Effects of histamine H 3 receptor ligands in experimental models of anxiety and depression

Abstract Histamine H 3 receptor ligands have been proposed to be of potential therapeutic interest for the treatment of different central nervous system disorders; however, the psychopharmacological properties of these drugs have not been studied extensively. In this work, we investigated the possible involvement of histamine H 3 receptor function in experimental models of anxiety (elevated plus-maze) and depression (forced swimming test). Male Sprague-Dawley rats were treated IP with the histamine H 3 receptor agonist R--methylhistamine (10 mg / kg) or the histamine H 3 receptor antagonist thioperamide (0.2, 2 and 10 mg /kg) and 30 min afterwards the time spent in the open arms of an elevated plus-maze was registered for 5 min. The immobility time of male OF1 mice in the forced swimming test was recorded for 6 min, 1 h after the IP administration of R--methylhistamine (10 and 20 mg / kg), thioperamide (0.2, 2, 10 and 20 mg / kg) or another histamine H 3 receptor antagonist, clobenpropit (5 mg / kg). The locomotor activity of mice was checked in parallel by means of an activity meter. Both saline controls and active drug controls were used in all the paradigms. Neither thioperamide nor R--methylhistamine significantly changed animal behaviour in the elevated plus-maze. R--methylhistamine and the higher dose of thioperamide assayed (20 mg / kg) were also inactive in the forced swimming test. By contrast, thioperamide (0.2-10 mg / kg) dose-dependently decreased immobility, the effect being significant at 10 mg /kg (33 % reduction of immobility); clobenpropit produced an effect qualitatively similar (24 % reduction of immobility). None of these histamine H 3 receptor antagonists affected locomotor activity. These preliminary results suggest that the histamine H 3 receptor blockade could be devoid of anxiolytic potential but have antidepressant effects. Besides, the stimulation of these receptors does not seem to be followed by changes in the behavioural parameters studied

From the bacterial citrus microbiome to the selection of potentially host-beneficial microbes

Citrus is the most cultivated fruit crop worldwide. The modern citrus industry needs new bioproducts to overcome phytopathological threats, tolerate stresses and increase yield and quality. Mutualistic microbes from roots significantly impact host physiology and health and are a potentially beneficial resource. The bacterial microbiome can be surveyed to select potentially host-beneficial microbes. To achieve this goal, a prevalent “core-citrus” bacterial microbiome was obtained by picking those operational taxonomic units (OTUs) shared among samples within and across two Citrus rootstock genotypes grown in the same soil for more than 20 years. A sub-selection of main OTUs from the defined "core-citrus" microbiome was made based on abundance, host-enriched versus bulk soil, and rhizosphere-indicator species. In parallel, an extensive census of the cultivable microbiota was performed to collect a large number of bacterial citrus isolates. Metataxonomic data were linked to cultured microbes, matching 16S rRNA gene sequences from bacterial isolates with those counterpart OTU reference sequences from the selected bacterial "core-citrus" microbiome. This approach allowed selection of potentially host-beneficial bacteria to mine for agricultural probiotics in future biotechnological applications required for the citrus industry

Differential clinical characteristics and prognosis of intraventricular conduction defects in patients with chronic heart failure

Intraventricular conduction defects (IVCDs) can impair prognosis of heart failure (HF), but their specific impact is not well established. This study aimed to analyse the clinical profile and outcomes of HF patients with LBBB, right bundle branch block (RBBB), left anterior fascicular block (LAFB), and no IVCDs. Clinical variables and outcomes after a median follow-up of 21 months were analysed in 1762 patients with chronic HF and LBBB (n = 532), RBBB (n = 134), LAFB (n = 154), and no IVCDs (n = 942). LBBB was associated with more marked LV dilation, depressed LVEF, and mitral valve regurgitation. Patients with RBBB presented overt signs of congestive HF and depressed right ventricular motion. The LAFB group presented intermediate clinical characteristics, and patients with no IVCDs were more often women with less enlarged left ventricles and less depressed LVEF. Death occurred in 332 patients (interannual mortality = 10.8%): cardiovascular in 257, extravascular in 61, and of unknown origin in 14 patients. Cardiac death occurred in 230 (pump failure in 171 and sudden death in 59). An adjusted Cox model showed higher risk of cardiac death and pump failure death in the LBBB and RBBB than in the LAFB and the no IVCD groups. LBBB and RBBB are associated with different clinical profiles and both are independent predictors of increased risk of cardiac death in patients with HF. A more favourable prognosis was observed in patients with LAFB and in those free of IVCDs. Further research in HF patients with RBBB is warranted

PROYECTO DE CURSO DE POSTGRADO A DISTANCIA SOBRE FARMACOLOGIA DE LAS DROGAS DE ABUSO

La Universidad San Pablo CEU, en colaboración con la Agencia Antidroga de la Comunidad de Madrid, ha organizado en distintas ocasiones un curso de postgrado sobre"Farmacología de las Drogas de Abuso" que fue acreditado como Actividad de Formación Continuada por el Sistema Nacional de Salud. Durante la difusión de este curso se detectó la necesidad de formación a distancia en este campo por parte de una serie de personas que por impedimentos espaciales o temporales no podían ajustarse a las exigencias de una actividad presencial, planteándose por tanto la posibilidad de elaborar una edición especial del curso a través de Internet. Debido a que la Educación a Distancia a través de redes digitales es un medio relativamente poco conocido en los entornos docentes habituales, el firmante de este trabajo estimó necesario aumentar sus conocimientos mediante la realización de un Curso de Especialista sobre este tema en la Universidad de Murcia. Se presenta aquí el proyecto final de dicho curso, en el que se aborda el diseño de una edición online del curso de postgrado sobre Farmacología de las Drogas de Abuso

Proyecto de Curso de postgrado a distancia sobre Farmacología de las drogas de abuso

La Universidad San Pablo CEU, en colaboración con la Agencia Antidroga de la Comunidad de Madrid, ha organizado en distintas ocasiones un curso de postgrado sobre "Farmacología de las Drogas de Abuso" que fue acreditado como Actividad de Formación Continuada por el Sistema Nacional de Salud. Durante la difusión de este curso se detectó la necesidad de formación a distancia en este campo por parte de una serie de personas que por impedimentos espaciales o temporales no podían ajustarse a las exigencias de una actividad presencial, planteándose por tanto la posibilidad de elaborar una edición especial del curso a través de Internet. Debido a que la Educación a Distancia a través de redes digitales es un medio relativamente poco conocido en los entornos docentes habituales, el firmante de este trabajo estimó necesario aumentar sus conocimientos mediante la realización de un Curso de Especialista sobre este tema en la Universidad de Murcia. Se presenta aquí el proyecto final de dicho curso, en el que se aborda el diseño de una edición online del curso de postgrado sobre Farmacología de las Drogas de Abuso

¿Qué es la Investigación Traslacional?

La emergencia de la denominada �Investigación Traslacional� ha suscitado numerosas dudas sobre su significado real, su oportunidad o sobre las posibles amenazas que pueda suponer para otros tipo de investigación, pero ante todo responde a un enfoque novedoso cuyo fin último está en procurar un beneficio significativo al paciente en el lapso de tiempo más corto posible. En esta breve revisión se consideran de forma crítica los aspectos diferenciales que conforman su naturaleza

Contribución de los estudios preclínicos al conocimiento y terapéutica de la depresión

La neurobiología de la depresión ha sido ampliamente estudiada mediante el análisis experimental de la conducta y la utilización de técnicas bioquímicas y farmacológicas diversas. Los métodos utilizados, sin embargo, son cuestionables desde su misma concepción. En esta revisión se analizan las aportaciones proporcionadas por los modelos animales de depresión basados en el estrés, deprivación social o manipulación de áreas cerebrales específicas; además se examina la contribución indirecta del estudio farmacológico de los antidepresivos. A pesar de las limitaciones teóricas, puede afirmarse que el estudio experimental de la depresión contribuye significativamente al conocimiento de aspectos básicos como son los sustratos neuronales y los mecanismos neuroquímicos implicados; en consecuencia, las técnicas descritas permiten progresar en la investigación de la terapéutica de la depresión

Yohimbine does not affect opioid receptor activation but prevents adenylate cyclase regulation by morphine in NG108-15 cells

[Aims]: Yohimbine has been shown to modulate the pharmacological actions of opioid drugs in a way that could be of potential therapeutic interest. This work tries to study if this interaction involves the impairment of opioid receptor activation at the cellular level by studying the effects of morphine and yohimbine on NG108-15 neuroblastoma x glioma hybrid cells. [Main methods]: [35S]GTPγS binding assays were performed to study δ-opioid and α2B-adrenoceptor activation by opioid and adrenoceptor agonists in the presence and absence of yohimbine. The effect of morphine was also studied after 6 h pre-incubations with morphine, yohimbine and combinations of these drugs taking into account previous results showing an interaction between both drugs in these conditions. Forskolin-induced cAMP accumulation was also studied by immunoassay in cells incubated with morphine for 6 h in the presence and absence of naloxone and yohimbine. [Key findings]: Yohimbine behaved as a competitive antagonist/inverse agonist on α2B- adrenoceptors but did not modify G-protein activation by morphine, either in acute conditions or after 6 h of incubation. However, morphine-induced inhibition of cAMP accumulation was prevented both by naloxone and yohimbine when these drugs were present in the incubation medium. [Significance]: Yohimbine seems to desensitise adenylate cyclase to the inhibitory effect of opioid-activated G proteins. This cellular effect could underlie the antagonistic actions of yohimbine on many pharmacological effects of the opioid both in vitro and in vivo. © 2011 Elsevier Inc. All rights reserved.Peer Reviewe

Antiproliferative and cytotoxic effects of grape pomace and grape seed extracts on colorectal cancer cell lines

Grape pomace is the source of bioactive compounds (anthocyanins, flavonols, flavan‐3‐ols, and stilbenes) which exhibit antiproliferative actions on cell cultures. We have investigated the antitumoral effects of grape pomace and grape seed extracts on colon cancer cells (Caco‐2, HT‐29) and fibroblasts. Crude extracts prepared from white and red pomace, and grape seeds, reduced the viability and proliferation of Caco‐2. HT‐29 cells were resistant to these actions. Purified extracts were then prepared from the same sources and compared with the LDH test; again, all three extracts were active and purified extract from grape seed was the most potent and specific on Caco‐2 cells. HT‐29 cells were more sensitive to these purified extracts. The biological activity resided almost exclusively in the flavonol and flavan‐3‐ols subfractions, rather than the anthocyanin subfraction. Preliminary results on the mechanisms involved in these effects revealed downregulation of Myc gene expression in HT‐29 and upregulation of Ptg2 in Caco‐2 cells