Neuroglobin Facilitates Neuronal Oxygenation through Tropic Migration under Hypoxia or Anemia in Rat: How Does the Brain Breathe? / 神经科学通报·英文版

The discovery of neuroglobin (Ngb), a brain- or neuron-specific member of the hemoglobin family, has revolutionized our understanding of brain oxygen metabolism. Currently, how Ngb plays such a role remains far from clear. Here, we report a novel mechanism by which Ngb might facilitate neuronal oxygenation upon hypoxia or anemia. We found that Ngb was present in, co-localized to, and co-migrated with mitochondria in the cell body and neurites of neurons. Hypoxia induced a sudden and prominent migration of Ngb towards the cytoplasmic membrane (CM) or cell surface in living neurons, and this was accompanied by the mitochondria. In vivo, hypotonic and anemic hypoxia induced a reversible Ngb migration toward the CM in cerebral cortical neurons in rat brains but did not alter the expression level of Ngb or its cytoplasm/mitochondria ratio. Knock-down of Ngb by RNA interference significantly diminished respiratory succinate dehydrogenase (SDH) and ATPase activity in neuronal N2a cells. Over-expression of Ngb enhanced SDH activity in N2a cells upon hypoxia. Mutation of Ngb at its oxygen-binding site (His64) significantly increased SDH activity and reduced ATPase activity in N2a cells. Taken together, Ngb was physically and functionally linked to mitochondria. In response to an insufficient oxygen supply, Ngb migrated towards the source of oxygen to facilitate neuronal oxygenation. This novel mechanism of neuronal respiration provides new insights into the understanding and treatment of neurological diseases such as stroke and Alzheimer's disease and diseases that cause hypoxia in the brain such as anemia.

Sinovite e tenossinovite no Brasil: uma análise dos benefícios auxílio-doença / Synovitis and tenosynovitis in Brazil: analysis of sickness benefit claims

OBJETIVO: Analisar os fatores pessoais associados à prevalência e duração dos benefícios auxílio-doença decorrentes de sinovite e tenossinovite (CID10 M65). MÉTODO: Estudo transversal referente aos benefícios auxílio-doença decorrentes de sinovite e tenossinovite concedidos pelo Instituto Nacional de Seguro Social aos empregados no Brasil em 2008. Dados sobre o ramo de atividade econômica (Classificação Nacional de Atividades Econômicas - CNAE divisão, classe), sexo, idade, espécie e duração dos benefícios foram coletados do Sistema Único de Benefícios. A população corresponde à média mensal dos vínculos empregatícios declarados ao Cadastro Nacional de Informações Sociais. RESULTADOS: Em 2008 foram concedidos 35.601 benefícios auxílio-doença decorrentes de sinovite e tenossinovite, com prevalência de 10,9/10.000 vínculos empregatícios. No conjunto dos benefícios auxílio-doença houve maior razão de prevalência (RP) acidentária (RP 1,2), sendo esta maior em mulheres (RP 3,3), e em trabalhadores com idade acima de 39 anos (RP 1,4). As CNAE 37-Esgoto (55,4) e 60-Atividade de rádio e TV (47,1) apresentaram as maiores prevalências, no entanto, 64-Atividade de serviços financeiros e 6422-Bancos múltiplos caracterizaram mais acidentes de trabalho (RP 3,2 e 3,8, respectivamente) e maior duração (70 e 73 dias, respectivamente). A maior duração de benefício ocorreu entre trabalhadores com idade superior a 39 anos. Tanto a CNAE-divisão 60-Atividade de rádio e TV, quanto a CNAE-classe 6010-Atividade de rádio apresentaram elevadas razões de feminilidade (RP 8,1 e 10,8, respectivamente). CONCLUSÃO: A incapacidade para o trabalho por sinovite e tenossinovite apresenta associação tanto da prevalência quanto da duração com o ramo de atividade, sexo, idade e espécie de benefício (previdenciário/acidentário). .

OBJECTIVE: To analyse the personal and occupational factors associated with the prevalence and duration of sickness benefit claims due to synovitis and tenosynovitis (CID10 M65). METHODS: Cross-sectional study regarding sickness benefit claims due to synovitis and tenosynovitis granted to employees by National Institute of Social Security in Brazil in 2008. Data on economic activity (Economic Activities National Classification - CNAE division, class), sex, age, type and duration of benefits were collected from the Unified Benefit System. The study's population consists of the average monthly employment contracts declared to the National Register of Social Information. RESULTS: In 2008, 35,601 employees were granted sickness benefits due to synovitis and tenosynovitis, with a prevalence of 10.9/10,000 employments. Sickness benefits showed higher prevalence rates (PR) for work-related claims (PR 1,2), mostly made by females (PR 3.3) and by workers older than 39 years (PR 1,4). The CNAE 37-Sewage (55.4) and 60-Broadcasting Activity (47.1) had the highest overall prevalence. However, the 64-Financial service activities, except insurance and pension funding and 6422-Multiple banks with commercial service had the highest rates of work-related claims (RP 3.2 and 3.8, respectively), and the longer duration (70 and 73 days, respectively). Workers older than 39 years had the highest durations of work disability claims. Both the CNAE-division 60-Broadcasting Activity, and the CNAE-class 6010-Radio showed a high activity ratio of females (PR 8.1 and 10.8, respectively). CONCLUSION: The work disability due to synovitis and tenosynovitis presents prevalence and duration associated with economic activity, sex, age and kind of benefit (non work-related and work-related claims). .

As infecções genitais podem alterar os resultados dos testes preditivos do parto prematuro? / Can genital infections alter the results of preterm birth predictive tests?

OBJETIVOS: Verificar se a presença de agentes infecciosos no conteúdo vaginal ou cervical pode alterar os resultados dos testes da proteína-1 fosforilada ligada ao fator de crescimento insulina-símile (phIGFBP-1) e das medidas do comprimento do colo uterino (CC) pela ultrassonografia transvaginal. MÉTODOS: Um total de 107 gestantes com antecedente de prematuridade espontânea foram submetidas ao teste da phIGFBP-1 e à realização da ultrassonografia transvaginal para medida do comprimento do colo uterino, a cada três semanas, entre 24 e 34 semanas. As infecções genitais foram pesquisadas imediatamente antes da realização dos testes. As pacientes foram distribuídas em quatro grupos (GA, GB, GC e GD) e dentro de cada grupo foi avaliada a correlação entre infecção genital e alteração nos testes utilizando a análise das razões de chance (OR) e o coeficiente de correlação de Pearson. RESULTADOS: Em cada grupo, mais de 50% das pacientes apresentaram infecção genital (GA 10/17; GB 28/42; GC 15/24; GD 35/53), sendo a vaginose bacteriana a principal alteração de flora vaginal. O resultado positivo para phIGFBP-1 (GA 10/10; GB 18/28; GC 15/15; GD 19/35) e CC≤20 mm (GA 10/10; GB 20/28; GC 10/15; GD 20/35) foram os resultados encontrados com maior frequência nas pacientes com infecção genital em todos os grupos. Porém, aplicando o coeficiente de correlação de Pearson foi identificada correlação entre infecção genital e positividade para os marcadores. CONCLUSÃO: A presença de alteração da flora vaginal e de outras infecções genitais não alteram significativamente os resultados do teste da phIGFBP-1 e da medida do colo uterino quando comparados aos casos sem infecção. No entanto, é necessária ...

PURPOSE: To determine if the presence of infectious agents in vaginal or cervical content can alter the results of the insulin-like growth factor binding protein-1 (phIGFBP-1) test and the measurement of cervical length (CC) by transvaginal ultrasonography. METHODS: A total of 107 pregnant women with a history of spontaneous preterm birth were submitted to the phIGFBP-1 test and to measurement of CC by transvaginal ultrasonography every 3 weeks, between 24 and 34 weeks of gestation. Genital infections were determined immediately before testing. The patients were distributed into four groups (GA, GB, GC, and GD) and the correlation between genital infection and changes in the tests was determined within each group based on the odds ratio (OR) and the Pearson correlation coefficient. RESULTS: In each group, over 50% of the patients had genital infections (GA 10/17; GB 28/42; GC 15/24; GD 35/53), with bacterial vaginosis being the main alteration of the vaginal flora. Positive results for phIGFBP-1(GA 10/10; GB 18/28; GC 15/15; GD 19/35) and CC≤20 mm (GA 10/10; GB 20/28; GC 10/15; GD 20/35) were obtained more frequently in patients with genital infection in all groups. Nonetheless, when applying the Pearson correlation coefficient we detected a poor correlation between genital infection and positivity for markers. CONCLUSION: The presence of changes in the vaginal flora and of other genital infections does not significantly alter the results of phIGFBP-1 and the measurement of cervical length when compared to cases without infection. However, more studies with larger samples are necessary to confirm these results. .

Spectrin interactions with globin chains in the presence of phosphate metabolites and hydrogen peroxide: implications for thalassaemia.

We have shown the differential interactions of the erythroid skeletal protein spectrin with the globin subunits of adult haemoglobin (HbA); these indicate a preference for alpha-globin over that for beta-globin and intact HbA in an adenosine 5'-triphosphate (ATP)-dependent manner. The presence of Mg/ATP led to an appreciable decrease in the binding affinity of the alpha-globin chain to spectrin and the overall yield of globin-spectrin cross-linked complexes formed in the presence of hydrogen peroxide. Similar effects were also seen in the presence of 2-,3-diphosphoglycerate (2,3 DPG), the other important phosphate metabolite of erythrocytes. The binding affinity and yield of cross-linked high molecular weight complexes (HMWCs) formed under oxidative conditions were significantly higher in alpha-globin compared with intact haemoglobin, HbA and the beta-globin chain. The results of this study indicate a possible correlation of the preferential spectrin binding of the alpha-globin chain over that of the beta-globin in the haemoglobin disorder beta-thalassaemia.

Human erythroid progenitors from adult bone marrow and cord blood in optimized liquid culture systems respectively maintained adult and neonatal characteristics of globin gene expression

In vitro suspension culture procedures for erythroid progenitor cells make it possible for us to obtain large cultures of erythrocyte populations for the investigation of globin gene switching. In this study we aimed to establish optimized culture systems for neonatal and adult erythroblasts and to explore the globin expression patterns in these culture systems. To culture CD34+ cells purified from human umbilical cord blood (CB) and adult bone marrow (BM), we respectively replaced the fetal bovine serum (FBS) with human cord serum and human adult serum. These CD34+ cells were then induced to erythroid differentiation. All the globin mRNA (including alfa-, xi-, vita-, gama-and epsilón-globin), the hemoglobin (Hb)-producing erythroid cells and the cellular distribution of fetal hemoglobin (Hb F) were identified during the culture process. The results showed that the globin expression pattern during erythroid differentiation in our culture systems closely recapitulated neonatal and adult patterns of globin expression in vivo, suggesting that our specially optimized culture systems not only overcame the higher Hb F levels in the BM-derived CD34+ culture in FBS-containing medium but also eliminated the disadvantages of low cell proliferation rate and low globin mRNA levels in serum-free medium.

The Agamma-195 (C->G) mutation in hereditary persistence of fetal hemoglobin is not associated with activation of a reporter gene in vitro

Hereditary persistence of fetal hemoglobin is an uncommon, benign disorder in which the expression of gamma-globin genes persists into adult life. Several point mutations have been associated with the increased gamma-globin gene promoter activity. We evaluated the -195 (C->G) mutation by a functional in vitro assay based on the luciferase reporter gene system. The results indicated that the increased promoter activity observed in vivo could not be reproduced in vitro under the conditions employed, suggesting that other factors may be involved in the overexpression of the gamma-globin gene containing the -195 (C->G) mutation. Furthermore, this is the first time that the -195 (C->G) mutation of the Agamma-globin gene has been evaluated by in vitro gene expression