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1.
Arch. Soc. Esp. Oftalmol ; 98(12): 718-722, dic. 2023. ilus
Artigo em Espanhol | IBECS | ID: ibc-228147

RESUMO

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)


Assuntos
Humanos , Masculino , Idoso , Neoplasias da Retina/diagnóstico , Linfoma de Células B/diagnóstico , Cirurgia Vitreorretiniana
2.
Arch Soc Esp Oftalmol (Engl Ed) ; 98(12): 718-722, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37813184

RESUMO

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.


Assuntos
Neoplasias Oculares , Linfoma Difuso de Grandes Células B , Edema Macular , Neoplasias da Retina , Uveíte Posterior , Masculino , Humanos , Idoso , Neoplasias da Retina/patologia , Corpo Vítreo , Edema Macular/diagnóstico , Edema Macular/etiologia , Neoplasias Oculares/diagnóstico , Neoplasias Oculares/patologia , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Linfoma Difuso de Grandes Células B/cirurgia
3.
Viruses ; 13(6)2021 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-34071924

RESUMO

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.


Assuntos
COVID-19/complicações , Sarcoidose/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/mortalidade , COVID-19/fisiopatologia , COVID-19/terapia , Estudos de Coortes , Comorbidade , Feminino , França , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Sarcoidose/mortalidade , Sarcoidose/fisiopatologia , Sarcoidose/terapia , Resultado do Tratamento
4.
Eur Neuropsychopharmacol ; 33: 126-138, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32057593

RESUMO

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.


Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Depressores do Sistema Nervoso Central/efeitos adversos , Endocanabinoides/genética , Endocanabinoides/metabolismo , Etanol/efeitos adversos , Mediadores da Inflamação/metabolismo , Animais , Ansiedade/psicologia , Emoções , Expressão Gênica/efeitos dos fármacos , Masculino , Memória/efeitos dos fármacos , Atividade Motora/efeitos dos fármacos , Psicologia do Adolescente , Desempenho Psicomotor/efeitos dos fármacos , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Ratos , Ratos Wistar , Receptores de Neuropeptídeo Y/efeitos dos fármacos , Receptores de Neuropeptídeo Y/genética , Receptores de Neuropeptídeo Y/metabolismo
6.
Eat Weight Disord ; 25(6): 1533-1542, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31605367

RESUMO

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.


Assuntos
Controle Interno-Externo , Estado Nutricional , Peso Corporal , Feminino , Humanos , Masculino , Psicometria , Reprodutibilidade dos Testes , Inquéritos e Questionários
8.
Eur J Intern Med ; 69: 77-85, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31521474

RESUMO

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 47 yrs.) who showed the following Scadding radiologic stages at diagnosis: stage 0 (n = 98), stage I (n = 395), stage II (n = 500), stage III (n = 195) and stage IV (n = 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.


Assuntos
Sarcoidose/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Radiografia , Sarcoidose/complicações , Sarcoidose/genética
9.
Sci Adv ; 5(5): eaau8857, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31123703

RESUMO

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.


Assuntos
Proteína Homóloga à Proteína-1 Relacionada à Autofagia/metabolismo , Autofagia , Ubiquitina-Proteína Ligases/genética , Proteínas Adaptadoras de Transdução de Sinal/antagonistas & inibidores , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Linhagem Celular , Transdiferenciação Celular , Humanos , Lisina/metabolismo , Camundongos , Camundongos Knockout , Distrofia Muscular do Cíngulo dos Membros/metabolismo , Distrofia Muscular do Cíngulo dos Membros/patologia , Mioblastos/citologia , Mioblastos/metabolismo , Ligação Proteica , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Ubiquitina-Proteína Ligases/antagonistas & inibidores , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação
10.
Sci Rep ; 8(1): 1061, 2018 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-29348651

RESUMO

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.


Assuntos
Afeto/efeitos dos fármacos , Alelos , Depressão/etiologia , Depressão/psicologia , Usuários de Drogas , N-Metil-3,4-Metilenodioxianfetamina/efeitos adversos , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Adolescente , Adulto , Feminino , Predisposição Genética para Doença , Homozigoto , Humanos , Adulto Jovem
12.
Psychopharmacology (Berl) ; 235(2): 481-490, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28735368

RESUMO

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.


Assuntos
Estimulação Acústica/efeitos adversos , Apatia/fisiologia , N-Metil-3,4-Metilenodioxianfetamina/farmacologia , Receptor 5-HT2A de Serotonina/fisiologia , Serotoninérgicos/farmacologia , Som/efeitos adversos , Estimulação Acústica/psicologia , Adulto , Afeto/efeitos dos fármacos , Afeto/fisiologia , Apatia/efeitos dos fármacos , Método Duplo-Cego , Emoções/efeitos dos fármacos , Emoções/fisiologia , Feminino , Humanos , Masculino , Autorrelato
13.
Psychopharmacology (Berl) ; 235(3): 709-717, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29143869

RESUMO

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.


Assuntos
Endocanabinoides/sangue , Transtornos da Memória/sangue , Transtornos da Memória/induzido quimicamente , N-Metil-3,4-Metilenodioxianfetamina/toxicidade , Aprendizagem Verbal/efeitos dos fármacos , Adulto , Ácidos Araquidônicos/sangue , Ácidos Araquidônicos/farmacologia , Método Duplo-Cego , Endocanabinoides/farmacologia , Feminino , Humanos , Ketanserina/farmacologia , Ketanserina/uso terapêutico , Masculino , Transtornos da Memória/prevenção & controle , Alcamidas Poli-Insaturadas/sangue , Alcamidas Poli-Insaturadas/farmacologia , Antagonistas do Receptor 5-HT2 de Serotonina/farmacologia , Antagonistas do Receptor 5-HT2 de Serotonina/uso terapêutico , Serotoninérgicos/toxicidade , Aprendizagem Verbal/fisiologia , Adulto Jovem
14.
Transplant Proc ; 49(10): 2292-2295, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29198663

RESUMO

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.


Assuntos
Técnicas de Cultura de Células/métodos , Diferenciação Celular/fisiologia , Células Epiteliais/fisiologia , Epitélio Corneano/citologia , Células-Tronco Pluripotentes Induzidas/fisiologia , Terapia Baseada em Transplante de Células e Tecidos/métodos , Células Cultivadas , Doenças da Córnea/cirurgia , Transplante de Córnea/métodos , Células Epiteliais/transplante , Epitélio Corneano/transplante , Humanos , Células-Tronco Pluripotentes Induzidas/transplante , Limbo da Córnea/citologia , Limbo da Córnea/fisiopatologia , Transplante de Células-Tronco/métodos
15.
Artigo em Inglês | MEDLINE | ID: mdl-28219712

RESUMO

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.


Assuntos
Alcaloides/metabolismo , Comportamento Animal/efeitos dos fármacos , Benzodioxóis/metabolismo , Benzodioxóis/farmacologia , Estimulantes do Sistema Nervoso Central/metabolismo , Estimulantes do Sistema Nervoso Central/farmacologia , Condicionamento Clássico/efeitos dos fármacos , Interações Medicamentosas , Etanol/metabolismo , Etanol/farmacologia , Pirrolidinas/metabolismo , Pirrolidinas/farmacologia , Animais , Benzodioxóis/administração & dosagem , Estimulantes do Sistema Nervoso Central/administração & dosagem , Etanol/administração & dosagem , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Microdiálise , Núcleo Accumbens/efeitos dos fármacos , Núcleo Accumbens/metabolismo , Pirrolidinas/administração & dosagem , Ratos , Ratos Sprague-Dawley , Catinona Sintética
16.
Urol Oncol ; 35(3): 117, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28159493

RESUMO

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.


Assuntos
Consumo de Bebidas Alcoólicas , Neoplasias Renais , Feminino , Humanos , Masculino , Estado Nutricional , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco
17.
Sci Rep ; 6: 30820, 2016 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-27476477

RESUMO

Whether the executive profile is different between obesity (OB) and morbid obesity (MO) remains unclear. Recent evidence suggests that physical activity (PA) can act as a cognitive enhancer. Irisin is a recently discovered hormone associated with some of the positive effects of PA. The objective of the study was to investigate the executive profile in OB and MO, and to explore the role of PA and irisin. 114 participants were included (21 OB, 44 MO and 49 healthy controls-HC) in the study and assessed with the Wisconsin Card Sorting Test, Stroop Color and Word Test, and Iowa Gambling Task. All participants were female, aged between 18 and 60 years. Results showed a similar dysfunctional profile on decision making in OB and MO compared with HC. Thus, no specific neuropsychological profiles between OB and MO can be clearly observed in our sample. However, a negative correlation was found between irisin and executive functioning. These results demonstrate a specific executive profile in OB and a relevant and negative modulation of irisin on executive functioning. Although irisin might be a promising target for the treatment of obesity, its effects on cognition might be considered when thinking about its therapeutic use.


Assuntos
Exercício Físico , Fibronectinas/metabolismo , Obesidade Mórbida , Adolescente , Adulto , Tomada de Decisões , Feminino , Humanos , Pessoa de Meia-Idade , Obesidade Mórbida/metabolismo , Obesidade Mórbida/fisiopatologia , Obesidade Mórbida/psicologia
18.
J Psychopharmacol ; 30(12): 1305-1312, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27562197

RESUMO

Recreational use of mephedrone, alone and in combination with alcohol, has increased over the past years. Pharmacological properties of mephedrone share similarities with methylenedioxymethamphetamine (MDMA), but its effect on neurocognitive function has not been well established in humans. The present study assessed the effect of mephedrone alone and after co-administration with alcohol on neurocognitive function. It was hypothesised that mephedrone would improve psychomotor performance but impair memory performance, when administered alone. Neurocognitive performance was expected to be impaired following mephedrone when combined with alcohol. Eleven participants received single doses of 200 mg mephedrone or placebo combined with 0.8 g/kg alcohol or placebo. Neurocognitive performance was assessed at baseline (T0), at one hour (T1) and four hours after (T2) mephedrone administration, by means of the Divided Attention Task (DAT), Critical Tracking Task (CTT), and the Spatial Memory Test (SMT). Mephedrone intoxication impaired short-term spatial memory at T1 and improved critical tracking performance at T2 Mephedrone alone did not affect divided attention, but did show an interaction with alcohol on reaction time at T2 Reaction time decreased when mephedrone was combined with alcohol as compared to alcohol alone. Alcohol intoxication impaired both short- and long-term spatial memory at T1 and divided attention at T1 and T2 Critical tracking performance was not affected by alcohol intoxication. The current findings support the hypothesis that mephedrone improves psychomotor performance, impairs spatial memory and does not affect divided attention performance. Stimulatory effects of mephedrone were not sufficient to compensate for the impairing effects of alcohol on most performance parameters.


Assuntos
Cognição/efeitos dos fármacos , Etanol/farmacologia , Metanfetamina/análogos & derivados , Desempenho Psicomotor/efeitos dos fármacos , Adulto , Atenção/efeitos dos fármacos , Estudos Cross-Over , Método Duplo-Cego , Humanos , Masculino , Memória de Curto Prazo/efeitos dos fármacos , Metanfetamina/farmacologia , N-Metil-3,4-Metilenodioxianfetamina/farmacologia , Tempo de Reação/efeitos dos fármacos , Adulto Jovem
19.
Eur Psychiatry ; 30(8): 924-31, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26647868

RESUMO

OBJECTIVE: Elevated physical activity has been observed in some patients with anorexia nervosa (AN) despite their emaciated condition. However, its effects on treatment outcome remain unclear. This study aimed to examine objectively measured physical activity in this clinical population and how it might be related to a partial hospitalization therapy response, after considering potential confounders. METHOD: The sample comprised 88 AN patients consecutively enrolled in a day hospital treatment program, and 116 healthy-weight controls. All participants were female and a baseline assessment took place using an accelerometer (Actiwatch AW7) to measure physical activity, the Eating Disorders Inventory-2 and the Depression subscale of the Symptom Checklist-Revised. Outcome was evaluated upon the termination of the treatment program by expert clinicians. RESULTS: Although AN patients and controls did not differ in the average time spent in moderate-to-vigorous physical activity (MVPA) (P=.21), nor daytime physical activity (P=.34), fewer AN patients presented a high physical activity profile compared to the controls (37% vs. 61%, respectively; P=.014). Both lower levels of MVPA and greater eating disorder severity had a direct effect on a poor treatment outcome. Depression symptoms in the patients were associated with lower MVPA, as well as with an older age, a shorter duration of the disorder and greater eating disorder psychopathology. CONCLUSIONS: There is a notable variation in the physical activity profile of AN patients, characterized by either low or very high patterns. Physical activity is a highly relevant issue in AN that must be taken into account during the treatment process.


Assuntos
Anorexia Nervosa/terapia , Depressão/terapia , Exercício Físico , Satisfação do Paciente , Adolescente , Adulto , Anorexia Nervosa/complicações , Anorexia Nervosa/psicologia , Depressão/complicações , Depressão/psicologia , Feminino , Humanos , Pacientes Internados/psicologia , Masculino , Atividade Motora , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
20.
Neuropharmacology ; 87: 198-205, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24667166

RESUMO

Previous studies have shown that single doses of MDMA can affect mood and impair memory in humans. The neuropharmacological mechanisms involved in MDMA-induced memory impairment are not clear. Memantine, an NMDA and alpha 7 nicotinic acetylcholine (ACh) receptor antagonist, was able to reverse MDMA-induced memory impairment in rats. This study investigated whether treatment with memantine can prevent MDMA-induced memory impairment in humans. 15 subjects participated in a double-blind, placebo controlled, within-subject design. Subjects received both pre-treatment (placebo/memantine 20 mg) (T1) and treatment (placebo/MDMA 75 mg) (T2) on separate test days. T1 preceded T2 by 120 min. Memory function was assessed 90 min after T2 by means of a Visual Verbal Learning Task, a Prospective Memory Task, the Sternberg Memory Task and the Abstract Visual Pattern Learning Task. Profile of Mood State and psychomotor performance were also assessed to control whether MDMA and memantine interactions would selectively pertain to memory or transfer to other domains as well. MDMA significantly impaired performance in the visual verbal learning task and abstract visual pattern learning task. Pre-treatment with memantine did not prevent MDMA-induced memory impairment in these two tasks. Both positive (vigour, arousal, elation) and negative mood effects (anxiety) were increased by MDMA. The responses were not altered by pretreatment with memantine which had no effect on memory or mood when given alone. These preliminary results suggest that memantine does not reverse MDMA-induced memory impairment and mood in humans. This article is part of the Special Issue entitled 'CNS Stimulants'.


Assuntos
Afeto/efeitos dos fármacos , Estimulantes do Sistema Nervoso Central/toxicidade , Memantina/farmacologia , Transtornos da Memória/induzido quimicamente , N-Metil-3,4-Metilenodioxianfetamina/toxicidade , Nootrópicos/farmacologia , Transtornos Relacionados ao Uso de Anfetaminas/sangue , Transtornos Relacionados ao Uso de Anfetaminas/tratamento farmacológico , Transtornos Relacionados ao Uso de Anfetaminas/psicologia , Estimulantes do Sistema Nervoso Central/sangue , Método Duplo-Cego , Feminino , Humanos , Masculino , Memantina/sangue , Memória/efeitos dos fármacos , Transtornos da Memória/sangue , Transtornos da Memória/prevenção & controle , N-Metil-3,4-Metilenodioxianfetamina/sangue , Nootrópicos/sangue , Testes Psicológicos , Desempenho Psicomotor/efeitos dos fármacos , Adulto Jovem
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