ABSTRACT
CONTEXT AND OBJECTIVE: Neonatal sepsis is associated with premature birth and maternal infection. Large-scale studies seek to define markers that identify neonates at risk of developing sepsis. Here, we examine whether the scientific evidence supports systematic use of polymorphism genotyping in cytokine and innate immunity genes, to identify neonates at increased risk of sepsis. DESIGN AND SETTING: Narrative literature review conducted at Fernandes Figueira Institute, Brazil. METHODS: The literature was searched in PubMed, Embase (Excerpta Medica Database), Lilacs (Literatura Latino-Americana e do Caribe em Ciências da Saúde), SciELO (Scientific Electronic Library Online) and Cochrane Library. From > 400,000 references, 548 were retrieved based on inclusion/exclusion criteria; 22 were selected for detailed analysis after quality assessment. RESULTS: The studies retrieved addressed the impact of gene polymorphisms relating to immune mechanisms (most often TNF-a, LT-a, IL-6, IL-1ß, IL-1ra, L-selectin, CD14 and MBL) or inflammatory mechanisms (ACE and angiotensin II receptors; secretory PLA2; and hemostatic factors). Despite initial reports suggesting positive associations between specific polymorphisms and increased risk of sepsis, the accumulated evidence has not confirmed that any of them have predictive power to justify systematic genotyping. CONCLUSIONS: Sepsis prediction through systematic genotyping needs to be reevaluated, based on studies that demonstrate the functional impact of gene polymorphisms and epidemiological differences among ethnically distinct populations.
Subject(s)
Cytokines/genetics , Immunity, Innate/genetics , Infant, Newborn, Diseases/genetics , Polymorphism, Genetic/genetics , Sepsis/genetics , Cytokines/immunology , Female , Genetic Markers , Genetic Predisposition to Disease , Genotyping Techniques/methods , Humans , Infant, Newborn , Infant, Newborn, Diseases/immunology , Male , Risk Assessment , Risk Factors , Sepsis/immunologyABSTRACT
CONTEXT AND OBJECTIVE: Neonatal sepsis is associated with premature birth and maternal infection. Large-scale studies seek to define markers that identify neonates at risk of developing sepsis. Here, we examine whether the scientific evidence supports systematic use of polymorphism genotyping in cytokine and innate immunity genes, to identify neonates at increased risk of sepsis. DESIGN AND SETTING: Narrative literature review conducted at Fernandes Figueira Institute, Brazil. METHODS: The literature was searched in PubMed, Embase (Excerpta Medica Database), Lilacs (Literatura Latino-Americana e do Caribe em Ciências da Saúde), SciELO (Scientific Electronic Library Online) and Cochrane Library. From > 400,000 references, 548 were retrieved based on inclusion/exclusion criteria; 22 were selected for detailed analysis after quality assessment. RESULTS: The studies retrieved addressed the impact of gene polymorphisms relating to immune mechanisms (most often TNF-a, LT-a, IL-6, IL-1β, IL-1ra, L-selectin, CD14 and MBL) or inflammatory mechanisms (ACE and angiotensin II receptors; secretory PLA2; and hemostatic factors). Despite initial reports suggesting positive associations between specific polymorphisms and increased risk of sepsis, the accumulated evidence has not confirmed that any of them have predictive power to justify systematic genotyping. CONCLUSIONS: Sepsis prediction through systematic genotyping needs to be reevaluated, based on studies that demonstrate the functional impact of gene polymorphisms and epidemiological differences among ethnically distinct populations. .
CONTEXTO E OBJETIVO: A sepse neonatal está associada ao parto prematuro e à infecção materna. Estudos em grande escala buscam marcadores que identifiquem neonatos em risco de desenvolver sepse. Examinamos aqui se a evidência científica apoia o uso sistemático de genotipagem dos polimorfismos em genes de citocinas e imunidade inata, para identificar neonatos com risco elevado de sepse. TIPO DE ESTUDO E LOCAL: Revis ão narrativa da literatura, Instituto Fernandes Figueira, Brasil. M ÉTODOS: Busca online da literatura foi feita no PubMed, Embase (Excerpta Medica Database), Lilacs (Literatura Latino-Americana e do Caribe em Ciências da Saúde), SciELO (Scientific Electronic Library Online) e Cochrane Library. De mais de 400.000 referências, 548 foram recuperadas com base nos critérios de inclusão/exclusão, e 22, selecionadas para análise detalhada após verificação da qualidade. RESULTADOS: Recuperamos estudos de impacto dos polimorfismos em genes relacionados com mecanismos imunes (mais frequentemente, TNF-a, LT-a, IL-6, IL-1 β, IL-1ra, L-selectin, CD14, e MBL) ou inflamatórios (ACE e receptores de angiotensina II; PLA2 secretória; fatores hemostáticos). Contrariando estudos que inicialmente sugeriram associação positiva entre polimorfismos específicos e risco aumentado de sepse, a evidência acumulada não confirmou, para qualquer deles, valor preditivo que justifique genotipagem sistemática para orientar antibioticoterapia. CONCLUSÕES: A previsão da sepse por meio de genotipagem sistemática precisa ser reavaliada, com base em estudos que demonstram o impacto funcional de polimorfismos gênicos e as diferenças epidemiológicas entre populações etnicamente distintas. .
Subject(s)
Female , Humans , Infant, Newborn , Male , Cytokines/genetics , Immunity, Innate/genetics , Infant, Newborn, Diseases/genetics , Polymorphism, Genetic/genetics , Sepsis/genetics , Cytokines/immunology , Genetic Markers , Genetic Predisposition to Disease , Genotyping Techniques/methods , Infant, Newborn, Diseases/immunology , Risk Assessment , Risk Factors , Sepsis/immunologyABSTRACT
BACKGROUND: Platelet-derived growth factor (PDGF) is a mitogen and chemoattractant for cells of mesenchymal origin. Over-expression of PDGF-B can promote formation of inflammatory lesions in the lungs of transgenic mice. Moreover, continuous exposure to PDGF inhibits collagen production by osteoblastic cells. Thus, the expression of mitogenic factors in an inflammatory context may limit the differentiated function of cells, and thereby limit repair following periodontal attachment and bone loss. The goals of the present study were to test whether PDGF is present at increased levels in inflamed gingiva and to localize its expression in gingival biopsies from individuals with chronic periodontitis. METHODS: Tissues obtained during therapeutic procedures from inflamed and control sites of 9 patients were subjected to protein extraction, descriptive histology by hematoxylin and eosin, or immunohistochemistry assays. Quantification was calculated with an enzyme-linked immunosorbent assay (ELISA) kit specific for PDGF-AB. For the immunolocalization, anti-PDGF-A and -B antibodies were employed. RESULTS: PDGF concentration in the total protein extract was approximately 3 times higher in the inflamed sites (0.60 +/- 0.18 ng/mg versus 0.20 +/- 0.05 ng/mg; P = 0.03). Immunohistochemistry revealed prominent expression of PDGF in the pocket epithelial cells as well as the adjacent connective tissue. In contrast, little or no expression was detected in control biopsies devoid of the pocket epithelium and granulation tissue. CONCLUSIONS: PDGF is present in increased levels in the human inflamed gingiva and is mainly localized to the pocket epithelium. It is possible that chronic expression of PDGF contributes to the inflammatory changes that occur during periodontal diseases.
Subject(s)
Gingiva/pathology , Periodontitis/pathology , Platelet-Derived Growth Factor/analysis , Adult , Aged , Antibodies , Chronic Disease , Coloring Agents , Connective Tissue/metabolism , Connective Tissue/pathology , Epithelial Cells/metabolism , Epithelial Cells/pathology , Female , Gingiva/metabolism , Humans , Male , Matched-Pair Analysis , Middle Aged , Periodontal Pocket/metabolism , Periodontal Pocket/pathology , Periodontitis/metabolism , Proteins/analysisABSTRACT
Estudo retrospectivo com revisäo dos casos clínicos de Sídrome do Desconforto Respiratório Agudo, realizado no período de out/88 a dez/90 na Unidade de Pacientes Graves do Instituto Fernandes Figueira. Os autores estudaram as características clínicas, radiológicas e histopatológicas de acordo com o estágio evolutivo da doença. Dentre 459 casos estudados, foram selecionados 49 (11 por cento). Onze casos tiveram exame anatomopatológico [biopsia (4), necropsia (8) e foram classificados de acordo com o estágio evolutivo em: fase exsudativa inicial, fase proliferativa celular e fase proliferativa fibrótica. Houve correlaçäo clínica radiológica e anatomopatológica nos casos confirmados com exame histológico. Os autores consideram importante estudos futuros em que a interaçäo entre a pesquisa clínica e experimental permita o melhor conhecimento desta Síndrome na populaçäo pediátrica
