Multi-Locus Models to Address Hb F Variability in Portuguese ß-Thalassemia Carriers.

Hb F production is under the influence of major quantitative trait loci (QTL). The present study aims: i) to replicate the association with Hb F for representative genetic variants in the three major Hb F QTLs in a Portuguese sample of ß-thalassemia (ß-thal) carriers; and ii) to test different genetic multi-locus models to account for the genetic component of Hb F variation. A population sample of 79 Portuguese ß-thal carriers (39 males, 40 females), aged between 2 to 70 years old, were genotyped for polymorphisms in the locus control region (LCR)-5' hypersensitive site 4 (5'HS4) rs16912979, XmnI-HBG2 rs7482144, BCL11A rs1427407 and HMIP rs66650371, using standard biomolecular procedures. Univariate linear regression models were used to test for genetic associations with Hb F. The minor alleles of the individual variants BCL11A rs1427407 (T) (0.165), HMIP rs66650371 (3 bp del) (0.247) and XmnI-HBG2 rs7482144 (T) (0.196), were found to be significantly associated with increased levels of Hb F (p = 0.029, p = 0.002 and p = 0.0004, respectively), explaining about 6.0, 12.0 and 15.0% of Hb F variation, respectively. In a multiple linear regression approach, the three loci accounted for about 30.0% of Hb F variance. Two genetic risk scores (GRS), rationalizing the number of minor alleles into a single genetic variable, explained about 30.0 and 32.0% of the Hb F variation. In conclusion, we replicated in ß-thal carriers previously reported associations with Hb F. Multi-locus models combining three representative variants of Hb F influencing QTLs can explain a larger amount of Hb F variability.

Neuroprotection During Neospora caninum Infection Is Related To the Release of Neurotrophic Factors BDNF and NGF.

Neospora caninum is a parasite that infects many animal species and has tropism for various tissues, particularly the nervous system, where it generally remains in cysts. Under N. caninum infection, glial cells activate immune responses by a Th2 profile, suggesting an immunologically privileged environment that controls parasite proliferation, with neuronal preservation. In this study, we investigated the role of soluble neurotrophic factors released by glial cells on neuronal integrity during N. caninum infection in vitro. Primary cultures of rat glial cells enriched in astrocytes were infected with N. caninum tachyzoites (1:1) for 24 hr. Neuron-glia co-cultures were cultured for 24 hr with conditioned medium from glial cells infected with N. caninum (CMNc) and from uninfected cultures (control). Cell viability was determined through a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test; astrocyte morphology and reactivity were determined through immunocytochemistry for glial fibrillar acid protein (GFAP) and the integrity of neurons through immunocytochemistry for ß-tubulin III. Expression of inflammatory cytokines and neurotrophic factors was determined through RT-qPCR. The MTT test demonstrated that 1:1 was the best parasite/host cell ratio, considering that it was enough to increase metabolism of glial cells when compared with control cultures and was not cytotoxic after 48 hr infection. N. caninum-infected glial cultures responded with astrogliosis characterized by an increase in GFAP expression and increase in IL-10 (2-fold), BDNF (1.6-fold), and NGF (1.7-fold) gene expression. In the neuron/glia co-cultures, it was observed that treatment with CMNc induced neuritis outgrowth without toxicity. Together, these results show that modulatory mechanisms by neurotrophic factors derived from glial cells, primarily astrocytes during the N. caninum infection, can favor neuroprotection.

A massive galaxy in its core formation phase three billion years after the Big Bang.

Most massive galaxies are thought to have formed their dense stellar cores in early cosmic epochs. Previous studies have found galaxies with high gas velocity dispersions or small apparent sizes, but so far no objects have been identified with both the stellar structure and the gas dynamics of a forming core. Here we report a candidate core in the process of formation 11 billion years ago, at redshift z = 2.3. This galaxy, GOODS-N-774, has a stellar mass of 100 billion solar masses, a half-light radius of 1.0 kiloparsecs and a star formation rate of solar masses per year. The star-forming gas has a velocity dispersion of 317 ± 30 kilometres per second. This is similar to the stellar velocity dispersions of the putative descendants of GOODS-N-774, which are compact quiescent galaxies at z ≈ 2 (refs 8-11) and giant elliptical galaxies in the nearby Universe. Galaxies such as GOODS-N-774 seem to be rare; however, from the star formation rate and size of this galaxy we infer that many star-forming cores may be heavily obscured, and could be missed in optical and near-infrared surveys.

The intense starburst HDF 850.1 in a galaxy overdensity at z ≈ 5.2 in the Hubble Deep Field.

The Hubble Deep Field provides one of the deepest multiwavelength views of the distant Universe and has led to the detection of thousands of galaxies seen throughout cosmic time. An early map of the Hubble Deep Field at a wavelength of 850 micrometres, which is sensitive to dust emission powered by star formation, revealed the brightest source in the field, dubbed HDF 850.1 (ref. 2). For more than a decade, and despite significant efforts, no counterpart was found at shorter wavelengths, and it was not possible to determine its redshift, size or mass. Here we report a redshift of z = 5.183 for HDF 850.1, from a millimetre-wave molecular line scan. This places HDF 850.1 in a galaxy overdensity at z ≈ 5.2, corresponding to a cosmic age of only 1.1 billion years after the Big Bang. This redshift is significantly higher than earlier estimates and higher than those of most of the hundreds of submillimetre-bright galaxies identified so far. The source has a star-formation rate of 850 solar masses per year and is spatially resolved on scales of 5 kiloparsecs, with an implied dynamical mass of about 1.3 × 10(11) solar masses, a significant fraction of which is present in the form of molecular gas. Despite our accurate determination of redshift and position, a counterpart emitting starlight remains elusive.

Análise crítica do atendimento da crise hipertensiva em Unidade de Pronto Atendimento de Itaperuna - Rio de Janeiro / Critical analysis of the treatment of hypertensive crises in Emergency Unit of Itaperuna - Rio de Janeiro

Fundamento: São frequentes os diagnósticos de crises hipertensivas nos postos de urgência, tornando-se importante o conhecimento dos aspectos relacionados a ocorrência e controle. Objetivo: Avaliar o perfil dos pacientes com diagnóstico de crise hipertensiva, prevalência e tratamento medicamentoso. Métodos: Perfil e fatores de risco dos pacientes com diagnóstico de crise hipertensiva atendidos em um Posto de Urgência do Município de Itaperuna, Rio de Janeiro, foram avaliados durante nove meses. Verificaram-se também os níveis pressóricos dos pacientes à admissão, os medicamentos administrados, bem como os níveis de redução da pressão arterial. Resultados: Foram avaliados 107 pacientes, 58 (54,2%) do sexo feminino e 49 (45,8%) do sexo masculino, com idade média de 59 anos. Os sintomas mais associados às crises hipertensivas na admissão foram cefaleia, fadiga, tonteira e prostração. A pressão arterial média na admissão foi de 188,00 mmHg x 106,84 mmHg para as pressões sistólica e diastólica, respectivamente. Os valores médios referentes à redução da pressão arterial, desde a admissão até a alta dos pacientes, foram de 21,48 mmHg para a sistólica e de 11,37 mmHg para a diastólica, após tratamentos nos quais o captopril foi a droga mais utilizada. Conclusão: A maioria dos pacientes apresenta urgência hipertensiva e as mulheres apresentam níveis mais elevados na pressão arterial sistólica, enquanto que os níveis masculinos da diastólica são mais elevados. O principal medicamento utilizado é o captopril e as reduções médias foram de 11,42% e de 10,64%, respectivamente, para as pressões sistólica e diastólica, desde a admissão até a alta do paciente.

Positividade dos anticorpos contra o vírus da hepatite C (anti-HCV) e do antígeno de superfície do vírus da hepatite B (AgHBs) em adultos infectados com o vírus da imunodeficiência humana (HIV) / The positiveness of antibodies against the virus of hepatitis C (anti-HCV) and of the antigen of surface of the virus of hepatitis B (AgHBs) in adults infected with the human immunodeficiency virus (HIV)

Objetivo: determinar a positividade do anti-HCV e do AgHBs em pacientes sororreagentes para o HIV, atendidos no Serviço de DST/Aids do Centro de Saúde Raul Travassos e em uma clínica particular, em Itaperuna, Rio de Janeiro. Método: foram analisados os prontuários de 110 pacientes testados para o vírus C por meio do seu anticorpo anti-HCV (método Elisa de terceira geração, Hepatitis C anti-HCV da Wiener lab.) e de 115 pacientes testados para o vírus B por meio do seu antígeno de superfície (AgHBs). Resultados: a coinfecção HIV/HCV foi detectada em 9% e a co-infecção HIV/HBV foi detectada em 12% da amostra. Não houve nenhum caso de co-infecção HIV-HCV-HBV.

Mercury intake by inflammatory phagocytes: in vivo cytology of mouse macrophages and neutrophils by X-ray elemental microanalysis coupled with scanning electron microscopy.

Phagocytes remove and store mercury (Hg) that enters the body. Macrophages and granulocytes respond in opposite ways to Hg: macrophages loose cell viability, and neutrophils become protected from apoptosis. We have investigated the cytology of early intake of Hg by macrophages and neutrophils after a short period (2-4 min) of in vivo exposure to HgCl2. The two types of phagocytes were attracted either to a subcutaneous air pouch or to the peritoneal cavity of BALB/c mice by in situ BSA injection. BSA caused, 72 hours later, inflammatory exudates where neutrophils (air-pouch cavity) or macrophages (peritoneal cavity) were the predominant cell type. A lethal dose of HgCl2 (25 mg) was then injected in the two inflammatory cavities. The mice died 2-4 min later and the cell exudates were harvested and studied by scanning electron microscopy coupled with X-ray elemental microanalysis (SEM-XRM). More than half of the phagocytes showed ingested Hg; a higher percentage of macrophages (around 70%) than neutrophils (around 50%) were positive for the metal. Intracellular particles of Hg were spheroid and presented a small diameter (less than 20 nm). They could be seen in large numbers inside phagocytes (up to 20-30 Hg dots per cell); they were scattered throughout the cytoplasm of the cells. The ability of phagocytes to ingest Hg increased as the BSA-induced inflammation progressed. We conclude that (i) Hg is quickly ingested as small particles by phagocytes; (ii) endocytosis of Hg increases with the degree of activation of phagocytes; and (iii) phagocytes internalize Hg by pinocytosis.

High-resolution identification of mercury in particles in mouse kidney after acute lethal exposure.

Contamination of the food chain by mercury is a major concern of Public Health of our day. Kidney and nervous system are the major targets of mercury toxicity in mammals. We show here that the detailed subcellular in vivo topography of microparticles of mercury in tissues can be achieved by scanning electron microscopy (SEM) coupled with X-ray elemental microanalysis (XRM). SEM-XRM offered the fine topography of mercury in the kidney of BALB/c mice that were submitted to an intraperitoneal lethal injection of mercuric chloride (HgCl2). All of the renal mercury was seen inside blood vessels located in both cortex and medulla of the mouse kidney. This blood-born mercury was organised in spheroid particles of less than 50 nm in diameter (31.4 +/- 14.1 nm). They were seen attached either to aggregates of plasma proteins or to the surface of blood cells. No evidence of internalisation of mercury by blood, endothelial or kidney cells was found. The average kidney density of mercury microspheres was 1920 +/- 1320 particles per mm2. We propose SEM-XRM as an elective approach to further investigations, at the subcellular level, on the quantitative dynamics of mercury particles in the tissues.

Quantification of particles of lethal mercury in mouse viscera: high-resolution study of mercury in cells and tissues.

To investigate the early visceral distribution of mercury (Hg), we have intraperitoneally injected a lethal dose of HgCl2 that killed BALB/c mice within 2-4 min. Scanning electron microscopy coupled with X-ray microanalysis (SEM-XRM) was used to detect and quantify Hg in situ in different organs. The highest density of Hg was seen in the liver (60.9+/-24.9 Hg particles per mm2 of tissue); this density was three and six times higher than those of renal or splenic Hg, respectively. Hg was scarce in the lungs and absent in the brain. Considering the relative weights of mouse viscera, our quantitative data show that the liver captured 89% of the visceral Hg; the kidneys captured 8.5% and the spleen just 1.7%. SEM-XRM revealed that most of the visceral Hg was associated with resident macrophages, a few Hg dots being detected on the surface of erythrocytes. We conclude that: (i) most intraperitoneally injected Hg was captured by liver Kupffer cells within minutes of injection; (ii) a 10-fold lower density of Hg particles was observed in the kidneys, and a 50-fold lower deposition of Hg was found in the spleen; (iii) SEM-XRM is an adequate method to quantify microparticles of Hg in tissues and cells.

In vivo ingestion of heavy metal particles of Se, Hg and W by murine macrophages. A study using scanning electron microscopy coupled with X-ray microanalysis.

Several heavy metals that are currently employed in industry may become polluters of work and natural environments. As particulate matter, heavy metals are suitable for entering the human body through the respiratory and digestive systems. They often end up inside phagocytes; the size of the microscopic particles modulates both their phagocytosis, and the physiology of macrophages. Here we have adopted an experimental model to investigate the ingestion of particles of three industrial heavy metals (Se, Hg, W) by murine peritoneal macrophages in vivo. The phagocytes were studied by scanning electron microscopy coupled with X-ray elemental microanalysis (SEM-XRM), a method that allows specific identification of Se, W and Hg in cells at high resolution. We found that Hg that was taken up by macrophages was organized into small, round particles (0.31 +/- 0.14 microm). This was in contrast with the larger size of intracellular particles of Se (2.37 +/- 1.84 microm) or W (1.75 +/- 1.34 microm). Ingested particles of Se and W, but not Hg, often caused bulging of the cell surface of macrophages. We conclude that particulate matters of Se, W and Hg are organized in particles of different size inside macrophages. This size difference is likely to be associated with distinct phlogistic activities of these heavy metals, Se and W causing a milder inflammatory reaction than Hg.