Selénio e a importância para o organismo humano

O selénio (Se) é um micronutriente essencial para o crescimento, desenvolvimento e normal metabolismo dos animais, incluindo o ser humano. É parte integrante de um conjunto de proteínas, as selenoproteínas, com ação antioxidante (protegendo as membranas celulares contra danos dos radicais livres), envolvidas no metabolismo das hormonas da tiróide, na regulação do crescimento e viabilidade celular, nas funções do sistema imune e na reprodução. É introduzido na dieta alimentar (principalmente nas formas de selenometionina e selenocisteína) através das plantas, e de produtos que delas derivam, que assimilam os compostos de selénio presentes no solo. Uma vez que a quantidade de selénio existente nos solos é muito variável, o teor nos alimentos vai depender da sua origem geográfica e, por consequência, a ingestão de selénio varia entre regiões e países. Baixos níveis de selénio estão associados a um declínio na função imune e problemas cognitivos. A deficiência de Se pode também ocasionar problemas musculares e cardiomiopatia. Concentrações reduzidas foram observadas em indíviduos com crises epiléticas e também em casos de pré-eclampsia. A deficiência de selénio pode também desenvolver-se durante a nutrição parenteral. Atualmente, a Dose Diária Recomendada (DDR) é de 55 μg/dia para homens e mulheres adultos e saudáveis. No entanto, existem evidências clínicas de que a ingestão em doses superiores (200-300 μg/dia) pode ter um papel benéfico na prevenção de alguns tipos de cancro e doenças cardiovasculares, na melhoria da resposta imunológica, como neuroprotetor e na fertilidade. O Se desempenha um papel importante na fertilidade masculina, sendo necessário na biossíntese da testosterona e na formação e normal desenvolvimento dos espermatozóides. Em mulheres grávidas o Se, ajuda a prevenir complicações antes e durante o parto e promove o normal desenvolvimento do feto. Como antioxidante o selénio vai combater os danos provocados pelos radicais livres, impedindo que estes exerçam o seu papel prejudicial no organismo. Sendo o sistema imunológico muito suscetível aos danos provocados pelo stress oxidativo, o Se vai exercer efeitos benéficos combatendo os danos por ele causados. Relativamente à capacidade viral, não é possível saber com exatidão qual a quantidade de Se necessária ou concentração ideal no plasma para evitar a ocorrência e desenvolvimento de infeções virais. No entanto, sabe-se que tem um efeito benéfico em pacientes HIV positivos e em indivíduos infetados com o vírus da hepatite (B ou C) contra a progressão para o neoplasia de fígado. Em teoria, a nível cardiovascular, este elemento pode exercer um efeito protetor, embora alguns estudos epidemiológicos não tenham mostrado uma associação clara entre o risco cardiovascular e os níveis selénio. A nível cerebral o Se vai atuar como neuroprotetor, prevenindo o aparecimento de patologias como demência e doença de Alzheimer. Apesar destes indicadores, a maioria dos países europeus, incluindo Portugal, regista uma deficiente ingestão de selénio por parte da população. A suplementação poderá constituir uma opção para garantir os níveis nutricionais recomendados e/ou ser utilizada com o objetivo de prevenir algumas doenças e o envelhecimento. No entanto o selénio pode também ser tóxico se ingerido em excesso, estando a dose máxima admissível fixada em 400 μg/dia. A intoxicação por selénio é chamada selenose e os sintomas comuns incluem: hálito a alho, distúrbios gastrointestinais, perda de cabelo, descamação das unhas, danos neurológicos e fadiga. Assim, atualmente acredita-se que enquanto indivíduos com baixo nível de Se podem obter benefícios da suplementação, esta pode ser prejudicial aqueles com valores normais ou elevados.

Host determinants of HIV-1 control in African Americans.

We performed a whole-genome association study of human immunodeficiency virus type 1 (HIV-1) set point among a cohort of African Americans (n = 515), and an intronic single-nucleotide polymorphism (SNP) in the HLA-B gene showed one of the strongest associations. We use a subset of patients to demonstrate that this SNP reflects the effect of the HLA-B*5703 allele, which shows a genome-wide statistically significant association with viral load set point (P = 5.6 x 10(-10)). These analyses therefore confirm a member of the HLA-B*57 group of alleles as the most important common variant that influences viral load variation in African Americans, which is consistent with what has been observed for individuals of European ancestry, among whom the most important common variant is HLA-B*5701.

Using decision analysis to improve malaria control policy making.

Malaria and other vector-borne diseases represent a significant and growing burden in many tropical countries. Successfully addressing these threats will require policies that expand access to and use of existing control methods, such as insecticide-treated bed nets (ITNs) and artemesinin combination therapies (ACTs) for malaria, while weighing the costs and benefits of alternative approaches over time. This paper argues that decision analysis provides a valuable framework for formulating such policies and combating the emergence and re-emergence of malaria and other diseases. We outline five challenges that policy makers and practitioners face in the struggle against malaria, and demonstrate how decision analysis can help to address and overcome these challenges. A prototype decision analysis framework for malaria control in Tanzania is presented, highlighting the key components that a decision support tool should include. Developing and applying such a framework can promote stronger and more effective linkages between research and policy, ultimately helping to reduce the burden of malaria and other vector-borne diseases.

Developing drugs for developing countries.

Infectious and parasitic diseases create enormous health burdens, but because most of the people suffering from these diseases are poor, little is invested in developing treatments. We propose that developers of treatments for neglected diseases receive a "priority review voucher." The voucher could save an average of one year of U.S. Food and Drug Administration (FDA) review and be sold by the developer to the manufacturer of a blockbuster drug. In a well-functioning market, the voucher would speed access to highly valued treatments. Thus, the voucher could benefit consumers in both developing and developed countries at relatively low cost to the taxpayer.

Chlamydia trachomatis Infection Leads to Defined Alterations to the Lipid Droplet Proteome in Epithelial Cells.

The obligate intracellular bacterium Chlamydia trachomatis is a major human pathogen and a main cause of genital and ocular diseases. During its intracellular cycle, C. trachomatis replicates inside a membrane-bound vacuole termed an "inclusion". Acquisition of lipids (and other nutrients) from the host cell is a critical step in chlamydial replication. Lipid droplets (LD) are ubiquitous, ER-derived neutral lipid-rich storage organelles surrounded by a phospholipids monolayer and associated proteins. Previous studies have shown that LDs accumulate at the periphery of, and eventually translocate into, the chlamydial inclusion. These observations point out to Chlamydia-mediated manipulation of LDs in infected cells, which may impact the function and thereby the protein composition of these organelles. By means of a label-free quantitative mass spectrometry approach we found that the LD proteome is modified in the context of C. trachomatis infection. We determined that LDs isolated from C. trachomatis-infected cells were enriched in proteins related to lipid metabolism, biosynthesis and LD-specific functions. Interestingly, consistent with the observation that LDs intimately associate with the inclusion, a subset of inclusion membrane proteins co-purified with LD protein extracts. Finally, genetic ablation of LDs negatively affected generation of C. trachomatis infectious progeny, consistent with a role for LD biogenesis in optimal chlamydial growth.

Pathophysiology of feline hyperadrenocorticism clinical. Case presentation

Hyperadrenocorticism is a rare endocrine disease in the cat; it is characterized by elevated blood cortisol level that generates numerous clinical signs including hyperglycemia, polyuria, polydipsia, polyphagia and skin diseases. The average age of onset is around 10 years. This disease usually occurs link with other endocrine disorders such as diabetes mellitus.The disease can be produced by functional alteration of the pituitary gland or the adrenal. A case report, with differential diagnosis and review of the literature, is presented.

Habitat for Humanity: Calibrating Best Practice Against the MDGs

Poverty alleviation lies at the heart of contemporary international initiatives on development. The key to development is the creation of an environment in which people can develop their potential, leading productive, creative lives in accordance with their needs, interests and faith. This entails, on the one hand, protecting the vulnerable from things that threaten their survival, such as inadequate nutrition, disease, conflict, natural disasters and the impact of climate change, thereby enhancing the poor’s capabilities to develop resilience in difficult conditions. On the other hand, it also requires a means of empowering the poor to act on their own behalf, as individuals and communities, to secure access to resources and the basic necessities of life such as water, food, shelter, sanitation, health and education. ‘Development’, from this perspective, seeks to address the sources of human insecurity, working towards ‘freedom from want, freedom from fear’ in ways that empower the vulnerable as agents of development (not passive recipients of benefaction).

Recognition of the magnitude of the problems confronted by the poor and failure of past interventions to tackle basic issues of human security led the United Nations (UN) in September 2000 to set out a range of ambitious, but clearly defined, development goals to be achieved by 2015. These are known as the Millennium Development Goals (MDGs). The intention of the UN was to mobilise multilateral international organisations, non-governmental organisations and the wider international community to focus attention on fulfilling earlier promises to combat global poverty. This international framework for development prioritises: the eradication of extreme poverty and hunger; achieving universal primary education; promoting gender equality and empowering women; reducing child mortality; improving maternal health; combating HIV/AIDS, malaria and other diseases; ensuring environmental sustainability; and developing a global partnership for development. These goals have been mapped onto specific targets (18 in total) against which outcomes of associated development initiatives can be measured and the international community held to account. If the world achieves the MDGs, more than 500 million people will be lifted out of poverty. However, the challenges the goals represent are formidable. Interim reports on the initiative indicate a need to scale-up efforts and accelerate progress.
Only MDG 7, Target 11 explicitly identifies shelter as a priority, identifying the need to secure ‘by 2020 a significant improvement in the lives of at least 100 million slum dwellers’. This raises a question over how Habitat for Humanity’s commitment to tackling poverty housing fits within this broader international framework designed to allievate global poverty. From an analysis of HFH case studies, this report argues that the processes by which Habitat for Humanity tackles poverty housing directly engages with the agenda set by the MDGs. This should not be regarded as a beneficial by-product of the delivery of decent, affordable shelter, but rather understood in terms of the ways in which Habitat for Humanity has translated its mission and values into a participatory model that empowers individuals and communities to address the interdependencies between inadequate shelter and other sources of human insecurity. What housing can deliver is as important as what housing itself is.

Examples of the ways in which Habitat for Humanity projects engage with the MDG framework include the incorporation of sustainable livelihoods strategies, up-grading of basic infrastructure and promotion of models of good governance. This includes housing projects that have also offered training to young people in skills used in the construction industry, microfinanced loans for women to start up their own home-based businesses, and the provision of food gardens. These play an important role in lifting families out of poverty and ensuring the sustainability of HFH projects. Studies of the impact of improved shelter and security of livelihood upon family life and the welfare of children evidence higher rates of participation in education, more time dedicated to study and greater individual achievement. Habitat for Humanity projects also typically incorporate measures to up-grade the provision of basic sanitation facilities and supplies of safe, potable drinking water. These measures not only directly help reduce mortality rates (e.g. diarrheal diseases account for around 2 million deaths annually in children under 5), but also, when delivered through HFH project-related ‘community funds’, empower the poor to mobilise community resources, develop local leadership capacities and even secure de facto security of tenure from government authorities.

In the process of translating its mission and values into practical measures, HFH has developed a range of innovative practices that deliver much more than housing alone. The organisation’s participatory model enables both direct beneficiaries and the wider community to tackle the insecurities they face, unlocking latent skills and enterprise, building sustainable livelihood capabilities. HFH plays an important role as a catalyst for change, delivering through the vehicle of housing the means to address the primary causes of poverty itself. Its contribution to wider development priorities deserves better recognition. In calibrating the success of HFH projects in terms of units completed or renovated alone, the significance of the process by which HFH realises these outcomes is often not sufficiently acknowledged, both within the organisation and externally. As the case studies developed in the report illustrate, the methodologies Habitat for Humanity employs to address the issue of poverty housing within the developing world, place the organisation at the centre of a global strategic agenda to address the root causes of poverty through community empowerment and the transformation of structures of governance.

Given this, the global network of HFH affiliates constitutes a unique organisational framework to faciliate sharing resources, ideas and practical experience across a diverse range of cultural, political and institutional environments. This said, it is apparent that work needs to be done to better to faciliate the pooling of experience and lessons learnt from across its affiliates. Much is to be gained from learning from less successful projects, sharing innovative practices, identifying strategic partnerships with donors, other NGOs and CBOs, and engaging with the international development community on how housing fits within a broader agenda to alleviate poverty and promote good governance.

A unique homologue of the eukaryotic protein-modifier ubiquitin present in the bacterium Bacteroides fragilis, a predominant resident of the human gastro-intestinal tract

In the complete genome sequences of Bacteroides fragilis NCTC9343 and 638R, we have discovered a gene, ubb, the product of which has 63% identity to human ubiquitin and cross-reacts with antibodies raised against bovine ubiquitin. The sequence of ubb is closest in identity (76%) to the ubiquitin gene from a Migratory Grasshopper entomopoxvirus, suggesting acquisition by inter-kingdom horizontal gene transfer. We have screened clinical isolates of B. fragilis from diverse geographical regions and found that ubb is present in some, but not all strains. The gene is transcribed and the mRNA translated in B. fragilis, but deletion of ubb did not have a detrimental effect on growth. BfUbb has a predicted signal sequence; both full length and processed forms were detected in whole cell extracts, while the processed form was found in concentrated culture supernatants. Purified recombinant BfUbb inhibited in vitro ubiquitination and was able to covalently bind the human E1 activating enzyme, suggesting it could act as a suicide substrate in vivo. B. fragilis is one of the predominant members of the normal human resident gastro-intestinal microbiota with estimates up to >1011 cells g-1 of faeces by culture. These data indicate that the gastro-intestinal tract of some individuals could contain a significant amount of aberrant ubiquitin with the potential to inappropriately activate the host immune system and/or interfere with eukaryotic ubiquitin activity. This discovery could have profound implications in relation to our understanding of human diseases such as inflammatory bowel and autoimmune diseases.

Mutation altering the miR-184 seed region causes keratoconus with cataract

MicroRNAs (miRNAs) bind to complementary sequences within the 3? untranslated region (UTR) of mRNAs from hundreds of target genes, leading either to mRNA degradation or suppression of translation. We found that a mutation in the seed region of miR-184 (MIR184) is responsible for familial severe keratoconus combined with early-onset anterior polar cataract, by deep sequencing of a linkage region known to contain the mutation. The mutant form fails to compete with miR-205 (MIR205) for overlapping target sites on the 3? UTRs of INPPL1 and ITGB4. Although these target genes and miR-205 are expressed widely, the phenotype is restricted to the cornea and lens because of the very high expression of miR-184 in these tissues. Our finding highlights the tissue-specificity of a gene network regulated by a miRNA. Awareness of the important function of miRNAs may aid identification of susceptibility genes and new therapeutic targets for treatment of both rare and common diseases.

Scurvy in the Great Irish Famine: Evidence of Vitamin C Deficiency From a Mid-19th Century Skeletal Population

Scurvy has increasingly been recognized in archaeological populations since the 1980s but this study represents the first examination of the paleopathological findings of scurvy in a known famine population. The Great Famine (1845–1852) was a watershed in Irish history and resulted in the death of one million people and the mass emigration of just as many. It was initiated by a blight which completely wiped out the potato—virtually the only source of food for the poor of Ireland. This led to mass starvation and a widespread occurrence of infectious and metabolic diseases. A recent discovery of 970 human skeletons from mass burials dating to the height of the famine in Kilkenny City (1847–1851) provided an opportunity to study the skeletal manifestations of scurvy—a disease that became widespread at this time due to the sudden lack of Vitamin C which had previously almost exclusively been provided by the potato. A three-scale diagnostic reliance approach has been employed as a statistical aid for diagnosing the disease in the population. A biocultural approach was adopted to enable the findings to be contextualized and the etiology and impact of the disease explored. The results indicate that scurvy indirectly influenced famine-induced mortality. A sex and stature bias is evident among adults in which males and taller individuals displayed statistically significantly higher levels of scorbutic lesions. The findings have also suggested that new bone formation at the foramen rotundum is a diagnostic criterion for the paleopathological identification of scurvy, particularly among juveniles. Am J Phys Anthropol, 2012. © 2012 Wiley Periodicals, Inc.