Chronic cannabinoid administration to periadolescent rats modulates the metabolic response to acute cocaine in the adult brain

Purpose: To analyze brain metabolic response to acute cocaine in male and female Wistar rats with or without a history of cannabinoid exposure during periadolescence. Procedures: The synthetic cannabinoid agonist CP 55,940 (CP) or its vehicle (VH), were administered to male and female rats during periadolescence. When these animals reached adulthood, saline and cocaine-induced changes in 2-deoxy-2-[18F]fluoro D glucose (FDG) uptake were studied by positron emission tomography. Results: The baseline (post-saline) metabolism in the septal nuclei was higher in CP-females than in VH-females, although septal metabolism was lower in CP-females after cocaine, reaching similar values to those of VH-females at baseline. Cocaine did not affect metabolism in VH-females. Periadolescent cannabinoid treatment did not influence baseline metabolism in males although cocaine reduced the FDG uptake in the dorsal striatum of males that received the VH but not CP. Conclusions: These results suggest that cannabinoids during periadolescence modify baseline and cocaine-evoked brain metabolism in a sex-dependent manner. In the case of CP-females, the involvement of septal metabolic alterations in their susceptibility to the rewarding effects of cocaine should be further investigated.This work was supported by grants from the Ministerio de Educación y Ciencia (Grants nº SAF2004-08148 and SAF2007-064890); Ministerio de Sanidad y Consumo (Grants RD06/ 00170029 of Instituto de Salud Carlos III, PNSD 2004 2007 and 2008 2010); Dirección General de Investigación de la Comunidad de Madrid (Grant S-SAL/0261/2006, I+D CANNAB-CM Consortium); and UNED (Plan de Promoción de la Investigación) to EA, and grants from the “Ministerio de Ciencia y Tecnología” (TEC2004-07052-C02-01/TCM), “Ministerio de Sanidad y Consumo” (CIBER CB06/01/0079, PNSD 2007 2010, FIS CP08/00017), “Ministerio de Industria” (CENIT program) and “Fundación de Investigación Médica Mutua Madrileña” (2007 2010 and 2008 2011) to MD.Publicad

Brain metabolism in lewis and fischer 344 rats after morphine self-administration and extinction: a PET imaging study

Proceeding of: The 72nd Annual Scientific Meeting of the College on Problems of Drug Dependence, Scottsdale, Arizona, June 12-17, 2010.MICINN (SAF2007-064890); Ministerio de Sanidad y Consumo (RD06/001/0029 y CP08/00017 del ISC III; Plan Nacional sobre Drogas 2004-2007 y 2008-2010); Fundación Mutua Madrileña; and CAM (S-SAL/0261/2006)

Augmented acquisition of cocaine self-administration and altered brain glucose metabolism in adult female but not male rats exposed to a cannabinoid agonist during adolescence

Marijuana consumption during adolescence has been proposed to be a stepping stone for adult cocaine addiction. However, experimental evidence for this hypothesis is missing. In this work we chronically injected male and female Wistar rats with either the cannabinoid agonist CP 55,940 (CP; 0.4 mg/kg) or its corresponding vehicle. Adult acquisition (seven 30 min daily sessions) and maintenance (fourteen 2 h daily sessions) of cocaine self administration (1 mg/kg), food reinforced operant learning under conditions of normal (ad libitum access to food), and high motivation (food restriction schedule) were measured. Additionally, brain metabolic activity was analyzed by means of [18F] fluorodeoxyglucose positron emission tomography. During the acquisition phase, female CP treated rats showed a higher rate of cocaine self administration as compared to vehicle treated females and males; no differences were found between both male groups. This effect disappeared in the maintenance phase. Moreover, no differences among groups were evident in the food reinforced operant task, pointing to the cocaine specific nature of the effect seen in self administration rather than a general change in reward processing. Basal brain metabolic activity also changed in CP treated females when compared to their vehicle treated counterparts with no differences being found in the males; more specifically we observed a hyper activation of the frontal cortex and a hypo activation of the amygdalo entorhinal cortex. Our results suggest that a chronic exposure to cannabinoids during adolescence alters the susceptibility to acquire cocaine self administration, in a sex specific fashion. This increased susceptibility could be related to thechanges in brain metabolic activity induced by cannabinoids during adolescenceThis work was supported by Grants FIS G03/05 (Red de Trastornos Adictivos), BSO2001-1099, FIS 01-05-01, Plan Nacional sobre Drogas (PNSD) 2001–2003, PNSD 2004–2007, GR-SAL/0260/2004 to EA and Grants INT/2012/ 2002, CB06/01/0079, and CENIT (2006–2009) to MDPublicad

The management of acute venous thromboembolism in clinical practice. Results from the European PREFER in VTE Registry

Venous thromboembolism (VTE) is a significant cause of morbidity and mortality in Europe. Data from real-world registries are necessary, as clinical trials do not represent the full spectrum of VTE patients seen in clinical practice. We aimed to document the epidemiology, management and outcomes of VTE using data from a large, observational database. PREFER in VTE was an international, non-interventional disease registry conducted between January 2013 and July 2015 in primary and secondary care across seven European countries. Consecutive patients with acute VTE were documented and followed up over 12 months. PREFER in VTE included 3,455 patients with a mean age of 60.8 ± 17.0 years. Overall, 53.0 % were male. The majority of patients were assessed in the hospital setting as inpatients or outpatients (78.5 %). The diagnosis was deep-vein thrombosis (DVT) in 59.5 % and pulmonary embolism (PE) in 40.5 %. The most common comorbidities were the various types of cardiovascular disease (excluding hypertension; 45.5 %), hypertension (42.3 %) and dyslipidaemia (21.1 %). Following the index VTE, a large proportion of patients received initial therapy with heparin (73.2 %), almost half received a vitamin K antagonist (48.7 %) and nearly a quarter received a DOAC (24.5 %). Almost a quarter of all presentations were for recurrent VTE, with >80 % of previous episodes having occurred more than 12 months prior to baseline. In conclusion, PREFER in VTE has provided contemporary insights into VTE patients and their real-world management, including their baseline characteristics, risk factors, disease history, symptoms and signs, initial therapy and outcomes

Morphine self-administration effects on the structure of cortical pyramidal cells in addiction-resistant rats

12 pages, 4 figures, 4 tables.-- PMID: 18657522 [PubMed].-- Printed version published Sep 16, 2008.Repeated administration of drugs of abuse is thought to induce a variety of persistent changes in both behavior and brain morphology, including modifications of neurons from the brain regions involved in addiction. We have studied the morphology of the basal dendritic arbor of cortical pyramidal neurons in addiction-resistant Fischer 344 strain rats that self-administered morphine. Pyramidal neurons in the prelimbic and motor cortex were intracellularly injected with Lucifer Yellow in fixed tissue and they were reconstructed in three dimensions using Neurolucida software. Morphine self-administration did not produce significant changes in the structure of the dendritic arbors or in the spine density of pyramidal neurons in either the prelimbic or motor cortex of F344 rats. Moreover, pyramidal cell morphology did not differ in these two cortical areas in saline self-administered animals. However, when the structure of these cortical pyramidal cells from Fischer 344 rats was compared with that previously reported in addiction-prone Lewis rats in the same cortical areas, significant morphological differences were found between both strains. Indeed, these differences were not only observed following morphine self-administration but also in saline self-administered control animals. We suggest that strain differences in the structure of pyramidal cells in certain cortical areas might represent an anatomical substrate for the distinct vulnerability to the reinforcing effects of morphine exhibited by Fischer 344 and Lewis rats in operant self-administration paradigms.Morphine sulphate was kindly provided by the “Dirección General de Estupefacientes” (Spain). This work was supported by the “Ministerio de Educación y Ciencia” (grants BFI 2003–02745, BFU2006–13395 and “Genómica y Proteómica” GEN2003–20651-C06–06 to J DeF) and by the “Fondo de Inversiones Sanitarias” FIS01–05–01; the “Plan Nacional sobre Drogas” PNSD2000–2003; the “Comunidad Autónoma de Madrid” CAM08.8/0010.1/2003, “Plan de Promoción de la Investigación en la UNED” and “Salud y Farmacia” SAF2007–64890 grants to EA. IB-Y is a “Juan de la Cierva” postdoctoral fellow of the Ministry of Science and Technology.Peer reviewe

Aplicación al currículum del Proyecto de Inteligencia Harvard en la zona rural

Aplica el Proyecto de Inteligencia Harvard a las áreas de Lengua y Matemáticas en las etapas de Infantil y Primaria. Los objetivos son: prevenir y compensar las desigualdades de permanencia y promoción del alumnado de la zona rural en el sistema educativo; proporcionar al alumnado una respuesta educativa continua tanto en el aspecto intelectual como en el afectivo; implicar a los padres en el proceso educativo de sus hijos; potenciar el desarrollo intelectual y de razonamiento del alumnado; sobre todo aquellos con necesidades educativas especiales; favorecer la adquisición de estrategias para su mejor desenvolvimiento en la vida; desarrollar la autoestima y la autoconfianza en el alumnado. Se han aplicado las series: I, Fundamentos del Razonamiento; II, Comprensión del Lenguaje y V, Toma de decisiones. Elabora materiales para la evaluación inicial (anexos I, II y III), el desarrollo de las áreas currículares (anexos IV-VIII) y la evaluación final (anexos X y XI).Madrid (Comunidad Autónoma). Consejería de Educación y CulturaMadridMadrid (Comunidad Autónoma). Subdirección General de Formación del Profesorado. CRIF Las Acacias; General Ricardos 179 - 28025 Madrid; Tel. + 34915250893ES

Impact on clinical practice of the implementation of guidelines for the toxicity management of targeted therapies in kidney cancer. The protect-2 study.

Journal Article;BACKGROUND The impact of such recommendations after their implementation of guidelines has not usually been evaluated. Herein, we assessed the impact and compliance with the Spanish Oncology Genitourinary Group (SOGUG) Guidelines for toxicity management of targeted therapies in metastatic renal cell carcinoma (mRCC) in daily clinical practice. METHODS Data on 407 mRCC patients who initiated first-line targeted therapy during the year before and the year after publication and implementation of the SOGUG guideline program were available from 34 Spanish Hospitals. Adherence to SOGUG Guidelines was assessed in every cycle. RESULTS Adverse event (AE) management was consistent with the Guidelines as a whole for 28.7 % out of 966 post-implementation cycles compared with 23.1 % out of 892 pre-implementation cycles (p = 0.006). Analysis of adherence by AE in non-compliant cycles showed significant changes in appropriate management of hypertension (33 % pre-implementation vs. 44.5 % post-implementation cycles; p < 0.0001), diarrhea (74.0 % vs. 80.5 %; p = 0.011) and dyslipemia (25.0 % vs. 44.6 %; p < 0.001). CONCLUSIONS Slight but significant improvements in AE management were detected following the implementation of SOGUG recommendations. However, room for improvement in the management of AEs due to targeted agents still remains and could be the focus for further programs in this direction.This study was funded by Pfizer, S.L.U. Medical writing assistance was provided by Esther Tapia, PhD and was founded by Pfizer.Ye