Differential actions of eplerenone and spironolactone on the protective effect of testosterone against cardiomyocyte apoptosis in vitro

©2010. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ This document is the Accepted version of a Published Work that appeared in final form in Revista Española de cardiología. To access the final edited and published work see https://doi.org/10.1016/s1885-5857(10)70162-6Introduction and objectives: Testosterone deficiency is associated with a poor prognosis in patients with heart failure. It is not clear whether testosterone reduces cardiomyocyte apoptosis or whether the effect of spironolactone, an aldosterone receptor blocker with progestogenic and anti-androgen activity, differs from that of the selective aldosterone blocker eplerenone. Methods: Apoptosis induced by hyperosmotic stress in the embryonic rat heart cell line H9c2 was monitored by measuring cell viability, DNA fragmentation and caspase-3, -8 and -9 activation. The effect of testosterone was investigated in the presence or absence of spironolactone and eplerenone. Results: Exposure to sorbitol (0.6 M, 3 h) decreased cell viability and increased DNA fragmentation and caspase-3, -8 and -9 activation. These effects were all significantly reduced by testosterone, 100 nM (P< .01). Pretreatment with spironolactone, 10 .M, blocked the effects of testosterone, decreased cell viability (P< .01) and increased caspase activation (P< .01). In contrast, eplerenone, 10 .M, increased cell viability (P< .001) without altering the effect on caspase activation. These actions were not modified by the androgen receptor blocker flutamide. They were mediated by SAPK/JNK and ERK1/2 signaling pathways (P< .01). Conclusions: Testosterone appears to have a protective effect against cardiomyocyte apoptosis which is antagonized by spironolactone but not by eplerenone. These effects await confirmation in in vivo models, but their presence could have clinical and therapeutic implications

Fracture energy of coarse recycled aggregate concrete using the wedge splitting test method: influence of water-reducing admixtures

The aim of this study is to evaluate the effect of the replacement levels of coarse natural aggregates with recycled aggregates and water-reducing admixtures on the fracture energy of concrete. Four mixes with 0, 20, 50 and 100% replacement ratios are produced per concrete family: without admixture, with plasticizer and with superplasticizer. The experimental fracture energy is tested using the wedge splitting test method on notched specimens at 28 days. The results prove that the incorporation of up to 20% coarse recycled aggregates led to improved energy absorption capacity of concrete mixes with water-reducing admixtures, reaching 1.5% for concrete with normal plasticizer and 7.0% for concrete with superplasticizer. Furthermore, the compressive strength, slump, and fresh density are tested in order to evaluate the effect of water-reducing admixtures on recycled aggregate concrete with different ratios of coarse natural aggregate replacement, allowing to conclude that the use of plasticizers and superplasticizers improves the behaviour of recycled aggregate concrete for all these properties

Mapping the Asymmetric Thick Disk I. A Search for Triaxiality

A significant asymmetry in the distribution of faint blue stars in the inner Galaxy, Quadrant 1 (l = 20 to 45 degrees) compared to Quadrant 4 was first reported by Larsen & Humphreys (1996). Parker et al (2003, 2004) greatly expanded the survey to determine its spatial extent and shape and the kinematics of the affected stars. This excess in the star counts was subsequently confirmed by Juric et al. (2008) using SDSS data. Possible explanations for the asymmetry include a merger remnant, a triaxial Thick Disk, and a possible interaction with the bar in the Disk. In this paper we describe our program of wide field photometry to map the asymmetry to fainter magnitudes and therefore larger distances. To search for the signature of triaxiality, we extended our survey to higher Galactic longitudes. We find no evidence for an excess of faint blue stars at l > 55 degrees including the faintest magnitude interval. The asymmetry and star count excess in Quadrant 1 is thus not due to a triaxial Thick Disk.Comment: 36 pages, 8 figures. Accepted by Astronomical Journa

Extractos polifenólicos de las hojas de Ilex paraguariensis y Larrea divaricata y su potencial antioxidante y antiCOVID-19

Yerba mate (Ilex paraguariensis A.St. Hil) and jarilla (Larrea divaricata Cav.) leaves are commonly used as tea infusions in some Latin American countries. This study was conducted to evaluate the antioxidant activity (FRAP, ABTS, and DPPH) and the inhibitory potential of yerba mate and jarilla extracts on the 3CL protease (Mpro) from coronavirus SARS-COV-2 by a molecular docking approach. The main bioactive compounds present in the plant extracts were identified by HPLC-MS. According to the results, the extracts of yerba mate and jarilla showed high antioxidant activity in DPPH (&gt; 91 %), ABTS (&gt; 90 %), and FRAP (&gt; 47 mg TE/g) assays. Additionally, the phenolic compounds present in yerba mate, quercetin-3-O-rutinoside (rutin) (-9.60 kcal/mol) and 3,4-dicaffeoylquinic acid (-8.20 kcal/mol) were more effective on Mpro than the antiviral drugs remdesivir and ribavirin. The compounds rutin and 3,4-dicaffeoylquinic acid have a high affinity and interaction with one of the catalytic residues Cys145 of Mpro. The glycosylation of phenolic compounds affects biological activities: positively anti-COVID-19 and negatively antioxidant. The results suggest that extracts of yerba mate and jarilla leaves could enhance the body's antioxidant defenses and can be used to improve health.Las hojas de yerba mate (Ilex paraguariensis A.St. Hil) y jarilla (Larrea divaricata Cav.) se usan comúnmente como infusión de té en algunos países de América Latina. Este estudio se realizó para evaluar la actividad antioxidante (FRAP, ABTS y DPPH) y el potencial inhibitorio de los extractos de yerba mate y jarilla sobre la proteasa 3CL (Mpro) de coronavirus SARS-COV-2 por enfoque de acoplamiento molecular. Los principales compuestos bioactivos presentes en los extractos de plantas fueron identificados por HPLC-MS. De acuerdo con los resultados, los extractos polifenólicos de yerba mate y jarilla presentaron alta actividad antioxidante en los ensayos DPPH (&gt; 91 %), ABTS (&gt; 90 %) y FRAP (&gt; 47 mg TE/g). Además, los compuestos fenólicos presentes en la yerba mate, quercetina-3-O-rutinósido (rutina) (-9,60 kcal/mol) y ácido 3,4-dicafeoilquínico (-8,20 kcal/mol) han demostrado ser más efectivos (en Mpro) que los medicamentos antivirales remdesivir y ribavirin. Los compuestos rutina y ácido 3,4-dicafeoilquínico tienen alta afinidad e interacción con uno de los residuos catalíticos Cys145 de Mpro. Estos resultados sugieren que las hojas de yerba mate y jarilla podrían potenciar las defensas antioxidantes del organismo y podrían beneficiar la salud

Contenido de carbono y nitrógeno de la biomasa microbiana en suelos de La Habana.

La presente investigacion fue diseñada con el objetivo de calcular el carbono (C) y el nitrogeno(N) inmovilizado en la biomasa microbiana de cuatro suelos Ferraliticos Rojos de la Provincia de La Habana, Cuba,empleando la metodologia de gfumigacion extracción en el año 2006. Se colectaron muestras de cuatro sitios (Bainoa, LaSalud, Quivican y Guanajay), los cuales mostraron diferencias en las caracteristicas fisico-quimicas, incluyendo diferencias en contenido de materia organica entre 2,8 y 5%. La sensibilidad de las metodologías empleadas fue valorada utilizandoel error estandar de las medias como parametro estadístico. Los niveles de C inmovilizados en la biomasa microbianaen los suelos estudiados, variaron entre 289 y 425 ƒÊg/g de suelo y tuvieron una correlacion altamente significativa con el contenido de materia organica del suelo. Los contenidosde N inmovilizados variaron entre 62 y 90 ƒÊg/g de suelo yse observo tambien una correlacion signifi cativa entre esteparametro y el contenido de nitrogeno total. El error estandarde la media para las determinaciones del C microbiano vario entre 2 y 16 y fueron ligeramente superiores a lo hallado en reportes anteriores; mientras que los errores observados en las determinaciones del N microbiano se mantuvieron entre losrangos considerados adecuados. Finalmente la metodologia fue adaptada a las condiciones del laboratorio

Estado actual de la gestión de residuos de construcción y demolición: limitaciones

Construction has grown exponentially in recent decades. This development has also brought large production of debris from construction and demolition. These wastes have reached the environment and generated a very important pollution in the landscape, soil and water. Equally it represents a loss of potential resources; because these wastes still have capacity to be recovered. Both central and regional government have published numerous standards, in recent years, to establish guidelines for a proper management, reuse and recycling of this debris. This paper analyzes the current status of this legislation, their gaps and their degree of implementation.El sector de la construcción ha crecido de forma exponencial en las últimas décadas y con él, la producción de residuos generados, estimándose esta en 2 kg por habitante y día, lo que representa una magnitud escalofriante. Para solucionar este problema la administración promueve comportamientos ecológicos respecto a la gestión de residuos de construcción y demolición (producción y posterior manejo y utilización de los mismos) a través de la redacción de normas que regulen el tema. Estas normas presentan importantes carencias y limitaciones. Si estas carencias y limitaciones no se resuelven, el proceso encaminado a mejorar la sostenibilidad se interrumpe y las medidas tomadas hasta el momento se vuelven ineficaces. Este trabajo pretende poner de manifiesto estos problemas a fin de evitarlos, de forma que todos los agentes implicados conozcan el importante papel que desempeñan en la correcta gestión

Assessment of Platelet REACtivity After Transcatheter Aortic Valve Replacement : The REAC-TAVI Trial

The REAC-TAVI (Assessment of platelet REACtivity after Transcatheter Aortic Valve Implantation) trial enrolled patients with aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR) pre-treated with aspirin + clopidogrel, aimed to compare the efficacy of clopidogrel and ticagrelor in suppressing high platelet reactivity (HPR) after TAVI. Current recommendations support short-term use of aspirin + clopidogrel for patients with severe AS undergoing TAVR despite the lack of compelling evidence. This was a prospective, randomized, multicenter investigation. Platelet reactivity was measured at 6 different time points with the VerifyNow assay (Accriva Diagnostics, San Diego, California). HPR was defined as (P2Y reaction units (PRU) ≥208. Patients with HPR before TAVR were randomized to either aspirin + ticagrelor or aspirin + clopidogrel for 3 months. Patients without HPR continued with aspirin + clopidogrel (registry cohort). The primary endpoint was non-HPR status (PRU <208) in ≥70% of patients treated with ticagrelor at 90 days post-TAVR. A total of 68 patients were included. Of these, 48 (71%) had HPR (PRU 273 ± 09) and were randomized to aspirin + ticagrelor (n = 24, PRU 277 ± 08) or continued with aspirin + clopidogrel (n = 24, PRU 269 ± 49). The remaining 20 patients (29%) without HPR (PRU 133 ± 12) were included in the registry. Overall, platelet reactivity across all the study time points after TAVR was lower in patients randomized to ticagrelor compared with those treated with clopidogrel, including those enrolled in the registry (p < 0.001). The primary endpoint was achieved in 100% of patients with ticagrelor compared with 21% with clopidogrel (p < 0.001). Interestingly, 33% of clopidogrel responder patients at baseline developed HPR status during the first month after TAVR. HPR to clopidogrel is present in a considerable number of patients with AS undergoing TAVR. Ticagrelor achieves a better and faster effect, providing sustained suppression of HPR to these patients. (Platelet Reactivity After TAVI: A Multicenter Pilot Study [REAC-TAVI]; NCT02224066