The association between serum copper and anaemia in the adult Second National Health and Nutrition Examination Survey (NHANES II) population

Though common in older adults, anaemia is unexplained in about one-third of cases. As a rare cause of anaemia and neutropenia, Cu deficiency could account for some cases of unexplained anaemia. We examined the relationship between serum Cu and unexplained anaemia among 11 240 participants in the Second National Health and Nutrition Examination Survey (NHANES II): 638 (5.7 % of all adults) were anaemic; 421 (3.7 %) were not explained by deficiencies of vitamin B12, folate or Fe, chronic illness or renal disease. Spline regression showed a U-shaped relationship between serum Cu levels and unexplained anaemia, indicating that both high and low serum Cu levels are associated with unexplained anaemia in adults. Chronic inflammation and mild Fe deficiency could account for the association between unexplained anaemia and elevated Cu levels. On the other hand, the finding of hypocupraemia in a subset of adults with unexplained anaemia suggests that Cu deficiency may be a common reversible cause of anaemia in adults

Initial Assessment of Variability of Responses to Toxicants in Donor-Specific Endothelial Colony Forming Cells

There is increased interest in using high throughput in vitro assays to characterize human population variability in response to toxicants and drugs. Utilizing primary human endothelial colony-forming cells (ECFCs) isolated from blood would be highly useful for this purpose because these cells are involved in neonatal and adult vasculogenesis. We characterized the cytotoxicity of four known toxic chemicals (NaAsO2, CdCl2, tributyltin [TBT], and menadione) and their four relatively nontoxic counterparts (Na2HAsO4, ZnCl2, SnCl2, and phytonadione, respectively) in eight ECFC clones representing four neonatal donors (2 male and 2 female donors, 2 clones per donor). ECFCs were exposed to 9 concentrations of each chemical in duplicate; cell viability was evaluated 48 h later using the fluorescent vital dye fluorescent dye 5-Carboxyfluorescein Diacetate (CFDA), yielding concentration-effect curves from each experiment. Technical (day-to-day) variability of the assay, assessed from three independent experiments, was low: p-values for the differences of results were 0.74 and 0.64 for the comparison of day 2 vs. day 1 and day 3 vs. day 1, respectively. The statistical analysis used to compare the entire concentration-effect curves has revealed significant differences in levels of cytotoxicity induced by the toxic and relatively nontoxic chemical counterparts, demonstrating that donor-specific ECFCs can clearly differentiate between these two groups of chemicals. Partitioning of the total variance in the nested design assessed the contributions of between-clone and between-donor variability for different levels of cytotoxicity. Individual ECFC clones demonstrated highly reproducible responses to the chemicals. The most toxic chemical was TBT, followed by NaAsO2, CdCl2, and Menadione. Nontoxic counterparts exhibited low cytotoxicity at the higher end of concentration ranges tested. Low variability was observed between ECFC clones obtained from the same donor or different donors for CdCl2, NaAsO2, and TBT, but for menadione, the between-donor variability was much greater than the between-clone variability. The low between-clone variability indicates that an ECFC clone may represent an individual donor in cell-based assays, although this finding must be confirmed using a larger number of donors. Such confirmation would demonstrate that an in vitro ECFC-based testing platform can be used to characterize the inter-individual variability of neonatal ECFCs exposed to drugs and/or environmental toxicants

МИОЦЕНОВЫЙ И ДЕВОНСКИЙ МАГМАТИЗМ В СОЧЛЕНЕНИИ ТУВИНО-МОНГОЛЬСКОГО МАССИВА И СИБИРСКОГО КРАТОНА: ОБЩИЙ КОМПОНЕНТ МАНТИЙНЫХ ИСТОЧНИКОВ И ЕГО ПРОИСХОЖДЕНИЕ

Devonian dikes of the Urik-Belaya and Shagayte-Gol-Urik zones and Miocene lavas of the Urik volcanic field are spatially associated with each other at the structural junction between the Neoproterozoic Tuva-Mongolian massif and Siberian craton. The former dike belt is represented by basalts and basaltic andesites of tholeiitic series and the latter one by trachybasalts, trachyandesitic basalts of moderately alkaline series and trachybasalts, phonotephrites of highly alkaline one. The Urik volcanic field is composed of trachybasalts and trachyandesitic basalts of moderately alkaline series. A partial similarity between magmatic series of different age is found in terms of major oxides, trace elements, and Sr, Pb isotopes. The common component corrected for age was defined through its converging mixing trends with those of the lithospheric mantle and crust. The component identification was a basis for deciphering the nature of isotopic and geochemical heterogeneity of evolved magmatic sources. It was inferred that the common component characterizes either a modified (depleted) reservoir of the lower mantle or, more likely, a local region of the convecting asthenospheric mantle that underlies the Tuva-Mongolian massif. The latter interpretation assumes the formation of a locally convecting asthenosphere in the middle Neoproterozoic, along with the development of the Oka zone at the massif, and puts constrains on later sufficient processing of the asthenosphere due to rising plumes or subducting slabs.В структурном сочленении неопротерозойского Тувино-Монгольского массива с Сибирским кратоном пространственно совмещены между собой девонские дайки Урик-Бельского и Шагайтэ-Гол-Урикского поясов и миоценовые лавы Урикского вулканического поля. Первый дайковый пояс представлен базальтами-андезибазальтами толеитовой серии, второй – трахибазальтами-трахиандезибазальтами умереннощелочной серии с локальным распространением трахибазальтов-фонотефритов серии повышенной щелочности. Урикское вулканическое поле образуют трахибазальты-трахиандезибазальты умереннощелочной серии. Выявлено частичное сходство концентраций петрогенных оксидов, микроэлементов и изотопных отношений стронция и свинца разновозрастных магматических серий. С поправкой на возраст определен общий компонент магматических расплавов по сходящимся трендам его смешения с компонентами мантийной части литосферы и коры. Идентификация компонента послужила основой для расшифровки характера изотопно-геохимической гетерогенности разновозрастных магматических источников. Сделан вывод о том, что общий компонент характеризует либо модифицированный (обедненный) нижнемантийный резервуар, либо, что более вероятно, локальную область конвектирующей астеносферной мантии, подстилающей Тувино-Монгольский массив. В последней интерпретации допускается образование локального конвектирующего объема астеносферы в середине неопротерозоя, одновременно с заложением и развитием Окинской зоны массива, и накладываются ограничения на последующие существенные преобразования астеносферы под влиянием поднятия плюмового или погружения слэбового материала

Daily intake of antioxidants in relation to survival among adult patients diagnosed with malignant glioma

<p>Abstract</p> <p>Background</p> <p>Malignant glioma is a rare cancer with poor survival. The influence of diet and antioxidant intake on glioma survival is not well understood. The current study examines the association between antioxidant intake and survival after glioma diagnosis.</p> <p>Methods</p> <p>Adult patients diagnosed with malignant glioma during 1991-1994 and 1997-2001 were enrolled in a population-based study. Diagnosis was confirmed by review of pathology specimens. A modified food-frequency questionnaire interview was completed by each glioma patient or a designated proxy. Intake of each food item was converted to grams consumed/day. From this nutrient database, 16 antioxidants, calcium, a total antioxidant index and 3 macronutrients were available for survival analysis. Cox regression estimated mortality hazard ratios associated with each nutrient and the antioxidant index adjusting for potential confounders. Nutrient values were categorized into tertiles. Models were stratified by histology (Grades II, III, and IV) and conducted for all (including proxy) subjects and for a subset of self-reported subjects.</p> <p>Results</p> <p>Geometric mean values for 11 fat-soluble and 6 water-soluble individual antioxidants, antioxidant index and 3 macronutrients were virtually the same when comparing all cases (n = 748) to self-reported cases only (n = 450). For patients diagnosed with Grade II and Grade III histology, moderate (915.8-2118.3 mcg) intake of fat-soluble lycopene was associated with poorer survival when compared to low intake (0.0-914.8 mcg), for self-reported cases only. High intake of vitamin E and moderate/high intake of secoisolariciresinol among Grade III patients indicated greater survival for all cases. In Grade IV patients, moderate/high intake of cryptoxanthin and high intake of secoisolariciresinol were associated with poorer survival among all cases. Among Grade II patients, moderate intake of water-soluble folate was associated with greater survival for all cases; high intake of vitamin C and genistein and the highest level of the antioxidant index were associated with poorer survival for all cases.</p> <p>Conclusions</p> <p>The associations observed in our study suggest that the influence of some antioxidants on survival following a diagnosis of malignant glioma are inconsistent and vary by histology group. Further research in a large sample of glioma patients is needed to confirm/refute our results.</p

A Variable Age of Onset Segregation Model for Linkage Analysis, with Correction for Ascertainment, Applied to Glioma

BackgroundWe propose a 2-step model-based approach, with correction for ascertainment, to linkage analysis of a binary trait with variable age of onset and apply it to a set of multiplex pedigrees segregating for adult glioma.MethodsFirst, we fit segregation models by formulating the likelihood for a person to have a bivariate phenotype, affection status and age of onset, along with other covariates, and from these we estimate population trait allele frequencies and penetrance parameters as a function of age (N = 281 multiplex glioma pedigrees). Second, the best fitting models are used as trait models in multipoint linkage analysis (N = 74 informative multiplex glioma pedigrees). To correct for ascertainment, a prevalence constraint is used in the likelihood of the segregation models for all 281 pedigrees. Then the trait allele frequencies are reestimated for the pedigree founders of the subset of 74 pedigrees chosen for linkage analysis.ResultsUsing the best-fitting segregation models in model-based multipoint linkage analysis, we identified 2 separate peaks on chromosome 17; the first agreed with a region identified by Shete and colleagues who used model-free affected-only linkage analysis, but with a narrowed peak: and the second agreed with a second region they found but had a larger maximum log of the odds (LOD).ConclusionsOur approach was able to narrow the linkage peak previously published for glioma.ImpactWe provide a practical solution to model-based linkage analysis for disease affection status with variable age of onset for the kinds of pedigree data often collected for linkage analysis

Human Exposure to Selected Animal Neurocarcinogens: A Biomarker-Based Assessment and Implications for Brain Tumor Epidemiology

This review is based on the proceedings from the Second Lebow Conference held in Chicago in 2007. The conference concentrated on developing a framework for innovative studies in the epidemiology of environmental exposures, focusing specifically on the potential relationship with brain tumors. Researchers with different perspectives, including toxicology, pharmacokinetics, and epidemiological exposure assessment, exchanged information and ideas on the use of biomarkers of exposure in molecular epidemiology studies and summarized the current knowledge on methods and approaches for biomarker-based exposure assessment. This report presents the state of science regarding biomarker-based exposure assessment of the 4 most common neurocarcinogens: acrylamide, 1,3-butadiene, N-nitroso compounds, and polycyclic aromatic hydrocarbons. Importantly, these chemicals are also carcinogenic in other organs; therefore, this discussion is useful for environmental epidemiologists studying all cancer types