C-Enrichment of Urinary Uric Acid after L-[Ring-2- 13 C]Histidine Dose in Adult Humans

Abstract: We determined whether ring-2 carbon of histidine is folate-dependently transferred to carbons 8 (C8) and/or 2 (C2) in urinary uric acid in humans. Two adults collected each urine void for four days. Aliquots of urine for the first day were used for baseline values; then the subjects ingested 0.7 g (3.3 mmol) of L-[ring-2-13 C]histidine and collected urine for three experimental days. Aliquots were analyzed for percentage 13 C-content at C2 and C8 by a liquid-chromatography-mass spectrometry method. Percentage enrichment was determined by subtracting time-of-day paired baseline percentage 13 C-content from experimental percentage 13 C-content for each void. C2 was predominantly 13 C-enriched in the majority of voids. The percentage enrichments at C2 for two subjects were 0.14 (±0.028 [SEM], n = 26) and 0.18 (±0.049, n = 21), whereas at C8, they were 0.008 (±0.006) and −0.005 (±0.008), respectively. The mean C2-enrichments were significantly greater than zero (p < 0.01), whereas those of C8 were not (p > 0.2). The enrichment had a diurnal rhythm peaking in the morning. Our results may be useful in the estimation of the timing for the administration of drugs that interfere with purine nucleotide biosynthesis in the treatment of cancer and autoimmune disease

Group life insurance in Kuwait : problems and prospects

The Kuwaiti government obliged firms to cover part of employee's risks through legislation in 1965 and 1977. Employers should cover risks as death or job injury due to or during work. This had affected the group life insurance (GLI) market. The thesis examines the economics of this market. Problem of choosing the right life table with respect to Kuwaiti mortality rates is tested. The efficiency of using English life tables to estimate mortality rates in Kuwait GLI market is examined. The effects of GLI underwriters on the market are investigated. The Social Security Services (SSS) are offered for Kuwaitis only, Non-Kuwaitis face more economical insecurity than Kuwaitis do. Therefore, the demand for employees' group investment plan to cover future security facing Kuwaiti and non-Kuwaiti workers, in particular, is also considered. The thesis suggests several methods to solve the problems facing the Kuwait GLI market. Kuwaiti Mortality rates are estimated using data from both the Social Security Association (SSA) and a sample of term group life insurees to be compared with English and American life tables. Methods of avoiding lack of information, adverse selection, and moral hazard in Kuwait GLI market are proposed. Finally, the advantages of introducing group investment plan are examined, and it was shown that these could alleviate SSS problems. Use of group investment plan should reduce the cost of the SSS for Kuwaitis, secure part of Non-Kuwaitis risks, and assist insurers to avoid or reduce their economic problems

Effect of paternal folate deficiency on placental folate content and folate receptor α expression in rats

We investigated the effect of paternal folate status on folate content and expression of the folate transporter folate receptor α (FRα) in rat placental tissues. Rats were mated after males were fed a diet containing 0 mg of folic acid/kg of diet (paternal folate-deficient, PD) or 8 mg folic acid/kg of diet (paternal folate-supplemented, PS) for 4 weeks. At 20 days of gestation, the litter size, placental weight, and fetal weight were measured, and placental folate content (n = 8/group) and expression of FRα (n = 10/group) were analyzed by microbiological assay and Western blot analysis, respectively. Although there was no difference observed in litter size or fetal weight, but significant reduction (10%) in the weight of the placenta was observed in the PD group compared to that in the PS group. In the PD group, placental folate content was significantly lower (by 35%), whereas FRα expression was higher (by 130%) compared to the PS group. Our results suggest that paternal folate status plays a critical role in regulating placental folate metabolism and transport

Zinc status and growth of Korean infants fed human milk, casein-based, or soy-based formula: three-year longitudinal study

To evaluate the effect of feeding methods on growth and zinc nutritional status of infants early in life, we monitored from birth to 36 months in 51 infants who were exclusively fed human milk (HM, n = 20), casein-based formula (CBF, n = 12), or soy-based formula (SBF, n = 19) during the first five months of life. Zinc status was assessed by analyzing serum zinc concentrations and zinc intakes. Zinc contents in HM and formulas were measured. Zinc intake was estimated by weighing infants before and after feeding in the HM group and by collecting formula-intake records in the CBF and SBF groups. After solid foods were introduced, all foods consumed were also included to estimate zinc intake. The growth of infants in all groups was similar to that established for normal Korean infants. Human milk zinc concentrations declined as lactation progressed. Zinc concentrations in all formulas tested in this study were higher than HM and were also higher than those claimed by the manufacturers. During the first twelve months, mean serum zinc concentrations of infants were similar in all groups, although infants in the HM group consistently had the lowest zinc intake among the groups, and the overall zinc intake in infants fed SBF was highest. This finding could be explained by the different zinc bioavailability of HM and formulas. In conclusion, infants fed HM, CBF or SBF has normal growth up to three years of age, although HM contained the lowest zinc concentration followed by CBF, then SBF

Biomarkers of vitamin B-12 status in NHANES: a roundtable summary123456

A roundtable to discuss the measurement of vitamin B-12 (cobalamin) status biomarkers in NHANES took place in July 2010. NHANES stopped measuring vitamin B-12–related biomarkers after 2006. The roundtable reviewed 3 biomarkers of vitamin B-12 status used in past NHANES—serum vitamin B-12, methylmalonic acid (MMA), and total homocysteine (tHcy)—and discussed the potential utility of measuring holotranscobalamin (holoTC) for future NHANES. The roundtable focused on public health considerations and the quality of the measurement procedures and reference methods and materials that past NHANES used or that are available for future NHANES. Roundtable members supported reinstating vitamin B-12 status measures in NHANES. They noted evolving concerns and uncertainties regarding whether subclinical (mild, asymptomatic) vitamin B-12 deficiency is a public health concern. They identified the need for evidence from clinical trials to address causal relations between subclinical vitamin B-12 deficiency and adverse health outcomes as well as appropriate cutoffs for interpreting vitamin B-12–related biomarkers. They agreed that problems with sensitivity and specificity of individual biomarkers underscore the need for including at least one biomarker of circulating vitamin B-12 (serum vitamin B-12 or holoTC) and one functional biomarker (MMA or tHcy) in NHANES. The inclusion of both serum vitamin B-12 and plasma MMA, which have been associated with cognitive dysfunction and anemia in NHANES and in other population-based studies, was preferable to provide continuity with past NHANES. Reliable measurement procedures are available, and National Institute of Standards and Technology reference materials are available or in development for serum vitamin B-12 and MMA

Biomarkers of folate status in NHANES: a roundtable summary123456

A roundtable to discuss the measurement of folate status biomarkers in NHANES took place in July 2010. NHANES has measured serum folate since 1974 and red blood cell (RBC) folate since 1978 with the use of several different measurement procedures. Data on serum 5-methyltetrahydrofolate (5MTHF) and folic acid (FA) concentrations in persons aged ≥60 y are available in NHANES 1999–2002. The roundtable reviewed data that showed that folate concentrations from the Bio-Rad Quantaphase II procedure (Bio-Rad Laboratories, Hercules, CA; used in NHANES 1991–1994 and NHANES 1999–2006) were, on average, 29% lower for serum and 45% lower for RBC than were those from the microbiological assay (MA), which was used in NHANES 2007–2010. Roundtable experts agreed that these differences required a data adjustment for time-trend analyses. The roundtable reviewed the possible use of an isotope-dilution liquid chromatography–tandem mass spectrometry (LC-MS/MS) measurement procedure for future NHANES and agreed that the close agreement between the MA and LC-MS/MS results for serum folate supported conversion to the LC-MS/MS procedure. However, for RBC folate, the MA gave 25% higher concentrations than did the LC-MS/MS procedure. The roundtable agreed that the use of the LC-MS/MS procedure to measure RBC folate is premature at this time. The roundtable reviewed the reference materials available or under development at the National Institute of Standards and Technology and recognized the challenges related to, and the scientific need for, these materials. They noted the need for a commutability study for the available reference materials for serum 5MTHF and FA

Homocysteine, Iron and Cardiovascular Disease: A Hypothesis

Elevated circulating total homocysteine (tHcy) concentrations (hyperhomocysteinemia) have been regarded as an independent risk factor for cardiovascular disease (CVD). However, several large clinical trials to correct hyperhomocysteinemia using B-vitamin supplements (particularly folic acid) have largely failed to reduce the risk of CVD. There is no doubt that a large segment of patients with CVD have hyperhomocysteinemia; therefore, it is reasonable to postulate that circulating tHcy concentrations are in part a surrogate marker for another, yet-to-be-identified risk factor(s) for CVD. We found that iron catalyzes the formation of Hcy from methionine, S-adenosylhomocysteine and cystathionine. Based on these findings, we propose that an elevated amount of non-protein-bound iron (free Fe) increases circulating tHcy. Free Fe catalyzes the formation of oxygen free radicals, and oxidized low-density lipoprotein is a well-established risk factor for vascular damage. In this review, we discuss our findings on iron-catalyzed formation of Hcy from thioethers as well as recent findings by other investigators on this issue. Collectively, these support our hypothesis that circulating tHcy is in part a surrogate marker for free Fe, which is one of the independent risk factors for CVD