterized using Biolayer interferometry (BLI), Surface plasmon resonance (SPR), Microscale Thermophoresis (MST) and/or Isothermal titration calorimetry (ITC). For protein-protein interactions, we mostly used BLI or SPR, whereas for proteinsmall compound analysis MST was generally best. Protein aggregation-dissociation was monitored by size exclusion chromatography with multiangle light scattering (SEC-MALS). Results: Candidates proven by thermal shift assays to bind to RBD/spike protein without affecting the integrity of these proteins were subjected to quantitative affinity measurements. We successfully demonstrated that BLI, SPR and MST can be used to follow the interactions between SARS-CoV- 2 proteins and the putative drug candidates, as well as to monitor the interference with Spike-Ace2 binding of potential drug candidates. While BLI and SPR displayed reproducible results in the measurement of protein-protein interaction (applied to soluble ACE2 used as a decoy), they were less suitable for measuring the binding of small molecules. The fact that most small compounds were only soluble in organic solvents made difficult to obtain a low signal/noise while using BLI, necessary for the assessment of the binding. We overcame that problem by using MST. After dilution of the compounds to the final experimental concentrations, the technique could detect a significant binding signal enough to calculate binding parameters. MST also allowed to measure the degree of interference that each compound was having on RBD/Spike-ACE2 interaction. The pipeline has been customized and validated with compounds of very different nature provided by different groups belonging to the PTI and other external laboratories, as well as with different Ace2 decoys designed at the IBV. Conclusions: The interactomics platform at the IBV has been used to successfully develop two different antiviral approaches in order to fight COVID-19. It has allowed technical specialization of the staff as well as the development, in a very short period of time, of two ambitious projects. We have demonstrated that we can perform interactomic characterization for challenging projects as well as provide information about binding of antivirals to potential new SARS-CoV-2 variants of concern