Trimethylamine N-oxide does not impact viability, ROS production and mitochondrial membrane potential of adult rat cardiomyocytes

Trimethylamine N-oxide (TMAO) is an organic compound derived from dietary choline and L-carnitine. It behaves as an osmolyte, a protein stabilizer, and an electron acceptor, showing different biological functions in different animals. Recent works point out that, in humans, high circulating levels of TMAO are related to the progression of atherosclerosis and other cardiovascular diseases. However, studies on a direct role of TMAO in cardiomyocyte parameters are still limited. The purpose of this work is to study the effects of TMAO on isolated adult rat cardiomyocytes. TMAO in both 100 µM and 10 mM concentrations, from 1 to 24 h of treatment, does not affect cell viability, sarcomere length, intracellular ROS, and mitochondrial membrane potential. Furthermore, the simultaneous treatment with TMAO and known cardiac insults, such as H2O2 or doxorubicin, does not affect the treatment’s effect. In conclusion, TMAO cannot be considered a direct cause or an exacerbating risk factor of cardiac damage at the cellular level in acute conditions

Trimethylamine N-Oxide (TMAO) Impairs Purinergic Induced Intracellular Calcium Increase and Nitric Oxide Release in Endothelial Cells

Trimethylamine N-oxide (TMAO) is a diet derived compound directly introduced through foodstuff, or endogenously synthesized from its precursors, primarily choline, L-carnitine, and ergothioneine. New evidence outlines high TMAO plasma concentrations in patients with overt cardiovascular disease, but its direct role in pathological development is still controversial. The purpose of the study was to evaluate the role of TMAO in affecting key intracellular factors involved in endothelial dysfunction development, such as reactive oxygen species, mitochondrial health, calcium balance, and nitric oxide release using bovine aortic endothelial cells (BAE-1). Cell viability and oxidative stress indicators were monitored after acute and prolonged TMAO treatment. The role of TMAO in interfering with the physiological purinergic vasodilatory mechanism after ATP stimulation was defined through measurements of the rise of intracellular calcium, nitric oxide release, and eNOS phosphorylation at Ser1179 (eNOSSer1179). TMAO was not cytotoxic for BAE-1 and it did not induce the rise of reactive oxygen species and impairment of mitochondrial membrane potential, either in the basal condition or in the presence of a stressor. In contrast, TMAO modified the purinergic response affecting intracellular ATP-induced calcium increase, nitric oxide release, and eNOSSer1179. Results obtained suggest a possible implication of TMAO in impairing the endothelial-dependent vasodilatory mechanism

El uso de la metodología de las áreas de interés según el currículo creativo y su contribución en el aprendizaje autónomo en niñas de 4 años de una institución privada de Miraflores

La presente tesis describe y analiza la aplicación de la metodología de trabajo por áreas de interés según el Currículo Creativo en niñas de 4 años, para evaluar su contribución en el proceso de aprendizaje autónomo y desarrollo integral. El estudio fue realizado a través de un análisis descriptivo aplicado en una institución privada mediante observaciones de aula durante un período de 4 meses. La metodología de trabajo por áreas de interés ofrece una educación individualizada, la cual incentiva el aprendizaje en los niños, a través de un mayor sentido de seguridad y confianza en sí mismos. Esta metodología se realiza en un ambiente acogedor y motivador, centrándose en el respeto y la autodeterminación, con el fin de maximizar sus capacidades y habilidades, buscando que ellos sean los principales constructores de su aprendizaje. Con los resultados obtenidos se puede afirmar que más del 90% de la muestra logra los indicadores previstos en cada área, lo cual evidencia que la metodología de las áreas de interés, favorece el desarrollo del aprendizaje autónomo.Tesi

Modeling the Distribution of New MRI Cortical Lesions in Multiple Sclerosis Longitudinal Studies

Objective: Recent studies have shown the relevance of the cerebral grey matter involvement in multiple sclerosis (MS). The number of new cortical lesions (CLs), detected by specific MRI sequences, has the potential to become a new research outcome in longitudinal MS studies. Aim of this study is to define the statistical model better describing the distribution of new CLs developed over 12 and 24 months in patients with relapsing-remitting (RR) MS. Methods: Four different models were tested (the Poisson, the Negative Binomial, the zero-inflated Poisson and the zeroinflated Negative Binomial) on a group of 191 RRMS patients untreated or treated with 3 different disease modifying therapies. Sample size for clinical trials based on this new outcome measure were estimated by a bootstrap resampling technique. Results: The zero-inflated Poisson model gave the best fit, according to the Akaike criterion to the observed distribution of new CLs developed over 12 and 24 months both in each treatment group and in the whole RRMS patients group adjusting for treatment effect. Conclusions: The sample size calculations based on the zero-inflated Poisson model indicate that randomized clinical trials using this new MRI marker as an outcome are feasible

L'agente OO-Garlic in missione: contro la sindrome metabolica

Ciao, sono il Signor Garlic (ma per gli amici sono l’Agente 00-Garlic). I miei antenati erano molto tristi per via del loro odore cattivo che teneva tutti lontano. Per fortuna con il tempo gli scienziati hanno scoperto che nella puzza che circonda noi della stirpe Garlic si nascondono dei superpoteri! I miei poteri aumentano se vengo trasformato e la mia pelle diventa più scura, infatti inizio a produrre tanto H2S che è un’arma speciale contro i nemici più forti. Così chi è a conoscenza delle fortissime proprietà che possiedo, mi chiama in aiuto per sconfiggere nemici molto cattivi per la salute. Uno dei più grandi nemici per tutti noi si chiama sindrome metabolica... Continua a leggere..

L'agente OO-Garlic in missione: contro la sindrome metabolica

Ciao, sono il Signor Garlic (ma per gli amici sono l’Agente 00-Garlic). I miei antenati erano molto tristi per via del loro odore cattivo che teneva tutti lontano. Per fortuna con il tempo gli scienziati hanno scoperto che nella puzza che circonda noi della stirpe Garlic si nascondono dei superpoteri! I miei poteri aumentano se vengo trasformato e la mia pelle diventa più scura, infatti inizio a produrre tanto H2S che è un’arma speciale contro i nemici più forti. Così chi è a conoscenza delle fortissime proprietà che possiedo, mi chiama in aiuto per sconfiggere nemici molto cattivi per la salute. Uno dei più grandi nemici per tutti noi si chiama sindrome metabolica... Continua a leggere..