Activity-dependent switch of GABAergic inhibition into glutamatergic excitation in astrocyte-neuron networks.

Interneurons are critical for proper neural network function and can activate Ca2+ signaling in astrocytes. However, the impact of the interneuron-astrocyte signaling into neuronal network operation remains unknown. Using the simplest hippocampal Astrocyte-Neuron network, i.e., GABAergic interneuron, pyramidal neuron, single CA3-CA1 glutamatergic synapse, and astrocytes, we found that interneuron-astrocyte signaling dynamically affected excitatory neurotransmission in an activity- and time-dependent manner, and determined the sign (inhibition vs potentiation) of the GABA-mediated effects. While synaptic inhibition was mediated by GABAA receptors, potentiation involved astrocyte GABAB receptors, astrocytic glutamate release, and presynaptic metabotropic glutamate receptors. Using conditional astrocyte-specific GABAB receptor (Gabbr1) knockout mice, we confirmed the glial source of the interneuron-induced potentiation, and demonstrated the involvement of astrocytes in hippocampal theta and gamma oscillations in vivo. Therefore, astrocytes decode interneuron activity and transform inhibitory into excitatory signals, contributing to the emergence of novel network properties resulting from the interneuron-astrocyte interplay.

Astrocytes in endocannabinoid signalling.

Astrocytes are emerging as integral functional components of synapses, responding to synaptically released neurotransmitters and regulating synaptic transmission and plasticity. Thus, they functionally interact with neurons establishing tripartite synapses: a functional concept that refers to the existence of communication between astrocytes and neurons and its crucial role in synaptic function. Here, we discuss recent evidence showing that astrocytes are involved in the endocannabinoid (ECB) system, responding to exogenous cannabinoids as well as ECBs through activation of type 1 cannabinoid receptors, which increase intracellular calcium and stimulate the release of glutamate that modulates synaptic transmission and plasticity. We also discuss the consequences of ECB signalling in tripartite synapses on the astrocyte-mediated regulation of synaptic function, which reveal novel properties of synaptic regulation by ECBs, such as the spatially controlled dual effect on synaptic strength and the lateral potentiation of synaptic efficacy. Finally, we discuss the potential implications of ECB signalling for astrocytes in brain pathology and animal behaviour.

Pauta de tratamiento inicial en pacientes con osteoporosis: uso de antirresortivos y suplementos farmacológicos (calcio y vitamina D) en la práctica clínica / Initial treatment trends in patient with osteoporosis: use of antiresorptive agents and pharmacologic supplements (calcium and vitamin D) in clinical practice

Objetivo. Describir el porcentaje de prescripción de suplementos farmacológicos en pacientes que inician pauta de tratamiento con antirresortivos (TAR) en pacientes con osteoporosis y por especialidades médicas. Diseño. Estudio transversal, con recogida de información retrospectiva, naturalístico y multicéntrico. Emplazamiento. Participaron 88 médicos españoles de atención primaria (AP), unidades de metabolismo óseo y mineral (UMO)/reumatología y ginecología. Participantes. Mujeres con osteoporosis que inician tratamiento TAR en los 12-36 meses previos a la visita. Mediciones principales. Variables clínicas generales y relativas al tratamiento de la osteoporosis (TAR, suplementos farmacológicos) y encuesta de opinión sobre suplementos farmacológicos. Resultados. Se incluyó a 480 pacientes. La edad media ± DE era de 65,8 ± 9,2 años. Se prescribieron suplementos farmacológicos en el 69,6% de las pacientes, siendo más frecuente en aquellas pacientes tratadas en consultas de UMO/reumatología (89,1%) que en las pacientes tratadas en AP (60,3%) y en ginecología (55,6%). En la encuesta realizada a los médicos el 72% de los médicos de UMO/reumatología y el 66,7% de ginecólogos respondieron que los suplementos de vitamina D son necesarios en el tratamiento habitual de la osteoporosis frente al 38,5% de los médicos de AP (p=0,058). Conclusiones. El uso de suplementos farmacológicos en la pauta inicial de tratamiento con TAR representa más del 60% de la muestra, aunque se detectan diferencias según tipo de especialista, con un mayor porcentaje de pacientes con suplementos en las consultas de UMO/Reumatología que en AP y ginecología, pese a que las guías recomiendan el uso mayoritario de suplementos farmacológicos en estas pacientes (AU)

Initial treatment trends in patient with osteoporosis: use of antiresorptive agents and pharmacologic supplements (calcium and vitamin D) in clinical practice objetive To describe the percentage of prescription of pharmacologic supplements in patients starting antiresorptive treatment (ART) for osteoporosis by specialists. Design. Cross-sectional, naturalistic, multicenter study with retrospective data collection. Patients and methods. 88 Spanish primary care (PC) physicians participated as well as those from Bone Metabolism Unit / Rheumatology and Gynecology units. Patients were females with osteoporosis who started ART in the 12 to 36 months prior to the visit. Main outcomes. General clinical variables and those related to osteoporosis treatment (both ART and pharmacologic supplements) and an opinion survey on pharmacologic supplements. Results. 480 patients were included. Mean age (SD) was 65.8 (9.2) years. Pharmacologic supplements were prescribed in 69.6% of patients and were more frequent in patients treated in Bone Metabolism/Rheumatology Units (89.1%) than patients treated by PC (60.3%) and Gynecology (55.6%). In the physician survey, 72% of the Bone Metabolism / Rheumatology Unit physicians responded that the Vitamin D supplements were necessary for treatment of osteoporosis vs. 38.5% of PC physicians (p=0.058). Conclusions. The use of pharmacologic supplements in the onset of treatment with ART represents more than 60% of the sample, although differences were seen between specialists, with a greater percentage of patients with supplements in the Bone Metabolism/Rheumatology Units than in PC and Gynecology, despite guidelines primarily recommend the use of pharmacologic supplements in these patients (AU)

Observational study of treatment compliance in women initiating antiresorptive therapy with or without calcium and vitamin D supplements in Spain.

OBJECTIVE: The aims of this study were to evaluate the compliance with antiresorptive therapy (ART) and supplements in Spain and to analyze the validity of the different treatment compliance assessment methods. METHODS: A cross-sectional study with retrospective data collection was carried out in women starting ART, evaluating indirect objective compliance, self-reported compliance, and the Morisky-Green questionnaire. RESULTS: A total of 480 women with a mean (SD) age of 65.8 (9.2) years were studied. Of these women, 62.9% received calcium and/or vitamin D supplements in addition to ART. According to the objective compliance method, 76.9% of the women were compliers (≥80%) with bisphosphonates; 69.4%, with selective estrogen receptor modulators; and 61.8%, with supplements (P < 0.01). Using the self-reported compliance, we identified 91% compliers with antiresorptive drugs and 75% with supplements. Using the Morisky-Green test, we classified 60.8% of the women as compliers with antiresorptive drugs and 48.4% with supplements. Combining the objective and self-reported compliance, 29.5% of the women did not adequately comply with ART and 56% with the drug supplements. CONCLUSIONS: With all three compliance measures, supplements were the treatment yielding the lowest percentage of compliers. Bisphosphonates constituted the treatment offering the best objective compliance: 38.2% of the women with drug supplements and between 23.1% and 30.6% of the women with ART failed to exceed the theoretical value of 80% regarded as representing good compliance.

[Initial treatment trends in patient with osteoporosis: use of antiresorptive agents and pharmacologic supplements (calcium and vitamin D) in clinical practice]. / Pauta de tratamiento inicial en pacientes con osteoporosis: uso de antirresortivos y suplementos farmacológicos (calcio y vitamina D) en la práctica clínica.

OBJECTIVE: To describe the percentage of prescription of pharmacologic supplements in patients starting antiresorptive treatment (ART) for osteoporosis by specialists. DESIGN: Cross-sectional, naturalistic, multicenter study with retrospective data collection. PATIENTS AND METHODS: 88 Spanish primary care (PC) physicians participated as well as those from Bone Metabolism Unit / Rheumatology and Gynecology units. Patients were females with osteoporosis who started ART in the 12 to 36 months prior to the visit. MAIN OUTCOMES: General clinical variables and those related to osteoporosis treatment (both ART and pharmacologic supplements) and an opinion survey on pharmacologic supplements. RESULTS: 480 patients were included. Mean age (SD) was 65.8 (9.2) years. Pharmacologic supplements were prescribed in 69.6% of patients and were more frequent in patients treated in Bone Metabolism/Rheumatology Units (89.1%) than patients treated by PC (60.3%) and Gynecology (55.6%). In the physician survey, 72% of the Bone Metabolism / Rheumatology Unit physicians responded that the Vitamin D supplements were necessary for treatment of osteoporosis vs. 38.5% of PC physicians (p=0.058). CONCLUSIONS: The use of pharmacologic supplements in the onset of treatment with ART represents more than 60% of the sample, although differences were seen between specialists, with a greater percentage of patients with supplements in the Bone Metabolism/Rheumatology Units than in PC and Gynecology, despite guidelines primarily recommend the use of pharmacologic supplements in these patients.

Modulation of osteoblast activity by serum from diabetic and non-diabetic patients on hemodialysis: a three-dimensional culture study.

BACKGROUND: The aims of our study were to develop a three-dimensional model based on normal human osteoblasts and to determine, with this method, the osteoblastic response to sera of non-diabetic and diabetic patients on hemodialysis for chronic renal failure. METHODS: A protocol for culture of osteoblastic cells in three-dimensional meshworks of bovine type I collagen was developed. The effect on cultures of sera from three groups of patients was studied: 1) 12 diabetic patients on hemodialysis [age: 65 +/- 5.2 years; sex: 6 men, 6 women; duration of dialysis treatment: 21.25 (641) months]; 2) 12 non-diabetic patients on hemodialysis [age: 65.5 +/- 5.4 years; sex: 6 men, 6 women; duration of dialysis treatment: 21.35 (6-40) months]; and 3) 12 healthy volunteer donors (age: 64.2 +/- 4.9 years; 6 men, 6 women). The three-dimensional cultures obtained were processed in the same way as undecalcified bone biopsies, sectioned and stained. A histomorphometrical study was conducted. Parameters calculated were cell number, volume of newly-formed collagen, volume of newly-formed collagen per cell, mineral volume and mineral volume per cell. RESULTS: Number of osteoblastic cells was significantly higher in non-diabetic than in diabetic and control serum-treated cultures. Newly-formed collagen volume was significantly higher in non-diabetic serum-treated cultures than in controls. Deposited mineral volume was significantly lower in diabetic and non-diabetic serum-treated cultures compared to control serum-treated cultures. CONCLUSIONS: The model of three-dimensional culture proposed in the present study is useful in the study of different osteoblast functions including the rate of collagen formation and mineralization.

Tratamiento de la osteoporosis con calcio y vitamina D. Revisión sistemática / Treatment of osteoporosis with calcium and vitamin D. Systematic review Background: Systematic review of the efficacy of calcium and vitamin D for the treatment of osteoporosis

Fundamento: Revisión sistemática de la eficacia del calcio y la vitamina D en el tratamiento de la osteoporosis. Material y método: Revisión de la base de datos MEDLINE entre 1966 y mayo de 1998, mediante las palabras clave: osteoporosis, calcium, vitamin D (y términos relacionados) y ensayo clínico aleatorizado. Revisión de las ediciones electrónicas de Best Evidence, Cochrane Library, resúmenes de congresos y bibliografía de dos libros de texto. Revisión ascendente de la bibliografía. Todas las revisiones se realizaron de forma independiente por dos de los autores. Tabulación de los parámetros de diseño y resultados principales de los ensayos identificados a partir de los artículos primarios. Calificación metodológica de los estudios por parte de 2 observadores independientes. Tabulación de los resultados y juicio evaluativo. Resultados: Se han incluido 11 estudios sobre calcio, ocho sobre vitamina D y 12 sobre calcitriol y otros derivados de la hormona. Los estudios con calcio son fundamentalmente sobre población no clínica y en tres se analiza eficacia sobre tasa de fracturas. Los resultados fueron positivos en poblaciones con ingestión basal baja y aporte elevado del fármaco. Los ensayos con vitamina D se realizaron sobre población no clínica o ingresados en instituciones. Los ensayos con calcitriol se llevaron a cabo fundamentalmente en pacientes con fractura osteoporótica y tuvieron peores puntuaciones de validez metodológica. La heterogeneidad de los estudios impidió un metaanálisis de los diferentes tratamientos. En los estudios de calcio se observó de forma más uniforme la eficacia clínica. La concordancia entre observadores fue buena (k = 0,81) y no hubo correlación significativa entre tamaños muestrales y efecto en los diferentes estudios. Conclusiones: El tratamiento con calcio es eficaz en población con una ingestión baja de calcio que recibe aportes importantes. La vitamina D es eficaz fundamentalmente, asociada a calcio, en población deficitaria. El calcitriol y otros derivados de la hormona tienen una eficacia más controvertida (AU)

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