Reseñas

Guillermo OLAGÜE de ROS ; Jorge MOLERO MESA ; Alfredo MENÉNDEZ NAVARRO ; Mikel ASTRAIN GALLART ; Esther ROSADO CAMACHO ; José VALENZUELA CANDELARIO, Catálogo de la biblioteca histórica del Hospital San Juan de Dios de Granad

Preclinical discovery of duloxetine for the treatment of depression

Introduction: Affective disorders, including major depressive disorder (MDD), are among the most severely disabling mental disorders, and in many cases areIntroduction: Affective disorders, including major depressive disorder (MDD), are among the most severely disabling mental disorders, and in many cases are associated with poor treatment outcomes. From the emergence of the monoamine hypothesis of depression, the first-line treatment for MDD had mainly acted by inhibiting monoamine reuptake, and thereby increasing these levels in the synaptic cleft. However, in recent years, several newantidepressant drugs have appeared, including duloxetine, a dual serotonin (5-HT) and noradrenaline (NA) reuptake inhibitor recommended for the treatment of MDD. Areas covered: The article reviews and discusses the biochemical and functional profile of duloxetine splitting the review into acute and long-term treatment with this dual monoamine reuptake inhibitor. In addition, the authors summarize available preclinical behavioral research data, which have demonstrated among other effects, the antidepressant-like activity of duloxetine in several animal models. The authors focus on the most recent literature on synaptic neuroplasticity modulation of this antidepressant drug. Finally, the authors briefly mention other approved indications of duloxetine. Expert opinion: Duloxetine inhibits 5-HT and NA reuptake, effectively desensitizes various autoreceptors and promotes neuroplasticity. Clinically, duloxetine is an effective antidepressant that is well tolerated and has significant efficacy in the treatment of MDD. associated with poor treatment outcomes. From the emergence of the monoamine hypothesis of depression, the first-line treatment for MDD had mainly acted by inhibiting monoamine reuptake, and thereby increasing these levels in the synaptic cleft. However, in recent years, several new antidepressant drugs have appeared, including duloxetine, a dual serotonin (5-HT) and noradrenaline (NA) reuptake inhibitor recommended for the treatment of MDD

Neurotrophins Role in Depression Neurobiology: A Review of Basic and Clinical Evidence

Depression is a neuropsychiatric disorder affecting a huge percentage of the active population especially in developed countries. Research has devoted much of its attention to this problematic and many drugs have been developed and are currently prescribed to treat this pathology. Yet, many patients are refractory to the available therapeutic drugs, which mainly act by increasing the levels of the monoamines serotonin and noradrenaline in the synaptic cleft. Even in the cases antidepressants are effective, it is usually observed a delay of a few weeks between the onset of treatment and remission of the clinical symptoms. Additionally, many of these patients who show remission with antidepressant therapy present a relapse of depression upon treatment cessation. Thus research has focused on other possible molecular targets, besides monoamines, underlying depression. Both basic and clinical evidence indicates that depression is associated with several structural and neurochemical changes where the levels of neurotrophins, particularly of brain-derived neurotrophic factor (BDNF), are altered. Antidepressants, as well as other therapeutic strategies, seem to restore these levels. Neuronal atrophy, mostly detected in limbic structures that regulate mood and cognition, like the hippocampus, is observed in depressed patients and in animal behavioural paradigms for depression. Moreover, chronic antidepressant treatment enhances adult hippocampal neurogenesis, supporting the notion that this event underlies antidepressants effects. Here we review some of the preclinical and clinical studies, aimed at disclosing the role of neurotrophins in the pathophysiological mechanisms of depression and the mode of action of antidepressants, which favour the neurotrophic/neurogenic hypothesis

Development of the Happiness Index in a country

[EN] In this paper, a Happiness Index is built through the Human Dignity Respect Index which is explained by Author (2014). The index is created using three main values: development, freedom and equality. But the equality is explained by solidarity, justice and peace. Then, the Happiness Index is developed with this five concepts. The aim of this paper is to obtain the minimum quantitative variables to explain these values as well as to obtain a generic formula, which allows measuring the happiness of a country/region. The term “generic” is introduced because this formula could be extrapolated to any country. The variables to obtain the Development Index are health (Life Expectancy at birth), income (Gross National Income per capita), education (Mean year of schooling and Expected years of schooling) and education quality (Primary school teachers trained to teach, Performance of 15-year-old students in reading, mathematics and science, Pupil–teacher ratio, primary school and Public expenditure on education). The Freedom Index is calculated through Net migration rate, International inbound tourists, Exports and imports and Research and development expenditure. In the case of Solidarity Index, the variables are At-risk-ofpoverty rate, Share of total population living in a dwelling with a leaking roof, damp walls, floors or foundation, or rot in window frames of floor and Material Deprivation rate. Prison population and Homicide rate are the variables which are used to obtain the Peace Index. Finally, the Justice Index is calculated with Police Officers, Professional Judges, Prison population and Crimes and violence. In this work the index is calculated for a selection of countries of European Union (Austria, Croatia, Cyprus, Czech, France, Iceland, Latvia, Lithuan, Portugal, Slovenia, Spain, Sweden and United Kingdom). This selection is produced because the data information is not available for all countries. The data information is obtained from EUROSTAT and the Human Development Report (UNDP, 2014). Finally, the Happiness Index has been compared with Overall Life Satisfaction Index from UNDP (2014).Sanz García, M.; Caselles, A.; Micó Ruiz, JC.; Soler Fernández, D. (2016). Development of the Happiness Index in a country. En Systems&design:beyond processes and thinking. Editorial Universitat Politècnica de València. 807-818. https://doi.org/10.4995/IFDP.2016.3096OCS80781

El balneario de Bellús en los siglos XVIII y XIX, a través de los tratados de hidrología médica

The present work aims to explain the situation of the valencian bathing place in Bellús, through some treatises of medical hydrology from the 18th and 19th centuries which belong to the Library and Historico-medical Museum of Valencia. The architectural and technical conditions of the building are described, as well as the methods of water analysis and the therapeutical use of water.El presente trabajo pretende dar a conocer la situación del balneario valenciano de Bellús, a través de los tratados de hidrología médica de los siglos XVIII y XIX que se conservan en la Biblioteca y Museo Historicomédicos de Valencia. Para ello se describe las condiciones arquitectónicas y técnicas del edificio, así como los diversos análisis de las aguas y su utilización terapéutica

A nationwide study of chronic pain prevalence in the general Spanish population, identifying clinical subgroups through cluster analysis.

Objective. This study aims to assess the prevalence of chronic pain, its characteristics, and its impact on the general Spanish population. Also, to establish chronic pain patient subgroups according to the characteristics of pain and to identify variables specifically associated with each subgroup. Design. Telephone-based, cross-sectional nationwide study. Subjects. A sample of 1,957 individuals representative of the Spanish population. Methods. Data were collected through telephone interviews. A subject was considered to have chronic pain if they had suffered pain (at least 4 days a week) during the last 3 months. The subjects were divided into two subgroups through a cluster analysis, and a regression model was established to determine the variables most specifically associated with these subgroups. Results. The prevalence of chronic pain was 16.6% (95% confidence interval: 14.9–18.3) and among these subjects, more than 50% referred to limitations in their daily activities, 30% felt sad and/or anxious, and 47.2% indicated that their pain was affecting their family life. Two subgroups of subjects with pain were identified: 1) characterized by generalized pain in more than one location and of a long evolution (150 months); and 2) characterized by pain localized to only one site with a shorter duration (100 months). Individuals who felt anxious because of their pain and those who considered that their pain was affecting their family were more likely to belong to group 1. Conclusions. Pain affects an important proportion of the Spanish adult population and that it has a strong personal impact. Two pain groups were clearly distinguished by their clinical characteristics

Including an environmental quality index in a demographic model

This paper presents a new well-being index which allows environmental quality to be measured through CO2 emissions, renewable energies and nuclear power. Its formula derives from a geometric mean used to calculate which things in the human production system warm the planet and which do not. This index has been introduced into a gender-defined stochastic population dynamic mathematical model which measures well-being in a country. The main variables in this model are rates of death, birth, emigration and immigration, as well as three UN indices: Human Development Index, Gender Development Index and Gender Empowerment Index. This model has been extended with variables that allow an environmental quality evaluation, and it has been validated for Spain during the 2001-2010 period. Moreover, a sensitivity analysis has been carried on the simulated future trend (2011-2020) to see which environmental quality variables refer more to deaths, births or the Human Development Index. Copyright © 2016 Inderscience Enterprises Ltd.Sanz-García, MT.; Caselles Moncho, A.; Micó Ruiz, JC.; Soler Fernández, D. (2016). Including an environmental quality index in a demographic model. International Journal of Global Warming. 9(3):362-396. doi:10.1504/IJGW.2016.075448S3623969

Depressive-like states heighten the aversion to painful stimuli in a rat model of comorbid chronic pain and depression.

BACKGROUND: Chronic pain and depression are two complex states with sensory/somatic and emotional components, and they may mutually exacerbate one another in conditions of comorbidity, leading to a poorer prognosis. METHODS: The authors have evaluated the sensory and emotional components in a rat model combining chronic constriction injury (CCI, a model of chronic neuropathic pain) with unpredictable chronic mild stress (CMS, an experimental model of depression). In addition, the phosphorylation/activation of the extracellular signal-regulated kinases 1 and 2 and neuronal density was also evaluated in the anterior cingulate cortex. Four groups were tested: sham-control, sham-CMS, CCI-control, and CCI-CMS. RESULTS: CMS selectively heightens aversion to painful experiences in animals subjected to CCI, as measured in the place escape/avoidance test at 20, 25, and 30 min (CCI-CMS (mean±SEM): 75.68±3.32, 66.75±4.70, 77.54±3.60 vs. CCI-control: 44.66±6.07, 43.17±6.92, 52.83±5.92, respectively), in conjunction with an increase in the accumulation of phosphorylation/activation of the extracellular signal-regulated kinases (CCI-CMS: 4.17±0.52 vs. sham-control: 0.96±0.05) and a decrease in neuronal density in the anterior cingulate cortex. In contrast, chronic pain did not exacerbate the characteristic profile of depression (anhedonia and behavioral despair) in rats subjected to CMS. Furthermore, depression enhances the perception of some specific modalities of sensorial pain such as cold allodynia but has no influence on mechanical threshold. CONCLUSIONS: These findings support the theory that depression leads to emotional dysfunction in the interpretation of pain in patients suffering chronic pain. In addition, combined animal models of pain-depression may provide a valuable tool to study the comorbidity of pain and depression

Welfare and Human Population in Austria

A model for a general human population dynamics is presented to approach the demographic stability problem. The main model variables are demographic variables per sexes (births, deaths, emigration, immigration and population) and some well-being variables given by the UN: Human Development Index, Gender Development Index and Gender Empowerment Index. The model is presented in deterministic and stochastic formulations and it has been validated for the case of Austria in the 1999-2009 periodSanz García, MT.; Micó Ruiz, JC.; Caselles Moncho, A.; Soler Fernández, D. (2013). Welfare and Human Population in Austria. Systema: Connecting Matter, Life, Culture and Technology. 1(2):60-82. http://hdl.handle.net/10251/61946S60821

Pain and depression comorbidity causes asymmetric plasticity in the locus coeruleus neurons

There is strong comorbidity between chronic pain and depression, although the neural circuits and mechanisms underlying this association remain unclear. By combining immunohistochemistry, tracing studies and western blotting, with the use of different DREADDS (designer receptor exclusively activated by designer drugs) and behavioural approaches in a rat model of neuropathic pain (chronic constriction injury), we explore how this comorbidity arises. To this end, we evaluated the time-dependent plasticity of noradrenergic locus coeruleus neurons relative to the site of injury: ipsilateral (LCipsi) or contralateral (LCcontra) locus coeruleus at three different time points: short (2 days), mid (7 days) and long term (30-35 days from nerve injury). Nerve injury led to sensorial hypersensitivity from the onset of injury, whereas depressive-like behaviour was only evident following long-term pain. Global chemogenetic blockade of the LCipsi system alone increased short-term pain sensitivity while the blockade of the LCipsi or LCcontra relieved pain-induced depression. The asymmetric contribution of locus coeruleus modules was also evident as neuropathy develops. Hence, chemogenetic blockade of the LCipsi -> spinal cord projection, increased pain-related behaviours in the short term. However, this lateralized circuit is not universal as the bilateral chemogenetic inactivation of the locus coeruleus-rostral anterior cingulate cortex pathway or the intra-rostral anterior cingulate cortex antagonism of alpha1- and alpha2-adrenoreceptors reversed long-term pain-induced depression. Furthermore, chemogenetic locus coeruleus to spinal cord activation, mainly through LCipsi, reduced sensorial hypersensitivity irrespective of the time post-injury. Our results indicate that asymmetric activation of specific locus coeruleus modules promotes early restorative analgesia, as well as late depressive-like behaviour in chronic pain and depression comorbidity.This study was supported by grants cofinanced by the 'Fondo Europeo de Desarrollo Regional' (FEDER)-UE 'A way to build Europe' from the `Ministerio de Economia y Competitividad' (MINECO: RTI2018-099778-B-I00) and by the 'Ministerio de SaludInstituto de Salud Carlos III' (PI18/01691); the 'Consejeria de Salud de la Junta de Andalucia' (PI-0134-2018); the 'Programa Operativo de Andalucia FEDER, Iniciativa Territorial Integrada ITI 2014-2020 Consejeria Salud, Junta de Andalucia' (PI-0080-2017); the "Consejeri ' a de Transformacion Economica, Industria, Conocimiento y Universidades, Junta de Andalucia" (PEMP-00082020), Instituto de Investigacion e Innovacion en Ciencias Biomedicas de Cadiz (INiBICA LI19/06IN-CO22); the `Consejeri ' a de Economia, Innovacion, Ciencia y Empleo de la Junta de Andalucia' (CTS-510); the 'Centro de Investigacion Biomedica en Red de Salud Mental-CIBERSAM' (CB/07/09/0033) and the Academy of Finland (315043)