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Background: The potential role of the gut microbiome as a predictor of immune-mediated HIV-1 control in the absence of antiretroviral therapy (ART) is still unknown. In the BCN02 clinical trial, which combined the MVA.HIVconsv immunogen with the latency-reversing agent romidepsin in early-ART treated HIV-1 infected individuals, 23% (3/13) of participants showed sustained low-levels of plasma viremia during 32 weeks of a monitored ART pause (MAP). Here, we present a multi-omics analysis to identify compositional and functional gut microbiome patterns associated with HIV-1 control in the BCN02 trial. Results: Viremic controllers during the MAP (controllers) exhibited higher Bacteroidales/Clostridiales ratio and lower microbial gene richness before vaccination and throughout the study intervention when compared to non-controllers. Longitudinal assessment indicated that the gut microbiome of controllers was enriched in pro-inflammatory bacteria and depleted in butyrate-producing bacteria and methanogenic archaea. Functional profiling also showed that metabolic pathways related to fatty acid and lipid biosynthesis were significantly increased in controllers. Fecal metaproteome analyses confirmed that baseline functional differences were mainly driven by Clostridiales. Participants with high baseline Bacteroidales/Clostridiales ratio had increased pre-existing immune activation-related transcripts. The Bacteroidales/Clostridiales ratio as well as host immune-activation signatures inversely correlated with HIV-1 reservoir size. Conclusions: The present proof-of-concept study suggests the Bacteroidales/Clostridiales ratio as a novel gut microbiome signature associated with HIV-1 reservoir size and immune-mediated viral control after ART interruption. Video abstract. This study was funded by Instituto de Salud Carlos III through the project “PI16/01421” (co-funded by European Regional Development Fund “A way to make Europe”). The project was sponsored in part by Grifols and received funding from the European Union’s Horizon 2020 Research and Innovation Programme under Grant Agreement N° 847943 (MISTRAL). The BCN02 clinical trial was an investigator-initiated study funded by the ISCIII PI15/01188 grant, the HIVACAT Catalan research program for an HIV vaccine and the Fundació Gloria Soler. Some sub-analyses of the BCN02 trial were partly funded by the European Union’s Horizon 2020 research and innovation program under grant agreement 681137-EAVI2020 and by NIH grant P01-AI131568. A.Bu lab was supported by grants from the Canadian Institutes of Health Research (HB3-164066) and the National Institutes for Health Research (R01DK112254). J.M.P lab was supported by grant PID2019-109870RB-I00 from the Spanish Ministry of Science and Innovation and in part by Grifols. J.M.M. received a personal 80:20 research grant from Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain, during 2017–21.

In Spain, 1.5 million essential < 60-year-old workers were vaccinated with a first AstraZeneca vaccine dose. After assessing the cases of thrombosis with thrombocytopenia associated to this vaccine, the European Medicines Agency (EMA) supported the administration of 2 doses of the AstraZeneca vaccine with no age restrictions. Nevertheless, Spain decided not to administer the second dose of this vaccine to < 60-year-olds. The government sponsored a clinical trial (CombiVacS) to assess the immunogenicity response to a Pfizer/BioNTech vaccine dose in adults primed with the AstraZeneca vaccine. The positive results backed the Public Health Commission and the Spanish Ministry of Health to offer the Pfizer/BioNTech vaccine as the booster. Nevertheless, regional public health authorities—responsible for administering vaccines—believed that, following the EMA’s decision, an AstraZeneca booster dose should be given. The public confrontation of these 2 positions forced the Spanish Health Ministry to request the signature of an informed consent form to those individuals willing to receive the AstraZeneca vaccine booster and rejecting the Pfizer/BioNTech vaccine dose. Eventually, it was decided that these essential workers could choose the vaccine but signing an informed consent form. All relevant information was posted on the Ministry of Health and regional health authorities’ websites and provided to potential vaccine recipients at vaccination sites. Most individuals (≥ 75%) chose the AstraZeneca vaccine: perhaps because they likely trusted the EMA more than the CombiVacS results. This unprecedented and massive exercise of individual autonomy about the choice of COVID-19 vaccines from 2 different platforms has shown that adequately informed persons can autonomously weigh their options, regardless of government decisions. Exercising individual autonomy may contribute to the success of future COVID-19 booster vaccination campaigns.

The HIV pandemic and the spectrum of diseases associated with its syndrome (AIDS) were noted for the first time in the early 1980s in the United States, with cases of death from pneumonia associated with Kaposi's sarcoma. The epidemiological investigation carried out by different teams in the United States –but mainly focusing on the Centers for Disease Control and Prevention– is portrayed in the film And the band played on (1993), by Roger Spottiswoode. Almost 30 years after its release, the film is still iconic and closely portrays the events of the investigation. This article presents a detailed analysis of the research process, the bioethical issues involved, and the psychological factors that allows to analyze the group and social confrontations of the epidemiological event that marked a before and after in the 20th century. It is suggested to use the film as a teaching tool. La pandemia de VIH (virus de inmunodeficiencia humana) y el espectro de enfermedades de su síndrome (SIDA) se registran por primera vez a principios de los años 1980 en Estados Unidos, con casos de muerte por neumonías asociados con el sarcoma de Kaposi. La investigación epidemiológica llevada a cabo por distintos equipos en los Estados Unidos –haciendo foco principalmente en el Centro para el Control y Prevención de Enfermedades– aparece retratada en la película En el filo de la duda / And the band played on (1993), de Roger Spottiswoode. Casi 30 años luego de su estreno, la película es sumamente actual y retrata de manera muy ajustada los hechos sucedidos en la investigación. En este artículo se presenta un análisis detallado del proceso investigativo, las cuestiones bioéticas implicadas y los factores psicológicos que permiten analizar los enfrentamientos grupales y sociales del acontecimiento epidemiológico que marcó un antes y un después en el siglo XX. Se sugiere utilizar la película como herramienta docente.

The use of commercial films in medical education is an increasingly widespread pedagogical resource, and particularly the Cinemeducation method provides a theoretical basis as well as documented background on this pedagogical innovation. In this paper, we propose the use of a commercial film for teaching pharmacology, particularly pharmacovigilance and adverse effects of drugs, topics that are usually very complex for medical students. The rigorous method followed in the choice of the film and its scenes is detailed, as well as the methodological sequence of its use in class. The selected film, La fille de Brest by Emmanuelle Bercot, is based on the true story of Irène Frachon, a French doctor who begins to detect cases of cardiotoxicity associated with the consumption of a drug and undertakes a legal battle against the pharmaceutical company that produces and distributes it. The film reveals in detail the epidemiological study carried out at Brest Hospital and also the role of safety, pharmacovigilance and public health agencies in a complex plot that allows key aspects of pharmacovigilance to be discussed with medical students.

The use of commercial films in medical education is an increasingly widespread pedagogical resource, and particularly the Cinemeducation method provides a theoretical basis as well as documented background on this pedagogical innovation. In this paper, we propose the use of a commercial film for teaching pharmacology, particularly pharmacovigilance and adverse effects of drugs, topics that are usually very complex for medical students. The rigorous method followed in the choice of the film and its scenes is detailed, as well as the methodological sequence of its use in class. The selected film, La fille de Brest by Emmanuelle Bercot, is based on the true story of Irène Frachon, a French doctor who begins to detect cases of cardiotoxicity associated with the consumption of a drug and undertakes a legal battle against the pharmaceutical company that produces and distributes it. The film reveals in detail the epidemiological study carried out at Brest Hospital and also the role of safety, pharmacovigilance and public health agencies in a complex plot that allows key aspects of pharmacovigilance to be discussed with medical students. El uso de películas comerciales en la educación médica es un recurso pedagógico cada vez más extendido, y particularmente el método de Cinema-educación proporciona tanto una base teórica como antecedentes documentados sobre esta forma de innovación pedagógica. En esta ocasión, proponemos la utilización de una película comercial para la enseñanza de la farmacología, particularmente de la farmacovigilancia y los efectos indeseabless de los medicamentos, temas que suelen ser muy complejos para estudiantes de Medicina. Se detalla el método riguroso de selección del film y sus escenas, así como la secuencia metodológica de su utilización en clase. La película elegida, La doctora de Brest (2016) de Emmanuelle Bercot, se basa en la historia real de Irène Frachon, una médica francesa que comienza a detectar casos de cardiotoxicidad asociados al consumo de un medicamento y libra una batalla judicial contra la compañía farmacéutica que lo produce y comercializa. El film revela en detalle el estudio epidemiológico llevado a cabo en el Hospital de Brest y también el papel de las agencias de seguridad, farmacovigilancia y salud pública en una trama compleja que permite debatir con los estudiantes de Medicina aspectos clave de la farmacovigilancia.

Contains fulltext : 178122.pdf (Publisher’s version ) (Closed access) Heavy cannabis use is associated with reduced motivation. The basal ganglia, central in the motivation system, have the brain's highest cannabinoid receptor density. The frontal lobe is functionally coupled to the basal ganglia via segregated frontal-subcortical circuits conveying information from internal, self-generated activity. The basal ganglia, however, receive additional influence from the sensory system to further modulate purposeful behaviors according to the context. We postulated that cannabis use would impact functional connectivity between the basal ganglia and both internal (frontal cortex) and external (sensory cortices) sources of influence. Resting-state functional connectivity was measured in 28 chronic cannabis users and 29 controls. Selected behavioral tests included reaction time, verbal fluency and exposition to affective pictures. Assessments were repeated after one month of abstinence. Cannabis exposure was associated with (1) attenuation of the positive correlation between the striatum and areas pertaining to the 'limbic' frontal-basal ganglia circuit, and (2) attenuation of the negative correlation between the striatum and the fusiform gyrus, which is critical in recognizing significant visual features. Connectivity alterations were associated with lower arousal in response to affective pictures. Functional connectivity changes had a tendency to normalize after abstinence. The results overall indicate that frontal and sensory inputs to the basal ganglia are attenuated after chronic exposure to cannabis. This effect is consistent with the common behavioral consequences of chronic cannabis use concerning diminished responsiveness to both internal and external motivation signals. Such an impairment of the fine-tuning in the motivation system notably reverts after abstinence.

The Alcohol Program of the Spanish Network on Addictive Disorders-RTA requires a longitudinal study to address different research questions related to alcoholism. The cohort study (CohRTA) focuses on patients seeking treatment for alcohol use disorder, as a multicentre, collaborative research project aimed to improve secondary prevention and early diagnosis of pathological processes associated with the disorder. Methods: multicentre cohort study in adults (> 18 years) seeking their first treatment of the disorder. Patients sign an informed consent and data is collected in an online platform specifically designed for the study; patients are also requested to provide biological samples that are stored in a biobank. Baseline and prospective, socio-demographic, epidemiological, clinical and treatment data are collected. Currently there are 10 participating centres that expect to recruit more than 1,000 patients. Results: As of December 2015, 344 patients (77% men) were included. Median age at admission was 50 years (IQR: 43-55 years). Median age at the start of alcohol consumption was 15 years (IQR: 14-18 years) and 61% of cases reported antecedents of alcohol use disorder in the family. During the 30 days prior to admission, alcohol consumption amounted to 12.5 SDU/day (IQR: 7.1-20 SDU/day), 72% of the patients were tobacco smokers and 30% currently used cocaine. Organising an open cohort of patients with alcohol use disorder may be crucial to better understand the clinical consequences of alcoholism in Spain. This cohort may potentiate quantitative and qualitative research within the Spanish Network on Addictive Disorders-RTA/RETICS. Having a well-established, representative cohort of patients will increase translational research on consequences of alcoholism in our country.

Hydroxytyrosol [2-(3,4-dihydroxyphenyl)ethanol] is a potent bioactive molecule with multiple health benefits that is present in olive oil and wine. In humans, ethanol intake induces the formation of small amounts of hydroxytyrosol through the alteration of dopamine metabolism (1). In rats, tyrosol is converted into hydroxytyrosol. It has been postulated that wine components (specifically tyrosol and ethanol) act synergistically generating important amounts of hydroxytyrosol (2). The aim of this study was to assess the contribution of tyrosol and/or ethanol on hydroxytyrosol recovery in the urine of healthy volunteers. The effect of white wine (WW; a source of ethanol with low phenolic content) and/or pure tyrosol on the urinary excretion of total hydroxytyrosol was evaluated. Tyrosol, hydroxytyrosol and their metabolites were quantified by LC-MS/MS. Results showed that (i) WW increased hydroxytyrosol urinary recovery, (ii) pure tyrosol also increased this recovery, and (iii) the combination of WW+tyrosol resulted in an exponential increase of hydroxytyrosol. These data demonstrates the in vivo formation of hydroxytyrosol from tyrosol in humans and evidences the synergistic effect of ethanol and tyrosol on hydroxytyrosol endogenous formation. These results open a new venue in our understanding of health beneficial effects associated to the intake of moderate doses of wine., Journal of International Society of Antioxidants in Nutrition & Health, Vol 3, No 4 (2016)

Olive oil polyphenols have shown protective effects on cardiovascular risk factors. Their consumption decreased oxidative stress biomarkers and improved some features of the lipid profile. However, their effects on LDL concentrations in plasma and LDL atherogenicity have not yet been elucidated.Our objective was to assess whether the consumption of olive oil polyphenols could decrease LDL concentrations [measured as apolipoprotein B-100 (apo B-100) concentrations and the total number of LDL particles] and atherogenicity (the number of small LDL particles and LDL oxidizability) in humans.The study was a randomized, cross-over controlled trial in 25 healthy European men, aged 20-59 y, in the context of the EUROLIVE (Effect of Olive Oil Consumption on Oxidative Damage in European Populations) study. Volunteers ingested 25 mL/d raw low-polyphenol-content olive oil (LPCOO; 366 mg/kg) or high-polyphenol-content olive oil (HPCOO; 2.7 mg/kg) for 3 wk. Interventions were preceded by 2-wk washout periods. Effects of olive oil polyphenols on plasma LDL concentrations and atherogenicity were determined in the sample of 25 men. Effects on lipoprotein lipase (LPL) gene expression were assessed in another sample of 18 men from the EUROLIVE study.Plasma apo B-100 concentrations and the number of total and small LDL particles decreased (mean ± SD: by 5.94% ± 16.6%, 11.9% ± 12.0%, and 15.3% ± 35.1%, respectively) from baseline after the HPCOO intervention. These changes differed significantly from those after the LPCOO intervention, which resulted in significant increases of 6.39% ± 16.6%, 4.73% ± 22.0%, and 13.6% ± 36.4% from baseline (P0.03). LDL oxidation lag time increased by 5.0% ± 10.3% from baseline after the HPCOO intervention, which was significantly different only relative to preintervention values (P = 0.038). LPL gene expression tended to increase by 26% from baseline after the HPCOO intervention (P = 0.08) and did not change after the LPCOO intervention.The consumption of olive oil polyphenols decreased plasma LDL concentrations and LDL atherogenicity in healthy young men. This trial was registered at www.controlled-trials.com as ISRCTN09220811.

[ES]El presente artículo analiza la película Coma dirigida por Michael Chricton en 1978 e inspirada en la novela del mismo nombre de Robin Cook. Bajo el formato de thriller médico, muestra una serie de casos de coma que suceden en pacientes jóvenes y sanos sometidos a intervenciones quirúrgicas menores. La protagonista descubre que los afectados son traslados a una institución donde se les extraen los órganos para su comercio ilegal. También investiga la causa del coma, consecuencia de la intoxicación homicida con monóxido de carbono mientras los pacientes se encuentran en quirófano. La película tiene el interés docente de estimular la comprensión de los fenómenos de transporte de oxígeno por la hemoglobina, así como su afinidad por diversos gases, como el dióxido de carbono y el monóxido de carbono. Los estudiantes deben aplicar sus conocimientos fisiológicos para comprender cómo se realiza la intoxicación y sus características clínicas, así como las bases de su tratamiento., [EN]We analyze the movie Coma directed by Michael Chricton in 1978 and inspired in the novel of the same name that was written by Robin Cook. The film is a medical thriller that shows several cases of patients who dropped in coma in a hospital during simple surgical procedures of minimal risk. Patients were young and healthy and the appearance of coma was unexpected and unexplainable. The heroine is a resident from surgery who discovers that affected patients are moved to the same long care institution. There, their organs are illegally removed to be used in patients who need them and who pay huge amounts of money. She also investigates the cause of coma and discovers that patients are poisoned with carbon monoxide during surgical procedures. The film has a teaching interest to stimulate the understanding of blood oxygen transport by hemoglobin, as well as the knowledge of affinity to this molecule by several gases, as oxygen, carbon monoxide and carbon dioxide. Students may also learn how to apply physiological concepts to understand the carbon monoxide intoxication, the clinical signs and symptoms, and the scientific bases of its treatment.

Objetivo: Describir la secuencia de hechos acontecidos respecto al caso Glivec® en la India y analizar las opiniones generadas en diferentes ámbitos. Método: Búsqueda sistemática de artículos sobre la patente de imatinib (Glivec®) en la India. Se seleccionaron los que describían los acontecimientos, las decisiones de las instancias implicadas y las opiniones en la prensa general y científica, con identificación de las fechas y de los argumentos de las partes implicadas. Resultados: De los 886 documentos obtenidos se seleccionaron 40, publicados entre 2003 y 2013, mayoritariamente de tipo periodístico y comentarios. El caso duró 7 años, desde el rechazo de la patente presentada por Novartis ante la oficina de patentes de la India en 2006 hasta la ratificación de esta decisión por el tribunal supremo en 2013. Entre las controversias surgidas destacaron los argumentos en defensa de la ley de patentes India, promulgada para favorecer el acceso a los medicamentos en los países del Tercer Mundo. El fallo judicial ha recibido el apoyo de diversas instituciones, si bien un análisis objetivo implica considerar también los argumentos presentados por las empresas farmacéuticas y otras instituciones. Conclusión: El caso Glivec® ha planteado el debate sobre la adecuación de las normas internacionales, su aplicabilidad en el entorno económico y su adaptación en cada país. Este caso, y otros, deberían contribuir a la reflexión sobre el sistema internacional de patentes a fin de preservar la salud de la población más necesitada de una atención sanitaria adecuada en equilibrio con la protección de la propiedad intelectual y la innovación. Objective: To describe the sequence of events involving the Glivec® case in India and to analyze the opinions generated in distinct settings. Method: We performed a systematic search for articles concerning the imatinib (Glivec®) patent in India. We selected those sources that described the events, decisions of the authorities involved, and press and scientific opinions. Dates and arguments presented by the involved parties were clearly identified. Results: Of 886 documents initially obtained, we selected 40 documents published between 2003 and 2013. Most of them were press news and commentaries. The process lasted 7 years, starting in 2006 when the Indian Patent Office rejected the patent application filed by Novartis. It ended in 2013 when the Indian Supreme Court upheld this decision. It was argued that the Indian Patent Law would facilitate access to medicines in the Third World and the final decision has received support by the general population. Although the court's final decision has been supported by several institutions, an objective analysis should also take into account the arguments of the pharmaceutical companies and other entities. Conclusion: The Glivec® case gave rise to an intense debate on the appropriateness of international standards on patents, their applicability and how they should be adopted in each country. This case, as well as other cases, should serve to stimulate reflection on the international patent system and to achieve scenarios in which the health of the poorest populations is protected but also balanced against intellectual property protection and innovation.

El uso de películas comerciales ha sido habitual para fomentar el aprendizaje en diversas experiencias universitarias, especialmente en estudios en ciencias de la salud. En el presente trabajo se presenta una dilatada experiencia con dicho método docente llevada a cabo con los estudios de biología en la Facultad de Ciencias de la Salud y de la Vida de la Universitat Pompeu Fabra. Desde el inicio de los estudios, se utilizaron diversas películas en todos los cursos de la carrera que sirvieron para fomentar el aprendizaje de objetivos docentes muy diversos. En concreto se ha utilizado habitualmente el cine como herramienta docente en siete asignaturas ubicadas en los cinco cursos del currículo. En todos los casos, la experiencia fue muy bien valorada y mantiene su continuidad en los nuevos grados de Medicina y de Biología Humana que se imparten en el centro. Popular movies have been used in a wide range of university courses for different teaching purposes, especially in studies of health sciences. This paper describes an experience of using such didactic approach in a wide range of subjects in the bachelor of Biology at the Pompeu Fabra University. Since the beginning of the studies, several films were used to promote the learning of diverse educational objectives. Specifically, seven subjects located in the five courses of the curriculum have been commonly used films as a teaching tool. In all cases, the experience was highly valued and it is continued in the new degree studies of Human Biology and Medicine.

La utilización de películas comerciales para ilustrar conflictos bioéticos es una experiencia frecuente en la docencia universitaria de ciencias de la salud. En este ámbito, la investigación clínica es un importante paradigma para conocer cómo los principios éticos pueden aplicar en situaciones de análisis complejo. En el presente artículo se analiza el interés de una película comercial, Al cruzar el límite/ Extreme Measures (1996) de Michael Apted, para presentar el difícil debate de aplicación de los principios de autonomía, justicia, beneficencia y no maleficencia. El film presenta diversas situaciones en el marco de un argumento policíaco inspirado en el libro del médico norteamericano Michael Palmer. Los autores comentan las fortalezas y las debilidades de la película, así como aquellos aspectos que pueden plantearse en el debate de la película, y sugieren su posible utilidad para debatir cómo los factores personales pueden influenciar la toma de decisiones en situaciones límite. La principal conclusión es que Al cruzar el límite puede ser un instrumento útil a pesar de que se necesitan pruebas empíricas para confirmarla.

[ES] La presente invención se refiere a nuevos derivados amidas de ácidos grasos conjugados con anfetaminas, que se comportan como ligando s duales de los receptores cannabionides tipo 1 (CBl ) y del subtipo alfa de los receptores activados por el proliferador de peroxisomas (PPAR-alfa), y como potentes agentes inhibidores de la oxidación de la Lipoproteína de Baja Densidad (LDL), así como a su procedimiento de preparación, y su utilización como herramienta farmacológica y como fármacos para modular las acciones reguladas por los citados receptores, como la inducción de la saciedad y control de ingesta, la disminución de la grasa corporal y la regulación del metabolismo lipídico, [EN] The invention relates to novel fatty acid amide derivatives conjugated with amphetamines, which behave as dual ligands of type 1 cannabinoid (CB 1) receptors and of the alpha subtype of the peroxisome proliferator activated receptors (PP ARalfa) and as potent inhibitors of low-density lipoprotein (LDL) oxidation. The invention also relates to the preparation method thereof and to the use of same as a pharmacological tool and as drugs for modulating the actions regulated by the aforementioned receptors, as well as for inducing satiety and controlling intake, reducing body fat and regulating fat metabolismo, Fundació IMIM, Fundación IMABIS - Instituto Mediterráneo para el Avance de la Biotecnología y la Investigación Sanitaria, Consejo Superior de Investigaciones Científicas (España), A1 Solicitud de patente con informe sobre el estado de la técnica

Resumen tomado de la publicación En las últimas décadas las técnicas de neuroimagen han contribuido en gran medida al estudio 'in vivo' de los efectos neurobiológicos del consumo agudo y crónico de sustancias de abuso. El incremento en los últimos años del consumo de alcohol y cannabis, así como las graves consecuencias asociadas al consumo de opiáceos han contribuido al aumento del interés por estudiar los efectos de estas sustancias en el sistema nervioso central. Los objetivos de esta revisión son: (1) presentar los hallazgos más actualizados de neuroimagen en el estudio de los correlatos cerebrales del consumo de opiáceos, alcohol y cannabis, teniendo en cuenta: (i) la administración aguda de estas sustancias, (ii) el craving, y (iii) los efectos asociados al consumo crónico (2) discutir las implicaciones de estos hallazgos para una mejor comprensión de los procesos adictivos y su tratamiento. Los resultados sugieren que el consumo de estas tres drogas está asociado con alteraciones estructurales y funcionales en varias regiones del córtex frontal y el sistema límbico, con sutiles diferencias en la intensidad y extensión de estas alteraciones. A su vez, estas regiones muestran una mayor activación durante la inducción de estados de craving, y muestran alteraciones durante la neuroactivación mediante tareas cognitivas. Las alteraciones cerebrales observadas se han relacionado con síntomas clínicos, como la co-ocurrencia de trastornos psquiátricos, la intensidad del craving en condiciones naturales, o la probabilidad de recaídas. Por tanto, el uso de técnicas basadas en la modulación del funcionamiento cerebral puede contribuir a mejorar el tratamiento de estas adicciones. Valencia Universidad de Valladolid. Facultad de Educación y Trabajo Social. Biblioteca; Campus Miguel Delibes. Paseo de Belén, 1; 47011 Valladolid; +34983423435; +34983423436; edts@uva.es ESP

En las últimas décadas las técnicas de neuroimagen han contribuido en gran medida al estudio in vivo de los efectos neurobiológicos del consumo agudo y crónico de sustancias de abuso. El incremento en los últimos años del consumo de alcohol y cannabis, así como las graves consecuencias asociadas al consumo de opiáceos han contribuido al aumento del interés por estudiar los efectos de estas sustancias en el sistema nervioso central. Los objetivos de esta revisión son: (1) presentar los hallazgos más actualizados de neuroimagen en el estudio de los correlatos cerebrales del consumo de opiáceos, alcohol y cannabis, teniendo en cuenta: (i) la administración aguda de estas sustancias, (ii) el craving, y (iii) los efectos asociados al consumo crónico (2) discutir las implicaciones de estos hallazgos para una mejor comprensión de los procesos adictivos y su tratamiento. Los resultados sugieren que el consumo de estas tres drogas está asociado con alteraciones estructurales y funcionales en varias regiones del córtex frontal y el sistema límbico, con sutiles diferencias en la intensidad y extensión de estas alteraciones. A su vez, estas regiones muestran una mayor activación durante la inducción de estados de craving, y muestran alteraciones durante la neuroactivación mediante tareas cognitivas. Las alteraciones cerebrales observadas se han relacionado con síntomas clínicos, como la co-ocurrencia de trastornos psquiátricos, la intensidad del craving en condiciones naturales, o la probabilidad de recaídas. Por tanto, el uso de técnicas basadas en la modulación del funcionamiento cerebral puede contribuir a mejorar el tratamiento de estas adicciones.

En los últimos años ha aumentado el interés por el estudio de los correlatos neurobiológicos del consumo de drogas psicoestimulantes, como la cocaína o el éxtasis. La aplicación de las técnicas de neuroimagen ha permitido examinar in vivo los efectos agudos de la administración de estas sustancias, los correlatos cerebrales del deseo intenso por consumirlas (craving), o las alteraciones funcionales o morfológicas asociadas al consumo crónico. Los objetivos de esta revisión son: (1) explicar brevemente las técnicas de neuroimagen utilizadas en la investigación de drogodependencias (2) presentar los hallazgos más actualizados de neuroimagen en el estudio de los correlatos cerebrales del consumo de cocaína y MDMA, teniendo en cuenta (i) la administración aguda de la sustancia, (ii) el craving, y (iii) los efectos asociados al consumo crónico (3) discutir las implicaciones de estos hallazgos para una mejor comprensión de los procesos adictivos y su tratamiento. Los resultados sugieren que ambas sustancias producen alteraciones cerebrales comunes en regiones como el cortex frontal, estructuras límbicas (ínsula, amígdala e hipocampo) y ganglios basales, predominantemente lateralizadas en el hemisferio derecho. Mientras que la administración aguda se asocia a hiperactivación en estas regiones, que también tienden a activarse en experimentos de inducción de craving, durante la abstinencia permanecen hipoactivadas o se evidencian cambios estructurales.La funcionalidad de estas regiones se corresponde con los deficits neuropsicológicos observados en individuos drogodependientes; incluyendo alteraciones de la motivación por reforzadores naturales, el procesamiento emocional, la memoria, las funciones ejecutivas y la toma de decisiones.

Introducción: En el presente artículo describimos un estudio piloto utilizando los minicasos, conjuntamente con las clases magistrales, en la docencia de la farmacología. Material y Métodos: Se utilizaron 9 minicasos. Consistían en un texto de 5 líneas con dos preguntas, relacionadas con el tema de la clase magistral. Se entregaban al inicio de ésta y se concedía a los estudiantes 5 minutos al finalizarla para responderlas. La participación era voluntaria. Los textos se corregían y se podía obtener hasta 1 punto adicional a la nota del examen. Se evaluó la opinión de los estudiantes mediante una encuesta diseñada al efecto. Resultados: De los 69 estudiantes matriculados 43 respondieron. Entregaron una media de 7,6 minicasos y puntuaron 7,5 su utilidad para entender mejor la disciplina, 5,9 el grado de dificultad y 7,3 su interés. Sobre las razones en participar, puntuaron 8,5 la posibilidad de obtener el extrabonus, 7,5 el conocer mejor los temas y 6,8 el desafío de resolver el problema. El 67% señaló que habían aumentado su asistencia a las clases magistrales y el 95% que los resolverían sin extrabonus. Todos participarían en experiencias futuras de este tipo. Conclusiones: Los minicasos pueden ser un método eficiente para mejorar la asistencia de los estudiantes a las clases magistrales y mejorar la comprensión de éstas. Introduction: We report here a preliminary study using mini-cases or very short problems in conjunction with traditional lectures for teaching medical students. Material and Methods: We used nine mini-cases in our lectures on pharmacology. Mini-cases consist of a five-line text with two questions on the subject of the lecture. They were delivered just before the lecture, and students were given five minutes to answer the questions at the end. Teachers evaluated their correctness and were able to award up to 1 extra point to the overall mark in the regular exam. At the end of term the experience was evaluated by asking students to answer ten questions anonymously. Results: Forty-three (out of 69) answered the questionnaire. They handed in a mean of 7.6 mini-cases and gave a mean score of 7.5 for their usefulness in understanding the subject better, 5.9 for the degree of difficulty and 7.3 for their interest. When asked about their reasons for taking part, they scored 8.5 for the possibility of obtaining an extra mark, 7.5 for the idea that they would understand the subjects better and 6.8 for the challenge of solving the problem. Around 67% reported that mini-cases increased attendance at lectures and 95% said they World participate even if extra marks were not available. All participants reported that they would participate in similar experiences in the future. Conclusion: We conclude that mini-cases may be a cost-effective method for improving students' attendance at lectures, as well as their understanding.

7 pages, 3 figures, 3 tables.-- PMID: 12569443 [PubMed].-- Printed version published Feb 28, 2003., 3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) is consumed as the racemate but some metabolic steps are enantioselective. In addition, chiral properties are preserved during MDMA biotransformation. A quantitative analytical methodology using gas chromatography/mass spectrometry (GC/MS) to determine enantioselective disposition in the body of MDMA and its main metabolites including 3,4-methylenedioxyamphetamine (MDA), 4-hydroxy-3-methoxymethamphetamine (HMMA), and 4-hydroxy-3-methoxyamphetamine (HMA) was developed. Plasma and urine samples were collected from a male volunteer. The analysis of MDMA, MDA, and 4-hydroxy-3-methoxy metabolites by GC/MS required a two-step derivatization procedure. The first step consisted of derivatization of the amine with enantiomerically pure Mosher's reagent ((R)-MTPCl). Triethylamine was used as a base to neutralize hydrochloric acid formed during the reaction allowing quantitative derivatization, which resulted in a substantial improvement in the sensitivity of the method compared with other previously described techniques. Further treatment with ammonium hydroxide was required since both amine and hydroxyl groups underwent derivatization in the reaction. Ammonium hydroxide breaks bonds formed with hydroxyl groups without affecting amine derivatives. The second derivatization step using hexamethyldisilazane was needed for metabolites containing phenol residues. This derivatization method permitted the stereochemically specific study of MDMA and its main monohydroxylated metabolites by GC/MS. A detailed study of the chemical reactions involved in the derivatization steps was indispensable to develop a straightforward, sensitive, and reproducible method for the analysis of the parent drug compound and its metabolites., This study was funded by research grants FIS 98/0181, FIS 01/1336, and CIRIT 2001SGR00407.

Simple Summary UR-144 is a synthetic cannabinoid found in herbal incenses for recreational use as a substitute of cannabis. It is a cannabinoid receptor agonist with effects on the central nervous system similar to those of THC. Several cases of intoxication involving UR-144 consumption have been reported. An observational study was carried out to assess UR-144 acute pharmacological effects in comparison with cannabis measuring biomarkers of disposition in oral fluid. Both UR-144 and THC increased blood pressure and heart rate. THC induced stimulant-like and high effects significantly more than those of UR-144 and the two parent drugs could be measured in oral fluid as biomarkers of consumption within 3 h following smoking of the substance. Abstract Synthetic cannabinoids (SCs) are one of the most frequent classes of new psychoactive substances monitored by the EU Early Warning System and World Health Organization. UR-144 is a SC with a relative low affinity for the CB1 receptor with respect to that for the CB2 receptor. As with other cannabinoid receptor agonists, it has been monitored by the EU Early Warning System since 2012 for severe adverse effects on consumers. Since data for UR-144 human pharmacology are very limited, an observational study was carried out to evaluate its acute pharmacological effects following its administration using a cannabis joint as term of comparison. Disposition of UR-144 and delta-9-tetrahydrocannibinol (THC) was investigated in oral fluid. Sixteen volunteers smoked a joint prepared with tobacco and 1 or 1.5 mg dose of UR-144 (n = 8) or cannabis flowering tops containing 10 or 20 mg THC (n = 8). Physiological variables including systolic and diastolic blood pressure, heart rate and cutaneous temperature were measured. A set of Visual Analog Scales (VAS), the Addiction Research Centre Inventory (ARCI)-49-item short form version and the Evaluation of the Subjective Effects of Substances with Abuse Potential (VESSPA-SSE) were administered to evaluate subjective effects. Oral fluid was collected at baseline, 10, 20, 40 min and 1, 2, 3 and 4 h after smoking, for UR-144 or THC concentration monitoring. Results showed significant statistical increases in both systolic and diastolic blood pressure and heart rate after both UR-144 and cannabis smoking. Both substances produced an increase in VAS related to stimulant-like and high effects, but scores were significantly higher after cannabis administration. No hallucinogenic effects were observed. Maximal oral fluid UR-144 and THC concentrations appeared at 20 and 10 min after smoking, respectively. The presence of UR-144 in oral fluid constitutes a non-invasive biomarker of SC consumption. The results of this observational study provide valuable preliminary data of the pharmacological effects of UR-144, showing a similar profile of cardiovascular effects in comparison with THC but lower intensity of subjective effects. Our results have to be confirmed by research in a larger sample to extensively clarify pharmacological effects and the health risk profile of UR-144.

The consumption of synthetic cannabinoids (SCs) has significantly increased in the last decade and the analysis of SCs and their metabolites in human specimens is gaining interest in clinical and forensic toxicology. A pilot study has been carried out using a combination of an initial last generation gas chromatography-mass spectrometry (GC-MS) screening method for the determination of JWH-122, JWH-210, UR-144) in oral fluid (OF) of consumers and an ultra-high performance liquid chromatography high resolution mass spectrometry (UHPLC-HRMS) confirmatory method for the quantification of the parent compounds and their metabolites in the same biological matrix. OF samples were simply liquid-liquid extracted before injecting in both chromatographic systems. The developed methods have been successfully validated and were linear from limit of quantification (LOQ) to 50 ng/mL OF. Recovery of analytes was always higher than 70% and matrix effect always lower than 15% whereas intra-assay and inter-assay precision and accuracy were always better than 16%. After smoking 1 mg JWH-122 or UR-144 and 3 mg JWH-210, maximum concentration of 4.00&ndash, 3.14 ng/mL JWH-122, 8.10&ndash, 7.30 ng/mL JWH-210 ng/mL and 7.40 and 6.81 ng/mL UR-144 were measured by GC-MS and UHPLC-HRMS respectively at 20 min after inhalation. Metabolites of JWH 122 and 210 were quantified in OF by UHPLC-HRMS, while that of UR144 was only detectable in traces. Our results provide for the first time information about disposition of these SCs and their metabolites in consumers OF. Last generation GC-MS has proven useful tool to identify and quantify parent SCs whereas UHPLC-HRMS also confirmed the presence of SCs metabolites in the OF of SCs consumers.

Previous research has shown that a single dose of MDMA induce a dissociative state, by elevating feelings of depersonalization and derealization. Typically, it is assumed that action on the 5-HT2A receptor is the mechanism underlying these psychedelic experiences. In addition, other studies have shown associations between dissociative states and biological parameters (heart rate, cortisol), which are elevated by MDMA. In order to investigate the role of the 5-HT2 receptor in the MDMA-induced dissociative state and the association with biological parameters, a placebo-controlled within-subject study was conducted including a single oral dose of MDMA (75 mg), combined with placebo or a single oral dose of the 5-HT2 receptor blocker ketanserin (40 mg). Twenty healthy recreational MDMA users filled out a dissociative states scale (CADSS) 90 min after treatments, which was preceded and followed by assessment of a number of biological parameters (cortisol levels, heart rate, MDMA blood concentrations). Findings showed that MDMA induced a dissociative state but this effect was not counteracted by pre-treatment with ketanserin. Heart rate was the only biological parameter that correlated with the MDMA-induced dissociative state, but an absence of correlation between these measures when participants were pretreated with ketanserin suggests an absence of directional effects of heart rate on dissociative state. It is suggested that the 5-HT2 receptor does not mediate the dissociative effects caused by a single dose of MDMA. Further research is needed to determine the exact neurobiology underlying this effect and whether these effects contribute to the therapeutic potential of MDMA.