Lack of association between the 5-HTTLPR and positive screening for mental disorders among children exposed to urban violence and maltreatment

Objective: To ascertain whether genetic variations in the serotonin transporter gene (5-HTTLPR 44-bp insertion/deletion polymorphism) influence an increase in depressive and anxiety symptoms in children and adolescents exposed to high levels of violence. Methods: Saliva samples were collected from a group of children who were working on the streets and from their siblings who did not work on the streets. DNA was extracted from the saliva samples and analyzed for 5-HTTLPR polymorphism genotypes. Results: One hundred and seventy-seven children between the ages of 7 and 14 years were analyzed (114 child workers and 63 siblings). Data on socioeconomic conditions, mental symptoms, and presence and severity of maltreatment and urban violence were collected using a sociodemographic inventory and clinical instruments. There was no positive correlation between the 5-HTTLPR polymorphism and presence of mental symptoms in our sample, although the children were exposed to high levels of abuse, neglect, and urban violence. Conclusions: Despite previous studies that associated adult psychiatric disorders with the 5-HTTLPR polymorphism and a history of childhood maltreatment, no such association was found in this sample of children at risk.Universidade Federal de São Paulo (UNIFESP) Department of PsychiatryOcular Genetic InstituteCollege of Public Health, USPUniversidade de São Paulo (USP) Institute of Mathematics and StatisticsKing's College London Institute of Psychiatry Health Service and Population Research DepartmentUNIFESP, Department of PsychiatrySciEL

Screening, production and biochemical characterization of a new fibrinolytic enzyme produced by Streptomyces sp. (Streptomycetaceae) isolated from Amazonian lichens

Thrombosis is a pathophysiological disorder caused by accumulation of fibrin in the blood. Fibrinolytic proteases with potent thrombolytic activity have been produced by diverse microbial sources. Considering the microbial biodiversity of the Amazon region, this study aimed at the screening, production and biochemical characterization of a fibrinolytic enzyme produced by Streptomyces sp. isolated from Amazonian lichens. The strain Streptomyces DPUA1576 showed the highest fibrinolytic activity, which was 283 mm2. Three variables at two levels were used to assess their effects on the fibrinolytic production. The parameters studied were agitation (0.28 - 1.12 g), temperature (28 - 36 ºC) and pH (6.0 - 8.0); all of them had significant effects on the fibrinolytic production. The maximum fibrinolytic activity (304 mm2) was observed at 1.12 g, 28 ºC, and pH of 8.0. The crude extract of the fermentation broth was used to assess the biochemical properties of the enzyme. Protease and fibrinolytic activities were stable during 6 h, at a pH ranging from 6.8 to 8.4 and 5.8 to 9.2, respectively. Optimum temperature for protease activity ranged between 35 and 55 °C, while the highest fibrinolytic activity was observed at 45 ºC. Proteolytic activity was inhibited by Cu2+ and Co2+ ions, phenylmethylsulfonyl fluoride (PMSF) and pepstatin A, which suggests that the enzyme is a serine protease. Enzymatic extract cleaved fibrinogen at the subunits A-chain, A-chain, and -chain. The results indicated that Streptomyces sp. DPUA 1576 produces enzymes with fibrinolytic and fibrinogenolytic activity, enzymes with an important application in the pharmaceutical industry.The authors grateful acknowledge the financial support of Fundação de Amparo a Pesquisa do Estado de Pernambuco (FACEPE, Pernambuco, Brazil, N. 0158-2.12/11), CNPq/ RENORBIO (National Counsel of Technological and Scientific Development, N.55146/2010-3) and National Council for the Improvement of Higher Education (CAPES, Brazil) for the scholarship. The author thanks editor and reviewers for their review and comments.info:eu-repo/semantics/publishedVersio

An. Acad. Bras. Ciênc.

Abstract Mesenchymal stem cells present clinical potential to recover and regenerate injured tissues in diverse pathologies. The in vitro expansion and characterization of these cells contribute to elucidation of the mechanisms of senescence and strategies involving cell therapies. This study aimed to compare specific characteristics between initial and advanced passages of mesenchymal stem cells derived from adipose tissue and bone marrow. Both cell types were characterized according to immunophenotype, osteogenic differentiation, genomic instability, migration assay, doubling population time and colony forming ability. Our results demonstrated that both cell types were able to maintain an immunophenotypic profile typical of mesenchymal stem cells during increasing passages. Adipose stem cells at initial passage presented greater migration capacity compared to advanced passage cells, and advanced passage cells proliferated faster than initial passage cells. Bone marrow stem cells at early passages presented higher osteogenic potential than advanced. At advanced passages they presented higher colony forming capacity and genetic damage than those at initial passage. These results suggest that mesenchymal stem cells maintained in culture presented characteristics of senescence that should be monitored prior the use in regenerative medicine and cells derived from bone marrow at initial passage have better potential for therapeutic use in bone tissue engineering

Inflammasome-Mediated IL-1β Production in Humans with Cystic Fibrosis

Inflammation and infection are major determinants of disease severity and consequently, the quality of life and outcome for patients with cystic fibrosis (CF). Interleukin-1 beta (IL-1β) is a key inflammatory mediator. Secretion of biologically active IL-1β involves inflammasome-mediated processing. Little is known about the contribution of IL-1β and the inflammasomes in CF inflammatory disease. This study examines inflammasome-mediated IL-1β production in CF bronchial epithelial cell lines and human patients with CF.Bronchial epithelial cell lines were found to produce negligible amounts of basal or stimulated IL-1β compared to hematopoeitic cells and they did not significantly upregulate caspase-1 activity upon inflammasome stimulation. In contrast, peripheral blood mononuclear cells (PBMCs) from both CF and healthy control subjects produced large amounts of IL-1β and strongly upregulated caspase-1 activity upon inflammasome stimulation. PBMCs from CF patients and controls displayed similar levels of caspase-1 activation and IL-1β production when stimulated with inflammasome activators. This IL-1β production was dependent on NF-κB activity and could be enhanced by priming with LPS. Finally, chemical inhibition of CFTR activity in control PBMCs and THP-1 cells did not significantly alter IL-1β or IL-8 production in response to P. aeruginosa.Hematopoeitic cells appear to be the predominant source of inflammasome-induced pro-inflammatory IL-1β in CF. PBMCs derived from CF subjects display preserved inflammasome activation and IL-1β secretion in response to the major CF pathogen Pseudomonas aeruginosa. However, our data do not support the hypothesis that increased IL-1β production in CF subjects is due to an intrinsic increase in NF-κB activity through loss of CFTR function