Identification of a Hemolysis Threshold That Increases Plasma and Serum Zinc Concentration.

Background: Plasma or serum zinc concentration (PZC or SZC) is the primary measure of zinc status, but accurate sampling requires controlling for hemolysis to prevent leakage of zinc from erythrocytes. It is not established how much hemolysis can occur without changing PZC/SZC concentrations.Objective: This study determines a guideline for the level of hemolysis that can significantly elevate PZC/SZC.Methods: The effect of hemolysis on PZC/SZC was estimated by using standard hematologic variables and mineral content. The calculated hemolysis threshold was then compared with results from an in vitro study and a population survey. Hemolysis was assessed by hemoglobin and iron concentrations, direct spectrophotometry, and visual assessment of the plasma or serum. Zinc and iron concentrations were determined by inductively coupled plasma spectrometry.Results: A 5% increase in PZC/SZC was calculated to result from the lysis of 1.15% of the erythrocytes in whole blood, corresponding to ∼1 g hemoglobin/L added into the plasma or serum. Similarly, the addition of simulated hemolysate to control plasma in vitro caused a 5% increase in PZC when hemoglobin concentrations reached 1.18 ± 0.10 g/L. In addition, serum samples from a population nutritional survey were scored for hemolysis and analyzed for changes in SZC; samples with hemolysis in the range of 1-2.5 g hemoglobin/L showed an estimated increase in SZC of 6% compared with nonhemolyzed samples. Each approach indicated that a 5% increase in PZC/SZC occurs at ∼1 g hemoglobin/L in plasma or serum. This concentration of hemoglobin can be readily identified directly by chemical hemoglobin assays or indirectly by direct spectrophotometry or matching to a color scale.Conclusions: A threshold of 1 g hemoglobin/L is recommended for PZC/SZC measurements to avoid increases in zinc caused by hemolysis. The use of this threshold may improve zinc assessment for monitoring zinc status and nutritional interventions

A moderate increase in dietary zinc reduces DNA strand breaks in leukocytes and alters plasma proteins without changing plasma zinc concentrations.

BackgroundFood fortification has been recommended to improve a population's micronutrient status. Biofortification techniques modestly elevate the zinc content of cereals, but few studies have reported a positive impact on functional indicators of zinc status.ObjectiveWe determined the impact of a modest increase in dietary zinc that was similar to that provided by biofortification programs on whole-body and cellular indicators of zinc status.DesignEighteen men participated in a 6-wk controlled consumption study of a low-zinc, rice-based diet. The diet contained 6 mg Zn/d for 2 wk and was followed by 10 mg Zn/d for 4 wk. To reduce zinc absorption, phytate was added to the diet during the initial period. Indicators of zinc homeostasis, including total absorbed zinc (TAZ), the exchangeable zinc pool (EZP), plasma and cellular zinc concentrations, zinc transporter gene expression, and other metabolic indicators (i.e., DNA damage, inflammation, and oxidative stress), were measured before and after each dietary-zinc period.ResultsTAZ increased with increased dietary zinc, but plasma zinc concentrations and EZP size were unchanged. Erythrocyte and leukocyte zinc concentrations and zinc transporter expressions were not altered. However, leukocyte DNA strand breaks decreased with increased dietary zinc, and the level of proteins involved in DNA repair and antioxidant and immune functions were restored after the dietary-zinc increase.ConclusionsA moderate 4-mg/d increase in dietary zinc, similar to that which would be expected from zinc-biofortified crops, improves zinc absorption but does not alter plasma zinc. The repair of DNA strand breaks improves, as do serum protein concentrations that are associated with the DNA repair process. This trial was registered at clinicaltrials.gov as NCT02861352

A refined, rapid and reproducible high resolution melt (HRM)-based method suitable for quantification of global LINE-1 repetitive element methylation

<p>Abstract</p> <p>Background</p> <p>The methylation of DNA is recognized as a key mechanism in the regulation of genomic stability and evidence for its role in the development of cancer is accumulating. LINE-1 methylation status represents a surrogate measure of genome-wide methylation.</p> <p>Findings</p> <p>Using high resolution melt (HRM) curve analysis technology, we have established an in-tube assay that is linear (r > 0.9986) with a high amplification efficiency (90-105%), capable of discriminating between partcipant samples with small differences in methylation, and suitable for quantifying a wide range of LINE-1 methylation levels (0-100%)--including the biologically relevant range of 50-90% expected in human DNA. We have optimized this procedure to perform using 2 μg of starting DNA and 2 ng of bisulfite-converted DNA for each PCR reaction. Intra- and inter-assay coefficients of variation were 1.44% and 0.49%, respectively, supporting the high reproducibility and precision of this approach.</p> <p>Conclusions</p> <p>In summary, this is a completely linear, quantitative HRM PCR method developed for the measurement of LINE-1 methylation. This cost-efficient, refined and reproducible assay can be performed using minimal amounts of starting DNA. These features make our assay suitable for high throughput analysis of multiple samples from large population-based studies.</p

Fortification and health: challenges and opportunities.

Fortification is the process of adding nutrients or non-nutrient bioactive components to edible products (e.g., food, food constituents, or supplements). Fortification can be used to correct or prevent widespread nutrient intake shortfalls and associated deficiencies, to balance the total nutrient profile of a diet, to restore nutrients lost in processing, or to appeal to consumers looking to supplement their diet. Food fortification could be considered as a public health strategy to enhance nutrient intakes of a population. Over the past century, fortification has been effective at reducing the risk of nutrient deficiency diseases such as beriberi, goiter, pellagra, and rickets. However, the world today is very different from when fortification emerged in the 1920s. Although early fortification programs were designed to eliminate deficiency diseases, current fortification programs are based on low dietary intakes rather than a diagnosable condition. Moving forward, we must be diligent in our approach to achieving effective and responsible fortification practices and policies, including responsible marketing of fortified products. Fortification must be applied prudently, its effects monitored diligently, and the public informed effectively about its benefits through consumer education efforts. Clear lines of authority for establishing fortification guidelines should be developed and should take into account changing population demographics, changes in the food supply, and advances in technology. This article is a summary of a symposium presented at the ASN Scientific Sessions and Annual Meeting at Experimental Biology 2014 on current issues involving fortification focusing primarily on the United States and Canada and recommendations for the development of responsible fortification practices to ensure their safety and effectiveness

Association of Pediatric Heart Transplant Coronary Vasculopathy with Abnormal Hemodynamic Measures

Objective.  Transplant coronary artery disease (TCAD) is the limiting factor to long‐term cardiac allograft survival; however, presymptomatic diagnosis remains challenging. To that concern, we evaluated the association of abnormal catheter‐derived filling pressures with TCAD in pediatric heart transplant (HTx) recipients.Design, Patients, Outcome Measures.  Data from 52 presymptomatic pediatric HTx patients were analyzed. Catheter‐derived right ventricular end‐diastolic pressure (RVEDP) and pulmonary capillary wedge pressure (PCWP) were recorded. Biopsies were collected to verify the absence of rejection.Results.  TCAD was diagnosed an average of 8.3 years post‐HTx in 20 (38%) patients, six of whom died and four of whom underwent retransplantation. Catheter‐derived pressure measurements showed that RVEDP was elevated in TCAD compared with non‐TCAD patients (9.5 ± 6.0 vs. 5.4 ± 4.7; P= .005), as was the PCWP (12.9 ± 5.7 vs. 9.1 ± 5.7; P= .012). Results from logistic regression analysis showed RVEDP > 10 mm Hg or PCWP > 12 mm Hg was associated with TCAD (OR = 5.2; P= .010).Conclusions.  In this series, elevated ventricular filling pressures measured during routine surveillance catheterizations were associated with angiographic TCAD. Recognizing the association between elevated RVEDP/PCWP and TCAD may prompt earlier diagnosis and treatment of this potentially lethal process.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111940/1/j.1747-0803.2010.00470.x.pd

Associations between long chain polyunsaturated fatty acids and cardiovascular lipid risk factors in youth with type 1 diabetes: SEARCH Nutrition Ancillary Study

In this longitudinal study we explored the relationships between plasma n-3 and n-6 polyunsaturated fatty acids (PUFAs) and Δ5 and Δ6 desaturase activities (D5D and D6D, respectively) and fasting lipids in youth with type 1 diabetes (T1D)

Resonance line-profile calculations based on hydrodynamical models of cataclysmic variable winds

We present synthetic line profiles as predicted by the models of 2-D line- driven disk winds due to Proga, Stone & Drew. We compare the model line profiles with HST observations of the cataclysmic variable IX Vel. The model wind consists of a slow outflow that is bounded on the polar side by a fast stream. We find that these two components of the wind produce distinct spectral features. The fast stream produces profiles which show features consistent with observations. These include the appearance of the P-Cygni shape for a range of inclinations, the location of the maximum depth of the absorption component at velocities less than the terminal velocity, and the transition from absorption to emission with increasing inclination. However the model profiles have too little absorption or emission equivalent width. This quantitative difference between our models and observations is not a surprise because the line-driven wind models predict a mass loss rate that is lower than the rate required by the observations. We note that the model profiles exhibit a double-humped structure near the line center which is not echoed in observations. We identify this structure with a non-negligible redshifted absorption which is formed in the slow component of the wind where the rotational velocity dominates over expansion velocity. We conclude that the next generation of disk wind models, developed for application to CVs, needs to yield stronger wind driving out to larger disk radii than do the present models.Comment: LaTeX, 19 pages, to appear in Ap