Haptoglobin Phenotype, Preeclampsia Risk and the Efficacy of Vitamin C and E Supplementation to Prevent Preeclampsia in a Racially Diverse Population

Haptoglobin's (Hp) antioxidant and pro-angiogenic properties differ between the 1-1, 2-1, and 2-2 phenotypes. Hp phenotype affects cardiovascular disease risk and treatment response to antioxidant vitamins in some non-pregnant populations. We previously demonstrated that preeclampsia risk was doubled in white Hp 2-1 women, compared to Hp 1-1 women. Our objectives were to determine whether we could reproduce this finding in a larger cohort, and to determine whether Hp phenotype influences lack of efficacy of antioxidant vitamins in preventing preeclampsia and serious complications of pregnancy-associated hypertension (PAH). This is a secondary analysis of a randomized controlled trial in which 10,154 low-risk women received daily vitamin C and E, or placebo, from 9-16 weeks gestation until delivery. Hp phenotype was determined in the study prediction cohort (n = 2,393) and a case-control cohort (703 cases, 1,406 controls). The primary outcome was severe PAH, or mild or severe PAH with elevated liver enzymes, elevated serum creatinine, thrombocytopenia, eclampsia, fetal growth restriction, medically indicated preterm birth or perinatal death. Preeclampsia was a secondary outcome. Odds ratios were estimated by logistic regression. Sampling weights were used to reduce bias from an overrepresentation of women with preeclampsia or the primary outcome. There was no relationship between Hp phenotype and the primary outcome or preeclampsia in Hispanic, white/other or black women. Vitamin supplementation did not reduce the risk of the primary outcome or preeclampsia in women of any phenotype. Supplementation increased preeclampsia risk (odds ratio 3.30; 95% confidence interval 1.61-6.82, p<0.01) in Hispanic Hp 2-2 women. Hp phenotype does not influence preeclampsia risk, or identify a subset of women who may benefit from vitamin C and E supplementation to prevent preeclampsia

Inducing mineral precipitation in groundwater by addition of phosphate

<p>Abstract</p> <p>Background</p> <p>Induced precipitation of phosphate minerals to scavenge trace elements from groundwater is a potential remediation approach for contaminated aquifers. The success of engineered precipitation schemes depends on the particular phases generated, their rates of formation, and their long term stability. The purpose of this study was to examine the precipitation of calcium phosphate minerals under conditions representative of a natural groundwater. Because microorganisms are present in groundwater, and because some proposed schemes for phosphate mineral precipitation rely on stimulation of native microbial populations, we also tested the effect of bacterial cells (initial densities of 10⁵and 10⁷mL^-1) added to the precipitation medium. In addition, we tested the effect of a trace mixture of propionic, isovaleric, formic and butyric acids (total concentration 0.035 mM).</p> <p>Results</p> <p>The general progression of mineral precipitation was similar under all of the study conditions, with initial formation of amorphous calcium phosphate, and transformation to poorly crystalline hydroxylapatite (HAP) within one week. The presence of the bacterial cells appeared to delay precipitation, although by the end of the experiments the overall extent of precipitation was similar for all treatments. The stoichiometry of the final precipitates as well as Rietveld structure refinement using x-ray diffraction data indicated that the presence of organic acids and bacterial cells resulted in an increasing <it>a </it>and decreasing <it>c </it>lattice parameter, with the higher concentration of cells resulting in the greatest distortion. Uptake of Sr into the solids was decreased in the treatments with cells and organic acids, compared to the control.</p> <p>Conclusions</p> <p>Our results suggest that the minerals formed initially during an engineered precipitation application for trace element sequestration may not be the ones that control long-term immobilization of the contaminants. In addition, the presence of bacterial cells appears to be associated with delayed HAP precipitation, changes in the lattice parameters, and reduced incorporation of trace elements as compared to cell-free systems. Schemes to remediate groundwater contaminated with trace metals that are based on enhanced phosphate mineral precipitation may need to account for these phenomena, particularly if the remediation approach relies on enhancement of <it>in situ </it>microbial populations.</p

Modifier Effects between Regulatory and Protein-Coding Variation

Genome-wide associations have shown a lot of promise in dissecting the genetics of complex traits in humans with single variants, yet a large fraction of the genetic effects is still unaccounted for. Analyzing genetic interactions between variants (epistasis) is one of the potential ways forward. We investigated the abundance and functional impact of a specific type of epistasis, namely the interaction between regulatory and protein-coding variants. Using genotype and gene expression data from the 210 unrelated individuals of the original four HapMap populations, we have explored the combined effects of regulatory and protein-coding single nucleotide polymorphisms (SNPs). We predict that about 18% (1,502 out of 8,233 nsSNPs) of protein-coding variants are differentially expressed among individuals and demonstrate that regulatory variants can modify the functional effect of a coding variant in cis. Furthermore, we show that such interactions in cis can affect the expression of downstream targets of the gene containing the protein-coding SNP. In this way, a cis interaction between regulatory and protein-coding variants has a trans impact on gene expression. Given the abundance of both types of variants in human populations, we propose that joint consideration of regulatory and protein-coding variants may reveal additional genetic effects underlying complex traits and disease and may shed light on causes of differential penetrance of known disease variants

Influence of Uranium on Bacterial Communities: A Comparison of Natural Uranium-Rich Soils with Controls

This study investigated the influence of uranium on the indigenous bacterial community structure in natural soils with high uranium content. Radioactive soil samples exhibiting 0.26% - 25.5% U in mass were analyzed and compared with nearby control soils containing trace uranium. EXAFS and XRD analyses of soils revealed the presence of U(VI) and uranium-phosphate mineral phases, identified as sabugalite and meta-autunite. A comparative analysis of bacterial community fingerprints using denaturing gradient gel electrophoresis (DGGE) revealed the presence of a complex population in both control and uranium-rich samples. However, bacterial communities inhabiting uraniferous soils exhibited specific fingerprints that were remarkably stable over time, in contrast to populations from nearby control samples. Representatives of Acidobacteria, Proteobacteria, and seven others phyla were detected in DGGE bands specific to uraniferous samples. In particular, sequences related to iron-reducing bacteria such as Geobacter and Geothrix were identified concomitantly with iron-oxidizing species such as Gallionella and Sideroxydans. All together, our results demonstrate that uranium exerts a permanent high pressure on soil bacterial communities and suggest the existence of a uranium redox cycle mediated by bacteria in the soil

Attenuation of Chondrogenic Transformation in Vascular Smooth Muscle by Dietary Quercetin in the MGP-Deficient Mouse Model

RATIONALE: Cartilaginous metaplasia of vascular smooth muscle (VSM) is characteristic for arterial calcification in diabetes and uremia and in the background of genetic alterations in matrix Gla protein (MGP). A better understanding of the molecular details of this process is critical for the development of novel therapeutic approaches to VSM transformation and arterial calcification. OBJECTIVE: This study aimed to identify the effects of bioflavonoid quercetin on chondrogenic transformation and calcification of VSM in the MGP-null mouse model and upon TGF-β3 stimulation in vitro, and to characterize the associated alterations in cell signaling. METHODS AND RESULTS: Molecular analysis revealed activation of β-catenin signaling in cartilaginous metaplasia in Mgp-/- aortae in vivo and during chondrogenic transformation of VSMCs in vitro. Quercetin intercepted chondrogenic transformation of VSM and blocked activation of β-catenin both in vivo and in vitro. Although dietary quercetin drastically attenuated calcifying cartilaginous metaplasia in Mgp-/- animals, approximately one-half of total vascular calcium mineral remained as depositions along elastic lamellae. CONCLUSION: Quercetin is potent in preventing VSM chondrogenic transformation caused by diverse stimuli. Combined with the demonstrated efficiency of dietary quercetin in preventing ectopic chondrogenesis in the MGP-null vasculature, these findings indicate a potentially broad therapeutic applicability of this safe for human consumption bioflavonoid in the therapy of cardiovascular conditions linked to cartilaginous metaplasia of VSM. Elastocalcinosis is a major component of MGP-null vascular disease and is controlled by a mechanism different from chondrogenic transformation of VSM and not sensitive to quercetin

Abordagem diagnóstica e terapêutica da toxoplasmose em gestantes e as repercussões no recém-nascido Diagnostic and therapeutic management of toxoplasmosis in pregnancy and the effect in the newborn

OBJETIVO:Avaliar a abordagem diagnóstica e terapêutica da toxoplasmose de gestantes que apresentaram IgM positiva para a doença e o acompanhamento de seus filhos em um hospital público no Rio de Janeiro, RJ. MÉTODOS: Estudo transversal retrospectivo de 2003 a 2006, realizado por meio da análise dos prontuários de 98 gestantes com sorologia IgM positiva para toxoplasmose e seus filhos (99 crianças). O seguimento das crianças com e sem infecção congênita foram analisados, assim como a apresentação clínica daquelas com infecção congênita e os testes diagnósticos utilizados para identificar a infecção pelo Toxoplasma gondii durante a gestação. RESULTADOS: O diagnóstico sorológico foi realizado em 76 pacientes no segundo e terceiro trimestre gestacional. Em 36 gestantes, a determinação dos níveis séricos de IgM foi o único teste diagnóstico realizado para infecção pelo toxoplasma. Em 49 gestantes, os índices de IgM, pela técnica ELFA, foram baixos. O teste de avidez de IgG foi realizado em 62 gestantes e somente 13 o realizaram no primeiro trimestre gestacional. O tratamento específico para toxoplasmose foi empregado em 93 gestantes. A taxa de transmissão vertical foi de 4%. Manifestações clínicas de toxoplasmose congênita foram encontradas em todas as crianças infectadas. Todas as crianças não infectadas apresentaram declínio de IgG específica para toxoplasmose ao longo do acompanhamento ambulatorial; a idade média de IgG comprovadamente negativa nessas crianças foi de 5,4 meses. CONCLUSÕES: Os resultados sugerem que uma sorologia positiva para IgM, como um único marcador sorológico para detectar infecção recente, tem um valor limitado.<br>OBJECTIVE: To analyze the diagnostic and therapeutic approach of pregnant women with positive IgM test for toxoplasmosis and the follow-up of their children in a public hospital of Rio de Janeiro, Brazil. METHODS: This cross-sectional retrospective study from 2003 to 2006 enrolled 98 pregnant women with positive IgM test for toxoplasmosis and 99 children. The follow-up of the children with or without congenital infection was reviewed, as well as the clinical presentation of those with congenital infection and the laboratory tests used to diagnose the infection by Toxoplasma gondii during pregnancy. RESULTS: Toxoplasmosis was diagnosed in the second and third trimesters of pregnancy in 76 patients. In 36 pregnant women, determination of the serum levels of IgM was the only laboratory method used to diagnose the infection. Low IgM levels analyzed by ELFA were detected in 49 pregnant women. IgG avidity test was performed in 62 patients and in 13% of them the exam was carried out during the first trimester of pregnancy. Specific treatment for toxoplasmosis was applied in 93 women. Vertical transmission rate was 4%. Clinical manifestation of congenital toxoplasmosis was found in all infected children. All non-infected children showed a decrease in IgG serum levels for toxoplasmosis during the follow-up. The mean age for negativation of IgG serum levels in these children was 5.4 months. CONCLUSIONS: Our results suggest that the use of a positive IgM test to toxoplasmosis as the only antibody marker to detect recent infection has a limited value