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ntroducción: La enseñanza de la Farmacología tradicionalmente se ha caracterizado por la transmisión de información donde las estrategias pedagógicas se han centrado en el profesor, privilegiando el conocimiento teórico, las clases magistrales y los exámenes memorísticos. Es imprescindible la introducción de elementos nuevos para aumentar la participación activa del estudiante en la construcción del conocimiento y en la evaluación del logro de sus competencias; el desarrollo de la creatividad y el trabajo en equipo. Esta metodología busca romper la noción de enseñanza tradicional, cambiar la idea de una evaluación por la nota a una evaluación con una motivación propia (del estudiante), para internalizar el conocimiento y hacerlo parte desu estructura de pensamiento. Objetivo: Desarrollar una estrategia de enseñanza y evaluación que permita a los estudiantes participar activamente. Materiales y métodos: Participaron 172 estudiantes que cursaron la asignatura de Farmacología y Terapéutica "B", entre marzo y septiembre de 2017. Se desarrollaron cuatro actividades individuales y complementarias relacionadas con la prescripción de medicamentos, para la evaluación del proceso y desempeño de los estudiantes se emplearon rúbricas normalizadas de evaluación, se aplicó una encuestade percepción a los estudiantes sobre la utilidad de la estrategia en su formación. Resultados: Los resultados muestran un buen desempeño de los estudiantes en las actividades de prescripción de medicamentos, un mejoramiento significativo en el desempeño al comparar los resultados. Los estudiantes consideran que la estrategia es útil para el desarrollo de sus competencias profesionales, les permite tener un papel activo en el proceso de aprendizaje y la metodología de evaluación les permite reconocer los elementos que deben reforzar para llegar a un óptimo desarrollo de su competencia

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Previously, we found out that in ovariectomized female rats, estrogen and progesterone produce a memory deficit which is reverted by the intrahippocampal administration of allopregnanolone. Here, we study the possible interplay between allopregnanolone and hippocampal serotonergic activity. Ovariectomized rats injected subcutaneously with estrogen and progesterone were subsequently injected in the dorsal hippocampus with vehicle, allopregnanolone alone or allopregnanolone shortly after 8OH-DPAT, a predominantly 5HT1A-7 receptor agonist. Then, the subjects were sequentially tested in: (1) an inhibitory avoidance task and (2) K+-evoked [3H]-serotonin ex vivo release through superfusion experiments. Allopregnanolone increased the K+-evoked [3H]-serotonin release compared to control. 8OH-DPAT infusions reversed the effects of allopregnanolone on memory and K+-evoked [3H]-serotonin release. These results suggest that allopregnanolone memory improvement could be mediated, at least in part, through modulation of the hippocampal serotonergic system reactivity.

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During the development of the sympathetic nervous system, signals from tropomyosin-related kinase receptors (Trks) and p75 neurotrophin receptors (p75) compete to regulate survival and connectivity. During this process, nerve growth factor (NGF)- TrkA signaling in axons communicates NGF-mediated trophic responses in signaling endosomes. Whether axonal p75 signaling contributes to neuronal death and how signaling endosomes contribute to p75 signaling has not been established. Using compartmentalized sympathetic neuronal cultures (CSCGs) as a model, we observed that the addition of BDNF to axons increased the transport of p75 and induced death of sympathetic neurons in a dynein-dependent manner. In cell bodies, internalization of p75 required the activity of JNK, a downstream kinase mediating p75 death signaling in neurons. Additionally, the activity of Rab5, the key GTPase regulating early endosomes, was required for p75 death signaling. In axons, JNK and Rab5 were required for retrograde transport and death signaling mediated by axonal BDNF-p75 in CSCGs. JNK was also required for the proper axonal transport of p75-positive endosomes. Thus, our findings provide evidence that the activation of JNK by p75 in cell bodies and axons is required for internalization to a Rab5-positive signaling endosome and the further propagation of p75-dependent neuronal death signals.

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Estudios han demostrado que el aceite de oliva (O) con sus compuestos fenólicos tienen efectos positivos en diversos biomarcadores fisiológicos. Análisis previos han demostrado que los bisfosfonatos, son potentes inhibidores de la resorción ósea. Estudiar el efecto del tratamiento combinado de alendronato (AL) y pamidronato (PA) y de O sobre la regeneración ósea. Las fórmulas se dosificaron 0,5 mg/kg de peso para AL, y de 0,6 mg/kg de peso para PA. El O se administró en la dieta, 50 g/Kg. Cincuenta y cuatro ratas macho de la línea Wistar se dividieron en 6 grupos. El grupo control (C), recibió semanalmente 0,3 ml/100 g de solución salina vía subcutánea. El grupo (AL) recibió semanalmente por vía subcutánea en el miembro posterior izquierdo. El grupo (PA) se colocó igual que el grupo anterior. El grupo (O) fue tratado en la alimentación y en las áreas de la cirugía recibieron inyección subcutánea con solución fisiológica. El grupo (ALO) recibió tratamiento combinado con AL y O. El grupo (PAO) se trató igual al anterior. Se obtuvieron muestras de fémur en tiempos 15, 30, 60 y 90 días, que se incluyeron en solución fisiológica y mantenidos a -20 C. Los estudios estadísticos se realizaron a través del análisis de la variancia a dos y tres criterios de clasificación. Sólo el factor días influye significativamente sobre los valores. Las diferencias entre drogas no resultaron estadísticamente significativas. Tampoco se verificó interacción significativa entre los factores Droga y etapa. Los valores más elevados de fuerza de ruptura aplicada, se registraron a los 90 días. No se encontraron diferencias significativas en los ensayos biomecánicos, poniendo de manifiesto la acción sistémica de los fármacos. Estas acciones fueron benéficas al aumentar la rigidez.

Studies have shown that olive oil (O) with its phenolic compounds have positive effects on various physiological biomarkers. Previous analyzes have shown that bisphosphonates are potent inhibitors of bone resorption. The objective of this work was to study the effect of combined treatment with alendronate (AL) and pamidronate (PA) and O on bone regeneration. Formulas 0.5 mg/kg for AL dosed, and 0.6 mg/kg for PA. O was administered in the diet, 50 g/kg. Fifty-four male Wistar rats were divided into 6 groups. The control group (C) received weekly 0.3 mL/100 g of saline subcutaneously. Group (AL) received weekly subcutaneously in the left posterior limb. Group (PA) was placed as the previous group. Group (O) was treated in food and in the areas of surgery received subcutaneous injection with saline. The (ALO) group received combined treatment with Al and O. The group (PAO) was treated the same as before. Femur samples at times 15, 30, 60 and 90 days, were included in physiological solution and maintained at -20 °C were obtained. Statistical studies were conducted through analysis of variance to two and three classification criteria. The ANOVA showed that only days factor significantly influences the values of the variables (p <0.05). The differences between drugs were not statistically significant (p> 0.05). Nor was there significant drug interaction between factors and stage (p> 0.05) was verified. The highest values of force rupture applied occurred at 90 days. No significant differences were found in the biomechanical testing, demonstrating the systemic action of drugs. These actions were beneficial to increase rigidity.

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Estudios previos han demostrado que los bisfosfonatos son potentes inhibidores de la resorción ósea. El aceite de oliva (O) es rico en ácidos grasos monoinsaturados con potentes propiedades anti-oxidantes. El objetivo de este estudio fue estudiar el efecto del tratamiento de alendronato (AL) y pamidronato (PA) y de O sobre la regeneración tisular. Las fórmulas se dosificaron 0,5 mg/kg de peso para AL, y de 0,6 mg/kg de peso para PA. El O se administró en la dieta, 50 g/ Kg. Cincuenta y cuatro ratas macho de la línea Wistar se dividieron en 6 grupos. El grupo control (C), recibió semanalmente 0,3 ml/100g de peso corporal de solución salina vía subcutánea. El grupo (AL) recibió semanalmente por vía subcutánea en el miembro posterior izquierdo. El grupo (PA) se colocó igual que el grupo anterior. El grupo (O) fue tratado en la alimentación y en las áreas de la cirugía recibieron inyección subcutánea con solución fisiológica. El grupo (ALO) recibió tratamiento combinado con AL y O. El grupo (PAO) se trató igual al anterior. La cirugía consistió en una incisión longitudinal en las tibias realizando un defecto circular en la parte plana de cada tibia hasta llegar al hueso medular. Se tomaron radiografías a los 0, 7, 15, 30, 60 y 90 días y fueron analizadas con el Software Image Pro Plus. Los estudios estadísticos se realizaron a través del análisis de la variancia a dos y tres criterios de clasificación. Se evidencio un incremento en la densidad mineral ósea promedio (DMO) conforme avanza el tiempo en todos los grupos, siendo evidentes con PA a los 60 días. El tratamiento O mostró eficacia en la remodelación ósea, observándose un pico a los 60 días. Esto sugiere que O representa una opción terapéutica para el tratamiento de las patologías óseas.

Previous studies have shown that bisphosphonates are potent inhibitors of bone resorption. Olive oil (O) is rich in monounsaturated fatty acids with potent anti-oxidant properties. The objective of this work was to study the effect of alendronate treatment (AL) and pamidronate (PA) and O on tissue regeneration. Formulas 0.5 mg / kg for AL dosed, and 0.6 mg / kg for PA. O was administered in the diet, 50 g / kg. Fifty-four male rats Wistar were divided into 6 groups. The control group (C) received weekly 0.3 ml / 100g body weight of saline subcutaneously. The group (AL) received a weekly dose subcutaneously in the left posterior limb. The group (PA) was placed as the previous group. The group (O) was treated in food and in the areas of surgery received subcutaneousinjection with saline. The group (ALO) received combined treatment with Al and O. The group (PAO) was treated the same as before. Surgery consisted of a longitudinal incision in the warm using a circular on the flat side of each tibia until the medullary bone defect. X-rays at 0, 7, 15, 30, 60 and 90 days were taken and analyzed with Image Pro Plus Software. Statistical studies were conducted through analysis of variance to two and three classification criteria. Results: an increase in the average bone mineral density (BMD) was evident as time progresses in all groups, with PA still evident at 60 days. Or treatment showed efficacy in bone remodeling observed a peak at 60 days. Conclusions: This suggests that O represents a therapeutic option for the treatment of bone disease.

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The hypothalamic release of glutamate and GABA regulates neurosecretory functions that may control the onset of puberty. This release may be influenced by neurosteroids such as allopregnanolone. Using superfusion experiments we examined the role of allopregnanolone on the K(+)-evoked and basal [(3)H]-glutamate and [(3)H]-GABA release from mediobasal hypothalamus and anterior preoptic area in prepubertal, vaginal opening and pubertal (P) rats and evaluated its modulatory effect on GABAA and NMDA (N-methyl-d-aspartic acid) receptors. Also, we examined the hypothalamic activity and mRNA expression of 3α-hydroxysteroid oxidoreductase (3α-HSOR) - enzyme that synthesizes allopregnanolone - using a spectrophotometric method and RT-PCR, respectively. Allopregnanolone increased both the K(+)-evoked [(3)H]-glutamate and [(3)H]-GABA release in P rats, being the former effect mediated by the modulation of NMDA receptors - as was reverted by Mg(2+) and by the NMDA receptor antagonist AP-7 and the latter by the modulation of NMDA and GABAA receptors - as was reverted by Mg(2+) and the GABAA receptor antagonist bicuculline. The neurosteroid also increased the basal release of [(3)H]-glutamate in VO rats in an effect that was dependent on the modulation of NMDA receptors as was reverted by Mg(2+). On the other hand we show that allopregnanolone reduced the basal release of [(3)H]-GABA in P rats although we cannot elucidate the precise mechanism by which the neurosteroid exerted this latter effect. The enzymatic activity and the mRNA expression of 3α-HSOR were both increased in P rats regarding the other two studied stages of sexual development. These results suggest an important physiological function of allopregnanolone in the hypothalamus of the P rat where it might be involved in the 'fine tuning' of neurosecretory functions related to the biology of reproduction of the female rats.

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INTRODUCTION: Adenosine A2A and A2B receptor intracellular pathway is associated with either increasing endothelial nitric oxide (NO) synthase (eNOS) expression or eNOS activation (i.e., tyrosine 1177 phosphorylation); a mechanism linked to pro or anti-proliferative effects depending of the cell type. However, there are no reports in pre-eclampsia. OBJECTIVES: Investigate whether NO signaling pathway is involved in fetal endothelium proliferation induced by adenosine receptor activation in early and late-onset pre-eclampsia. METHODS: Human umbilical vein endothelial cells (HUVEC) were isolated from normal (n=25), late-onset pre-eclampsia (n=11) and early-onset pre-eclampsia (n=22). Adenosine A2A and A2B expression was evaluated by immunocytochemistry and Western blot. Cell proliferation was analyzed using MTS-assay in absence or presence of non-selective adenosine receptor agonist (NECA 10µM), adenosine A2A receptor selective agonist (CGS-21680, 100nM), and/or the antagonists ZM-241385 (0-100µM) or MRS-1754 (0-1µM) for A2A and A2B receptors during 24h. In parallel experiments NOS inhibitor (L-NAME, 100µM) was used in co-incubation by either adenosine receptor agonist or antagonists. Nitrite concentration in the culture medium and protein nitration assessed by Western blot were measured in cells exposed to CGS-21680 (30min). RESULTS: Early-onset pre-eclampsia was associated to low A2A (∼70%), but high (∼2-fold) A2B adenosine receptor protein abundance compared with normal or late-onset pre-eclampsia. Basally, HUVEC from early-onset showed a low (∼42%), whereas late-onset exhibited high proliferation (∼1.5-fold) compared with normal pregnancy. Cell proliferation was increased by CGS-21680 (∼2-fold) in late-onset or normal pregnancy and ∼5-fold in early-onset pre-eclampsia compared with respective control. NECA increased cell proliferation only in normal cells. Stimulatory effect of CGS-21680, was inhibited by ZM-241385 in normal pregnancies (Ki, 25nM) and late-onset (Ki 50nM) but not in early-onset (Ki ambiguous). Interestingly, MRS-1754 showed an increase in cell proliferation in a dose-response manner only in early-onset group. L-NAME partially blocked (∼25%) the stimulatory effect of CGS-21680 in late-onset and normal pregnancy. Interestingly, L-NAME revert the maximal stimulatory effect of MRS-1754 observed in early-onset. Total and phosphorylated eNOS protein was reduced (∼50%) in early-onset pre-eclampsia compared to late-onset or normal pregnancy. In turn, cells from late-onset pre-eclampsia exhibited high (∼2-fold) eNOS phosphorylation compared with normal pregnancy. In normal pregnancy, CGS-21680 (30min) increased (∼2-fold) the eNOS phosphorylation and nitrotyrosine formation, without changes in nitrite levels, but non-significant changes were observed in early or late-onset pre-eclamptic cells. CONCLUSION: Fetal endothelium from early-onset exhibits a predominant anti-proliferative effect mediated by adenosine A2B receptors activation, whereas the stimulatory effect of adenosine A2A receptors prevails in cells from late-onset pre-eclampsia. Both pro and anti-proliferative effects seem mediated by a nitric oxide-depended intracellular pathway. Supported by FONDECYT 1100684, Conicyt Anillo ACT73.

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INTRODUCTION: Elevated uric acid levels during the first or third trimester of gestation have been associated with poor perinatal outcomes in women with hypertensive pregnancies. OBJECTIVES: Investigate whether uric acid levels are related to adverse perinatal outcomes in Chilean hypertensive women. METHODS: It is a post-hoc analysis from a retrospective study including clinical records (n=416) of women with diagnosis of hypertension in pregnancy treated in the Hospital Clínico Herminda Martin, Chillán, Chile. From these records, 86 showed quantification of uric acid plasma levels at the moment of hypertension diagnosis ((3) 140/90mmHg; at 34±5weeks). Women were divided into three groups, considering uric acid levels below 25th percentile (Low group, n=27, <3.7mg/dl), from 25th to 75th percentile (Middle group, n=38, 3.8 to 5.7mg/dl) and above 75th percentile (High group, n=21, >5.8mg/dl) for the studied population. RESULTS: In the entire group of hypertensive women, the uric acid/creatinine ratio was positively related to hospitalization days (p=0.04), and negatively associated with newborn weight (p=0.02) and size (p=0.01). ANOVA analysis did not show statistical differences in age, parity, systolic, diastolic or media blood pressure, body mass index, proteinuria, hepatic enzymes or hypoxia perinatal in women with low, middle or high uric acid levels. However, women with high uric acid levels showed a longer-hospitalization period (∼1.2days more), less platelet count (∼40×10(3)/ml) and high creatinine plasma levels (∼0.2mg/dl) and their babies showed less birth weight (∼800g) and were smaller (∼3cm) compared with women with low uric acid levels. Relative risk of intrauterine growth restriction in women with high levels of uric acid was 1.3 (CI, 0.96 to 1.73) compared with women with low levels. CONCLUSION: These data reinforce the general agreement about the utility of hyperuricemia in the prognosis of adverse perinatal outcomes in hypertensive pregnancies.

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Workshops are an important part of the IFPA annual meeting. At IFPA Meeting 2010 there were twelve themed workshops, six of which are summarized in this report. 1. The immunology workshop focused on normal and pathological functions of the maternal immune system in pregnancy. 2. The transport workshop dealt with regulation of ion and water transport across the syncytiotrophoblast of human placenta. 3. The epigenetics workshop covered DNA methylation and its potential role in regulating gene expression in placental development and disease. 4. The vascular reactivity workshop concentrated on methodological approaches used to study placental vascular function. 5. The workshop on epitheliochorial placentation covered current advances from in vivo and in vitro studies of different domestic species. 6. The proteomics workshop focused on a variety of techniques and procedures necessary for proteomic analysis and how they may be implemented for placental research.

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