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Neurosci Lett ; 701: 202-207, 2019 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-30826416


Auditory verbal hallucinations are common symptoms of post traumatic distress disorder. Previous studies have demonstrated alterations in the salience network (SN) in patients with post traumatic distress disorder and that hyperactivity of the SN is associated with AVHs in patients with psychosis. Patients with post traumatic distress disorder may benefit from aripiprazole; however, studies investigating the effect of aripiprazole on AVHs and activity in the SN in patients with post traumatic distress disorder are scarce. Therefore, we conducted an outcomes analysis using functional magnetic resonance imaging to explore the effects of add-on aripiprazole treatment on AVHs and brain functional connectivity in patients with post traumatic distress disorder. AVHs were alleviated by add-on aripiprazole treatment (Auditory Hallucination Rating Scale [AHRS] score reduced by ≥ 50%) in 22.7% of patients. Functional activity in the SN was obviously decreased in patients in whom AHRS scores were reduced ≥ 50% following add-on aripiprazole treatment compared to patients in whom AHRS scores were reduced by <50%. The decrease in functional connectivity within the SN was significantly correlated with the reduction in total AHRS scores. Although this study was associated with several limitations, the findings suggest that add-on aripiprazole treatment can alleviate AVHs in patients with post traumatic distress disorder by reducing activity in the SN.

Aripiprazol/uso terapêutico , Alucinações/tratamento farmacológico , Inibidores de Captação de Serotonina/uso terapêutico , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico , Adulto , Encéfalo/efeitos dos fármacos , Encéfalo/fisiopatologia , Feminino , Alucinações/fisiopatologia , Alucinações/psicologia , Humanos , Imagem por Ressonância Magnética , Masculino , Vias Neurais/efeitos dos fármacos , Transtornos de Estresse Pós-Traumáticos/fisiopatologia , Transtornos de Estresse Pós-Traumáticos/psicologia
Bull Environ Contam Toxicol ; 101(1): 75-79, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29802430


Perfluorooctane sulfonic acid (PFOS), as a potential endocrine disrupting chemical, is widely detected in the environment, wildlife and human. Currently few studies have documented the effects of chronic PFOS exposure on thyroid in aquatic organisms and the underlying mechanisms are largely unknown. The present study assessed the effect of chronic PFOS exposure on thyroid structure and function using zebrafish model. Zebrafish at 8 h post fertilization (hpf) were exposed to PFOS (250 µg/l) until 120 d post fertilization (dpf). Thyroid hormone (T3 and T4) level, thyroid morphology and thyroid function related gene expression were evaluated in zebrafish at 120 dpf. Our findings demonstrated that chronic PFOS exposure altered thyroid hormone level, thyroid follicular cell structure and thyroid hormone related gene expression, suggesting the validity of zebrafish as an alternative model for PFOS chronic toxicity screening.

Ácidos Alcanossulfônicos/toxicidade , Disruptores Endócrinos/toxicidade , Fluorcarbonetos/toxicidade , Glândula Tireoide/efeitos dos fármacos , Peixe-Zebra , Animais , Embrião não Mamífero/efeitos dos fármacos , Embrião não Mamífero/fisiologia , Glândula Tireoide/fisiologia
J Autism Dev Disord ; 47(5): 1341-1353, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28185043


The social difficulties of autism spectrum disorder (ASD) are typically explained as a disruption in the Shared Attention Mechanism (SAM) sub-component of the theory of mind (ToM) system. In the current paper, we explore the hypothesis that SAM's capacity to construct the self-other-object relations necessary for shared-attention arises from a self-categorization process, which is weaker among those with more autistic-like traits. We present participants with self-categorization and shared-attention tasks, and measure their autism-spectrum quotient (AQ). Results reveal a negative relationship between AQ and shared-attention, via self-categorization, suggesting a role for self-categorization in the disruption in SAM seen in ASD. Implications for intervention, and for a ToM model in which weak central coherence plays a role are discussed.

Atenção , Transtorno do Espectro Autista/psicologia , Cognição , Autoimagem , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Teoria da Mente , Adulto Jovem
Eur J Drug Metab Pharmacokinet ; 42(2): 201-211, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27037817


BACKGROUND AND OBJECTIVE: Dexmedetomidine is a highly selective alpha2-adrenoceptor agonist with sedative and analgesic properties which is also used in pediatric anesthesia. Although the pharmacokinetics of dexmedetomidine have been studied in pediatric patients, there are no data for Chinese children available. As alterations in pharmacokinetics due to ethnicity cannot be ruled out, it was the aim of this study to characterize the pharmacokinetics of dexmedetomidine in Chinese pediatric patients. METHODS: Thirty-nine children aged 1-9 years undergoing surgery were enrolled in the study. Dexmedetomidine was administered as short intravenous infusion of 1-2 µg/kg in 10 min. Venous blood samples were drawn until 480 min after stopping of infusion. Dexmedetomidine plasma concentrations were measured with high-performance liquid chromatography and mass spectrometry. Pharmacokinetic modeling was performed by population analysis using linear compartment models. RESULTS: Data of 36 patients (age 1-9 years, weight 10-27 kg) were analyzed. The pharmacokinetics of dexmedetomidine were best described by a two-compartment model with an allometric power model and estimates standardized to 70 kg body weight. The population estimates (95 % CI) per 70 kg bodyweight were: clearance 36.2 (33.3-41.1) l/h, central volume of distribution 84.3 (70.3-91.4) l, intercompartmental clearance 82.8 (63.6-136.6) l/h, peripheral volume of distribution 114 (95-149) l, and terminal half-life 4.4 (3.6-5.3) h. Age did not show any influence on weight-adjusted parameters. CONCLUSIONS: Chinese children showed a similar clearance, but larger volumes of distribution and longer terminal half-life when compared to studies in Caucasians. TRIAL REGISTRATION: ChiCTR-OPC-14005659.

Grupo com Ancestrais do Continente Asiático , Dexmedetomidina/farmacocinética , Hipnóticos e Sedativos/farmacocinética , Modelos Biológicos , Criança , Pré-Escolar , China , Cromatografia Líquida de Alta Pressão/métodos , Dexmedetomidina/administração & dosagem , Feminino , Meia-Vida , Humanos , Hipnóticos e Sedativos/administração & dosagem , Lactente , Infusões Intravenosas , Modelos Lineares , Masculino , Espectrometria de Massas , Distribuição Tecidual
J Chromatogr B Analyt Technol Biomed Life Sci ; 1023-1024: 30-5, 2016 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-27179189


A rapid, sensitive, and selective ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was developed and validated for the determination and pharmacokinetic investigation of dexmedetomidine in children's plasma. Sample preparation was accomplished through a simple one-step deproteinization procedure with 0.2mL of acetonitrile to a 0.1mL plasma sample. Plasma samples were separated by UPLC on an Acquity UPLC BEH C18 column using a mobile phase consisting of acetonitrile-0.1% formic acid in water with gradient elution. The total run time was 3.1min and the elution of dexmedetomidine was at 1.24min. The detection was performed on a triple quadrupole tandem mass spectrometer in the multiple reaction-monitoring mode using the respective transitions m/z 201.3→95.1 for dexmedetomidine and m/z 204.2→98.0 for the internal standard, respectively. The calibration curve was linear over the range of 0.05-10ng/mL with a lower limit of quantitation of 0.05ng/mL. Mean recovery rate of dexmedetomidine in plasma was in the range of 86.7-89.1%. Intra-day and inter-day precision were both <11.6%. This method was successfully applied in pharmacokinetic study after commencement of 1.0µg/kg dexmedetomidine infusion in children.

Cromatografia Líquida de Alta Pressão/métodos , Dexmedetomidina/sangue , Dexmedetomidina/farmacocinética , Espectrometria de Massas em Tandem/métodos , Pré-Escolar , Dexmedetomidina/química , Humanos , Lactente , Limite de Detecção , Modelos Lineares , Reprodutibilidade dos Testes
Neurotoxicol Teratol ; 33(6): 721-6, 2011 Nov-Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21964161


Trimethyltin chloride (TMT) is a neurotoxicant that is widely present in the aquatic environment, primarily from the manufacture of PVC plastic, but few studies have evaluated aquatic neurotoxicity. We have examined TMT dose-dependent malformation and neurobehavioral toxicity in the embryonic zebrafish model. Exposure of embryos to TMT (0-10 µM) from 48 to 72 hours post fertilization (hpf) elicited a concentration-related increase (0-100%) in malformation incidence with an EC(25) of 5.55 µM. TMT also significantly modulated the frequency of tail flexion, the earliest motor behavior observed in developing zebrafish, and the ability to respond to a mechanical tail touch. Exposure to 5 µM TMT from 48 to 72 hpf modulated the photomotor response at 4 and 5 days post fertilization and significantly promoted apoptosis in the tail. Our study demonstrates the morphological and behavioral sensitivity of the developing zebrafish to TMT and establishes a platform for future identification of the affected pathways and chemical modulators of TMT toxicity.

Comportamento Animal/efeitos dos fármacos , Embrião não Mamífero/efeitos dos fármacos , Síndromes Neurotóxicas/embriologia , Compostos de Trimetilestanho/toxicidade , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/embriologia , Animais , Apoptose/efeitos dos fármacos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Embrião não Mamífero/anormalidades , Embrião não Mamífero/patologia , Desenvolvimento Embrionário/efeitos dos fármacos , Síndromes Neurotóxicas/patologia , Síndromes Neurotóxicas/fisiopatologia , Cauda/anormalidades , Cauda/efeitos dos fármacos , Cauda/embriologia , Cauda/patologia , Peixe-Zebra/anormalidades