Polymorphisms in arsenic(+III oxidation state) methyltransferase (AS3MT) predict gene expression of AS3MT as well as arsenic metabolism

Background

Arsenic (As) occurs as monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) in humans, and the methylation pattern demonstrates large interindividual differences. The fraction of urinary MMA is a marker for susceptibility to As-related diseases.

Objectives

We evaluated the impact of polymorphisms in five methyltransferase genes on As metabolism in two populations, one in South America and one in Southeast Asia. The methyltransferase genes were arsenic(+III oxidation state) methyltransferase (AS3MT), DNA-methyltransferase 1a and 3b (DNMT1a and DNMT3b, respectively), phosphatidylethanolamine N-methyltransferase (PEMT), and betaine-homocysteine methyltransferase (BHMT). AS3MT expression was analyzed in peripheral blood.

Methods

Subjects were women exposed to As in drinking water in the Argentinean Andes [n = 172; median total urinary As (U-As), 200 μg/L] and in rural Bangladesh (n = 361; U-As, 100 μg/L; all in early pregnancy). Urinary As metabolites were measured by high-pressure liquid chromatography/inductively coupled plasma mass spectrometry. Polymorphisms (n = 22) were genotyped with Sequenom, and AS3MT expression was measured by quantitative real-time polymerase chain reaction using TaqMan expression assays.

Results

Six AS3MT polymorphisms were significantly associated with As metabolite patterns in both populations (p ≤ 0.01). The most frequent AS3MT haplotype in Bangladesh was associated with a higher percentage of MMA (%MMA), and the most frequent haplotype in Argentina was associated with a lower %MMA and a higher percentage of DMA. Four polymorphisms in the DNMT genes were associated with metabolite patterns in Bangladesh. Noncoding AS3MT polymorphisms affected gene expression of AS3MT in peripheral blood, demonstrating that one functional impact of AS3MT polymorphisms may be altered levels of gene expression.

Conclusions

Polymorphisms in AS3MT significantly predicted As metabolism across these two very different populations, suggesting that AS3MT may have an impact on As metabolite patterns in populations worldwide.     

Seroprevalence of hepatitis B and hepatitis C markers in adolescents in Southern Brazil

This study was carried out to determine the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) markers among adolescents aged between 10 and 16 years old, who are elementary school students in the city of Chapecó, Santa Catarina State, Brazil. The study involved a cross-sectional survey that included 418 volunteers, from March to July, 2008. Serology comprised HBsAg, anti-HBc, anti-HBs and anti-HCV. Tests were performed using automated Microparticle Enzyme Immunosorbant Assay (Abbott, AxSYM System, Wiesbaden, Germany). The prevalence of HBsAg was found to be 0.2% (95%CI: 0.0-1.3), and the prevalence of anti-HBc was found to be 1.4% (95%CI: 0.5-3.1). Regarding anti-HBs, 48.6% had titers greater than 10UI/L. None of the volunteers presented reactive results for anti-HCV. This study showed a low prevalence of HBV and HCV markers of infection and a great number of volunteers immunized against HBV. Finally this study shows the importance of proper health campaigns and policies in reducing those prevalences.     

Regional influence on early consumption of foods other than breast milk in infants less than 6 months of age in Brazilian State capitals and the Federal District

The aim was to assess regional influences on food consumption in infants less than six months of age. A cross-sectional study was conducted in a sample of 18,929 infants participating in the Second Survey on Breastfeeding Prevalence in Brazilian State Capitals and the Federal District in 2008. Consumption rates for tea, fruit juices, formula milk, and porridge were calculated for the State capitals from the five geographic regions of the country. Food consumption was estimated by logit analyses and Poisson models. Differences in food consumption profile were observed between the different regions: tea was more common in State capitals in the South (RP = 2.37), while non-maternal milk (RP = 1.50 and 1.47) and juices (RP = 1.57 and 1.55) were more frequent in the Northeast and Southeast, respectively. Porridge was more common in the Northeast (RP = 3.0). Brazil's geographic regions thus display different infant feeding patterns. Public policy should take cultural diversity into account when planning strategies to improve infant nutrition and health.     

The relationship between social capital, social support and the adequate use of prenatal care

This study investigated the relationship between social capital and social support and the adequate use of prenatal care. A follow-up study involving 1,485 pregnant women was conducted in two cities in the Rio de Janeiro State, Brazil. Demographic and socioeconomic characteristics, social support and social capital data were collected during the first trimester of pregnancy. The post-partum period included information on levels of prenatal care utilization, social networks, parity, obstetric and gestational risk and prenatal care attendance. Hierarchized multinomial logistic regression was used in the statistical analysis. Prenatal care use above adequate levels was associated with high social capital at the city level (aggregated social capital), socioeconomic status and working during pregnancy. Lower non-aggregated contextual and compositional social capital, gestational risk and pattern of prenatal care were associated with inadequate prenatal care utilization. Contextual social capital and social support were found to be social determinants for the appropriate use of prenatal care.     

Synthesis, trypanocidal activity and molecular modeling studies of 2-alkylaminomethylquinoline derivatives

Research and development of new drugs effective in the treatment of Trypanosoma cruzi infections are a real need for the 16 million people infected in the Americas. In a previous work, a quinoline derivative substituted by a 2-piperidylmethyl moiety showed to be active against Chagas disease and was considered a lead compound for further optimization. A series of ten analogous derivatives were tested against epimastigotes as a first approach. In view of their promising results, six of them were evaluated against the blood and intracellular replicative forms of the parasite in humans. Among them, compound 12 which possesses a 6-acetamidohexylamino substituent showed remarkable improvement in activity against epimastigotes, trypomastigotes and amastigotes compared with the structure lead, as well as a good selectivity index for the two parasite stages present in humans. In addition, treatment of infected mice with compound 12 induced a significant reduction in parasitemia compared with non-treated mice. Molecular modeling studies were performed by computational methods in order to elucidate the factors determining these experimental bioactivities.     

Burden of disease and costs of treating rotavirus diarrhea in Mexican children for the period 2001-2006

Objectives

To estimate the health impact and the costs of treatment associated with rotavirus diarrhea in six yearly cohorts (2001-2006) of Mexican infants.

Methods

The perspective of study is from the health care system. We estimated the effect of rotavirus diarrhea on disability adjusted life years (DALYS) and diarrhea treatment costs in hypothetical cohorts of infants who are followed from birth up to five years of age beginning in years from 2001 to 2006. We used information from administrative databases on mortality and health care from the National System of Information on Health and from the Mexican Institute for Social Security to feed a decision analysis to project the burden of disease and costs of treatment.

Results

Estimates of DALYS were 19,426 in 2001 and decreased by 28.9% for 2006 meanwhile costs of treatment were relatively constant, estimated at US$ 38.7 million and increased only by 5%.

Conclusion

Rotavirus diarrhea in Mexican children is a major disease burden, presenting significant treatment costs. Rotavirus diarrhea mortality is decreasing; however this has not led to a steady decrease in treatment costs in the 6 years period of analysis. A sensitivity analysis showed that incidences of rotavirus diarrhea as well as the parameters associated with health-care access were the main factors, which had a significant effect on the projected burden of disease and costs.     

Validity and reliability of clinical tests for assessing hip passive stiffness

Inadequate levels of hip passive joint stiffness have been associated with the occurrence of movement dysfunction, development of pathologies and reduction in performance. Clinical tests, designed to evaluate hip joint stiffness, may allow the identification of improper stiffness levels. The purpose of this study was to determine the concurrent validity as well as the intra- and inter-examiners reliabilities of clinical measures used to assess hip passive stiffness during internal rotation. Fifteen healthy participants were subjected to test-retest evaluations by two examiners. Two clinical measures were performed: 'position of first detectable resistance' and 'change in passive resistance torque'. The results of these tests were compared to the passive stiffness measured with an isokinetic dynamometer (gold standard measure). A significant correlation was found between the stiffness measured with the isokinetic dynamometer and the clinical measures of 'position of first detectable resistance' (r=-0.85 to -0.86, p<0.001) and 'change in passive resistance torque' (r=0.78 to 0.84, p≤0.001). The Intraclass Correlation Coefficients for intra- and inter-examiners reliabilities varied from 0.95 to 0.99. Thus, the results demonstrated that the clinical measures have adequate validity and reliability for obtaining information on hip passive stiffness during internal rotation.     

Von Willebrand disease in children: diagnosis and management of a pediatric cohort in one single center in Argentina

Clinical and laboratory data of children with von Willebrand disease (VWD) types have been derived from retrospective studies and small case series. This article reports on the clinical and laboratory data of a large pediatric cohort in one single Argentinian center. The biological and clinical responses to desmopressin and replacement therapies are also described. Over a 15-year period, 194 of 1150 children (16.9%) were diagnosed as having type 1 VWD (80%), type 2 VWD (19%), and type 3 VWD (1%). The distribution of the different type 2 VWD subtypes was type 2A VWD, 43%; type 2B VWD, 32%; type 2M VWD, 19%; and type 2N VWD, 6%. Eighty patients with type 1 VWD and 12 patients with type 2 VWD were prospectively evaluated to desmopressin (DDAVP) response. A complete response was observed in all children with type 1 VWD, whereas 40% of the children with severe type 1 VWD and with type 2 VWD achieved a complete response. All the children who received DDAVP as prophylaxis or treatment for bleeding had good clinical evolution. Considering the restricted availability of specialized hemostasis centers, we believe our clinical and laboratory approach appropriate for the detection of patients with different types of VWD. Further studies are necessary to determine epidemiological aspects of VWD in Argentina to estimate the necessary facilities and trained personnel for the diagnosis and management of patients with VWD.