Efficacy and safety of the metformin-mazindol anorectic combination in rat

The current study investigates the anorectic interaction and safety of the mazindol-metformin combination in rats. Isobologram and interaction index were used to determine anorectic interaction between mazindol and metformin in the sweetened milk model. The safety profile of the mazindol-metformin combination was determined by measuring anxiety, blood pressure, hematic biometry and blood chemistry. An acute dose of mazindol and metformin administered per os, individually or as a mixture, has reduced the milk consumption in rats in a dose-dependent manner. Theoretical effective dose 40 (ED40t) did not differ from the experimental effective dose 40 (ED40e) obtained with the mazindol-metformin mixture in the anorexia experiments, by Student´s t-test. In addition, the interaction index confirmed the additive anorectic effect between both drugs. A single oral dose of ED40e mazindol-metformin mixture induced anxiolysis in the elevated plus-maze test. Moreover, oral administration of mazindol-metformin combination for 3 months significantly decreased glycemia, but not blood pressure nor other parameters of hematic biometry and blood chemistry. Results suggest that mazindol-metformin combination exerts an additive anorectic effect, as well as anxiolytic and hypoglycemic properties. Mazindol-metformin combination might be useful in obese patients with anxiety disorders or diabetes risk factors

Prevalence of bleeding secondary to anticoagulation and mortality in patients with atrial fibrillation admitted with SARS-CoV-2 infection.

Atrial fibrillation (AF) is common in patients admitted with severe COVID-19. However, there is limited data about the management of chronic anticoagulation therapy in these patients. We assessed the anticoagulation and incidence of major cardiovascular events in hospitalized patients with AF and COVID-19. We retrospectively investigated all consecutive patients with AF admitted with COVID-19 between March and May 2020 in 9 Spanish hospitals. We selected a control group of non-AF patients consecutively admitted with COVID-19. We compared baseline characteristics, incidence of major bleeding, thrombotic events and mortality. We used propensity score matching (PSM) to minimize potential confounding variables, as well as a multivariate analysis to predict major bleeding and death. 305 patients admitted with AF and COVID-19 were included. After PSM, 151 AF patients were matched with 151 control group patients. During admission, low-molecular-weight heparin was the principal anticoagulant and the incidence of major bleeding and mortality were higher in the AF group [16 (10.6%) vs 3 (2%), p=0.003; 52 (34.4%) vs 35 (23.2%), p=0.03, respectively]. The multivariate analysis showed the presence of AF as independent predictor of in-hospital major bleeding and mortality in COVID-19 patients. In AF group, a secondary multivariate analysis identified high levels of D-dimer as independent predictor of in-hospital major bleeding. AF patients admitted with COVID-19 represent a population at high risk for bleeding and mortality during admission. It seems advisable to individualize anticoagulation therapy during admission, considering patient specific bleeding and thrombotic risk.S

Nuevos escenarios para la docencia universitaria : entornos híbridos y pedagogías emergentes.

Memorias del IX Simposio Internacional de Docencia Universitaria (SIDU)Los trabajos reunidos en esta Memoria representan una contribución importante al campo de la educación y de la docencia universitaria, en tanto muestran distintas maneras de responder a las problemáticas educativas cotidianas y presentan propuestas para afrontar los retos emergentes en el campo de la educación superior. Invitamos a los lectores a realizar una lectura atenta y crítica de los trabajos compilados en esta publicación. Estamos seguros de que este acercamiento propiciará la reflexión y el análisis riguroso de los objetos de estudio abordados por los autores, y estimulará la generación de nuevos proyectos de investigación, intervención e innovación educativa que incidan en el desarrollo de mejores prácticas de docencia en educación media superior y superior.Pimera edición digitaldoi.org/10.56019/EDU-CETYS.2024.182

Epidemiología y registro de las cardiopatías congénitas en Costa Rica Epidemiology and registry of congenital heart disease in Costa Rica

OBJETIVO: Caracterizar la población de niños que nacen con cardiopatías congénitas (CC) en Costa Rica y evaluar sus procesos de registro. MÉTODOS: Estudio observacional exploratorio que incluyó a todos los niños con CC diagnosticadas en el Hospital Nacional de Niños entre el 1 de mayo de 2006 y el 1 de mayo de 2007. Tomando en cuenta los niños menores de 1 año y su respectiva cohorte de nacimientos, se estimaron prevalencias con intervalos de confianza de 95% (IC95%) según sexo, tipo de cardiopatía, edad al diagnóstico, edad materna, residencia habitual y malformaciones extracardiacas asociadas. Se compararon los datos con el Centro de Registro de Enfermedades Congénitas (CREC). RESULTADOS: Durante el período estudiado se diagnosticaron 534 casos con CC. Los casos en menores de 1 año fueron 473 dentro de una cohorte de nacimientos de 77 140 -prevalencia de 0,6% (IC95%: 0,5-0,7). Con base en datos del CREC, se demostró que al nacimiento no se detectan 71% de los casos. La edad promedio al diagnóstico en niños menores de 1 año fue de 46,6 días. No hubo diferencias por sexo. La prevalencia de CC en hijos de madres de 35 años o más fue significativamente mayor, aunque al excluir las cromosomopatías este riesgo perdió su significancia estadística. Las provincias del país con puertos marítimos fueron las de mayor riesgo en hijos de madres adolescentes. Las CC más frecuentes fueron los defectos del tabique interventricular e interauricular, persistencia del conducto arterioso, estenosis valvular pulmonar, defectos del tabique aurículo ventricular, coartación de aorta y tetralogía de Fallot. El 34% de las CC fueron múltiples, 11,2% se asociaron a cromosomopatías y 19% tenían malformaciones congénitas asociadas. CONCLUSIONES: La prevalencia de CC en Costa Rica está dentro del rango informado a nivel mundial. Se halló que en el CREC había un importante subregistro de CC debido principalmente a los criterios de edad aplicados. Los resultados sugieren que la edad materna (menores de 20 años y mayores de 34 años) es un factor asociado a la ocurrencia de CC.<br>OBJECTIVE: Characterize the population of children born with congenital heart disease (CHD) in Costa Rica and evaluate the country's registry processes. METHODS: Exploratory observational study that included all children with CHD diagnosed at the National Children's Hospital between 1 May 2006 and 1 May 2007. Considering children under 1 year of age and their respective birth cohort, prevalence was estimated by sex, type of heart disease, age at diagnosis, maternal age, habitual residence, and associated extracardiac malformations, with 95% confidence intervals (95% CI). The data was compared with those of the Congenital Disease Registry Center (CREC). RESULTS: During the period studied, 534 cases with CHD were diagnosed. There were 473 cases in children under 1 year of age in a birth cohort of 77 140 children. Prevalence was 0.6% (95% CI: 0.5-0.7). Based on CREC data, it was demonstrated that 71% of the cases were not detected at birth. The average age of diagnosis in infants under 1 year of age was 46.6 days. There were no differences by sex. Prevalence of CHD in children of mothers aged 35 years or over was significantly higher. However, when chromosomal abnormalities were excluded, the risk was no longer statistically significant. The provinces in the country with maritime ports were the areas with the highest risk in children of adolescent mothers. The most common CHDs were ventricular and atrial septal defects, patent ductus arteriosus, pulmonary valve stenosis, atrioventricular septal defects, coarctation of the aorta, and tetralogy of Fallot. Thirtyfour percent of the cases of CHD were multiple, 11.2% were associated with chromosomal abnormalities, and 19% had associated congenital malformations. CONCLUSIONS: CHD prevalence in Costa Rica is within the range reported globally. Significant underreporting of CHD was found in the CREC, primarily due to the age criteria applied. The results suggest that maternal age (under 20 and over 34) is a factor associated with CHD

Magnetic and Viscoelastic Response of Magnetorheological Elastomers Based on a Combination of Iron Nano- and Microparticles

In this paper, we discuss the creation of a hybrid magnetorheological elastomer that combines nano- and microparticles. The mixture contained 45 wt.% fillers, with combinations of either 0% nanoparticles and 100% microparticles or 25% nanoparticles and 75% microparticles. TGA and FTIR testing confirmed the materials’ thermal and chemical stability, while an SEM analysis determined the particles’ size and morphology. XRD results were used to determine the crystal size of both nano- and microparticles. The addition of reinforcing particles, particularly nanoparticles, enhanced the stiffness of the composite materials studied, but their overall strength was only minimally affected. The computed interaction parameter relative to the volume fraction was consistent with the previous literature. Furthermore, the study observed a magnetic response increment in composite materials reinforced with nanoparticles above 30 Hz. The isotropic material containing only microparticles had a lower storage modulus than the isotropic sample with nanoparticles without a magnetic field. However, when a magnetic field was applied, the material with only microparticles exhibited a higher storage modulus than the samples with nanoparticles

GPR55 and GPR119 Receptors Contribute to the Processing of Neuropathic Pain in Rats

Orphan G-protein-coupled receptors (GPCR) comprise a large number of receptors which are widely distributed in the nervous system and represent an opportunity to identify new molecular targets in pain medicine. GPR55 and GPR119 are two orphan GPCR receptors whose physiological function is unclear. The aim was to explore the participation of spinal GPR55 and GPR119 in the processing of neuropathic pain in rats. Mechanical allodynia was evaluated using von Frey filaments. Protein localization and modulation were measured by immunohistochemistry and western blotting, respectively. Intrathecal administration of CID16020046 (selective GPR55 antagonist) or AS1269574 (selective GPR119 agonist) produced a dose-dependent antiallodynic effect, whereas O1062 (GPR55 agonist) and G-protein antagonist peptide dose-dependently prevented the antiallodynic effect of CID16020046 and AS1269574, respectively. Both GPR55 and GPR119 receptors were expressed in spinal cord, dorsal root ganglia and sciatic nerve, but only GPR119 was downregulated after 14 days of spinal nerve ligation. Data suggest that GPR55 and GPR119 participate in the processing of neuropathic pain and could be useful targets to manage neuropathic pain disorders

Efficacy and safety of the metformin-mazindol anorectic combination in rat

The current study investigates the anorectic interaction and safety of the mazindol-metformin combination in rats. Isobologram and interaction index were used to determine anorectic interaction between mazindol and metformin in the sweetened milk model. The safety profile of the mazindol-metformin combination was determined by measuring anxiety, blood pressure, hematic biometry and blood chemistry. An acute dose of mazindol and metformin administered per os, individually or as a mixture, has reduced the milk consumption in rats in a dose-dependent manner. Theoretical effective dose 40 (ED40t) did not differ from the experimental effective dose 40 (ED40e) obtained with the mazindol-metformin mixture in the anorexia experiments, by Student′s t-test. In addition, the interaction index confirmed the additive anorectic effect between both drugs. A single oral dose of ED40e mazindol-metformin mixture induced anxiolysis in the elevated plus-maze test. Moreover, oral administration of mazindol-metformin combination for 3 months significantly decreased glycemia, but not blood pressure nor other parameters of hematic biometry and blood chemistry. Results suggest that mazindol-metformin combination exerts an additive anorectic effect, as well as anxiolytic and hypoglycemic properties. Mazindol-metformin combination might be useful in obese patients with anxiety disorders or diabetes risk factors

PISA 2012 : PISA en el Perú. Informe pedagógico de resultados PISA 2012 en Matemática

El presente Informe pedagógico de resultados PISA 2012 tiene como propósito central difundir las características principales del marco teórico que sustenta la evaluación de la competencia matemática, los resultados en el proceso correspondiente al 2012 así como proponer un conjunto de recomendaciones pedagógicas que guíen las intervenciones de los docentes a partir de los hallazgos de dichos resultados. Así, el primer capítulo, describe e ilustra conceptos tales como competencia matemática y las variables o categorías y subcategorías con las que esta competencia se operacionaliza en cada una de las preguntas usadas para su evaluación. Se incluyen en este capítulo algunos ítemes liberados de dominio público que ilustren de mejor manera cada una de las categorías y subcategorías mencionadas. El segundo capítulo presenta los resultados correspondientes al proceso PISA 2012. Estos resultados se brindan tanto por puntaje promedio como por la proporción de estudiantes en cada uno de los niveles de desempeño de la competencia matemática en general. Asimismo se brindan resultados comparativos con otros países de la región y por cada una de las subcategorías desarrolladas en el capítulo precedente. El tercer y último capítulo, brinda un conjunto de recomendaciones de tipo pedagógico que incluye pautas para el uso de los ítemes liberados en las clases de matemática, propuestas de aprendizaje con atención a la diversidad y sesiones para cada uno de los cuatro primeros grados del nivel secundario. Todos estos aportes con el común denominador de considerar tanto la concepción de matemática como las variables o categorías que el marco PISA plantea

Possible involvement of peripheral TRP channels in the hydrogen sulfide-induced hyperalgesia in diabetic rats

Abstract Background Peripheral diabetic neuropathy can be painful and its symptoms include hyperalgesia, allodynia and spontaneous pain. Hydrogen sulfide (H2S) is involved in diabetes-induced hyperalgesia and allodynia. However, the molecular target through which H2S induces hyperalgesia in diabetic animals is unclear. The aim of this study was to determine the possible involvement of transient receptor potential (TRP) channels in H2S-induced hyperalgesia in diabetic rats. Results Streptozotocin (STZ) injection produced hyperglycemia in rats. Intraplantar injection of NaHS (an exogenous donor of H2S, 3–100 µg/paw) induced hyperalgesia, in a time-dependent manner, in formalin-treated diabetic rats. NaHS-induced hyperalgesia was partially prevented by local intraplantar injection of capsazepine (0.3–3 µg/paw), HC-030031 (100–316 µg/paw) and SKF-96365 (10–30 µg/paw) blockers, at 21 days post-STZ injection. At the doses used, these blockers did not modify formalin-induced nociception. Moreover, capsazepine (0.3–30 µg/paw), HC-030031 (100–1000 µg/paw) and SKF-96365 (10–100 µg/paw) reduced formalin-induced nociception in diabetic rats. Contralateral injection of the highest doses used did not modify formalin-induced flinching behavior. Hyperglycemia, at 21 days, also increased protein expression of cystathionine-β-synthase enzyme (CBS) and TRPC6, but not TRPA1 nor TRPV1, channels in dorsal root ganglia (DRG). Repeated injection of NaHS enhanced CBS and TRPC6 expression, but hydroxylamine (HA) prevented the STZ-induced increase of CBS protein. In addition, daily administration of SKF-96365 diminished TRPC6 protein expression, whereas NaHS partially prevented the decrease of SKF-96365-induced TRPC6 expression. Concordantly, daily intraplantar injection of NaHS enhanced, and HA prevented STZ-induced intraepidermal fiber loss, respectively. CBS was expressed in small- and medium-sized cells of DRG and co-localized with TRPV1, TRPA1 and TRPC6 in IB4-positive neurons. Conclusions Our data suggest that H2S leads to hyperalgesia in diabetic rats through activation of TRPV1, TRPA1 and TRPC channels and, subsequent intraepidermal fibers loss. CBS enzyme inhibitors or TRP-channel blockers could be useful for treatment of painful diabetic neuropathy