Differentiation of normal and cancer cells induced by sulfhydryl reduction: biochemical and molecular mechanisms

We examined the morphological, biochemical and molecular outcome of a nonspecific sulfhydryl reduction in cells, obtained by supplementation of N-acetyl-L-cysteine (NAC) in a 0.1-10 mM concentration range. In human normal primary keratinocytes and in colon and ovary carcinoma cells we obtained evidences for: (i) a dose-dependent inhibition of proliferation without toxicity or apoptosis; (ii) a transition from a proliferative mesenchymal morphology to cell-specific differentiated structures; (iii) a noticeable increase in cell-cell and cell-substratum junctions; (iv) a relocation of the oncogenic beta-catenin at the cell-cell junctions; (v) inhibition of microtubules aggregation; (vi) upregulation of differentiation-related genes including p53, heat shock protein 27 gene, N-myc downstream-regulated gene 1, E-cadherin, and downregulation of cyclooxygenase-2; (vii) inhibition of c-Src tyrosine kinase. In conclusion, a thiol reduction devoid of toxicity as that operated by NAC apparently leads to terminal differentiation of normal and cancer cells through a pleiade of converging mechanisms, many of which are targets of the recently developed differentiation therapy

Acute respiratory viral infections in children in Rio de Janeiro and Teresópolis, Brazil

The frequency of viral pathogens causing respiratory infections in children in the cities of Rio de Janeiro and Teresópolis was investigated. Nasal swabs from children with acute respiratory illnesses were collected between March 2006 and October 2007. Specimens were tested for viral detection by conventional (RT)-PCR and/or real time PCR. Of the 205 nasal swabs tested, 64 (31.2%) were positive for at least one of the viral pathogens. Single infections were detected in 56 samples, 50 of those were caused by RNA viruses: 33 samples tested positive for rhinovirus, five for influenza A, five for metapneumovirus, four for coronavirus and, three for respiratory syncytial virus. For the DNA viruses, five samples were positive for bocavirus and one for adenovirus. Co-infections with these viruses were detected in eight samples. Our data demonstrate a high frequency of viral respiratory infections, emphasizing the need for a more accurate diagnosis particularly for the emerging respiratory viruses. The fact that the emerging respiratory viruses were present in 9.2% of the tested samples suggests that these viruses could be important respiratory pathogens in the country

Acute respiratory infections in children Infecções respiratórias agudas em crianças

Acute respiratory infections (ARI) are the leading cause of mortality in children under five years of age worldwide and most of these deaths are due to bronchiolitis and pneumonia. Recent evidence from studies using genome detection systems such as polymerase chain reaction or micro-array technology show that, in most cases, these deaths are caused or precipitated by viruses. In this paper, the definitions of upper and lower respiratory tract infections are reviewed. The principal signs of disease severity and the burden of viruses as causes of ARI are described. The prominent role of Respiratory Syncytial Virus is stressed, with data from epidemiological and clinical studies. Other important viral pathogens, such as Human Metapneumovirus, Human coronaviruses and Influenza are examined. The role of newly described viruses, such as bocavirus, is also discussed. The impact of HIV/AIDS in ARI burden and presentation assessed and the weight of Pneumocystis jiroveci and Mycobacterium tuberculosis infections is recognized. It is concluded that there is an urgent need to improve diagnostics, therapeutics and vaccines, as well as macro and micronutrient intake of children of the world, particularly in developing countries.<br>As infecções respiratórias agudas (IRA) são as principais causas da40 mortalidade mundial em crianças menores de cinco anos de idade e a maioria dessas mortes são próprias da bronquiolite e pneumonia. Recentes evidências de estudos usando sistemas de detecção no genoma tais como reação em cadeia da polimerase ou tecnologia de microarrays mostram que, na maioria dos casos, essas mortes são causadas ou precipitadas por vírus. Neste artigo, as definições das infecções dos tratos respiratórios superior e inferior são revisadas. Os principais sinais da gravidade da doença e a carga viral como causas da IRA estão descritas. O papel proeminente do vírus sincicial respiratório é enfatizado, com dados de estudos clínicos e epidemiológicos. Outros importantes patógenos virais, tais como o metapneumovírus humano, o coronavírus humano e influenza são examinados. O papel dos vírus recentemente descritos tais como o bocavírus, é também discutido. O impacto do HIV/AIDS na apresentação e ônus da IRA é avaliado e a sobrecarga das infecções de Pneumocystis jiroveci e Mycobacterium tuberculosis é reconhecidas. Conclui-se que há uma necessidade urgente de melhorar o diagnóstico, a terapêutica e as vacinas, bem como a ingestão de macro e micronutrientes das crianças do mundo, particularmente aquelas de países em desenvolvimento