Projection length stimulated by oxytocin is modulated by the inhibition of calcium signaling in U-87MG cells.

Neuropeptide oxytocin contributes to the regulation of glial cell morphology. The precise mechanisms, however, are not yet fully understood. In the present study, we have investigated whether an oxytocin-induced increase of intracellular calcium is required for cell extension in astrocyte-like U-87MG cells. Oxytocin (1 µM) significantly increased the length of the cell projections measured by the green-fluorescent protein labeled microtubule-associated protein after 48 h. The knockdown of oxytocin receptors (OXTR) in U-87MG cells prevented the elongation of the projections. Incubation of U-87MG cells in the presence of oxytocin, resulted in a significant increase of intracellular calcium, specifically blocked by the OXTR antagonist L-371,257. Both quercetin, which is a phosphoinositide 3-kinase inhibitor, and the phospholipase C inhibitor U-73122 reduced oxytocin-induced elevation of intracellular calcium concentration. Conversely, neither diltiazem, an L-type voltage-gated calcium channel blocker nor tetracaine, which is a blocker of the ryanodine receptors, showed an effect on intracellular calcium levels. Treatment of cells with quercetin, U-73122 and the voltage-gated calcium channel blockers cilnidipine, ω-agatoxin and mibefradil prevented the elongation of projections stimulated by oxytocin. Oxytocin treatment resulted in a significant increase in gene and protein expression of the scaffolding protein SHANK3. Our results clearly show that activation of OXTRs contributes to the elongation of cell projections in astrocyte-like U-87MG cells and that this effect is mediated by an extracellular calcium influx accompanied by an increase in scaffolding proteins expression.

Downregulation of Oxytocin Receptor Decreases the Length of Projections Stimulated by Retinoic Acid in the U-87MG Cells.

Oxytocin is a neuropeptide widely expressed in the brain. Oxytocin plays a role in both proliferation and differentiation of various cells. Previous studies have suggested that oxytocin could affect the morphology of neuronal cells, therefore the objective of the present study was to test whether (1) oxytocin receptor stimulation/inhibition by specific ligands may change cell morphology and gene expression of selected cytoskeletal proteins (2) oxytocin receptor silencing/knockdown may decrease the length of cell projections (3) oxytocin receptor knockdown may affect human glioblastoma U-87MG cell survival. We confirmed the stimulatory effect of retinoic acid (10 µM) and oxytocin (1 µM) on projection growth. The combination of retinoic acid (10 µM) and oxytocin receptor antagonist (L-371,257, 1 µM) decreased projections length. Contrary to our assumptions, oxytocin receptor silencing did not prevent stimulation of length of projection by retinoic acid. Retinoic acid's and oxytocin's stimulation of projections length was significantly blunted in U-87MG cells with oxytocin receptor knockdown. Cell viability was significantly decreased in U-87MG cells with oxytocin receptor knockdown. Significantly higher levels of mRNA for cytoskeletal proteins drebrin and vimentin were observed in response to oxytocin incubation for 48 h. The data obtained in the present study clearly show that oxytocin induces formation and elongation of cell projections in astrocyte-like U-87MG cells. The effect is mediated by oxytocin receptors and it is accompanied by an increase in gene expression of drebrin and vimentin. Thus, oxytocin receptor signaling, particularly in the glial cells, may play an important role in native cell life, differentiation processes, and tumor progression, as well.

Can we improve the birth weight prediction? The effect of normal BMI using a multivariate model.

OBJECTIVE: The construction of a predictive model that improves the estimation of the fetal weight (EFW). STUDY DESIGN: a comparative, descriptive study. One hundred forty pregnant women were recruited at two-stage sample in health department in Spain. They were classified in four groups depending on the pre-gestational BMI. Fetal weight at term was estimated by ultrasound at 33-35 weeks (EFW40w) by one gynecologist. A regression model was created with the variables that reacted to the newborn's weight, symphysis-fundal height (SFH), EFW40w, gestational age (GA), ferritin level and cigarettes smoked. RESULTS: A multivariate model was created for the NW group to estimate the fetal weight (EFWme), resulting in R2=0.727 (p<0.001). The differences of the averages obtained between EFW40w and EFWme, with the newborn's weight were significant (p<0.001). EFWme underestimates birth weight by 0.07 g (mean error 0.53%), and EFW40w overestimates it by 300.89 g (mean error 10.12%). In order to evaluate the predictive model and verify the predictions we used the Bland-Altman analysis. The average error in estimating the birth weight with EFWme was 1.94% underestimating the result, whereas the ultrasound error overestimated the result 10.93%. CONCLUSION: The multivariate model created for the NW group improves the accuracy of the ultrasound.

Objectivo: construir un modelo predictivo que mejore la estimación del peso del recién nacido (PFE). Material y Métodos: Estudio observacional dónde 140 gestantes fueron estudiadas mediante un muestreo bietápico en un Departamento de Salud en España. Fueron clasificadas en cuatro grupos dependiendo del IMC pregestacional materno. El peso proyectado al nacer fue estimado por la ecografía realizada entre las 33-35 semanas de gestación (PP40s). Se construyó un modelo de regresión con las variables que se reaccionaban con el peso al nacer, altura uterina (AU), PP40s, edad gestacional (EG), nivel de ferritina y cigarillos consumidos. Resultados: Se construyó un modelo multivariante para el grupo Normo-peso para estimar el peso al nacer (PFm) obteniendo una R2=0,727 (p.

[Cost-effectiveness analysis of fixed dose antihypertensive drugs]. / Análisis coste-eficacia de los antihipertensivos en dosis fijas.

OBJECTIVE: The aim of this study is to compare the efficiency of different fixed-dose combinations of renin-angiotensin-aldosterone system (RAAS) blockers and calcium channel blockers, to use it as a guide to assist the rational prescribing in antihypertensive therapy. METHODS: The efficacy of each drug was obtained from intervention studies randomized, double-blind, made with these combinations and a utility-cost modeling from the model proposed and used by NICE. The perspective of our analysis is the National Health System and the time horizon is long enough to achieve therapeutic goals. MAIN OUTCOME MEASURES: Cost per mmHg reduction in BP, percentage of reduction necessary to achieve the therapeutic goals for hypertension control and cost, and finally quantity and quality of life gained with these treatments in patients with hypertension, diabetes. RESULTS: We studied three fixed-dose combinations: amlodipine/olmesartán, amlodipine/valsartan and manidipine/delapril. The cost per mmHg systolic BP ranged from 24.93 to 12.34 €/mmHg, and diastolic BP ranged from 34.24 to 18.76 €/mmHg, depending on the drug used. For an initial value of 165mmHg systolic BP the most efficient treatment to achieve the therapeutic goal of hypertension control (<140mmHg) is manidipine/delapril with a cost of 67.76 €. The use of these drugs to control diabetic and hypertensive patients resulted in all cases being cost-effective (more effective and lower cost compared to "no treatment"). Manidipine/delapril showed the best relation cost-utility (1,970 €/QALY (quality-adjusted life year)) followed by amlodipine/olmesartan and amlodipine/valsartan (2,087 and 2,237 €/QALY, respectively).

Análisis coste-eficacia de los antihipertensivos en dosis fijas / Cost-effectiveness analysis of fixed dose antihypertensive drugs

Objetivo. Comparar la eficiencia de las combinaciones en dosis fijas del bloqueo del SRAA con antagonistas del calcio, para que sirva como guía de ayuda a la prescripción racional del tratamiento antihipertensivo. Metodología. La eficacia de cada uno de los medicamentos ha sido obtenida de los estudios de intervención aleatorizados, doble ciego, realizados con estas combinaciones y una modelización de coste utilidad a partir del modelo propuesto por el NICE. La perspectiva de nuestro análisis es la del Sistema Nacional de Salud y el horizonte temporal ha sido un tiempo suficiente para alcanzar objetivos terapéuticos. Mediciones principales Coste por mmHg de descenso de la PA; porcentaje de descenso necesario para alcanzar los objetivos terapéuticos de control de la HTA y su coste y, finalmente, cantidad y calidad de vida ganada con estos tratamientos en pacientes hipertensos-diabéticos. Resultados. Se estudiaron 3 combinaciones fijas: amlodipino/olmesartán, amlodipino/valsartán y manidipino/delapril. Respecto a la PAS el coste por mmHg de PA reducido osciló entre 24,93 y 12,34€/mmHg, y para la PAD los costes fueron de 34,24 y 18,76 €/mmHg, dependiendo del fármaco empleado. Para una cifra inicial de PAS de 165 mmHg hay 3 opciones terapéuticas que pueden alcanzar la cifra de objetivo terapéutico (< 140 mmHg), siendo la más eficiente manidipino/delapril con 67,76 €. Estos fármacos fueron coste-efectivos respecto al no tratamiento en el control de pacientes hipertensos diabéticos. El medicamento que mostró mejor relación coste-utilidad fue manidipino/delapril (1.970 €/AVAC) seguido de amlodipino/olmesartán y amlodipino/valsartán (2.087 y 2.237 €/AVAC) (AU)

Objective. The aim of this study is to compare the efficiency of different fixed-dose combinations of renin-angiotensin-aldosterone system (RAAS) blockers and calcium channel blockers, to use it as a guide to assist the rational prescribing in antihypertensive therapy. Methods. The efficacy of each drug was obtained from intervention studies randomized, double-blind, made with these combinations and a utility-cost modeling from the model proposed and used by NICE. The perspective of our analysis is the National Health System and the time horizon is long enough to achieve therapeutic goals. Main outcome measures. Cost per mmHg reduction in BP, percentage of reduction necessary to achieve the therapeutic goals for hypertension control and cost, and finally quantity and quality of life gained with these treatments in patients with hypertension, diabetes. Results. We studied three fixed-dose combinations: amlodipine/olmesartán, amlodipine/valsartan and manidipine/delapril. The cost per mmHg systolic BP ranged from 24.93 to 12.34 €/mmHg, and diastolic BP ranged from 34.24 to 18.76 €/mmHg, depending on the drug used. For an initial value of 165 mmHg systolic BP the most efficient treatment to achieve the therapeutic goal of hypertension control (< 140 mmHg) is manidipine/delapril with a cost of 67.76 €. The use of these drugs to control diabetic and hypertensive patients resulted in all cases being cost-effective (more effective and lower cost compared to "no treatment"). Manidipine/delapril showed the best relation cost-utility (1,970 €/QALY (quality-adjusted life year)) followed by amlodipine/olmesartan and amlodipine/valsartan (2,087 and 2,237 €/QALY, respectively) (AU)

Oxytetracycline as a predisposing condition for chalkbrood in honeybee.

Antibiotics, particularly oxytetracycline, have been discussed as a possible predisposing condition in the appearance of chalkbrood in the honeybee (Apis mellifera L.). Nevertheless, the scientific data to support this belief have been insufficient. We have developed a method to study the effects of this antibiotic as a predisposing factor under different circumstances. We conclude that oxytetracycline does not increase the risk of chalkbrood in susceptible worker brood in the short or mid-term.

[Efficacy of the APimicos-B to control and prevent chalkbrood disease in honey bees]. / Estudio de la eficacia del APimicos-B en el control y la prevención de la ascosferiosis en la abeja de la miel.

Chalkbrood disease in Apis mellifera is a fungal disease affecting developing brood, infested larvae become mummified. As it is a factorial disease, studies on this pathology are obstructed by the need of some predisposing conditions which must occur for such disease to develop. Thus, many questions are yet to be answered about which treatments to apply. The aim of this work is to evaluate the efficacy of the Apimicos-B, a treatment against chalk brood. To induce the disease, some pieces of combs containing susceptible worker brood both from infected and treated colonies and from infected and untreated colonies were cooled. No significant differences were registered (53.12% and 59.58% of mummification respectively).