Eficacia de la modulación farmacológica del sistema endocannabinoide cerebral en los trastornos de ansiedad y depresión humana

25 p. : il. -- Bibliogr.. p. 22-24Se presenta una memoria basada en una revisión exhaustiva a partir de la búsqueda en bancos de datos internacionales, especialmente PubMed, de las publicaciones biomédicas que hacen referencia a los ensayos clínicos en fase I y fase II que se han realizado hasta la fecha para evaluar la eficacia y seguridad en el ser humano de los inhibidores farmacológicos de los enzimas implicados en el metabolismo de los principales endocannabinoides cerebrales, especialmente de la enzima hidroxilasa de la amida de ácidos grasos FAAH que se encarga de la degradación de anandamida, y con especial atención al ensayo clínico suspendido al inicio de este año 2016 debido a la muerte de uno de los participantes. Para ello, en primer lugar se han revisado los estudios realizados en modelos animales que justifican el papel del sistema endocannabinoide cerebral como fuente de nuevas dianas farmacológicas para el desarrollo de fármacos útiles en el tratamiento de trastornos mentales con una elevada prevalencia en nuestra sociedad, como la ansiedad y la depresión humana. En segundo lugar, se han analizado los ensayos clínicos en fase I y en fase II realizados con inhibidores de la FAAH, con especial atención a las características del diseño del ensayo clínico en fase I realizado con la molécula BIA 10-2474 responsable de la muerte de uno de los participantes. En tercer lugar, se han analizado las posibles causas a partir de las conclusiones publicadas recientemente por el Comité Temporal de Expertos creado por la Agencia Francesa del Medicamento

Characterization of a double-hit mouse model of schizophrenia. Focus on inflammatory and epigenetic processes, pharmacological modulation and sex bias

333 p.Los déficits cognitivos de la esquizofrenia son un síntoma central, son indicadores del pronóstico de la enfermedad y son resistentes a los tratamientos actuales. Se sospecha que los antipsicóticos atípicos podrían empeorar los déficits cognitivos, y se ha propuesto que este proceso tiene lugar a través de una regulación epigenética de las histonas deacetilasas y que podría ser inducido por un exceso de actividad neuroinflamatoria. En la etiopatogenia de esquizofrenia se ha sugerido la existencia de eventos prenatales que generan vulnerabilidad y que posteriormente se reactivan por procesos estresantes durante la adolescencia, constituyendo un fenómeno de "doble-hit". Se considera que la fisio- y psicopatología de la enfermedad podría vincularse a ese fenómeno a través de un exceso de actividad neuroinflamatoria. Teniendo en cuenta todo lo anterior, la presente Tesis Doctoral se centra en la validación de un modelo animal ¿doble-hit¿ de esquizofrenia en ratones macho y hembra. El modelo doble-hit está basado en la activación inmune materna durante la gestación -mediante la administración de un análogo de ARN viral, denominado Poly (I:C)- seguido de un periodo de aislamiento social durante la pubertad. El modelo doble-hit ha demostrado poseer alteraciones comportamentales asociadas con esquizofrenia, así como alteraciones inflamatorias y epigenéticas relacionadas. con la enfermedad. Asimismo, se ha evaluado el efecto de un tratamiento crónico con antipsicóticos atípicos y fármacos anti-inflamatorios. Los hallazgos obtenidos en este trabajo demuestran que el modelo doble-hit es una herramienta válida para el estudio de la esquizofrenia

Eficacia de la modulación farmacológica del sistema endocannabinoide cerebral en los trastornos de ansiedad y depresión humana

25 p. : il. -- Bibliogr.. p. 22-24Se presenta una memoria basada en una revisión exhaustiva a partir de la búsqueda en bancos de datos internacionales, especialmente PubMed, de las publicaciones biomédicas que hacen referencia a los ensayos clínicos en fase I y fase II que se han realizado hasta la fecha para evaluar la eficacia y seguridad en el ser humano de los inhibidores farmacológicos de los enzimas implicados en el metabolismo de los principales endocannabinoides cerebrales, especialmente de la enzima hidroxilasa de la amida de ácidos grasos FAAH que se encarga de la degradación de anandamida, y con especial atención al ensayo clínico suspendido al inicio de este año 2016 debido a la muerte de uno de los participantes. Para ello, en primer lugar se han revisado los estudios realizados en modelos animales que justifican el papel del sistema endocannabinoide cerebral como fuente de nuevas dianas farmacológicas para el desarrollo de fármacos útiles en el tratamiento de trastornos mentales con una elevada prevalencia en nuestra sociedad, como la ansiedad y la depresión humana. En segundo lugar, se han analizado los ensayos clínicos en fase I y en fase II realizados con inhibidores de la FAAH, con especial atención a las características del diseño del ensayo clínico en fase I realizado con la molécula BIA 10-2474 responsable de la muerte de uno de los participantes. En tercer lugar, se han analizado las posibles causas a partir de las conclusiones publicadas recientemente por el Comité Temporal de Expertos creado por la Agencia Francesa del Medicamento

A novel double-hit animal model of schizophrenia: behavioural assessment in male and female mice

Background: A growing body of evidence support that maternal prenatal infections represent a risk factor for schizophrenia in offspring. Moreover, stressful events during critical neurodevelopmental periods, such as adolescence, may trigger the onset of the disease in predisposed individuals. Thus, a prenatal priming event (i.e. maternal infection during pregnancy) that would induce vulnerability, followed by a second stressful hit in peripuberty may lead to the onset of schizophreniaDisclosure statement: Supported by the Basque Government (IT1211-19), the European Union's Horizon 2020 research and innovation programme (Marie Sklodowska-Curie grant agreement No 747487) and SAF 2017-88126-R. NC is recipient of a FPI fellowship (PRE2018-084002) from MICINN

Behavioural Evaluation of a Translational Animal Model of Schizophrenia

Presented at 1st Meeting in Translational Pharmacology 38th SEF national meeting/9th SEFF meeting 19–20 June 2018, SpainSchizophrenia (SZ) is a chronic and disabling psychiatric disorder affecting about 1% of the population worldwide. Schizophrenia comprises positive and negative symptoms as well as cognitive deficits. Epidemiological and experimental studies indicate that infections during the gestational period represent a risk factor to develop SZ along lifetime, which in combination with stressful events in adolescence may lead to the SZ onset. The aim of the present study was to create a translational “double-hit” animal model of SZ in male and female mice, based in maternal immune activation (MIA, hit-1)—injection of poly(I:C) to pregnant dams, 7.5 mg/kg i.p.—and social isolation (SI, hit-2) in the peri-pubertal period (3–11 weeks). In the four experimental groups (hit-1, hit-2, double-hit and control) locomotion and anxiety were assessed using the Open Field Test (OFT), and the cognitive status (declarative/episodic memory) was evaluated by means of the Novel Object Recognition Test (NORT). No differences were observed in the spontaneous locomotor activity between any of the groups, neither in females nor in males. However, an increase in the percentage of time spent in the centre of the OFT was significantly associated to the hit-1 (MIA) only in female mice (F[1,53] = 4.252; P = 0.044, n = 57). Moreover, a significant decrease in the discrimination index in the NORT was also associated to the hit-1 (MIA) in the subgroup of female mice (F[1,55] = 7.266; P = 0.0093, n = 59). These preliminary results indicate that MIA produces a greater impact in female mice inducing an anxiolytic-like phenotype and cognitive impairments.Basque Government (IT616/13) MSCA-2016-IF 747487 to C.Muguruza

Risk factors for infections caused by carbapenem-resistant Enterobacterales: an international matched case-control-control study (EURECA)

Cases were patients with complicated urinary tract infection (cUTI), complicated intraabdominal (cIAI), pneumonia or bacteraemia from other sources (BSI-OS) due to CRE; control groups were patients with infection caused by carbapenem-susceptible Enterobacterales (CSE), and by non-infected patients, respectively. Matching criteria included type of infection for CSE group, ward and duration of hospital admission. Conditional logistic regression was used to identify risk factors. Findings Overall, 235 CRE case patients, 235 CSE controls and 705 non-infected controls were included. The CRE infections were cUTI (133, 56.7%), pneumonia (44, 18.7%), cIAI and BSI-OS (29, 12.3% each). Carbapenemase genes were found in 228 isolates: OXA-48/like, 112 (47.6%), KPC, 84 (35.7%), and metallo-beta-lactamases, 44 (18.7%); 13 produced two. The risk factors for CRE infection in both type of controls were (adjusted OR for CSE controls; 95% CI; p value) previous colonisation/infection by CRE (6.94; 2.74-15.53; <0.001), urinary catheter (1.78; 1.03-3.07; 0.038) and exposure to broad spectrum antibiotics, as categorical (2.20; 1.25-3.88; 0.006) and time-dependent (1.04 per day; 1.00-1.07; 0.014); chronic renal failure (2.81; 1.40-5.64; 0.004) and admission from home (0.44; 0.23-0.85; 0.014) were significant only for CSE controls. Subgroup analyses provided similar results. Interpretation The main risk factors for CRE infections in hospitals with high incidence included previous coloni-zation, urinary catheter and exposure to broad spectrum antibiotics

Famílies botàniques de plantes medicinals

Facultat de Farmàcia, Universitat de Barcelona. Ensenyament: Grau de Farmàcia, Assignatura: Botànica Farmacèutica, Curs: 2013-2014, Coordinadors: Joan Simon, Cèsar Blanché i Maria Bosch.Els materials que aquí es presenten són els recull de 175 treballs d’una família botànica d’interès medicinal realitzats de manera individual. Els treballs han estat realitzat per la totalitat dels estudiants dels grups M-2 i M-3 de l’assignatura Botànica Farmacèutica durant els mesos d’abril i maig del curs 2013-14. Tots els treballs s’han dut a terme a través de la plataforma de GoogleDocs i han estat tutoritzats pel professor de l’assignatura i revisats i finalment co-avaluats entre els propis estudiants. L’objectiu principal de l’activitat ha estat fomentar l’aprenentatge autònom i col·laboratiu en Botànica farmacèutica

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Colombian consensus recommendations for diagnosis, management and treatment of the infection by SARS-COV-2/ COVID-19 in health care facilities - Recommendations from expert´s group based and informed on evidence

La Asociación Colombiana de Infectología (ACIN) y el Instituto de Evaluación de Nuevas Tecnologías de la Salud (IETS) conformó un grupo de trabajo para desarrollar recomendaciones informadas y basadas en evidencia, por consenso de expertos para la atención, diagnóstico y manejo de casos de Covid 19. Estas guías son dirigidas al personal de salud y buscar dar recomendaciones en los ámbitos de la atención en salud de los casos de Covid-19, en el contexto nacional de Colombia