RESUMO
BACKGROUND: Genetic and epigenetic variations of the serotonin transporter gene (SLC6A4) have been related to the etiology of depression. The 5-HTTLPR polymorphism at the SLC6A4 promoter region has two variants, a short allele (S) and a long allele (L), in which the S allele results in lower gene transcription and has been associated with depression. The short S-allele of 5-HTTLPR polymorphism of this gene has been associated with depression. In addition to molecular mechanisms, exposure to early life risk factors such as maternal depression seems to affect the development of depression in postnatal life. The present study investigated the association of 5-HTTLPR polymorphism and CpG DNA methylation (5mC) levels of an AluJb repeat element at the SLC6A4 promoter region in mother-child pairs exposed to maternal depression. METHODS: We analyzed DNA samples from 60 subjects (30 mother-child pairs) split into three groups, with and without major depression disorder (DSM-IV) among children and mothers. The genotyping of 5-HTTLPR polymorphism and quantification of 5mC levels was performed by qualitative PCR and methylation-sensitive restriction enzyme digestion, and real-time quantitative PCR (MSRED-qPCR), respectively. RESULTS: The sample analyzed presented a higher frequency of S allele of 5-HTTLPR (67.5%). Despite the high frequency of this allele, we did not find statistically significant differences between individuals carrying at least one S allele between the depression and healthy control subjects, or among the mother-child pair groups with different patterns of occurrence of depression. In the group where the mother and child were both diagnosed with depression, we found a statistically significant decrease of the 5mC level at the SLC6A4 promoter region. LIMITATIONS: The limitations are the relatively small sample size and lack of gene expression data available for comparison with methylation data. CONCLUSION: In this study, we demonstrated a repeat element specific 5mC level reduction in mother-child pairs, concordant for the diagnosis of depression.
Assuntos
Transtorno Depressivo Maior/genética , Epigênese Genética , Mães , Regiões Promotoras Genéticas , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Adolescente , Adulto , Alelos , Estudos de Casos e Controles , Criança , Metilação de DNA , Feminino , Predisposição Genética para Doença/genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Adulto JovemRESUMO
Gastroschisis (GS) is an abdominal wall defect that results in histological and morphological changes leading to intestinal motility perturbation and impaired absorption of nutrients. Due to its anti-inflammatory, antioxidant, and neuroprotective effects, cannabidiol (CBD) has been used as a therapeutic agent in many diseases. Our aim was to test the effect of maternal CBD in the intestine of an experimental model of GS. Pregnant rats were treated over 3 days with CBD (30 mg/kg) after the surgical induction of GS (day 18.5 of gestation) and compared to controls. Fetuses were divided into 4 groups: 1) control (C); 2) C+CBD (CCBD); 3) gastroschisis (G), and 4) G+CBD (GCBD). On day 21.5 of gestation, the fetuses were harvested and evaluated for: a) body weight (BW), intestinal weight (IW), and IW/BW ratio; b) histometric analysis of the intestinal wall; c) immunohistochemically analysis of inflammation (iNOS) and nitrite/nitrate level. BW: GCBD was lower than CCBD (P<0.005), IW and IW/BW ratio: GCBD was smaller than G (P<0.005), GCBD presented lower thickness in all parameters compared to G (P<0.005), iNOS and nitrite/nitrate were lower concentration in GCBD than to G (P<0.005). Maternal use of CBD had a beneficial effect on the intestinal loops of GS with decreased nitrite/nitrate and iNOS expression.
Assuntos
Anti-Inflamatórios/uso terapêutico , Canabidiol/uso terapêutico , Enterite/prevenção & controle , Doenças Fetais/metabolismo , Gastrosquise/metabolismo , Intestinos/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Feminino , Doenças Fetais/patologia , Gastrosquise/patologia , Imuno-Histoquímica , Nitratos/metabolismo , Óxido Nítrico Sintase Tipo II/análise , Nitritos/metabolismo , Gravidez , Ratos , Ratos Sprague-DawleyRESUMO
The current literature has been discussing the risks and benefits of joint hypermobility (JHM) for careers in ballet This study aimed to evaluate the prevalence of JHM and joint hypermobility syndrome (JHS) in a group of ballet teachers and students, looking both at aspects related to the flexibility required to dance, as at the risk of injuries when hypermobility is associated with other symptoms, in the case of JHS. We evaluated ballet teachers and ballet students, with age ranging from 18 to 40 years. All participants completed identification and sociodemographic questionnaires and underwent a physical examination. JHM was assessed using the Beighton score with goniometry. Symptoms of JHS were evaluated according to the Brighton criteria. Final sample consisted of 77 participants, being 44 ballet students and 33 ballet teachers. The prevalence of JHM in the sample as a whole was 58 %. Teachers and students had no significant differences regarding the prevalence of JHM (p = 0.74) (OR 1.21; 95 % CI 0.48-3.07). However, the prevalence of JHS was significantly different (p = 0.04) between students (16 %) and teachers (36 %). Teachers were three times more likely than student to have JHS (OR 3.02; 95 % CI 1.03-8.85). Teachers and students also presented differences in the frequency of specific items of Beighton score and Brighton criteria. These data provide elements to discuss the relationship between hypermobility, ballet technique and selection for dance, suggesting that dancers with JHS could find in ballet teaching an alternative to maintain professional activity with dance, while remaining protected from the higher risk of injury that professional dancers may be exposed to.
Assuntos
Dança/fisiologia , Instabilidade Articular/epidemiologia , Instabilidade Articular/fisiopatologia , Adolescente , Adulto , Brasil/epidemiologia , Feminino , Humanos , Prevalência , Adulto JovemRESUMO
We have previously shown that the prophylactic treatment with cannabidiol (CBD) reduces inflammation in a model of acute lung injury (ALI). In this work we analyzed the effects of the therapeutic treatment with CBD in mice subjected to the model of lipopolysaccharide (LPS)-induced ALI on pulmonary mechanics and inflammation. CBD (20 and 80 mg/kg) was administered (i.p.) to mice 6 h after LPS-induced lung inflammation. One day (24 h) after the induction of inflammation the assessment of pulmonary mechanics and inflammation were analyzed. The results show that CBD decreased total lung resistance and elastance, leukocyte migration into the lungs, myeloperoxidase activity in the lung tissue, protein concentration and production of pro-inflammatory cytokines (TNF and IL-6) and chemokines (MCP-1 and MIP-2) in the bronchoalveolar lavage supernatant. Thus, we conclude that CBD administered therapeutically, i.e. during an ongoing inflammatory process, has a potent anti-inflammatory effect and also improves the lung function in mice submitted to LPS-induced ALI. Therefore the present and previous data suggest that in the future cannabidiol might become a useful therapeutic tool for the attenuation and treatment of inflammatory lung diseases.
Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Anti-Inflamatórios/uso terapêutico , Canabidiol/uso terapêutico , Lipopolissacarídeos/farmacologia , Pneumonia/prevenção & controle , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/complicações , Lesão Pulmonar Aguda/imunologia , Animais , Anti-Inflamatórios/administração & dosagem , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Canabidiol/administração & dosagem , Quimiotaxia de Leucócito/efeitos dos fármacos , Quimiotaxia de Leucócito/imunologia , Citocinas/sangue , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Injeções Intraperitoneais , Leucócitos/citologia , Leucócitos/imunologia , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/patologia , Masculino , Camundongos Endogâmicos C57BL , Peroxidase/metabolismo , Pneumonia/etiologia , Pneumonia/imunologia , Testes de Função RespiratóriaRESUMO
WHAT IS KNOWN AND OBJECTIVE: Antiepileptic drugs often produce serious adverse effects, and many patients do not respond to them properly. Phytocannabinoids produce anticonvulsant effects in preclinical and preliminary human studies, and appear to produce fewer adverse effects than available antiepileptic drugs. The present review summarizes studies on the anticonvulsant properties of phytocannabinoids. METHODS: Literature search using the PubMed database to identify studies on phytocannabinoids and epilepsy. RESULTS AND DISCUSSION: Preclinical studies suggest that phytocannabinoids, especially cannabidiol and cannabidivarin, have potent anticonvulsant effects which are mediated by the endocannabinoid system. Human studies are limited in number and quality, but suggest that cannabidiol has anticonvulsant effects in adult and infantile epilepsy and is well tolerated after prolonged administration. WHAT IS NEW AND CONCLUSION: Phytocannabinoids produce anticonvulsant effects through the endocannabinoid system, with few adverse effects. Cannabidiol and cannabidivarin should be tested in randomized, controlled clinical trials, especially in infantile epileptic syndromes.
Assuntos
Anticonvulsivantes/uso terapêutico , Canabinoides/uso terapêutico , Epilepsia/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Animais , Canabidiol/uso terapêutico , Córtex Cerebral/metabolismo , Ensaios Clínicos como Assunto , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Dronabinol/uso terapêutico , Avaliação Pré-Clínica de Medicamentos , Endocanabinoides/biossíntese , Humanos , Fitoterapia , Extratos Vegetais/químicaRESUMO
INTRODUCTION: Anxiety disorders may be associated with several non-psychiatric disorders. Current literature has been investigating the association between anxiety and joint hypermobility (JHM), with special interest in non-articular symptoms that may be related to autonomic dysfunction. This study investigated the association between anxiety and JHM in a sample of Brazilian university students. METHODS: Data were cross-sectionally collected in two Brazilian universities (N=2600). Participants completed three validated self-rating anxiety scales: Beck Anxiety Inventory (BAI), Social Phobia Inventory (SPIN) and the brief-version of SPIN (Mini-SPIN). They also answered the self-rating screening questionnaire for JHM: the Five-part Questionnaire for Identifying Hypermobility. RESULTS: Hypermobile women showed significantly higher scores in all the anxiety scales, when compared with men: BAI total score (t=3.77; p<0.001), its four subscales, SPIN score (t=2.71; p<0.007) and Mini-SPIN (t=2.58; p<0.01). Among BAI subscales, the autonomic subscale was shown to be more significantly (t=3.89; p<0.001) associated with joint hypermobility in women. CONCLUSIONS: The results of the present study support earlier evidence on the relationship between anxiety and JHM in women, showing specific gender-related features in this field. It also directs attention to non-articular symptoms that may be enrolled in this association.
Assuntos
Transtornos de Ansiedade/epidemiologia , Ansiedade/epidemiologia , Instabilidade Articular/epidemiologia , Estudantes/psicologia , Adulto , Ansiedade/psicologia , Transtornos de Ansiedade/diagnóstico , Transtornos de Ansiedade/psicologia , Brasil/epidemiologia , Feminino , Humanos , Instabilidade Articular/psicologia , Masculino , Distribuição por Sexo , Fatores Sexuais , Estudantes/estatística & dados numéricos , Inquéritos e Questionários , Universidades , Adulto JovemRESUMO
WHAT IS KNOWN AND OBJECTIVE: Cannabidiol (CBD) is the main non-psychotropic component of the Cannabis sativa plant. REM sleep behaviour disorder (RBD) is a parasomnia characterized by the loss of muscle atonia during REM sleep associated with nightmares and active behaviour during dreaming. We have described the effects of CBD in RBD symptoms in patients with Parkinson's disease. CASES SUMMARY: Four patients treated with CBD had prompt and substantial reduction in the frequency of RBD-related events without side effects. WHAT IS NEW AND CONCLUSION: This case series indicates that CBD is able to control the symptoms of RBD.
Assuntos
Canabidiol/uso terapêutico , Cannabis , Doença de Parkinson , Fitoterapia , Transtorno do Comportamento do Sono REM/tratamento farmacológico , Idoso , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Pharmacological treatments are available for alcohol, nicotine, and opioid dependence, and several drugs for cannabis-related disorders are currently under investigation. On the other hand, psychostimulant abuse and dependence lacks pharmacological treatment. Mesolimbic dopaminergic neurons mediate the motivation to use drugs and drug-induced euphoria, and psychostimulants (cocaine, amphetamine, and methamphetamine) produce their effects in these neurons, which may be modulated by the opioid system. Salvinorin A is a κ-opioid receptor agonist extracted from Salvia divinorum, a hallucinogenic plant used in magico-ritual contexts by Mazateca Indians in México. Salvinorin A and its analogues have demonstrated anti-addiction effects in animal models using psychostimulants by attenuating dopamine release, sensitization, and other neurochemical and behavioral alterations associated with acute and prolonged administration of these drugs. The objective of the present article is to present an overview of the preclinical evidence suggesting anti-addictive effects of salvinorin A and its analogues.
Assuntos
Transtornos Relacionados ao Uso de Anfetaminas/tratamento farmacológico , Transtornos Relacionados ao Uso de Cocaína/tratamento farmacológico , Diterpenos Clerodânicos/uso terapêutico , Analgésicos Opioides/isolamento & purificação , Analgésicos Opioides/farmacologia , Analgésicos Opioides/uso terapêutico , Animais , Modelos Animais de Doenças , Diterpenos Clerodânicos/isolamento & purificação , Diterpenos Clerodânicos/farmacologia , Dopamina/metabolismo , Neurônios Dopaminérgicos/metabolismo , Humanos , México , Receptores Opioides kappa/agonistas , Salvia/químicaRESUMO
WHAT IS KNOWN AND OBJECTIVE: Cannabis withdrawal in heavy users is commonly followed by increased anxiety, insomnia, loss of appetite, migraine, irritability, restlessness and other physical and psychological signs. Tolerance to cannabis and cannabis withdrawal symptoms are believed to be the result of the desensitization of CB1 receptors by THC. CASE SUMMARY: This report describes the case of a 19-year-old woman with cannabis withdrawal syndrome treated with cannabidiol (CBD) for 10 days. Daily symptom assessments demonstrated the absence of significant withdrawal, anxiety and dissociative symptoms during the treatment. WHAT IS NEW AND CONCLUSION: CBD can be effective for the treatment of cannabis withdrawal syndrome.
Assuntos
Canabidiol/uso terapêutico , Cannabis/efeitos adversos , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Adulto , Feminino , Humanos , Adulto JovemRESUMO
BACKGROUND: Neurodevelopmental alterations have been described inconsistently in psychosis probably because of lack of standardization among studies. The aim of this study was to conduct the first longitudinal and population-based magnetic resonance imaging (MRI) evaluation of the presence and size of the cavum septum pellucidum (CSP) and adhesio interthalamica (AI) in a large sample of patients with first-episode psychosis (FEP). METHOD: FEP patients (n=122) were subdivided into schizophrenia (n=62), mood disorders (n=46) and other psychosis (n=14) groups and compared to 94 healthy next-door neighbour controls. After 13 months, 80 FEP patients and 52 controls underwent a second MRI examination. RESULTS: We found significant reductions in the AI length in schizophrenia FEP in comparison with the mood disorders and control subgroups (longer length) at the baseline assessment, and no differences in any measure of the CSP. By contrast, there was a diagnosis×time interaction for the CSP length, with a more prominent increase for this measure in the psychosis group. There was an involution of the AI length over time for all groups but no diagnosis×time interaction. CONCLUSIONS: Our findings suggest that the CSP per se may not be linked to the neurobiology of emerging psychotic disorders, although it might be related to the progression of the disease. However, the fact that the AI length was shown to be shorter at the onset of the disorder supports the neurodevelopmental model of schizophrenia and indicates that an alteration in this grey matter junction may be a risk factor for developing psychosis.