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Se presenta el caso de un varón de 66años remitido por uveítis posterior con edema macular quístico recurrente en relación con posible enfermedad de Lyme previamente tratada. Debido a la recurrencia del edema macular pese al tratamiento corticoideo sistémico y local con dexametasona intravítrea, se instaura tratamiento biológico con adalimumab. Durante el seguimiento el paciente desarrolla lesiones subretinianas bilaterales compatibles con linfoma vitreorretiniano, por lo que se realiza vitrectomía, confirmando el diagnóstico de linfoma de célulaB grande.Se inicia tratamiento con quimioterapia sistémica con BRAM (carmustina, metotrexato, ara-C y rituximab), con buena respuesta. Dos años después, el paciente permanece sin recurrencias a nivel ocular ni sistémico.El linfoma vitreorretiniano es un tipo poco frecuente de linfoma primario del sistema nervioso central. El diagnóstico se ve frecuentemente retrasado debido a la inespecificidad de su sintomatología, que simula una uveítis posterior crónica; de ahí la importancia de la sospecha diagnóstica. (AU)
A 66-year-old man with posterior uveitis and recurrent cystic macular edema related to possible previously treated Lyme disease is presented. Due to the recurrence of macular edema despite systemic and local corticosteroid treatment with intravitreal dexamethasone, biological treatment with adalimumab was established. During follow-up, the patient developed bilateral subretinal lesions compatible with vitreoretinal lymphoma, so vitrectomy was performed, confirming the diagnosis of large B-cell lymphoma.Treatment with systemic chemotherapy with BRAM (carmustine, metotrexate, ara C, and rituximab) was started with a good answer. Two years later, the patient remains without ocular or systemic recurrences.Vitreoretinal lymphoma is a rare type of primary central nervous system lymphoma. The diagnosis is frequently delayed due to the nonspecific symptoms, which mimic chronic posterior uveitis, hence the importance with a diagnostic suspicion. (AU)
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Humanos , Masculino , Anciano , Neoplasias de la Retina/diagnóstico , Linfoma de Células B/diagnóstico , Cirugía VitreorretinianaRESUMEN
Introducción La desnutrición y la sarcopenia se asocian al aumento del riesgo de eventos adversos y peor evolución en los pacientes hospitalizados. La ecografía constituye una herramienta de utilidad en la evaluación de la composición corporal. Pacientes y métodos Se reclutaron 23 pacientes ingresados en una planta de hospitalización. Se recogieron las variables ecográficas del tejido muscular y tejido adiposo, así como su variación durante el ingreso. Correlacionándose con datos antropométricos, clínicos y analíticos. Resultados Observamos una correlación de las mediciones ecográficas con la duración de la hospitalización (grasa preperitoneal máxima: −0,585, grosor del recto femoral [RF]: −0,539, área del RF: −0,540), la fragilidad (RF: −0,599) y la dependencia (RF: 0,628). La capacidad de contracción del RF se correlacionó con el ejercicio semanal reportado (0,642). Conclusión El grosor del RF y de la grasa preperitoneal se correlacionan con el número de días de ingreso y la capacidad funcional, erigiéndose como variables pronósticas (AU)
Introduction Malnutrition and sarcopenia are associated with increased risk of adverse events and worse outcome in hospitalised patients. Ultrasonography is a useful tool in the assessment of body composition. Patients and methods Twenty-three patients admitted to a hospital ward were recruited. Ultrasonographic variables of muscle tissue and adipose tissue were collected, as well as their variation during admission. These were correlated with anthropometric, clinical and analytical data. Results We observed a correlation of ultrasound measurements with length of hospitalisation (maximum preperitoneal fat −0.585, rectus femoris thickness [RF] −0.539, RF area −0.540), frailty (RF −0.599) and dependency (RF 0.628). RF contractile capacity correlated with reported weekly exercise (0.642). Conclusion RF and preperitoneal fat thickness correlate with the number of days of admission and functional capacity, emerging as prognostic variables (AU)
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Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Evaluación Nutricional , Sarcopenia/diagnóstico por imagen , Obesidad/diagnóstico por imagen , Tejido Adiposo/diagnóstico por imagen , Hospitalización , Factores de Riesgo , Pronóstico , Ultrasonografía , Estudios ProspectivosRESUMEN
A 66-year-old man with posterior uveitis and recurrent cystic macular edema related to possible previously treated Lyme disease is presented. Due to the recurrence of macular edema despite systemic and local corticosteroid treatment with intravitreal dexamethasone, biological treatment with Adalimumab was established. During follow-up, the patient developed bilateral subretinal lesions compatible with Vitreoretinal Lymphoma (VRL), so vitrectomy was performed, confirming the diagnosis of large B-cell lymphoma. Treatment with systemic chemotherapy with BRAM-Carmustine, Metrotexate, Ara C, and Rituximab was started with a good answer. Two years later, the patient remains without ocular or systemic recurrences. Vitreoretinal Lymphoma is a rare type of primary central nervous system lymphoma. The diagnosis is frequently delayed due to the nonspecific symptoms, which mimic chronic posterior uveitis, hence the importance with a diagnostic suspicion.
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Neoplasias del Ojo , Linfoma de Células B Grandes Difuso , Edema Macular , Neoplasias de la Retina , Uveítis Posterior , Masculino , Humanos , Anciano , Neoplasias de la Retina/patología , Cuerpo Vítreo , Edema Macular/diagnóstico , Edema Macular/etiología , Neoplasias del Ojo/diagnóstico , Neoplasias del Ojo/patología , Linfoma de Células B Grandes Difuso/diagnóstico por imagen , Linfoma de Células B Grandes Difuso/cirugíaRESUMEN
INTRODUCTION: Malnutrition and sarcopenia are associated with increased risk of adverse events and worse outcome in hospitalised patients. Ultrasonography is a useful tool in the assessment of body composition. PATIENTS AND METHODS: Twenty-three patients admitted to a hospital ward were recruited. Ultrasonographic variables of muscle tissue and adipose tissue were collected, as well as their variation during admission. These were correlated with anthropometric, clinical and analytical data. RESULTS: We observed a correlation of ultrasound measurements with length of hospitalisation (maximum preperitoneal fat -0.585, rectus femoris thickness - RF -0.539, RF area -0.540), frailty (RF -0.599) and dependency (RF 0.628). RF contractile capacity correlated with reported weekly exercise (0.642). CONCLUSION: RF and preperitoneal fat thickness correlate with the number of days of admission and functional capacity, emerging as prognostic variables.
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Músculo Cuádriceps , Sarcopenia , Humanos , Músculo Cuádriceps/diagnóstico por imagen , Evaluación Nutricional , Sarcopenia/diagnóstico por imagen , Tejido Adiposo/diagnóstico por imagen , UltrasonografíaRESUMEN
To analyze the clinical characteristics and outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with sarcoidosis from a large multicenter cohort from Southern Europe and to identify the risk factors associated with a more complicated infection. We searched for patients with sarcoidosis presenting with SARS-CoV-2 infection (defined according to the European Centre for Disease Prevention and Control guidelines) among those included in the SarcoGEAS Registry, a nationwide, multicenter registry of patients fulfilling the American Thoracic Society/European Respiratory Society/World Association of Sarcoidosis and Other Granulomatous Disorders 1999 classification criteria for sarcoidosis. A 2:1 age-sex-matched subset of patients with sarcoidosis without SARS-CoV-2 infection was selected as control population. Forty-five patients with SARS-CoV-2 infection were identified (28 women, mean age 55 years). Thirty-six patients presented a symptomatic SARS-CoV-2 infection and 14 were hospitalized (12 required supplemental oxygen, 2 intensive care unit admission and 1 mechanical ventilation). Four patients died due to progressive respiratory failure. Patients who required hospital admission had an older mean age (64.9 vs. 51.0 years, p = 0.006), a higher frequency of baseline comorbidities including cardiovascular disease (64% vs. 23%, p = 0.016), diabetes mellitus (43% vs. 13%, p = 0.049) and chronic liver/kidney diseases (36% vs. 0%, p = 0.002) and presented more frequently fever (79% vs. 35%, p = 0.011) and dyspnea (50% vs. 3%, p = 0.001) in comparison with patients managed at home. Age- and sex-adjusted multivariate analysis identified the age at diagnosis of SARS-Cov-2 infection as the only independent variable associated with hospitalization (adjusted odds ratio 1.18, 95% conficence interval 1.04-1.35). A baseline moderate/severe pulmonary impairment in function tests was associated with a higher rate of hospitalization but the difference was not statistically significant (50% vs. 23%, p = 0.219). A close monitoring of SARS-CoV-2 infection in elderly patients with sarcoidosis, especially in those with baseline cardiopulmonary diseases and chronic liver or renal failure, is recommended. The low frequency of severe pulmonary involvement in patients with sarcoidosis from Southern Europe may explain the weak prognostic role of baseline lung impairment in our study, in contrast to studies from other geographical areas.
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COVID-19/complicaciones , Sarcoidosis/complicaciones , Adulto , Anciano , Anciano de 80 o más Años , COVID-19/mortalidad , COVID-19/fisiopatología , COVID-19/terapia , Estudios de Cohortes , Comorbilidad , Femenino , Francia , Hospitalización/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Sistema de Registros , Sarcoidosis/mortalidad , Sarcoidosis/fisiopatología , Sarcoidosis/terapia , Resultado del TratamientoRESUMEN
The adolescent brain displays high vulnerability to the deleterious effects of ethanol, including greater risk of developing alcohol use disorder later in life. Here, we characterized the gene expression of the endocannabinoid system (ECS) and relevant signaling systems associated with neuroinflammation and emotional behaviors in the brain of young adult control and ethanol-exposed (EtOH) rats. We measured mRNA levels of candidate genes using quantitative real time PCR in the medial prefrontal cortex (mPFC), amygdala and hippocampus. EtOH rats were generated by maintenance on an intermittent and voluntary ethanol consumption during adolescence using the two-bottle choice paradigm (4 days/week for 4 weeks) followed by 2 week-withdrawal, a time-point of withdrawal with no physical symptoms. Mean differences and effect sizes were calculated using t-test and Cohen's d values. In the mPFC and hippocampus, EtOH rats had significantly higher mRNA expression of endocannabinoid-signaling (mPFC: Ppara, Dagla, Daglb and Napepld; and hippocampus: Cnr2, Dagla and Mgll) and neuroinflammation-associated genes (mPFC: Gfap; and hippocampus: Aif1) than in controls. Moreover, EtOH rats had significantly higher mRNA expression of neuropeptide Y receptor genes (Npy1r, Npy2r and Npy5r) in the hippocampus. Finally, EtOH rats also displayed higher plasma endocannabinoid levels than controls. In conclusion, these results suggest that adolescent ethanol exposure can lead to long-term alterations in the gene expression of the ECS and other signaling systems involved in neuroinflammation and regulation of emotional behaviors in key brain areas for the development of addiction.
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Consumo de Bebidas Alcohólicas/efectos adversos , Depresores del Sistema Nervioso Central/efectos adversos , Endocannabinoides/genética , Endocannabinoides/metabolismo , Etanol/efectos adversos , Mediadores de Inflamación/metabolismo , Animales , Ansiedad/psicología , Emociones , Expresión Génica/efectos de los fármacos , Masculino , Memoria/efectos de los fármacos , Actividad Motora/efectos de los fármacos , Psicología del Adolescente , Desempeño Psicomotor/efectos de los fármacos , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Ratas , Ratas Wistar , Receptores de Neuropéptido Y/efectos de los fármacos , Receptores de Neuropéptido Y/genética , Receptores de Neuropéptido Y/metabolismoRESUMEN
No disponible
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Humanos , Femenino , Persona de Mediana Edad , Carbón Orgánico/administración & dosificación , Cianamida/envenenamiento , Imagen por Resonancia Magnética , Síndrome de Leucoencefalopatía Posterior/diagnóstico por imagen , Alcoholismo/tratamiento farmacológico , Ceguera Cortical/etiología , Edema Encefálico/etiología , Unidades de Cuidados IntensivosAsunto(s)
Carbón Orgánico/administración & dosificación , Cianamida/envenenamiento , Imagen por Resonancia Magnética , Síndrome de Leucoencefalopatía Posterior/diagnóstico por imagen , Alcoholismo/tratamiento farmacológico , Ceguera Cortical/etiología , Edema Encefálico/etiología , Femenino , Humanos , Unidades de Cuidados Intensivos , Persona de Mediana EdadRESUMEN
INTRODUCTION: The Multidimensional Weight Locus of Control Scale (MWLCS) measures a person's beliefs regarding the locus of control or lack of locus of control over his/her body weight. PURPOSE: We aim to evaluate the factorial structure and psychometric properties of the MWLCS with Spanish normal weight, overweight and obese samples. METHODS: The research was carried out in two different studies. The first included a sample of 140 normal weight participants, selected out of a 274 sample recruited with an online survey. Study 2 was carried out in a sample of 633 participants recruited from the PREDIMED-Plus study. Out of them, 558 participants fulfilled the weight criteria and were categorized into: overweight (BMI 25 - < 29.99; N = 170), obese class I (BMI 30 - < 34.99; N = 266), and obese class II (BMI 35 - < 39.99; N = 122). Exploratory (EFA) and confirmatory (CFA) factor analyses were used to evaluate the factor structure of the MWLCS, and reliabilities and Spearman's correlations were estimated. Invariance measurement was tested across the three subgroups of weight in Study 2. RESULTS: A three-factor structure indicating weight locus of control factors (internal, chance, and powerful others) was supported, both via EFA in the normal weight sample and CFA in the overweight and obese samples. In the normal weight sample, the powerful others dimension was positively related to BMI and the dimensions of the Dutch Eating Behaviors Questionnaire. Additionally, the scale showed evidence of scalar invariance across the groups with different weight conditions. CONCLUSIONS: This scale seems to be a psychometrically appropriate instrument and its use is highly recommended when designing interventions for overweight or obese individuals. LEVEL OF EVIDENCE: Level V, descriptive study.
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Control Interno-Externo , Estado Nutricional , Peso Corporal , Femenino , Humanos , Masculino , Psicometría , Reproducibilidad de los Resultados , Encuestas y CuestionariosRESUMEN
BACKGROUND: To analyze the association between Scadding radiological stages of sarcoidosis at diagnosis and the disease phenotype (epidemiology, clinical presentation and extrathoracic involvement) in one of the largest cohorts of patients with sarcoidosis reported from southern Europe. METHODS: The SARCOGEAS-Study Group includes a multicenter database of consecutive patients diagnosed with sarcoidosis according to the WASOG 1999 criteria. Extrathoracic disease at diagnosis was defined according to the 2014 instrument and the clusters proposed by Schupp et al. RESULTS: We analyzed 1230 patients (712 female, mean age 47â¯yrs.) who showed the following Scadding radiologic stages at diagnosis: stage 0 (nâ¯=â¯98), stage I (nâ¯=â¯395), stage II (nâ¯=â¯500), stage III (nâ¯=â¯195) and stage IV (nâ¯=â¯42). Women were overrepresented in patients presenting with extrathoracic/extrapulmonary disease, while the diagnosis was made at younger ages in patients presenting with BHL, and at older ages in those presenting with pulmonary fibrosis (q values <0.05). Multivariable adjusted analysis showed that patients presenting with pulmonary involvement (especially those with stages II and III) had a lower frequency of concomitant systemic involvement in some specific extrathoracic clusters (cutaneous-adenopathic/musculoskeletal, ENT and neuro-ocular/OCCC) but a higher frequency for others (hepatosplenic), in comparison with patients with extrapulmonary involvement (stages 0 and I). The presence of either BHL or fibrotic lesions did not influence the systemic phenotype of patients with pulmonary involvement. CONCLUSIONS: The key determinant associated with a differentiated systemic phenotype of sarcoidosis at diagnosis was interstitial pulmonary involvement rather than the individual Scadding radiological stage.
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Sarcoidosis/diagnóstico por imagen , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fenotipo , Radiografía , Sarcoidosis/complicaciones , Sarcoidosis/genéticaRESUMEN
Optimal autophagic activity is crucial to maintain muscle integrity, with either reduced or excessive levels leading to specific myopathies. LGMD2H is a muscle dystrophy caused by mutations in the ubiquitin ligase TRIM32, whose function in muscles remains not fully understood. Here, we show that TRIM32 is required for the induction of muscle autophagy in atrophic conditions using both in vitro and in vivo mouse models. Trim32 inhibition results in a defective autophagy response to muscle atrophy, associated with increased ROS and MuRF1 levels. The proautophagic function of TRIM32 relies on its ability to bind the autophagy proteins AMBRA1 and ULK1 and stimulate ULK1 activity via unanchored K63-linked polyubiquitin. LGMD2H-causative mutations impair TRIM32's ability to bind ULK1 and induce autophagy. Collectively, our study revealed a role for TRIM32 in the regulation of muscle autophagy in response to atrophic stimuli, uncovering a previously unidentified mechanism by which ubiquitin ligases activate autophagy regulators.
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Homólogo de la Proteína 1 Relacionada con la Autofagia/metabolismo , Autofagia , Ubiquitina-Proteína Ligasas/genética , Proteínas Adaptadoras Transductoras de Señales/antagonistas & inhibidores , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Animales , Línea Celular , Transdiferenciación Celular , Humanos , Lisina/metabolismo , Ratones , Ratones Noqueados , Distrofia Muscular de Cinturas/metabolismo , Distrofia Muscular de Cinturas/patología , Mioblastos/citología , Mioblastos/metabolismo , Unión Proteica , Interferencia de ARN , ARN Interferente Pequeño/metabolismo , Ubiquitina-Proteína Ligasas/antagonistas & inhibidores , Ubiquitina-Proteína Ligasas/metabolismo , UbiquitinaciónRESUMEN
The growing number of road vehicles is a major source of regional and global atmospheric pollution increasing concentrations of CO2 in the air, and levels of metals in air and soil. Nevertheless, the effects of these pollutants on plants growing at roadsides are poorly documented. We carried out an observational study of unmanipulated plants growing by the road, to identify the morpho-physiological responses in a perennial grass Dactylis glomerata. Firstly, we wanted to know the general effect of traffic intensity and ambient CO2 and its interactions on different plant traits. Accordingly, we analyzed the photosynthetic response by field A/Ci Response Curves, SLA, pigment pools, foliar nitrogen, carbohydrates and morphological traits in plants at three distances to the road. Secondly, we wanted to know if Dactylis glomerata plants can accumulate metals present on the roadside (Pb, Zn, Cu, and Sr) in their tissues and rhizosphere, and the effect of these metals on morphological traits. The MANCOVA whole model results shown: 1) a significant effect of road ambient CO2 concentration on morphological traits (not affected by traffic intensity, P interaction CO2 x traffic intensity>0.05), that was mainly driven by a significant negative relationship between the inflorescence number and ambient CO2; 2) a positive and significant relationship between ambient CO2 and the starch content in leaves (unaffected by traffic intensity); 3) a reduction in Jmax (electron transport rate) at high traffic intensity. These lines of evidences suggest a decreased photosynthetic capacity due to high traffic intensity and high levels of ambient CO2. In addition, Pb, Cu, Zn and Sr were detected in Dactylis glomerata tissues, and Cu accumulated in roots. Finally, we observed that Dactylis glomerata individuals growing at the roadside under high levels of CO2 and in the presence of metal pollutants, reduced their production of inflorescences.
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Dactylis/metabolismo , Emisiones de Vehículos , Dactylis/crecimiento & desarrollo , Monitoreo del Ambiente , Suelo , Contaminantes del Suelo/farmacocinéticaRESUMEN
MDMA exerts its main effects via the serotonergic system and the serotonin transporter. The gene coding for this transporter determines the expression rate of the transporter. Previously it was shown that healthy individuals with the short allelic variant ('s-group') of the 5-HTTLPR-polymorphism displayed more anxiety and negative mood, and had a lower transcriptional efficiency compared to individuals who are homozygous for the l-allele ('l-group'). The present study aimed to investigate the role of the 5-HTTLPR polymorphism in MDMA-induced mood effects. Four placebo-controlled, within-subject studies were pooled, including in total 63 polydrug ecstasy users (Ns-group = 48; Nl-group = 15) receiving MDMA 75 mg and placebo on two test days, separated by minimally 7 days. Mood was assessed by means of the Profile of Mood States. Findings showed that MDMA induced -independent of sex- a positive mood state, and as a side effect also increased two negative affect states, anxiety and confusion. Anxiety ratings were higher in the l-group and independent of treatment or sex. Depression ratings were lowered by MDMA in the female l-group. Findings indicate that the MDMA-induced reduction in self-rated depressive feelings is sex- and genotype-dependent, with females homozygous for the l-allele showing this beneficial effect.
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Afecto/efectos de los fármacos , Alelos , Depresión/etiología , Depresión/psicología , Consumidores de Drogas , N-Metil-3,4-metilenodioxianfetamina/efectos adversos , Proteínas de Transporte de Serotonina en la Membrana Plasmática/genética , Adolescente , Adulto , Femenino , Predisposición Genética a la Enfermedad , Homocigoto , Humanos , Adulto JovenRESUMEN
Experiments (Exp) I and II were conducted to compare raw whole soya beans (WSB), roasted (rWSB) or other protein sources as supplements of low-quality forages fed ad libitum to beef cattle, upon DM intake (DMI), ruminal and blood parameters, and animal performance. Exp I: treatments for wheat straw fed to four ruminally cannulated steers were (i) Control-WS: no supplement; (ii) WSB-WS: whole soya beans; (iii) rWSB-WS: roasted WSB; and (iv) SBM-WS: soybean meal-wheat midds mixture; all fed at 1.4 kg DM/day. Exp II: 12 steers grazed deferred grain sorghum (DS) receiving these treatments: (i) Control-DS: no supplement; (ii) WSB-DS: 1.26 kg DM/day whole soya beans; and (iii) SFM-DS: 1.35 kg DM/day of sunflower meal. In Exp I, WS DMI resulted 47, 52 and 41% greater for WSB-WS, rWSB-WS and SBM-WS, respectively, than Control-WS (p < .05). In Exp II, the DMI of DS was unaffected by supplementation; a substitution of DS by supplement was found for WSB-DS (p < .05); however, total diet and digestible DMI increased with supplementation (p < .05). Rumen pH in Exp I remained unaffected by supplementation, but N-NH3 as well as blood urea-N in Exp II increased (p < .05). In Exp II, average daily weight gains improved similarly with both supplements compared with Control-DS. Additionally, feed-to-gain ratio decreased (p < .05), being lower for WSB-DS (8.3) vs. SFM-DS (9.9). Roasting effects of WSB as a supplement for low-quality forages were not detected, and all protein sources increased total diet DMI and forage utilization. Only moderate cattle weight gains could be expected for unsupplemented DS.
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Alimentación Animal/análisis , Dieta/veterinaria , Suplementos Dietéticos , Glycine max/química , Valor Nutritivo , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Bovinos , Proteínas en la Dieta , Digestión/fisiología , Masculino , Rumen/fisiologíaRESUMEN
BACKGROUND: MDMA has been shown to induce feelings of sociability, a positive emotional bias and enhanced empathy. While previous research has used only visual emotional stimuli, communication entails more than that single dimension and it is known that auditory information is also crucial in this process. In addition, it is, however, unclear what the neurobiological mechanism underlying these MDMA effects on social behaviour is. Previously, studies have shown that MDMA-induced emotional excitability and positive mood are linked to the action on the serotonin (5-HT) 2A receptor. AIM: The present study aimed at investigating the effect of MDMA on processing of sounds (Processing of Affective Sounds Task (PAST)) and cognitive biases (Approach-Avoidance Task (AAT)) towards emotional and social stimuli and the role of 5-HT2A receptor in these effects. METHODS: Twenty healthy recreational users entered a 2 × 2, placebo-controlled, within-subject study with ketanserin (40 mg) as pre-treatment and MDMA (75 mg) as treatment. Behavioural (PAST, AAT) measures were conducted 90 min after treatment with MDMA, respectively, 120 min after ketanserin. Self-report mood measures and oxytocin concentrations were taken at baseline and before and after behavioural tests. RESULTS: Findings showed that MDMA reduced arousal elicited by negative sounds. This effect was counteracted by ketanserin pre-treatment, indicating involvement of the 5-HT2 receptor in this process. MDMA did not seem to induce a bias towards emotional and social stimuli. It increased positive and negative mood ratings and elevated oxytocin plasma concentrations. The reduction in arousal levels when listening to negative sounds was not related to the elevated subjective arousal. CONCLUSION: It is suggested that this decrease in arousal to negative stimuli reflects potentially a lowering of defences, a process that might play a role in the therapeutic process.
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Estimulación Acústica/efectos adversos , Apatía/fisiología , N-Metil-3,4-metilenodioxianfetamina/farmacología , Receptor de Serotonina 5-HT2A/fisiología , Serotoninérgicos/farmacología , Sonido/efectos adversos , Estimulación Acústica/psicología , Adulto , Afecto/efectos de los fármacos , Afecto/fisiología , Apatía/efectos de los fármacos , Método Doble Ciego , Emociones/efectos de los fármacos , Emociones/fisiología , Femenino , Humanos , Masculino , AutoinformeRESUMEN
BACKGROUND: Preclinical data have suggested involvement of the endocannabinoid (eCB) system in MDMA-induced memory impairment. Clinical research has shown that blockade of the 5-HT2 receptor nulls memory impairment during MDMA intoxication. Interestingly, studies have demonstrated that the eCB and the 5-HT system interact. It was hypothesized that MDMA would cause an increase in eCB concentrations together with a decrease in memory performance, and that combining MDMA with a 5-HT2 receptor blocker ketanserin would lead to a counteraction of the MDMA effects on eCB concentrations and memory. METHODS: Twenty healthy recreational polydrug users entered a double-blind placebo-controlled within-subject study. Participants received a pre-treatment (ketanserin 40 mg, placebo) followed 30 min later by a treatment (MDMA 75 mg, placebo). Verbal memory was tested by means of a 30-word learning test. Endocannabinoid concentrations (anandamide (2-AG); N-arachidonylethanolamine (AEA)) were assessed in blood at baseline, before (90 min post-treatment) and after cognitive tests (150 min post-treatment). RESULTS: Findings showed that MDMA impaired memory 90 min post-treatment in the word learning task. This effect was a replication of previous studies using the same dose of MDMA (75 mg) and the same learning paradigm. Contrary to our hypothesis, MDMA did not affect eCB concentrations, nor did ketanserin block MDMA-induced memory impairment. Ketanserin caused an increase in AEA concentrations, 180 min after administration. CONCLUSION: Current findings suggest that peripherally measured endocannabinoids are not associated with the verbal memory deficit during MDMA intoxication. TRIAL REGISTRATION NUMBER: NTR3691.
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Endocannabinoides/sangre , Trastornos de la Memoria/sangre , Trastornos de la Memoria/inducido químicamente , N-Metil-3,4-metilenodioxianfetamina/toxicidad , Aprendizaje Verbal/efectos de los fármacos , Adulto , Ácidos Araquidónicos/sangre , Ácidos Araquidónicos/farmacología , Método Doble Ciego , Endocannabinoides/farmacología , Femenino , Humanos , Ketanserina/farmacología , Ketanserina/uso terapéutico , Masculino , Trastornos de la Memoria/prevención & control , Alcamidas Poliinsaturadas/sangre , Alcamidas Poliinsaturadas/farmacología , Antagonistas del Receptor de Serotonina 5-HT2/farmacología , Antagonistas del Receptor de Serotonina 5-HT2/uso terapéutico , Serotoninérgicos/toxicidad , Aprendizaje Verbal/fisiología , Adulto JovenRESUMEN
BACKGROUND: Limbal stem cells (LSC) are progenitor cells in the ocular surface that renew the corneal epithelium. Limbal stem cell deficiency usually induces blindness through the loss of corneal transparency, and bilateral cases do not an accurate treatment because of the lack of an autologous source of stem cells. METHODS: Induced pluripotent stem cells (iPSC) are promising for use in cell therapy because of their autologous origin and the capability to differentiate into corneal epithelial cells. However, there are not standardized protocols to achieve a complete corneal epithelial differentiation. We examined the expression of several markers in a human episomal iPSC line after an induction period from embryoid bodies. RESULTS: Progenitor LSC and corneal epithelial differentiation markers, some extracellular matrix protein adhesion molecules, and wingless signaling pathway were studied. Overall, LSC progenitor and corneal epithelium differentiation markers increased after maintaining cell culture in specific conditions for 14 days, whereas pluripotency markers decreased. CONCLUSIONS: Our approach indicated that the optimal time point to initiate iPSC differentiation into LSC and corneal phenotypes, with the use of specific medium, is from 14 days after initial embryoid bodies treatment induction.
Asunto(s)
Técnicas de Cultivo de Célula/métodos , Diferenciación Celular/fisiología , Células Epiteliales/fisiología , Epitelio Corneal/citología , Células Madre Pluripotentes Inducidas/fisiología , Tratamiento Basado en Trasplante de Células y Tejidos/métodos , Células Cultivadas , Enfermedades de la Córnea/cirugía , Trasplante de Córnea/métodos , Células Epiteliales/trasplante , Epitelio Corneal/trasplante , Humanos , Células Madre Pluripotentes Inducidas/trasplante , Limbo de la Córnea/citología , Limbo de la Córnea/fisiopatología , Trasplante de Células Madre/métodosRESUMEN
Methylenedioxypyrovalerone (MDPV) is a new psychostimulant cathinone acting as a selective dopamine transporter blocker. Due to the concomitant consumption of ethanol (EtOH) and new psychoactive substances, it is of interest to explore a possible pharmacological interaction between MDPV and EtOH. In locomotor activity assays, EtOH (1g/kg i.p.) elicited a reduction in the stimulant effect induced by low doses of MDPV (0.1-0.3mg/kg, s.c.) in rats, jointly with a decrease in blood and brain MDPV concentrations. Experiments in rat liver microsomes showed different effects depending on the [MDPV]/[EtOH] relationship, evidencing, at certain concentrations, the enhancing effect of EtOH on MDPV metabolism. These suggest that EtOH interacts with MDPV at microsomal level, increasing its metabolic rate. The interaction between both substances was also supported by results in plasma EtOH concentration, which were significantly increased by MDPV, in such a manner that EtOH elimination rate was significantly reduced. The possible toxicological impact of this phenomenon deserves further investigation. In contrast, the rewarding properties of MDPV were unaltered by EtOH. Microdialysis experiments verified that, in the NAcc, both substances could also act synergistically, in such a manner that extracellular dopamine concentrations are maintained. Finally, if the psychostimulant effect induced by MDPV decreased with EtOH, it could favor the boosting and re-dosing in search of the desired effects. However, as the rewarding effect of each dose of the substance would not decrease, the addictive liability could increase considerably. Moreover, we must warn about the increase in EtOH concentrations when consumed concomitantly with MDPV.
Asunto(s)
Alcaloides/metabolismo , Conducta Animal/efectos de los fármacos , Benzodioxoles/metabolismo , Benzodioxoles/farmacología , Estimulantes del Sistema Nervioso Central/metabolismo , Estimulantes del Sistema Nervioso Central/farmacología , Condicionamiento Clásico/efectos de los fármacos , Interacciones Farmacológicas , Etanol/metabolismo , Etanol/farmacología , Pirrolidinas/metabolismo , Pirrolidinas/farmacología , Animales , Benzodioxoles/administración & dosificación , Estimulantes del Sistema Nervioso Central/administración & dosificación , Etanol/administración & dosificación , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Microdiálisis , Núcleo Accumbens/efectos de los fármacos , Núcleo Accumbens/metabolismo , Pirrolidinas/administración & dosificación , Ratas , Ratas Sprague-Dawley , Cathinona SintéticaRESUMEN
Epidemiologic studies have reported that moderate alcohol consumption is inversely associated with the risk of renal cancer. However, there is no information available on the associations in renal cancer subsites. From 1992 to 2010, 477,325 men and women in the European Prospective Investigation into Cancer and Nutrition cohort were followed for incident renal cancers (n = 931). Baseline and lifetime alcohol consumption was assessed by country-specific, validated dietary questionnaires. Information on past alcohol consumption was collected by lifestyle questionnaires. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated from Cox proportional hazard models. In multivariate analysis, total alcohol consumption at baseline was inversely associated with renal cancer; the HR and 95% CI for the increasing categories of total alcohol consumption at recruitment vs. the light drinkers category were 0.78 (0.62-0.99), 0.82 (0.64-1.04), 0.70 (0.55-0.90), and 0.91 (0.63-1.30), respectively, (ptrend = 0.001). A similar relationship was observed for average lifetime alcohol consumption and for all renal cancer subsites combined or for renal parenchyma subsite. The trend was not observed in hypertensive individuals and not significant in smokers. In conclusion, moderate alcohol consumption was associated with a decreased risk of renal cancer.