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1.
J Pediatr ; 244: 178-185.e3, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35031347

RESUMO

OBJECTIVE: To evaluate the severity and clinical outcomes of the SARS-CoV-2 gamma variant in children and adolescents hospitalized with COVID-19 in Brazil. STUDY DESIGN: In this observational retrospective cohort study, we performed an analysis of all 21 591 hospitalized patients aged <20 years with confirmed SARS-CoV-2 infection registered in a national database in Brazil. The cohort was divided into 2 groups according to the predominance of SARS-CoV-2 lineages (WAVE1, n = 11 574; WAVE2, n = 10 017). The characteristics of interest were age, sex, geographic region, ethnicity, clinical presentation, and comorbidities. The primary outcome was time to death, which was evaluated by competing-risks analysis, using cumulative incidence functions. A predictive Fine and Gray competing-risks model was developed based on the WAVE1 cohort with temporal validation in the WAVE2 cohort. RESULTS: Compared with children and adolescents admitted during the first wave, those admitted during the second wave had significantly more hypoxemia (52.5% vs 41.1%; P < .0001) and intensive care unit admissions (28.3% vs 24.9%; P < .0001) and needed more noninvasive ventilatory support (37.3% vs 31.6%; P < .0001). In-hospital deaths and death rates were 896 (7.7%) in the first wave and 765 (7.6%) in the second wave (P = .07). The prediction model of death included age, ethnicity, region, respiratory symptoms, and comorbidities. In the validation set (WAVE2), the C statistic was 0.750 (95% CI, 0.741-0.758; P < .0001). CONCLUSIONS: This large national study found a more severe spectrum of risk for pediatric patients with COVID-19 caused by the gamma variant. However, there was no difference regarding the probability of death between the waves.


Assuntos
COVID-19 , SARS-CoV-2 , Adolescente , COVID-19/epidemiologia , Criança , Hospitalização , Humanos , Pandemias , Estudos Retrospectivos
3.
J Pediatr Gastroenterol Nutr ; 66(2): 204-211, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29045346

RESUMO

OBJECTIVE: The pathophysiology of autoimmune hepatitis (AIH) may involve the activation of immune cells and changes in the expression of cellular markers. The aim of the present study was to characterize the immunophenotype markers of lymphocytes and monocytes in the peripheral blood of children and adolescents with type 1 AIH and AIH overlap with sclerosing cholangitis (overlap syndrome [OS]). METHODS: This is a cross-sectional study of 20 children and adolescents diagnosed with type 1 AIH and 19 with OS. Fifteen healthy subjects were included as controls. Flow cytometric analysis was used to identify markers of inflammation and autoimmunity. RESULTS: The total number of CD4 T cells was higher in the AIH patients compared with the controls. The number of CD4 T cells expressing CCR3 and CD28 was higher in the AIH group than in the control group. CD45RO was more highly expressed in the AIH group, whereas CD45RA was more highly expressed in the OS group. In regard to CD8 T lymphocytes, the CCR3 expression was higher in both groups of patients. Patients with OS had the highest expression of CD45RA and CD25. In monocytes, human leukocyte antigen DR (HLA-DR) was less expressed in both groups of patients. CONCLUSIONS: Complex phenotype features may be involved in the pathophysiology of AIH, accounting for changes in immune system regulation mechanisms. In conclusion, even after good response to treatment, patients still have immune activity signals at the cellular level.


Assuntos
Biomarcadores/sangue , Colangite Esclerosante/imunologia , Hepatite Autoimune/imunologia , Imunofenotipagem/métodos , Adolescente , Criança , Colangite Esclerosante/sangue , Estudos Transversais , Feminino , Citometria de Fluxo/métodos , Hepatite Autoimune/sangue , Humanos , Fígado/imunologia , Fígado/patologia , Linfócitos/imunologia , Masculino , Monócitos/imunologia , Adulto Jovem
4.
Carcinogenesis ; 38(11): 1112-1118, 2017 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-28968711

RESUMO

Lung cancer (LC) is a leading cause of cancer-related mortality. Although smoking is the major risk factor, ~15% of all cases occur in never-smokers, suggesting that genetic factors play a role in LC predisposition. Indeed, germline mutations in the TP53 gene predispose to multiple cancer types, including LC. To date, few studies compared the somatic and germline mutational profiles of LC cases by smoking status, and none was reported in Brazilians. Whole-exome sequencing (WES) was performed on two pools (seven smokers and six non-smokers) of tumor-derived DNA using the Illumina HiSeq2000 platform. Files from pools were analyzed separately using Ingenuity®Variant AnalysisTM and Mendel,MD. Validation of all candidate variants was performed by Sanger sequencing. Subsequently, validated mutations were analyzed in germline DNA from the same patients and in ethnically matched controls. In addition, a single recurring Brazilian TP53 germline mutation (R337H) was genotyped in 45 non-small-cell lung cancer patients.Four novel germline variants in the ATAD2, AURKA, PTPRD and THBS1 genes were identified exclusively in smoker patients, and four germline missense variants in PLCD1, RAD52, CP and CDC6 genes were identified solely in non-smokers. There were 4/45 (8.9%) germline carriers of the R337H TP53 mutation. In conclusion, the recurring Brazilian TP53 mutation should be genotyped in all non-small-cell lung cancer in Brazil, regardless of smoking status. Distinct pathogenic mutations and novel sequence variants are detected in Brazilian non-small-cell lung cancer patients, by smoking status. The contribution of these sequence variants to LC pathogenesis remains to be further explored.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Mutação em Linhagem Germinativa/genética , Neoplasias Pulmonares/genética , Fumar/genética , Adulto , Idoso , Brasil , Feminino , Predisposição Genética para Doença/genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Proteína Supressora de Tumor p53/genética
5.
J Pediatr Gastroenterol Nutr ; 63(1): 76-81, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-26825768

RESUMO

OBJECTIVES: This is a cohort study of 134 children and adolescents with a known diagnosis of autoimmune hepatitis (AIH). During follow-up, some of them developed autoimmune sclerosing cholangitis (ASC). This study describes the characteristics of the patients upon diagnosis, and their response to treatment and any complications, and compares the patients who developed ASC during follow-up (ASC group) with those who did not (AIH group). METHODS: A total of 73.1% of the patients were girls with a median age upon diagnosis of 10.41 (7.41-12.53) years. RESULTS: Of 134 patients, 28 (20.9%) developed cholestatic manifestations, with features of ASC. A few differences were observed between the AIH and ASC groups when they were analyzed by χ test, such as the smaller predominance of girls in ASC group (P = 0.04), and more common asymptomatic presentation in the ASC group (P = 0.01). Cirrhosis was observed in 68% of biopsies, with no significant difference between groups (P = 0.43). Of 16 deaths, 15 were in the AIH group and 1 in the ASC group (P = 0.22). Of 11 transplants, 10 were in the AIH group and one in the ASC group (P = 0.53). The presence of cirrhosis at baseline was associated with a smaller survival probability (P = 0.015). The survival rate by Kaplan-Meier method was 94% at 5 years and 80% at 10 years, and was similar in both the groups (P = 0.08). CONCLUSIONS: No statistically significant difference was observed between the groups in relation to prognosis and response to treatment.


Assuntos
Colangite Esclerosante/complicações , Hepatite Autoimune/mortalidade , Adolescente , Azatioprina/uso terapêutico , Brasil , Criança , Serviços de Saúde da Criança , Estudos de Coortes , Feminino , Hepatite Autoimune/complicações , Hepatite Autoimune/diagnóstico , Hepatite Autoimune/tratamento farmacológico , Humanos , Masculino , Prednisona/uso terapêutico , Prognóstico , Fatores Sexuais , Análise de Sobrevida
6.
Nephrology (Carlton) ; 19(11): 714-20, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24995698

RESUMO

AIM: The angiotensin type 2 (AT2 ) receptor takes part in the process of ureteric bud during kidney development. Therefore, the gene encoding AT2 receptor, the AGTR2 gene located in the X chromosome, is a potential candidate for genetic association with Congenital Anomalies of the Kidney and Urinary Tract (CAKUT). This study aimed to investigate whether AGTR2 gene polymorphisms are associated with CAKUT in general or even with common phenotypes of CAKUT in a Brazilian sample of paediatric patients. METHODS: We analyzed 290 paediatric patients with CAKUT and 262 healthy controls from the same geographic area. TaqMan single-nucleotide polymorphism (SNP) genotyping assays for AGTR2 gene at rs1403543, rs3736556, rs35474657, rs5193 and rs5194 were performed. The sample was in Hardy-Weinberg Equilibrium for all five SNPs. RESULTS: The presence of CAKUT in general was not significantly associated with the SNPs included in this study. However, when patients were segregated according to major phenotypes, the diagnosis of Ureteropelvic Junction Obstruction (UPJO) was significantly associated with AGTR2 gene polymorphisms at rs3736556 and at rs5194. On the other hand, the diagnoses of vesicoureteral reflux and of multicystic dysplastic kidney were not associated with AGTR2 gene polymorphisms. CONCLUSION: Our results support that the AGTR2 gene may contribute to the pathogenesis of UPJO and the genetic origin of CAKUT could vary according to phenotype expression.


Assuntos
Hidronefrose/congênito , Rim Displásico Multicístico/genética , Polimorfismo de Nucleotídeo Único , Receptor Tipo 2 de Angiotensina/genética , Obstrução Ureteral/genética , Brasil , Criança , Pré-Escolar , Feminino , Humanos , Hidronefrose/genética , Masculino , Fenótipo
7.
Braz J Psychiatry ; 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38598451

RESUMO

INTRODUCTION: Healthcare workers (HCWs) are at an increased risk of suicide compared to non-healthcare workers. This study aims to investigate the association between social support and suicidal ideation and behavior (SIB) during the COVID-19 pandemic among Brazilian HCWs. METHODS: This study utilizes data from 10,885 participants who answered the first (time point 1 - between May and June of 2020) and second (time point 2 - between December 2020 and February 2021) assessments of an online repeated cross-sectional survey for evaluating mental health and quality of life of HCWs during the COVID-19 pandemic in Brazil. Logistic regression analysis was conducted to investigate the relationship between social support as the independent variable (time point 1) and SIB as the outcomes (time point 2). RESULTS: Higher social support was associated with a significantly lower chance of reporting SIB in the month prior to follow-up assessment (adjusted odds ratio [AOR]: 0.71, CI 95% 0.66 - 0.76 and AOR 0.61, CI 95% 0.54 - 0.68, respectively). These associations were independent of sex, age, feelings of loneliness, and self-reported psychiatric disorders. CONCLUSION: Social support is associated with a lower chance of suicidality among HCWs, a protective role that is probably more evident for suicidal behavior.

8.
Ophthalmic Res ; 50(2): 117-22, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23867343

RESUMO

PURPOSE: To investigate the association between the CFH and ARMS2 gene polymorphisms and age-related macular degeneration (AMD) in a Brazilian cohort. METHODS: We examined 163 individuals with AMD and 154 controls recruited at the Department of Ophthalmology of the Universidade Federal de Minas Gerais, at the Instituto da Visão, and at the Centro Especializado em Olhos, in Brazil, between 2007 and 2012. Genotyping for CFH rs1061170 and ARMS2 rs10490924 single-nucleotide polymorphisms was performed. The odds ratios (OR) for all of the studied genotypes (heterozygous and homozygous) of both genes were calculated compared to homozygous ancestral alleles. RESULTS: Homozygosity for the CFH and ARMS2 at-risk allele was 33.3 and 23.6%, respectively, for AMD individuals and 10.3 and 7.1%, respectively, for controls (p < 0.0001). The OR was 7.2 (95% CI 3.6-14.5; p < 0.001) for the CFH at-risk genotype (CC) and 5.5 (95% CI 2.6-11.8; p < 0.0001) for ARMS2 (TT). Subjects homozygous for both polymorphisms had a much higher risk of developing AMD (n = 14 patients, OR 33.3, 95% CI 12.8-86.4). The proportion of ancestry in each group indicated that AMD patients had a higher European (Caucasian) component than controls. CONCLUSION: CFH and ARMS2 polymorphisms were strongly associated with AMD in this Brazilian cohort.


Assuntos
Degeneração Macular/genética , Polimorfismo de Nucleotídeo Único , Proteínas/genética , Idoso , Brasil/epidemiologia , Estudos de Coortes , Fator H do Complemento/genética , Etnicidade/etnologia , Feminino , Angiofluoresceinografia , Genótipo , Técnicas de Genotipagem , Humanos , Degeneração Macular/diagnóstico , Degeneração Macular/etnologia , Masculino , Razão de Chances , Reação em Cadeia da Polimerase em Tempo Real , Tomografia de Coerência Óptica
9.
J Pediatr (Rio J) ; 99(4): 413-422, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37068587

RESUMO

OBJECTIVE: The Child and Adolescent Behavior Inventory (CABI) is a cost-free 75 question-questionnaire developed by an Italian group to collect information from parents on the behavior of children and adolescents aged 6 to 18 years. It assesses different areas of children's behavior and psychopathology, including internalizing and externalizing symptoms, and can be used to identify children at risk of mental disorders both in clinical and epidemiological settings. In this study, the authors present a Brazilian-Portuguese adaptation of the CABI and its psychometric properties. METHODS: First, the authors conducted a rigorous transcultural adaptation of CABI's questions and instructions for the Brazilian context. In an online sample of 598 parents, the authors found high reliability (internal consistency) for the CABI's main subscales. RESULTS: Validity was supported by exploratory factor analysis (the authors found 6 factors representing several aspects of psychopathology both according to the DSM and HiTop models) and significant differences in most CABI's subscales between children with parent-reported psychopathology and typically developing ones. The present study suggests that the adapted version of CABI is a valid and reliable measure that can be used in Brazil. CONCLUSIONS: The CABI can be useful to the pediatrician to get fast but wide information from parents on the behavioral condition of their children or adolescents, and also to decide whether it is appropriate to consult a mental health professional.


Assuntos
Comportamento do Adolescente , Transtornos Mentais , Adolescente , Humanos , Criança , Brasil , Reprodutibilidade dos Testes , Comparação Transcultural , Transtornos Mentais/diagnóstico , Transtornos Mentais/psicologia , Inquéritos e Questionários , Psicometria
10.
BMC Med Genet ; 13: 101, 2012 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-23134754

RESUMO

BACKGROUND: Obesity has become a common human disorder associated with significant morbidity and mortality and adverse effects on quality of life. Sequence variants in two candidate genes, FTO and UCP-1, have been reported to be overrepresented in obese Caucasian population. The association of these genes polymorphisms with the obesity phenotype in a multiethnic group such as the Brazilian population has not been previously reported. METHODS: To assess the putative contribution of both FTO and UCP-1 to body mass index (BMI) and cardiovascular risk we genotyped SNPs rs9939609 (FTO) and rs6536991, rs22705565 and rs12502572 (UCP-1) from 126 morbidly obese subjects (BMI 42.9 ± 5.6 kg/m2, mean ± SE) and 113 normal-weight ethnically matched controls (BMI 22.6 ± 3.5 kg/m2, mean ± SE). Waist circumference, blood pressure, glucose and serum lipids were also measured. Each sample was also genotyped for 40 biallelic short insertion/deletion polymorphism (indels) for ethnic assignment and to estimate the proportion of European, African and Amerindian biogeographical ancestry in the Brazilian population. RESULTS: Cases did not differ from controls in the proportions of genomic ancestry. The FTO SNP rs9939609 and UCP-1 SNP rs6536991 were significantly associated with BMI (p= 0.04 and p<0.0001 respectively). An allele dose dependent tendency was observed for BMI for rs6536991 sample of controls. No other significant associations between any SNP and hypertension, hyperlipidemia and diabetes were noted after correction for BMI and no significant synergistic effect between FTO and UCP-1 SNPs with obesity were noted. There was not an association between rs9939609 (FTO) and rs6536991 (UCP-1) in with maximum weight loss after 1 year in 94 obese patients who underwent bariatric surgery. CONCLUSION: Our data are consistent with FTO rs9939609 and UCP-1 rs6536991 common variants as contributors to obesity in the Brazilian population.


Assuntos
Doenças Cardiovasculares/genética , Diabetes Mellitus/genética , Predisposição Genética para Doença , Canais Iônicos/genética , Proteínas Mitocondriais/genética , Obesidade Mórbida/genética , Polimorfismo de Nucleotídeo Único/genética , Proteínas/genética , Adulto , Dioxigenase FTO Dependente de alfa-Cetoglutarato , Brasil , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Proteína Desacopladora 1
11.
Graefes Arch Clin Exp Ophthalmol ; 250(2): 185-9, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21881842

RESUMO

PURPOSE: To investigate the association between VEGF gene polymorphism and age-related macular degeneration (AMD) in a Brazilian cohort. METHODS: We examined 160 affected individuals and 140 sex- and age-matched controls recruited at the Vision Institute and the Retina Department, São Geraldo Hospital, Minas Gerais Federal University, Brazil, between 2007 and 2011. Genotyping for the VEGF rs1413711 single nucleotide polymorphism (SNP) (+674C>T) was performed. The incidence rate ratios and 95% confidence interval (CI) for AMD for this genotype was calculated. The odds ratio (OR) was also assessed by using logistic regression, controlling for CFH and LOC387715 risk genotype. RESULTS: We observed a prevalence of homozygosity (TT genotype) of 18.1% for rs1413711 among AMD cases compared with 5.8% among controls (P < 0.002). The ORs for this polymorphism were 3.6 (95%CI 1.6-8.2) for homozygous subjects and 1.5 (95%CI 1.1-2.1, P < 0.01) if the subject had at least one risk allele. When we studied separately exudative and dry AMD groups, this polymorphism was statistically significant for both groups. Controlling for CFH and LOC387715 risk genotype the OR was 3.0 for VEGF homozygous, and the OR increases if the patient is homozygous for the three genes. CONCLUSION: The present data suggests that VEGF TT genotype is associated with AMD among Brazilian patients.


Assuntos
Degeneração Macular/genética , Polimorfismo de Nucleotídeo Único , Fator A de Crescimento do Endotélio Vascular/genética , Idoso , Idoso de 80 Anos ou mais , Brasil/epidemiologia , Feminino , Predisposição Genética para Doença , Genótipo , Homozigoto , Humanos , Incidência , Degeneração Macular/epidemiologia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Prevalência , Reação em Cadeia da Polimerase em Tempo Real
12.
Clin Neuropsychiatry ; 19(2): 114-120, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35601244

RESUMO

Objective: The population's adhesion to measures to ensure social distancing represents a great management challenge in a pandemic context. Despite of evidence shown that social distancing is effective, lack of adherence still persists in many countries. Therefore, it is challenging to separate the effectiveness of government measures, from social distancing driven by personal initiatives. Theory: It is possible that the output of protective behaviors, such as adherence to protective measures and staying in social isolation, is influenced by individual characteristics, such as personality traits or symptoms of mental distress of anxiogenic nature. We hypothesized that individuals with more expressive symptoms of fear or anxiety would have a more protective behavioral tendency in terms of risk exposure, leaving less home during the pandemic. In contrast, individuals with greater emotional stability, as they feel more secure and with a lower perception of risk, could go out more often. Method: A total of 2709 individuals from all regions of Brazil participated in the study (mean age = 42 years; 2134 women). Correlation analysis was performed to investigate the relationships between personality traits according to the big five model and Psychopathological Symptoms (BSI). Then, correlation analysis was performed to investigate how people that go out often differ from people that stay at home, in both symptoms and personality traits. Finally, to investigate the predictors for going out usually, we use multiple regression analysis, using gender, marital status, level of education, and personality traits. Results: During the second wave of COVID-19 in Brazil, individuals with higher emotional stability tended to leave home more than those with more expressive levels of anxiogenic dysregulation. These results reinforce the role of both personality traits and psychopathological symptoms in prophylactic behavior during COVID-19 pandemics. Conclusions: Individuals with greater emotional stability were more likely to leave home during the second wave of COVID-19 than those with higher levels of anxiogenic dysregulation.

13.
Cell Mol Neurobiol ; 31(1): 135-43, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20838877

RESUMO

It is well known that dopamine imbalances are associated with many psychiatric disorders and that the dopaminergic receptor D2 is the main target of antipsychotics. Recently it was shown that levels of two proteins implicated in dopaminergic signaling, Neuronal calcium sensor-1 (NCS-1) and DARPP-32, are altered in the prefrontal cortex (PFC) of both schizophrenic and bipolar disorder patients. NCS-1, which inhibits D2 internalization, is upregulated in the PFC of both patients. DARPP-32, which is a downstream effector of dopamine signaling, integrates the pathways of several neurotransmitters and is downregulated in the PFC of both patients. Here, we used PC12 cells stably overexpressing NCS-1 (PC12-NCS-1 cells) to address the function of this protein in DARPP-32 signaling pathway in vitro. PC12-NCS-1 cells displayed downregulation of the cAMP/PKA pathway, with decreased levels of cAMP and phosphorylation of CREB at Ser133. We also observed decreased levels of total and phosphorylated DARPP-32 at Thr34. However, these cells did not show alterations in the levels of D2 and phosphorylation of DARPP-32 at Thr75. These results indicate that NCS-1 modulates PKA/cAMP signaling pathway. Identification of the cellular mechanisms linking NCS-1 and DARPP-32 may help in the understanding the signaling machinery with potential to be turned into targets for the treatment of schizophrenia and other debilitating psychiatric disorders.


Assuntos
Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , AMP Cíclico/metabolismo , Proteínas Sensoras de Cálcio Neuronal/genética , Neuropeptídeos/genética , Animais , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Fosfoproteína 32 Regulada por cAMP e Dopamina/metabolismo , Regulação para Baixo/genética , Regulação para Baixo/fisiologia , Proteínas Sensoras de Cálcio Neuronal/metabolismo , Proteínas Sensoras de Cálcio Neuronal/fisiologia , Neuropeptídeos/metabolismo , Neuropeptídeos/fisiologia , Células PC12 , Fosforilação , Ratos , Receptores de Dopamina D2/metabolismo , Receptores de Dopamina D2/fisiologia , Transdução de Sinais/genética , Transdução de Sinais/fisiologia , Transfecção , Regulação para Cima/genética
14.
Cells ; 10(6)2021 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-34200513

RESUMO

Telomeres are aging biomarkers, as they shorten while cells undergo mitosis. The aim of this study was to evaluate whether psychiatric disorders marked by psychological distress lead to alterations to telomere length (TL), corroborating the hypothesis that mental disorders might have a deeper impact on our physiology and aging than it was previously thought. A systematic search of the literature using MeSH descriptors of psychological distress ("Traumatic Stress Disorder" or "Anxiety Disorder" or "depression") and telomere length ("cellular senescence", "oxidative stress" and "telomere") was conducted on PubMed, Cochrane Library and ScienceDirect databases. A total of 56 studies (113,699 patients) measured the TL from individuals diagnosed with anxiety, depression and posttraumatic disorders and compared them with those from healthy subjects. Overall, TL negatively associates with distress-related mental disorders. The possible underlying molecular mechanisms that underly psychiatric diseases to telomere shortening include oxidative stress, inflammation and mitochondrial dysfunction linking. It is still unclear whether psychological distress is either a cause or a consequence of telomere shortening.


Assuntos
Transtornos Mentais/metabolismo , Mitocôndrias/metabolismo , Estresse Oxidativo , Encurtamento do Telômero , Telômero/metabolismo , Humanos , Transtornos Mentais/genética , Mitocôndrias/genética , Telômero/genética
15.
J Negat Results Biomed ; 9: 4, 2010 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-20565907

RESUMO

BACKGROUND: Schizophrenia is the major psychiatry disorder, which the exact cause remains unknown. However, it is well known that dopamine-mediated neurotransmission imbalance is associated with this pathology and the main target of antipsychotics is the dopamine receptor D2. Recently, it was described alteration in levels of two dopamine signaling related proteins in schizophrenic prefrontal cortex (PFC): Neuronal Calcium Sensor-1 (NCS-1) and DARPP-32. NCS-1, which is upregulated in PFC of schizophrenics, inhibits D2 internalization. DARPP-32, which is decreased in PFC of schizophrenics, is a key downstream effector in transducing dopamine signaling. We previously demonstrated that antipsychotics do not change levels of both proteins in rat's brain. However, since NCS-1 and DARPP-32 levels are not altered in wild type rats, we treated wild type PC12 cells (PC12 WT) and PC12 cells stably overexpressing NCS-1 (PC12 Clone) with antipsychotics to investigate if NCS-1 upregulation modulates DARPP-32 expression in response to antipsychotics treatment. RESULTS: We chronically treated both PC12 WT and PC12 Clone cells with typical (Haloperidol) or atypical (Clozapine and Risperidone) antipsychotics for 14 days. Using western blot technique we observed that there is no change in NCS-1 and DARPP-32 protein levels in both PC12 WT and PC12 Clone cells after typical and atypical antipsychotic treatments. CONCLUSIONS: Because we observed no alteration in NCS-1 and DARPP-32 levels in both PC12 WT and Clone cells treated with typical or atypical antipsychotics, we suggest that the alteration in levels of both proteins in schizophrenic's PFC is related to psychopathology but not with antipsychotic treatment.


Assuntos
Antipsicóticos/farmacologia , Fosfoproteína 32 Regulada por cAMP e Dopamina/metabolismo , Proteínas Sensoras de Cálcio Neuronal/metabolismo , Neuropeptídeos/metabolismo , Animais , Western Blotting , Células Clonais , Células PC12 , Ratos
16.
Arch Womens Ment Health ; 13(3): 285-9, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20169377

RESUMO

Postpartum depression disorder (PPD) is a severe illness affecting around 15% of deliveries. Several evidences suggest that PPD is, at least, partially genetic determined. The gene encoding BDNF is a strong candidate for pathogenesis of PPD since that it has been observed decrease of serum BDNF in patients suffering from PPD. The gene encoding BDNF has a polymorphism (Val66Met) that alters the regulated protein secretion; the methionine variant being associated with insufficient secretion compared with the Valine variant. We hypothesized that BDNF gene Val66Met polymorphism could be associated with PPD. We assessed 227 subjects randomly selected who had delivery at a maternity hospital using EPDS. Differences in genotype frequency were calculated by chi (2) test. Logistic Regression Analyses was performed to verify the existence of interaction between biological, psychiatric and environmental variables and PPD. Difference between groups was tested with Student's t test. Tests were two-tailed and results significant when p < or = 0.05. No difference in BDNF genotype distribution was observed between the depressed and non-depressed women. Educational level, stress during pregnancy, bipolar disorder and anxiety was strongly associated with PPD. We were not able to show an association between BDNF polymorphisms and PPD. Further studies are necessary to both of confirm our results and improve validity of PPD diagnosis.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/genética , Depressão Pós-Parto/epidemiologia , Depressão Pós-Parto/genética , Polimorfismo Genético , Adolescente , Adulto , Brasil/epidemiologia , Feminino , Predisposição Genética para Doença , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Análise Multivariada , Estudos Retrospectivos
17.
Clin Endocrinol (Oxf) ; 71(4): 512-7, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19226263

RESUMO

CONTEXT: Congenital generalized lipodystrophy, or Berardinelli-Seip syndrome, is a rare autosomal recessive disease caused by mutations in either the BSCL2 or AGPAT2 genes. This syndrome is characterized by an almost complete loss of adipose tissue usually diagnosed at birth or early infancy resulting in apparent muscle hypertrophy. Common clinical features are acanthosis nigricans, hepatomegaly with or without splenomegaly and high stature. Acromegaloid features, cardiomyopathy and mental retardation can also be present. DESIGN: We investigated 11 kindreds from different geographical areas of Brazil (northeast and southeast). All coding regions as well as flanking intronic regions of both genes were examined. Polymerase chain reaction (PCR) amplifications were performed using primers described previously and PCR products were sequenced directly. RESULTS: Four AGPAT2 and two BSCL2 families harboured the same set of mutations. BSCL2 gene mutations were found in the homozygous form in four kindreds (c.412C>T c.464T>C, c.518-519insA, IVS5-2A>G), and in two kindreds compound mutations were found (c.1363C>T, c.424A>G). In the other four families, one mutation of the AGPAT2 gene was found (IVS3-1G>C and c.299G>A). CONCLUSIONS: We have demonstrated four novel mutations of the BSCL2 and AGPAT2 genes responsible for Berardinelli-Seip syndrome and Brunzell syndrome (AGPAT2-related syndrome).


Assuntos
1-Acilglicerol-3-Fosfato O-Aciltransferase/genética , Subunidades gama da Proteína de Ligação ao GTP/genética , Lipodistrofia Generalizada Congênita/genética , Adolescente , Adulto , Brasil , Pré-Escolar , Consanguinidade , Feminino , Humanos , Lactente , Masculino , Mutação , Linhagem , Mutação Puntual , Reação em Cadeia da Polimerase
18.
Am J Med Genet B Neuropsychiatr Genet ; 150B(4): 483-6, 2009 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-18698576

RESUMO

Previously the Slit and Trk-like family member 1 (SLITRK1) gene was identified as a candidate gene for Gilles de la Tourette Syndrome (GTS) based on a patient that carried a chromosomal inversion on 13q, as well as the identification of two rare DNA variants in the SLITRK1 gene. Since that report, studies have tested for the two rare variants in GTS and either did not find them, or when found, they did not segregate with the disorder in families, casting doubt on the relationship of this gene to GTS. We tested for these two rare variants and genotyped three polymorphisms that tag the currently identified major haplotypes of this gene in a sample of 154 nuclear families with GTS. In addition, the entire coding region was screened for novel DNA variants. We did not find the two reported rare variants in any of the probands or siblings in these families. We did however find significant evidence for association of a single polymorphism and of haplotypes of the three tagging polymorphisms. These findings provide the first support for the original finding indicating SLITRK1 as a susceptibility gene for GTS and indicate that further study of this gene in GTS is warranted.


Assuntos
Frequência do Gene/genética , Predisposição Genética para Doença , Proteínas de Membrana/genética , Proteínas do Tecido Nervoso/genética , Síndrome de Tourette/genética , Alelos , Genótipo , Haplótipos , Humanos , Linhagem , Polimorfismo de Nucleotídeo Único/genética
19.
J Pediatr (Rio J) ; 95(6): 736-743, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30236592

RESUMO

OBJECTIVE: To investigate the psychometric properties of the short or multimodal treatment study version of the Swanson, Nolan, and Pelham, Version IV (SNAP-IV) scale, which measures attention-deficit/hyperactivity disorder and oppositional defiant disorder symptoms. METHODS: Participants were 765 parents of children from 4 to 16 years old (641 non-attention-deficit/hyperactivity disorder and 124 attention-deficit/hyperactivity disorder children) from Belo Horizonte, Brazil, who reported sociodemographic characteristics and answered the SNAP-IV. Parents of the clinical sample also underwent the K-SADS-PL interview. RESULTS: Age was significantly associated with SNAP-IV hyperactivity-impulsivity problems (r=-0.14), but not with inattention or oppositional defiant disorder. Sex was a significant influence on attention-deficit/hyperactivity disorder and oppositional defiant disorder severity (all p<0.001), with boys showing higher scores in the full sample, but not within the attention-deficit/hyperactivity disorder group. Exploratory and confirmatory factor analysis supports a three-factor structure of the SNAP-IV scale. Moderate-to-strong correlations were found between SNAP-IV and K-SADS-PL measures. All SNAP-IV scales showed very high internal consistency coefficients (all above 0.91). SNAP-IV inattention scores were the most predictive of attention-deficit/hyperactivity disorder diagnosis (AUC: 0.877 for the averaging rating method and the raw sum method, and 0.874 for the symptom presence/absence method). CONCLUSION: The parent SNAP-IV showed good psychometric properties in a Brazilian school and clinical sample.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Pais , Adolescente , Brasil , Criança , Análise Fatorial , Feminino , Humanos , Masculino , Relações Pais-Filho , Psicometria , Reprodutibilidade dos Testes , Estudantes , Inquéritos e Questionários
20.
Epilepsy Res ; 154: 152-156, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31153103

RESUMO

The International League Against Epilepsy (ILAE) classification system for hippocampal sclerosis (HS) is based on location and extent of hippocampal neuron loss. Specific subgroups have a better surgical prognosis. Automated hippocampal subfields segmentation and volume measure could be obtained from high field MRI and used to pre-operatively classify the patients in ILAE subgroups to define best candidates for surgery. This prospective study included 86 MTLE patients, candidates to surgical treatment and ten healthy volunteers. Volumetric analysis of the hippocampal sublayers was performed through the Freesurfer software, using 3 Teslas volumetric T1 weighted MRI. We correlated the hippocampal subfields measures with the seizure control after one year from surgery. Volume loss in Cornu Amonis (CA) 1 and 4 were related to better surgical outcome after one year. Atrophy in CA 2 and CA 3 did not improve the prognosis. These results are in agreement with the ILAE classification of hippocampal subfields sclerosis.


Assuntos
Epilepsia do Lobo Temporal/diagnóstico por imagem , Epilepsia do Lobo Temporal/cirurgia , Hipocampo/diagnóstico por imagem , Hipocampo/cirurgia , Imageamento por Ressonância Magnética/métodos , Adulto , Feminino , Humanos , Imageamento por Ressonância Magnética/tendências , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Estudos Prospectivos , Resultado do Tratamento , Adulto Jovem
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