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1.
Sci Total Environ ; 948: 174725, 2024 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-39009158

RESUMO

The ubiquitous presence of nanoplastics (NPLs) in the environment is considered of great health concern. Due to their size, NPLs can cross both the intestinal and pulmonary barriers and, consequently, their presence in the blood compartment is expected. Understanding the interactions between NPLs and human blood components is required. In this study, to simulate more adequate real exposure conditions, the whole blood of healthy donors was exposed to five different NPLs: three polystyrene NPLs of approximately 50 nm (aminated PS-NH2, carboxylated PS-COOH, and pristine PS- forms), together with two true-to-life NPLs from polyethylene terephthalate (PET) and polylactic acid (PLA) of about 150 nm. Internalization was determined in white blood cells (WBCs) by confocal microscopy, once the different main cell subtypes (monocytes, polymorphonucleated cells, and lymphocytes) were sorted by flow cytometry. Intracellular reactive oxygen species (iROS) induction was determined in WBCs and cytokine release in plasma. In addition, hemolysis, coagulation, and platelet activation were also determined. Results showed a differential uptake between WBC subtypes, with monocytes showing a higher internalization. Regarding iROS, lymphocytes were those with higher levels, which was observed for different NPLs. Changes in cytokine release were also detected, with higher effects observed after PLA- and PS-NH2-NPL exposure. Hemolysis induction was observed after PS- and PS-COOH-NPL exposure, but no effects on platelet functionality were observed after any of the treatments. To our knowledge, this is the first study comprehensively evaluating the bloodstream kinetics and toxicity of NPL from different polymeric types on human whole blood, considering the role played by the cell subtype and the NPLs physicochemical characteristics in the effects observed after the exposures.


Assuntos
Microplásticos , Humanos , Microplásticos/toxicidade , Cinética , Nanopartículas/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Poliésteres/toxicidade , Poliestirenos/toxicidade , Leucócitos/efeitos dos fármacos
2.
J Intellect Disabil Res ; 68(11): 1253-1266, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38957043

RESUMO

BACKGROUND: Despite reported physical and functional improvements with aerobic and sprint interval training (SIT) protocols in individuals with intellectual disability (ID), it is not known if these interventions' effectivity would promote improvements in cardiac autonomic modulation. This study aimed to investigate if a 6-month SIT or a continuous aerobic programme could enhance physical performance and cardiac autonomic modulation at rest, during physical activity (PA) and after it in older adults with an ID. METHODS: This is a randomised control trial. Participants with ID (age: 50.58 ± 7.25) were allocated to one of three groups [multicomponent aerobic training group (MATG), multicomponent interval sprint training group (MISTG) and control group (CG)]. The programmes lasted 24 weeks, with three sessions/week, 75-90 min per session. The HRV was analysed at rest and recovery, the delta of heart rate (HR) was analysed during 6MWT, and the HR t-off kinetics was analysed in recovery after 6MWT. RESULTS: There were not found differences between groups, moments, or interaction for cardiac autonomic modulation at rest and recovery. During exercise, only MSITG showed a significant increase of HR between rest and the first 30 s of exercise (P < 0.05). Physical performance increased only in MSITG (P < 0.05), while CG showed a significant reduction (P < 0.01). CONCLUSIONS: The MSITG improved the physical performance and the vagal withdrawal at the beginning of the submaximal exercise. These findings suggest that high-intensity exercise may positively impact baroreflex function, mitigating the decline in autonomic reflex response capacity associated with aging in individuals with ID.


Assuntos
Sistema Nervoso Autônomo , Frequência Cardíaca , Deficiência Intelectual , Humanos , Masculino , Feminino , Sistema Nervoso Autônomo/fisiopatologia , Sistema Nervoso Autônomo/fisiologia , Deficiência Intelectual/fisiopatologia , Deficiência Intelectual/reabilitação , Frequência Cardíaca/fisiologia , Pessoa de Meia-Idade , Terapia por Exercício/métodos , Tolerância ao Exercício/fisiologia , Exercício Físico/fisiologia , Idoso , Adulto , Avaliação de Resultados em Cuidados de Saúde , Treinamento Intervalado de Alta Intensidade/métodos
3.
Environ Pollut ; 314: 120310, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36206893

RESUMO

Bisphenol A (BPA) is one of the main ubiquitous compounds released from plastics in the environment. This compound, considered an endocrine disruptor, poses a risk to aquatic wildlife and human population, being included in multiple environmental monitoring programmes. Following the regulations restricting BPA use in the last years, BPA-like chemicals have been produced and used as BPA substitutes. However, they are not commonly included in monitoring programs yet and their presence is thus misrepresented, despite showing similar endocrine disrupting potential. In this work, an analytical method for analysing bisphenol A and five of its analogues (Bisphenol S, B, F, AF and Tetrabromobisphenol A) is described, validated for water (riverine, sea and wastewater), sediment, and biota (fish and biofilm) and applied to monitor their presence in the Ebro River Delta (NE Spain). In addition, plastic litter was also collected to evaluate their role as potential source of bisphenols. All compounds except BPF were detected in the analysed samples. Wastewater treatment plants (WWTPs) were discarded as major sources of BPs into the natural aquatic environment, as no BPs were detected in treated effluents. Indeed, the high levels of BPs in the natural environment could be related with direct discharge of raw wastewater from small rural population nucleus. The analysis of riverine plastic leachates yielded 4 out of the 6 BPs analysed, strengthening the hypothesis that plastic debris are also a source of BPs in the natural environment. Whereas Bisphenol S and BPA were detected in water and, to a limited extent, in biota, less polar analogues (mainly BPAF and TBBPA) were not found in any of the water samples. Instead, these hydrophobic BPs were found in fish tissues and biofilm, pointing out plastics and microplastics as their possible vectors. Finally, biofilm demonstrated its potential as sentinel of chemical contamination in freshwater environment.


Assuntos
Disruptores Endócrinos , Animais , Humanos , Disruptores Endócrinos/análise , Plásticos , Águas Residuárias/análise , Água/análise , Espanha , Microplásticos , Prevalência , Compostos Benzidrílicos/análise , Peixes , Biota
4.
Eur J Med Genet ; 65(11): 104609, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36096471

RESUMO

BACKGROUND: Gastrointestinal stromal tumors have been detected in 25% of the necropsies performed on NF1 patients, but have been reported only in 7% of NF1 patients in the largest series. Such data imply an important gap between the true presence of tumors and those diagnosed. Few genotype-phenotype relationships have been described but to date none referring to abdominal tumors. OBJECTIVES: Evaluate retrospectively the efficacy of a regular and proactive follow-up of NF1 patients to early diagnose abdominal tumors and report their mutations. METHODS: Cohort study performed between 2010 and 2020, with 43 NF1 adult patients followed at our Dermatology department. RESULTS: Eight abdominal tumors were diagnosed in six patients, meaning that 14% of the followed patients developed an abdominal tumor. Five patients (83%) were asymptomatic. Five (83.3%) had a family history of NF1 with abdominal tumors (patients 1,2 and 3,4,5 were relatives). CONCLUSIONS: Although currently gastrointestinal routine screening investigations for asymptomatic patients are not recommended in the guidelines, the family aggregation in our series suggests it should be considered a close follow-up of the relatives of a patient with an NF1-related abdominal tumor. Also, for the first time, two mutations [c.2041C > T (p.Arg681Ter) and c.4537C > T (p.Arg1513*)] have been associated with family aggregation of abdominal tumors in NF1 patients.


Assuntos
Neoplasias Abdominais , Neurofibromatose 1 , Neoplasias Abdominais/complicações , Neoplasias Abdominais/genética , Estudos de Coortes , Genótipo , Humanos , Neurofibromatose 1/complicações , Neurofibromatose 1/genética , Neurofibromatose 1/patologia , Fenótipo , Estudos Retrospectivos
5.
Environ Res ; 212(Pt A): 113433, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35580665

RESUMO

The extent of the widespread, planetary contamination by plastic waste is difficult to fully capture. Nanoplastics (NPs) are currently in the center of research concerning plastic litter, both for the analytical challenges they pose and for their potential to provoke hazardous effects in organisms. However, there are still many unanswered questions in this multidisciplinary field, with a crucial missing piece being the quantification of NPs in fish tissues after in vivo exposures. Another relevant question that is still greatly unexplored is how a chronic exposure to NPs will affect fish health. This study aims to provide answers to both of these relevant knowledge gaps. To this end, goldfish (Carassius auratus) were exposed to 44 nm polystyrene (PS)-NPs via water for 30 days. Following the exposure, gastrointestinal tract, liver and muscle were sampled for PS-NPs analysis by means of size exclusion chromatography coupled to high resolution mass spectrometry. PS-NPs were detected in all liver and muscle samples of exposed fish, with higher concentrations in liver than in muscle, whereas no PS-NPs were detected in the gastrointestinal tract. Nevertheless, exposure to PS-NPs did not induce changes in hematology parameters nor in cortisol and glucose levels in plasma. On the other hand, even a relatively low concentration of PS-NPs was able to cause DNA damage, measured by an increase in erythrocyte nuclear abnormalities, suggesting that PS-NPs can reach the cell nucleus and cause genotoxicity. These results show for the first time that PS-NPs find their way to fish muscle after chronic exposure, where they bioaccumulate, but do not alter fish survival nor hematological or physiological stress indicators. The accumulation of PS-NPs in fish muscle can represent a threat to human health as a possible route of exposure to small-sized plastics. The present results in a model fish species open windows for future studies in edible fish species.


Assuntos
Nanopartículas , Poluentes Químicos da Água , Animais , Dano ao DNA , Peixes , Fígado , Microplásticos , Músculos , Nanopartículas/toxicidade , Plásticos/toxicidade , Poliestirenos/toxicidade , Poluentes Químicos da Água/toxicidade
6.
MethodsX ; 8: 101286, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34434806

RESUMO

Among natural freshwater pollutants, cyanotoxins, mycotoxins, and phytotoxins are the most important and less studied. Their identification in surface water is challenging especially cause of the lack of standards and established analytical parameters. Most target methods focus one or a single group of compounds with similar characteristics. Here we present an AIF fast method for the tentative identification of natural toxins in water. Respect to the previous method [1], it offers higher performances for the acquisition of unknown compounds at low levels for higher number of analytes. The key aspects of the method are: • The qualitative screening DIA-AIF workflow using Q Exactive Orbitrap. Both targeted and suspect screening bases have been combined with online databases and suspect list to retrieve candidates as suspect natural toxins and their metabolites or degradation products. • The in-silico analysis of mass spectrums allowed a fast structural characterization. • The workflow has been finally applied to real samples coming from the Czech Republic, Italy, and Spain allowing the determination of 17 suspect natural toxins, 4 of them confirmed. None toxin passed the limit of 1 µg/L taken from the legislation applied for microcystin LR and arbitrarily extended to all toxins.

7.
Sci Rep ; 11(1): 6315, 2021 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-33737699

RESUMO

There is a high interest on gut health in poultry with special focus on consequences of the intestinal diseases, such as coccidiosis and C. perfringens-induced necrotic enteritis (NE). We developed a custom gene expression panel, which could provide a snapshot of gene expression variation under challenging conditions. Ileum gene expression studies were performed through high throughput reverse transcription quantitative real-time polymerase chain reaction. A deep review on the bibliography was done and genes related to intestinal health were selected for barrier function, immune response, oxidation, digestive hormones, nutrient transport, and metabolism. The panel was firstly tested by using a nutritional/Clostridium perfringens model of intestinal barrier failure (induced using commercial reused litter and wheat-based diets without exogenous supplementation of enzymes) and the consistency of results was evaluated by another experiment under a coccidiosis challenge (orally gavaged with a commercial coccidiosis vaccine, 90× vaccine dose). Growth traits and intestinal morphological analysis were performed to check the gut barrier failure occurrence. Results of ileum gene expression showed a higher expression in genes involved in barrier function and nutrient transport in chickens raised in healthy conditions, while genes involved in immune response presented higher expression in C.perfringens-challenged birds. On the other hand, the Eimeria challenge also altered the expression of genes related to barrier function and metabolism, and increased the expression of genes related to immune response and oxidative stress. The panel developed in the current study gives us an overview of genes and pathways involved in broiler response to pathogen challenge. It also allows us to deep into the study of differences in gene expression pattern and magnitude of responses under either a coccidial vaccine or a NE.


Assuntos
Galinhas/microbiologia , Infecções por Clostridium/microbiologia , Enterite/microbiologia , Doenças das Aves Domésticas/microbiologia , Ração Animal/microbiologia , Animais , Infecções por Clostridium/genética , Clostridium perfringens/efeitos dos fármacos , Clostridium perfringens/patogenicidade , Coccidiose/genética , Coccidiose/microbiologia , Coccidiose/prevenção & controle , Suplementos Nutricionais , Eimeria/efeitos dos fármacos , Eimeria/patogenicidade , Enterite/genética , Enterite/prevenção & controle , Expressão Gênica/efeitos dos fármacos , Humanos , Doenças das Aves Domésticas/genética , Doenças das Aves Domésticas/prevenção & controle , Vacinas/farmacologia
8.
J Dairy Sci ; 103(2): 1759-1775, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31759594

RESUMO

Mastitis, often caused by intramammary infection (IMI), is a significant problem in dairy farming globally. Somatic cell count (SCC) is widely used as a parameter for screening IMI in cows that are then treated or culled. We investigated the potential of a new parameter, differential SCC (DSCC), to detect IMI at cow level when SCC is already known. We achieved this using bacterial culture (BC) and PCR to detect 4 categories of pathogens (major, minor, other, and any) in 2 Danish dairy herds. Quarter milk samples were collected from monthly dairy herd improvement samplings over 1 yr and analyzed with BC, whereas cow-level dairy herd improvement samples were analyzed using PCR. Days in milk, parity, and IMI status had a significant effect on DSCC. Using DSCC in addition to SCC significantly improved the indication of IMI compared with using only SCC in the any pathogen category in both herds as well as the minor pathogens category in herd 2 when BC was used for detection. When PCR was used to detect IMI, the use of DSCC in addition to SCC was significant for the other pathogens category in herd 1 and the minor pathogens category in herd 2. Thus, our data revealed that DSCC can add significant information describing IMI status even when SCC is already known; however, this depends on the causative pathogen. Future studies may address how to use DSCC in practice as well as consider the availability of temporal data to potentially gain insight into the course of infection.


Assuntos
Mastite Bovina/patologia , Leite/citologia , Animais , Bovinos , Contagem de Células/veterinária , Feminino , Mastite Bovina/diagnóstico , Mastite Bovina/microbiologia , Leite/microbiologia , Paridade , Gravidez
9.
Environ Res ; 176: 108565, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31280028

RESUMO

Emerging pollutants occur in complex mixtures in rivers and have the potential to interact with freshwater organisms. The chronic effects of nominal exposure to 3 µg/L of fullerenes (C60) and 1 µg/L of triclosan (TCS) alone and in a binary mixture, were evaluated using the freshwater snail Radix balthica. Pollutants accumulation, reproductive output and feeding behavior were selected as sublethal endpoints. After 21 days of exposure, we did not observe interactive effects between TCS and C60 on the studied endpoints, except for the accumulation of C60 in R. balthica in TCS + C60 treatment, which was lower than when the fullerenes were alone. Neither TCS nor C60 caused significant effects on reproduction, expressed as number of eggs per individual, but an increase in the clutch size was observed in treatments with TCS at the third week of exposure, independently of the presence of C60 (16.15 ± 1.67 and 18.9 ± 4.01 eggs/egg mass in TCS and TCS + C60 treatments, respectively, vs. 13.17 ±â€¯4.01 in control). The presence of C60 significantly enhanced the grazing activity of R. balthica during the first seven days (4.95 ±â€¯1.35 and 3.91 ±â€¯0.59% of the area grazed per individual in C60 and TCS + C60 treatments, respectively, vs 2.6 ±â€¯0.39% in control). The accumulation of TCS was quite similar in treatments where this pollutant was present (BAF ≈ 1007 L/kg d.w.); however, the accumulation of C60 was higher when the nanoparticles were alone (BAF = 254.88 L/kg d.w.) than when it was in the binary mixture (BAF = 7.79 L/kg d.w). Overall, although TCS has been listed as an endocrine disrupter compound, no significant effects on reproduction were observed in the assayed conditions. Regarding C60, the limited effects on feeding activity and the low BAF obtained in this experiment indicate that fullerenes do not have ecological consequences of relevance at the studied environmental concentrations in freshwater snails.


Assuntos
Fulerenos/toxicidade , Caramujos/fisiologia , Triclosan/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Comportamento Animal/efeitos dos fármacos , Água Doce , Reprodução/efeitos dos fármacos , Testes de Toxicidade
10.
Sci Total Environ ; 659: 1186-1198, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31096332

RESUMO

This study investigated the occurrence of 135 contaminants of emerging concern (CECs) - pharmaceuticals, pesticides, a set of endocrine disrupting compounds (EDCs) (parabens, bisphenols, hormones, triazoles, organophosphorus flame retardants and triclosan), UV-filters, perfluoroalkyl substances (PFASs) and halogenated flame retardants (HFRs) - in 59 fish samples, collected in 2010 in 4 Spanish Rivers (Guadalquivir, Júcar, Ebro and Llobregat). Of the 135 CECs, 76 including 8 pharmaceuticals, 25 pesticides, 10 EDCs, 5 UV-filters, 15 PFASs and 13 HFRs were detected. Pharmaceuticals were the less frequently found and at lower concentrations. Pesticides, EDCs, UV-filters, PFASs and HFRs were detected more frequently (>50% of the samples). The maximum concentrations were 15 ng/g dry weight (dw) for pharmaceuticals (diclofenac), 840 ng/g dw for pesticides (chlorpyrifos), 224 ng/g dw for EDCs (bisphenol A), 242 ng/g dw for UV-filters (EHMC), 1738 ng/g dw for PFASs (PFHxA) and 64 ng/g dw for HFRs (Dec 602). The contaminants detected in fish are commonly detected also in sediments. In light of current knowledge, the risk assessment revealed that there was no risk for humans related to the exposure to CECs via freshwater fish consumption. However, results provide detailed information on the mixtures of CECs accumulated that would be very useful to identify their effects on aquatic biota.


Assuntos
Monitoramento Ambiental , Peixes/metabolismo , Poluentes Químicos da Água/metabolismo , Animais , Disruptores Endócrinos/análise , Disruptores Endócrinos/metabolismo , Retardadores de Chama/análise , Retardadores de Chama/metabolismo , Água Doce/química , Sedimentos Geológicos/química , Éteres Difenil Halogenados/análise , Éteres Difenil Halogenados/metabolismo , Praguicidas/análise , Praguicidas/metabolismo , Rios/química , Espanha , Poluentes Químicos da Água/análise
11.
J Dairy Sci ; 102(2): 1428-1442, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30594383

RESUMO

Staphylococcus aureus is a major pathogen causing intramammary infections (IMI) in dairy cattle herds worldwide. Simulation models can be used to investigate the epidemiologic and economic outcomes of different control strategies against IMI. The transmission rate parameter is one of the most influential parameters on the outcomes of these simulation models. Very few studies have estimated the transmission rate parameter and investigated the transmission dynamics of Staph. aureus IMI in dairy cattle herds. The objective of our study was therefore to analyze the transmission dynamics of Staph. aureus in 2 Danish dairy herds participating in a longitudinal study. The 2 herds had 180 and 360 milking cows, and animals were tested at quarter level once per month over a period of 1 yr. We estimated the quarter-level prevalence to be 34% for herd 1 and 2.57% for herd 2. The daily quarter-level transmission rate was estimated to be 0.0132 and 0.0077 cases/quarter-day for herds 1 and 2, respectively, and the median duration of infection was estimated to be 91 and 64 d for herds 1 and 2, respectively. We also estimated the reproductive ratio at 1.21 for herd 1 and 0.52 for herd 2. The results can provide valuable information for simulation models to aid decision-making in terms of the prevention and control of Staph. aureus IMI in dairy cattle herds.


Assuntos
Mastite Bovina/transmissão , Infecções Estafilocócicas/veterinária , Animais , Bovinos , Indústria de Laticínios , Feminino , Estudos Longitudinais , Mastite Bovina/epidemiologia , Mastite Bovina/microbiologia , Mastite Bovina/prevenção & controle , Prevalência , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/prevenção & controle , Infecções Estafilocócicas/transmissão , Staphylococcus aureus
12.
Expert Opin Drug Metab Toxicol ; 14(2): 183-195, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29303006

RESUMO

INTRODUCTION: MDMA, 3,4-methylenedioxymethamphetamine, is a synthetic phenethylamine derivative with structural and pharmacological similarities to both amphetamines and mescaline. MDMA produces characteristic amphetamine-like actions (euphoria, well-being), increases empathy, and induces pro-social effects that seem to motivate its recreational consumption and provide a basis for its potential therapeutic use. Areas covered: The aim of this review is to present the main interindividual determinants in MDMA pharmacodynamics. The principal sources of pharmacodynamic variability are reviewed, with special emphasis on sex-gender, race-ethnicity, genetic differences, interactions, and MDMA acute toxicity, as well as possible therapeutic use. Expert opinion: Acute MDMA effects are more pronounced in women than they are in men. Very limited data on the relationship between race-ethnicity and MDMA effects are available. MDMA metabolism includes some polymorphic enzymes that can slightly modify plasma concentrations and effects. Although a considerable number of studies exist about the acute effects of MDMA, the small number of subjects in each trial limits evaluation of the different interindividual factors and does not permit a clear conclusion about their influence. These issues should be considered when studying possible MDMA therapeutic use.


Assuntos
Alucinógenos/administração & dosagem , N-Metil-3,4-Metilenodioxianfetamina/administração & dosagem , Serotoninérgicos/administração & dosagem , Animais , Interações Medicamentosas , Etnicidade , Feminino , Alucinógenos/efeitos adversos , Alucinógenos/farmacologia , Humanos , Masculino , N-Metil-3,4-Metilenodioxianfetamina/efeitos adversos , N-Metil-3,4-Metilenodioxianfetamina/farmacologia , Grupos Raciais , Serotoninérgicos/efeitos adversos , Serotoninérgicos/farmacologia , Fatores Sexuais , Transtornos Relacionados ao Uso de Substâncias/psicologia
13.
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
14.
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
15.
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
18.
Drug Test Anal ; 9(7): 1011-1016, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27717280

RESUMO

Since the appearance of recombinant human growth hormone (rhGH) in the 1980s, its expansion and acquisition through the black market has increased, so the detection of its abuse continues to be a challenge. New biomarkers that are more reliable and sensitive, allowing a larger detection window, are still needed. In this line, Fibronectin 1 (FN1) has been proposed as a potential genetic and protein biomarker of rhGH abuse in peripheral blood lymphocytes, serum, and plasma. However, logistic problems associated with current blood collection in sports drug testing point towards potential new alternative matrices that could be good candidates to be evaluated. Results obtained in this study showed high ELISA FN1 levels in one dried blood spot and in urine samples in ten healthy male volunteers treated with rhGH. Results showed that especially dried blood spots appear as a potential good matrix to detect rhGH abuse by means of FN1 biomarker. Copyright © 2016 John Wiley & Sons, Ltd.


Assuntos
Citocinas/sangue , Teste em Amostras de Sangue Seco/métodos , Hormônio do Crescimento Humano/administração & dosagem , Detecção do Abuso de Substâncias/métodos , Adulto , Dopagem Esportivo , Ensaio de Imunoadsorção Enzimática/métodos , Exercício Físico , Feminino , Fibronectinas , Hormônio do Crescimento Humano/sangue , Humanos , Masculino , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/sangue , Adulto Jovem
19.
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
20.
J Evol Biol ; 29(10): 2083-2097, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27364643

RESUMO

The sensory drive hypothesis proposes that environmental factors affect both signalling dynamics and the evolution of signals and receivers. Sound detection and equilibrium in marine fishes are senses dependent on the sagittae otoliths, whose morphological variability appears intrinsically linked to the environment. The aim of this study was to understand if and which environmental factors could be conditioning the evolution of this sensory structure, therefore lending support to the sensory drive hypothesis. Thus, we analysed the otolith shape of 42 rockfish species (Sebastes spp.) to test the potential associations with the phylogeny, biological (age), ecological (feeding habit and depth distribution) and biogeographical factors. The results showed strong differences in the otolith shapes of some species, noticeably influenced by ecological and biogeographical factors. Moreover, otolith shape was clearly conditioned by phylogeny, but with a strong environmental effect, cautioning about the use of this structure for the systematics of rockfishes or other marine fishes. However, our most relevant finding is that the data supported the sensory drive hypothesis as a force promoting the radiation of the genus Sebastes. This hypothesis holds that adaptive divergence in communication has significant influence relative to other life history traits. It has already been established in Sebastes for visual characters and organs; our results showed that it applies to otolith transformations as well (despite the clear influence of feeding and depth), expanding the scope of the hypothesis to other sensory structures.


Assuntos
Membrana dos Otólitos/anatomia & histologia , Percepção , Perciformes/fisiologia , Animais , Meio Ambiente , Peixes , Filogenia
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