The Essentiality of Arachidonic Acid in Infant Development.

Arachidonic acid (ARA, 20:4n-6) is an n-6 polyunsaturated 20-carbon fatty acid formed by the biosynthesis from linoleic acid (LA, 18:2n-6). This review considers the essential role that ARA plays in infant development. ARA is always present in human milk at a relatively fixed level and is accumulated in tissues throughout the body where it serves several important functions. Without the provision of preformed ARA in human milk or infant formula the growing infant cannot maintain ARA levels from synthetic pathways alone that are sufficient to meet metabolic demand. During late infancy and early childhood the amount of dietary ARA provided by solid foods is low. ARA serves as a precursor to leukotrienes, prostaglandins, and thromboxanes, collectively known as eicosanoids which are important for immunity and immune response. There is strong evidence based on animal and human studies that ARA is critical for infant growth, brain development, and health. These studies also demonstrate the importance of balancing the amounts of ARA and DHA as too much DHA may suppress the benefits provided by ARA. Both ARA and DHA have been added to infant formulas and follow-on formulas for more than two decades. The amounts and ratios of ARA and DHA needed in infant formula are discussed based on an in depth review of the available scientific evidence.

Efficacy and safety of arachidonic acid for treatment of school-age children in Schistosoma mansoni high-endemicity regions.

Arachidonic acid (ARA), an omega-6 fatty acid, is a potent schistosomicide that displayed significant and safe therapeutic effects in Schistosoma mansoni-infected schoolchildren in S. mansoni low-prevalence regions. We here report on ARA efficacy and safety in treatment of schoolchildren in S. mansoni high-endemicity areas of Kafr El Sheikh, Egypt. The study was registered with ClinicalTrials.gov (NCT02144389). In total, 268 schoolchildren with light, moderate, or heavy S. mansoni infection were assigned to three study arms of 87, 91, and 90 children and received a single dose of 40 mg/kg praziquantel (PZQ), ARA (10 mg/kg per day for 15 days), or PZQ combined with ARA, respectively. The children were examined before and after treatment for stool parasite egg counts and blood biochemical, hematological, and immunological parameters. ARA, like PZQ, induced moderate cure rates (50% and 60%, respectively) in schoolchildren with light infection and modest cure rates (21% and 20%, respectively) in schoolchildren with high infection. PZQ and ARA combined elicited 83% and 78% cure rates in children with light and heavy infection, respectively. Biochemical and immunological profiles were either unchanged or ameliorated after ARA therapy. Combination of PZQ and ARA might be useful for treatment of children with schistosomiasis in high-endemicity regions.

Phospholipid hydroperoxide glutathione peroxidase (Gpx4) is highly regulated in male turkey poults and can be used to determine dietary selenium requirements.

The dietary selenium recommendation for turkeys of 0.2 microg Se/g is higher than for many other species. Liver glutathione peroxidase-1 (Gpx1) activity levels determined using hydrogen peroxide (H(2)O(2)) in previous studies suggest that 0.2 microg Se/g may still be too low and that some of this Gpx1 activity might be due to phospholipid hydroperoxide Gpx (Gpx4). Thus we separated Gpx1 from Gpx4 by chromatography, demonstrated that 47% of the H(2)O(2) activity in Se-adequate turkey liver was due to Gpx4, and determined a factor for calculation of each activity. Day-old male poults were fed an Se-deficient torula diet (0.007 microg Se/g) supplemented with graded levels of Se (0-0.5 microg Se/g) for 27 days. Final body weights indicated a minimum Se requirement for growth of 0.05 microg Se/g. The liver had the highest Gpx4 activity in Se-adequate poults, and Gpx4 activity in Se-deficient liver decreased to 5% of Se-adequate levels, with an Se requirement of 0.29 microg Se/g. Liver Gpx1, gizzard Gpx1 and gizzard Gpx4 activities also had Se requirements of 0.28-0.30 microg Se/g, collectively yielding an Se requirement of 0.3 microg Se/g, which is three times higher than the requirements found in comparable rodent studies. We also sequenced partial cDNA clones for turkey Gpx1 (GQ502186) and Gpx4 (GQ502187), and found >60% identity with rodents and humans and >90% identity with chickens. Ribonuclease protection analysis showed that Gpx4 mRNA levels decrease substantially in Se-deficient turkey liver, unlike in rodents. These underlying differences in selenoprotein molecular biology may explain the elevated dietary Se requirements of turkeys.

Dietary zinc reduces osteoclast resorption activities and increases markers of osteoblast differentiation, matrix maturation, and mineralization in the long bones of growing rats.

The nutritional influence of zinc on markers of bone extracellular matrix resorption and mineralization was investigated in growing rats. Thirty male weanling rats were randomly assigned to consume AIN-93G based diets containing 2.5, 5, 7.5, 15 or 30 microg Zn/g diet for 24 days. Femur zinc increased substantially as zinc increased from 5 to 15 microg/g diet and modestly between 15 and 30 microg/g (P<.05). By morphological assessment, trabecular bone increased steadily as dietary zinc increased to 30 microg/g. Increasing dietary zinc tended to decrease Zip2 expression nonsignificantly and elevated the relative expression of metallothionen-I at 15 but not 30 microg Zn/g diet. Femur osteoclastic resorption potential, indicated by matrix metalloproteinases (MMP-2 and MMP-9) and carbonic anhydrase-2 activities decreased with increasing dietary zinc. In contrast to indicators of extracellular matrix resorption, femur tartrate-resistant acid and alkaline phosphatase activities increased fourfold as dietary zinc increased from 2.5 to 30 microg Zn/g. Likewise, 15 or 30 microg Zn/g diet resulted in maximum relative expression of osteocalcin, without influencing expression of core-binding factor alpha-1, collagen Type 1 alpha-1, or nuclear factor of activated T cells c1. In conclusion, increased trabecular bone with additional zinc suggests that previous requirement estimates of 15 microg Zn/g diet may not meet nutritional needs for optimal bone development. Overall, the up-regulation of extracellular matrix modeling indexes and concomitant decrease in resorption activities as dietary zinc increased from 2.5 to 30 microg/g provide evidence of one or more physiological roles for zinc in modulating the balance between bone formation and resorption.

Iron absorption by healthy women is not associated with either serum or urinary prohepcidin.

BACKGROUND: Although hepcidin is proposed as a regulator of iron absorption, this has not been assessed in humans. OBJECTIVE: Our objective was to assess the relation between serum or urinary prohepcidin and iron absorption in healthy premenopausal women. DESIGN: The subjects were 28 healthy women aged 22-51 y with normal hemoglobin concentrations (120-152 g/L). Absorption of 0.5 mg Fe with 0.2 microCi 59Fe tracer, both as FeSO4, was measured by whole-body scintillation counting 13 d after oral administration. Fasting blood and urine samples were collected the day of and 16 wk after the absorption measurement. Serum and urinary prohepcidin concentrations were measured by an enzyme-linked immunosorbent assay by using an antibody against amino acid residues 28-47 of the proregion. RESULTS: Mean (+/-SD) iron absorption was 36 +/- 19% (range: 4-81%), and serum ferritin (geometric x) was 27 microg/L (range: 4-122 microg/L), as commonly observed in healthy premenopausal women. Serum prohepcidin was 196 microg/L (range: 99-376 microg/L) and, in contrast with urinary prohepcidin, was relatively consistent for the women between 0 and 16 wk. Serum prohepcidin correlated directly with serum ferritin (R2 = 0.28, P < 0.01) but was unrelated to 59Fe absorption, in contrast to serum ferritin (R2 = 0.33, P < 0.01). CONCLUSIONS: Serum prohepcidin concentrations were relatively stable within subjects and correlated with serum ferritin. However, unlike serum ferritin, neither serum nor urinary prohepcidin concentrations were related to iron absorption in healthy women.

Selenium regulation of thioredoxin reductase activity and mRNA levels in rat liver.

Mammalian thioredoxin reductase (TRR; NADPH(2):oxidized thioredoxin oxidoreductase, E.C. 1.6.4.5) is a new member of the family of selenocysteine-containing proteins. TRR activity in Se-deficient rat liver is reported to decrease to 4.5 to 15% of the activity in Se-adequate rat liver, similar to the fall in Se-dependent glutathione peroxidase-1 activity. Both glutathione peroxidase-1 enzyme activity and mRNA levels decrease dramatically in Se deficiency, whereas glutathione peroxidase-4 activity only decreases to 40% of Se-adequate levels and mRNA level is little affected by Se deficiency. The purpose of these experiments is to study the effect of Se status on TRR mRNA levels and enzyme activity in our well-characterized rat model, and to compare this regulation directly to the regulation of other Se-dependent proteins in male weanling rats fed Se-deficient diets or supplemented with dietary Se for 28 days. In two experiments, TRR activity in Se-deficient liver decreased to 15% of Se-adequate activity as compared to 2% and 40% of Se-adequate levels for GPX1 and GPX4, respectively. Using ribonuclease protection analysis, we found that TRR mRNA levels in Se-deficient rat liver decreased to 70% of Se-adequate levels. This decrease in TRR mRNA was similar to the GPX4 mRNA decrease in Se-deficient liver in these experiments, whereas GPX1 mRNA levels decreased to 23% of Se-adequate levels. This study clearly shows that TRR represents a third pattern of Se regulation with dramatic down-regulation of enzyme activity in Se deficiency but with only a modest decrease in mRNA level. The conservation of TRR mRNA in Se deficiency suggests that this is a valued enzyme; the loss of TRR activity in Se deficiency may be the cause of some signs of Se deficiency.