18 research outputs found
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 StudentÂŽs 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
Is the production of embryos in small-cale farming an economically feasible enterprise?
The present assay attempts to evaluate the feasibility of using embryo transfer in small community farmers by in vivo study and by modelling the results obtained. From the total of 59 donor cows, 62.7% responded to treatment, with a significant difference (p = 0.002) in the percentage of the response between breeds, being 90.5% (19/21) in Holstein and 47.4% (18/38) in Brahman. A total of 283 embryos were graded as transferable, while 141 as non-transferable, without difference in the percentage of transferable embryo by breed (p = 0.18). The mean of transferable embryos graded as class I and II was not different between Holstein and Brahman (p = 0.96 and p = 0.92, respectively); besides, no differences were observed in the other grades (non-transferable). The highest difference in costs, regardless of its quality by breed, was seen in the lower levels of probable fertility of the embryo transferred, even reaching several hundred dollars. When modelling the expected costs for embryo produced and transferred, values can reach nearly 300.00. This technology seems to be viable on average or high-scale systems, having a superovulatory response between 60 and 80% with 4-6 transferrable embryos. Yet, in small-scale farming, due to the reduced number of donors and/or recipients, the costs surpass the economical feasibility of the technique. © 2015 Blackwell Verlag GmbH.El presente ensayo trata de evaluar la viabilidad de la utilizaciĂłn de la transferencia de embriones en los pequeños agricultores de la comunidad mediante un estudio in vivo y la elaboraciĂłn de modelos de los resultados obtenidos. Del total de 59 vacas donantes, el 62,7% respondiĂł al tratamiento, con una diferencia significativa (p = 0,002) en el porcentaje de respuesta entre las razas, siendo el 90,5% (19/21) en Holstein y el 47,4% (18/38) en Brahman. Un total de 283 embriones fueron calificados como transferibles, mientras que 141 como no transferibles, sin diferencia en el porcentaje de embriones transferibles por raza (p = 0,18). La media de embriones transferibles clasificados como clase I y II no fue diferente entre Holstein y Brahman (p = 0,96 y p = 0,92, respectivamente); ademĂĄs, no se observaron diferencias en los demĂĄs grados (no transferibles). La mayor diferencia de costos, independientemente de su calidad por raza, se observĂł en los niveles mĂĄs bajos de fertilidad probable del embriĂłn transferido, llegando incluso a varios cientos de dĂłlares. Al modelizar los costos esperados del embriĂłn producido y transferido, los valores pueden llegar a ser de casi 2000 dĂłlares cuando la fertilidad probable es sĂłlo del 10%. Sin embargo, cuando la fertilidad probable era del 60%, el costo del embriĂłn se acercaba a los 300 dĂłlares. Esta tecnologĂa parece ser viable en sistemas de media o alta escala, teniendo una respuesta superovulatoria entre el 60 y el 80% con 4-6 embriones transferibles. Sin embargo, en la agricultura a pequeña escala, debido al reducido nĂșmero de donantes y/o receptores, los costos superan la viabilidad econĂłmica de la tĂ©cnica.Universidad Nacional, Costa RicaEscuela de Medicina Veterinari
EpidemiologĂa y registro de las cardiopatĂas congĂ©nitas en Costa Rica Epidemiology and registry of congenital heart disease in Costa Rica
OBJETIVO: Caracterizar la poblaciĂłn de niños que nacen con cardiopatĂas congĂ©nitas (CC) en Costa Rica y evaluar sus procesos de registro. MĂTODOS: Estudio observacional exploratorio que incluyĂł 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%) segĂșn sexo, tipo de cardiopatĂa, edad al diagnĂłstico, edad materna, residencia habitual y malformaciones extracardiacas asociadas. Se compararon los datos con el Centro de Registro de Enfermedades CongĂ©nitas (CREC). RESULTADOS: Durante el perĂodo 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 demostrĂł que al nacimiento no se detectan 71% de los casos. La edad promedio al diagnĂłstico en niños menores de 1 año fue de 46,6 dĂas. No hubo diferencias por sexo. La prevalencia de CC en hijos de madres de 35 años o mĂĄs fue significativamente mayor, aunque al excluir las cromosomopatĂas este riesgo perdiĂł su significancia estadĂstica. Las provincias del paĂs con puertos marĂtimos fueron las de mayor riesgo en hijos de madres adolescentes. Las CC mĂĄs frecuentes fueron los defectos del tabique interventricular e interauricular, persistencia del conducto arterioso, estenosis valvular pulmonar, defectos del tabique aurĂculo ventricular, coartaciĂłn de aorta y tetralogĂa de Fallot. El 34% de las CC fueron mĂșltiples, 11,2% se asociaron a cromosomopatĂas y 19% tenĂan malformaciones congĂ©nitas asociadas. CONCLUSIONES: La prevalencia de CC en Costa Rica estĂĄ dentro del rango informado a nivel mundial. Se hallĂł que en el CREC habĂa 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 materialsâ thermal and chemical stability, while an SEM analysis determined the particlesâ 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 StudentâČs 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 PerĂș. Informe pedagĂłgico de resultados PISA 2012 en MatemĂĄtica
El presente Informe pedagĂłgico de resultados PISA 2012 tiene como propĂłsito central difundir las caracterĂsticas principales del marco teĂłrico que sustenta la evaluaciĂłn de la competencia matemĂĄtica, los resultados en el proceso correspondiente al 2012 asĂ como proponer un conjunto de recomendaciones pedagĂłgicas que guĂen las intervenciones de los docentes a partir de los hallazgos de dichos resultados. AsĂ, el primer capĂtulo, describe e ilustra conceptos tales como competencia matemĂĄtica y las variables o categorĂas y subcategorĂas con las que esta competencia se operacionaliza en cada una de las preguntas usadas para su evaluaciĂłn. Se incluyen en este capĂtulo algunos Ătemes liberados de dominio pĂșblico que ilustren de mejor manera cada una de las categorĂas y subcategorĂas mencionadas. El segundo capĂtulo presenta los resultados correspondientes al proceso PISA 2012. Estos resultados se brindan tanto por puntaje promedio como por la proporciĂłn de estudiantes en cada uno de los niveles de desempeño de la competencia matemĂĄtica en general. Asimismo se brindan resultados comparativos con otros paĂses de la regiĂłn y por cada una de las subcategorĂas desarrolladas en el capĂtulo precedente. El tercer y Ășltimo capĂtulo, brinda un conjunto de recomendaciones de tipo pedagĂłgico que incluye pautas para el uso de los Ătemes liberados en las clases de matemĂĄtica, propuestas de aprendizaje con atenciĂłn a la diversidad y sesiones para cada uno de los cuatro primeros grados del nivel secundario. Todos estos aportes con el comĂșn denominador de considerar tanto la concepciĂłn de matemĂĄtica como las variables o categorĂas 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, 3â100 ”g/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 (0.3â3 ”g/paw), HC-030031 (100â316 ”g/paw) and SKF-96365 (10â30 ”g/paw) blockers, at 21 days post-STZ injection. At the doses used, these blockers did not modify formalin-induced nociception. Moreover, capsazepine (0.3â30 ”g/paw), HC-030031 (100â1000 ”g/paw) and SKF-96365 (10â100 ”g/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-ÎČ-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