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Phaeochromocytoma and paraganglioma are highly heritable tumours; half of those associated with a germline mutation are caused by mutations in genes for Krebs’s cycle enzymes, including succinate dehydrogenase (SDH). Inheritance of SDH alleles is assumed to be Mendelian (probability of 50% from each parent). The departure from transmission of parental alleles in a ratio of 1:1 is termed transmission ratio distortion (TRD). We sought to assess whether TRD occurs in the transmission of SDHB pathogenic variants (PVs). This study was conducted with 41 families of a discovery cohort from Royal North Shore Hospital, Australia, and 41 families from a validation cohort from St. Bartholomew’s Hospital, United Kingdom (UK). Inclusion criteria were a clinically diagnosed SDHB PV and a pedigree available for at least two generations. TRD was assessed in 575 participants with the exact binomial test. The transmission ratio for SDHB PV was 0.59 (P = 0.005) in the discovery cohort, 0.67 (P < 0.001) in the validation cohort, and 0.63 (P < 0.001) in the combined cohort. No parent-of-origin effect was observed. TRD remained significant after adjusting for potential confounders: 0.67 (P < 0.001) excluding families with incomplete family size data; 0.58 (P < 0.001) when probands were excluded. TRD was also evident for SDHD PVs in a cohort of 81 patients from 13 families from the UK. The reason for TRD of SDHB and SDHD PVs is unknown, but we hypothesize a survival advantage selected during early embryogenesis. The existence of TRD for SDHB and SDHD has implications for reproductive counselling, and further research into the heterozygote state.

Medication errors are more prevalent in settings with acutely ill patients and heavy workloads, such as in an emergency department (ED). A pragmatic, controlled study compared partnered pharmacist medication charting (PPMC) (pharmacist-documented best-possible medication history [BPMH] followed by clinical discussion between a pharmacist and medical officer to co-develop a treatment plan and chart medications) with early BPMH (pharmacist-documented BPMH followed by medical officer-led traditional medication charting) and usual care (traditional medication charting approach without a pharmacist-collected BPMH in ED). Medication discrepancies were undocumented differences between medication charts and medication reconciliation. An expert panel assessed the discrepancies’ clinical significance, with ‘unintentional’ discrepancies deemed ‘errors’. Fewer patients in the PPMC group had at least one error (3.5%; 95% confidence interval [CI]: 1.1% to 5.8%) than in the early BPMH (49.4%; 95% CI: 42.5% to 56.3%) and usual care group (61.4%; 95% CI: 56.3% to 66.7%). The number of patients who need to be treated with PPMC to prevent at least one high/extreme error was 4.6 (95% CI: 3.4 to 6.9) and 4.0 (95% CI: 3.1 to 5.3) compared to the early BPMH and usual care group, respectively. PPMC within ED, incorporating interdisciplinary discussion, reduced clinically significant errors compared to early BPMH or usual care.

Maintaining reductive-oxidative (redox) balance is an essential feature in breast cancer cell survival, with cellular metabolism playing an integral role in maintaining redox balance through its supply of reduced NADPH. In the present studies, the effect of 1,25-dihydroxyvitamin D (1,25(OH)2D) on redox balance was investigated in early stages of breast cancer. Treatment with 1,25(OH)2D promoted oxidative stress in MCF10A-ras and MCF10A-ErbB2 breast epithelial cells, as measured by the decreased ratios of NADPH/NADP+ and reduced to oxidized glutathione (GSH/GSSG). The mRNA and protein expression of the enzyme pyruvate carboxylase (PC) was downregulated with 1,25(OH)2D treatment, suggesting a potential mechanism. Genetic depletion of PC in MCF10A-ras cells resulted in a decreased ratio of NADPH/NADP+ and GSH/GSSG, with 1,25(OH)2D treatment having no further effect. Mutation analysis confirmed the presence and functionality of a vitamin D response element in the PC gene promoter region. Collectively, these results provide evidence that 1,25(OH)2D promotes oxidative stress in early breast cancer progression through transcriptional downregulation of PC.

Both increased de novo fatty acid synthesis and higher neutral lipid accumulation are a common phenotype observed in aggressive breast cancer cells, making lipid metabolism a promising target for breast cancer prevention. In the present studies we demonstrate a novel effect of the active metabolite of vitamin D, 1α,25-dihydroxyvitamin D (1,25(OH)2D) on lipid metabolism in malignant breast epithelial cells. Treatment of MCF10CA1a breast epithelial cells with 1,25(OH)2D (10 nM) for five and seven days decreased the level of triacylglycerol, the most abundant form of neutral lipids, by 20%(±3.9) and 50%(±5.9), respectively. In addition, 1,25(OH)2D treatment for five days decreased palmitate synthesis from glucose, the major fatty acid synthesized de novo (48%±5.5 relative to vehicle). We have further identified the anaplerotic enzyme pyruvate carboxylase (PC) as a target of 1,25(OH)2D mediated regulation and hypothesized that 1,25(OH)2D regulates breast cancer cell lipid metabolism through inhibition of PC. PC mRNA expression was downregulated with 1,25(OH)2D treatment at two (73%±6 relative to vehicle) and five (56%±8 relative to vehicle) days. Decrease in mRNA abundance corresponded with a decrease in PC protein expression at five days of treatment (54%±12 relative to vehicle). Constitutive overexpression of PC in MCF10CA1a cells using a pCMV6-PC plasmid inhibited the effect of 1,25(OH)2D on both TAG accumulation and de novo palmitate synthesis from glucose. Together, these studies demonstrate a novel mechanism through which 1,25(OH)2D regulates lipid metabolism in malignant breast epithelial cells.

Breast cancer metastasis to the bone continues to be a major health problem, with approximately 80% of advanced breast cancer patients expected to develop bone metastasis. Although the problem of bone metastasis persists, current treatment options for metastatic cancer patients are limited. In this study, we investigated the preventive role of the active vitamin D metabolite, 1α,25-dihydroxyvitamin D (1,25(OH)2D), against the metastatic potential of breast cancer cells using a novel three-dimensional model (rMET) recapitulating multiple steps of the bone metastatic process. Treatment of MCF10CA1a and MDA-MB-231 cells inhibited metastasis in the rMET model by 70% (±5.7%) and 21% (±6%), respectively. In addition, 1,25(OH)2D treatment decreased invasiveness (20 ± 11% of vehicle) and decreased the capability of MCF10CA1a cells to survive in the reconstructed bone environment after successful invasion through the basement membrane (69 ± 5% of vehicle). An essential step in metastasis is epithelial-mesenchymal transition (EMT). Treatment of MCF10CA1a cells with 1,25(OH)2D increased gene (2.04 ± 0.28-fold increase) and protein (1.87 ± 0.20-fold increase) expression of E-cadherin. Additionally, 1,25(OH)2D treatment decreased N-cadherin gene expression (42 ± 8% decrease), a marker for EMT. Collectively, the present study suggests that 1,25(OH)2D inhibits breast cancer cell metastatic capability as well as inhibits EMT, an essential step in the metastatic process.

Although patients experience hair loss and dry skin which may be attributable to deficiency in essential fatty acids (EFAs), the impact of bariatric surgeries on EFA status is unknown. This study aimed to assess plasma phospholipid fatty acid profiles following adjustable gastric banding (AGB), which restricts dietary fat intake, versus Roux-en-Y gastric bypass (RYGB), which also promotes fat malabsorption. Serial measures were obtained before and 1 and 6 months from women undergoing RYGB (N = 13) and AGB (N = 5). Measures included the composition of plasma fatty acids in phospholipids, dietary intake, and body fat mass. Friedman and Mann–Whitney tests were used to assess differences over time and between groups, respectively, p

Background Omega-3 polyunsaturated fatty acid (PUFA) may benefit humans and animals with chronic inflammatory diseases. Hypothesis Omega-3 PUFA supplementation improves clinical signs, lung function, and airway inflammation in horses with recurrent airway obstruction (RAO) and inflammatory airway disease (IAD). Animals Eight research horses and 35 client-owned horses. Methods A pilot study examined the dose of PUFA that can alter plasma PUFA composition. Then, a randomized, controlled clinical trial was performed in horses with RAO and IAD. Horses were fed a complete pelleted diet with no hay and randomly assigned to 1 of 3 daily treatments for 2 months: 30 or 60 g of the supplement or 30 g of placebo. Clinical signs, lung function, plasma PUFA composition, and bronchoalveolar lavage fluid (BALF) cytology were evaluated. Data were expressed as median (25–75th percentiles). P

Artificial food colors (AFCs) are used to color many beverages, foods, and sweets in the United States and throughout the world. In the United States, the Food and Drug Administration (FDA) limits the AFCs allowed in the diet to 9 different colors. The FDA certifies each batch of manufactured AFCs to guarantee purity and safety. The amount certified has risen from 12 mg/capita/d in 1950 to 62 mg/capita/d in 2010. Previously, we reported the amounts of AFCs in commonly consumed beverages. In this article, the amounts of AFCs in commonly consumed foods and sweets are reported. In addition, the amount of sugars in each product is included. Amounts of AFCs reported here along with the beverage data show that many children could be consuming far more dyes than previously thought. Clinical guidance is given to help caregivers avoid AFCs and reduce the amount of sugars in children’s diets.

Artificial food colors (AFCs) are widely used to color foods and beverages. The amount of AFCs the Food and Drug Administration has certified over the years has increased more than 5-fold since 1950 (12 mg/capita/day) to 2012 (68 mg/capita/day). In the past 38 years, there have been studies of adverse behavioral reactions such as hyperactivity in children to double-blind challenges with AFCs. Studies that used 50 mg or more of AFCs as the challenge showed a greater negative effect on more children than those which used less. The study reported here is the first to quantify the amounts of AFCs in foods (specifically in beverages) commonly consumed by children in the United States. Consumption data for all foods would be helpful in the design of more challenge studies. The data summarized here should help clinicians advise parents about AFCs and beverage consumption.

This review examines the research on mechanisms by which artificial food colors (AFCs) and common foods may cause behavioral changes in children with and without attention-deficit/hyperactivity disorder (ADHD). Children with ADHD show excess inattention, impulsivity, and hyperactivity. Studies have shown that a subgroup of children (with or without ADHD) react adversely to challenges with AFCs. Many early studies found few children who reacted to challenges with 20-40 mg of AFCs. However, studies using at least 50 mg of AFCs showed a greater percentage of children who reacted to the challenge. Three types of potential mechanisms are explored: toxicological, antinutritional, and hypersensitivity. Suggestions for future studies in animals and/or children include dose studies as well as studies to determine the effects of AFCs on the immune system, the intestinal mucosa, and nutrient absorption. Given the potential negative behavioral effects of AFCs, it is important to determine why some children may be more sensitive to AFCs than others and to identify the tolerable upper limits of exposure for children in general and for children at high risk.

The tea catechin EGCG has been postulated to provide health benefits in humans, to some extent, as an antioxidant. The dose-response effect of dietary EGCG (0, 30, 60, or 120 mg/kg diet) was tested in rats under high versus low oxidative stress conditions that were created by feeding diets adequate in vitamin E and Se (Lox), or deficient in both (Hox) for six weeks. Effects on growth, quinone reductase (NQO1) activity, F2-isoprostanes and nutrient antioxidant amounts in the liver were evaluated as markers of nutrient deficiency and oxidative status. Under Hox conditions consumption of EGCG only at the lowest dose was partially associated with a protection against oxidative stress, reflected by a delay in growth deceleration, but no protection against lipid oxidation. Elevated liver NQO1 activity was observed in this group (>4-fold) increasing with the dose; but it was not associated with antioxidant protection. In contrast, under Lox conditions consumption of EGCG was associated with antioxidant activity reflected in a reduction (>30%) in F2-isoprostanes and protection of CoQ reduced status in the liver. Overall these results suggest that the antioxidant effect of EGCG in vivo depends on the level of oxidative stress and the presence of other nutrient antioxidants.

Beverage consumption has been implicated in weight gain, but questions remain about the veracity of the association, whether the relationship is causal and what property of beverages is responsible. It was hypothesized that food form is the most salient attribute. Thus, a randomized controlled trial of food form was conducted. Energy-matched beverage or solid forms of fruits and vegetables were provided to 34, lean or overweight/obese adults for two 8-week periods with a 3-week washout interspersed. Dietary compensation was incomplete (beverage 53% solid 78%) and body weight increased after the beverage (1.95 ± 0.33 kg) (77% fat mass) and solid (1.36 ± 0.30 kg) (85% fat mass) treatments (both P < 0.0005). Differences between food forms were not significant. The lean group had the highest dietary compensation (119%) and no significant weight change (0.84 ± 0.53 kg) after consuming the solid fruits and vegetables whereas the overweight/obese group had lower compensation and significant weight gain during the solid arm (46%, 1.77 ± 0.32 kg, P < 0.0001). In contrast, incomplete dietary compensation and weight gain occurred in both the lean (43%, 1.61 ± 0.44 kg, P = 0.003) and overweight/obese (61%, 2.22 ± 0.47 kg, P < 0.0005) groups during the beverage arm. Secondary analyses revealed the obese group gained more weight than the lean and overweight groups during the beverage intervention (P = 0.024). These data demonstrate energy consumed as beverages may be especially problematic for weight gain. They also indicate that advice to increase fruit and vegetable consumption should emphasize total energy intake because the additional energy contributed may promote weight gain, especially among overweight and obese individuals.

Advanced glycation end products (AGEs) result from non-enzymatic glycation of proteins and cause cellular oxidative stress in a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-dependent manner. Due to these effects, AGEs are implicated as a causal factor in diabetic complications. Several antioxidants, including vitamin E, improve cell viability and diminish markers of oxidative damage in cells exposed to AGEs. However, vitamin E has been studied in cell culture systems with primary focus on apoptosis and lipid peroxidation, while its influences on AGE-induced protein and DNA oxidation, intracellular antioxidant status and cell morphology remain largely unknown. Here, we verify the suppression of AGE-induced cell death and lipid peroxidation by 200 μM α-tocopherol in SH-SY5Y cells. We report the partial inhibition of DNA oxidation and a decrease in protein carbonyl formation by α-tocopherol with no effects on intracellular GSH concentrations. We observed that 2 mM N-acetyl cysteine (NAC) also had a suppressive effect on DNA and protein oxidation, but unlike α-tocopherol, it caused a marked increase in intracellular GSH. Finally, we compared the ability of both antioxidants to maintain neurites in SH-SY5Y cells and found that α-tocopherol had no effect on neurite loss due to AGEs, while NAC fully maintained cell morphology. Thus, while α-tocopherol suppressed AGE-induced macromolecule damage, it was ineffective against neurite degeneration. These results may implicate thiol oxidation and maintenance as a major regulator of neurite degeneration in this model.

Diabetes mellitus, a disease hallmarked by hyperglycemia, is one of the most common chronic diseases worldwide and new diagnoses are on an upward trajectory. Peripheral neuropathy (PN) affects at least 50% of diabetic patients. Unfortunately, medications available for patients with PN treat the symptoms but not the cellular damage, and come with severe side effects leading many to discontinue their use. The overall objective of this study was to gain a better understanding of the mechanism of action and potential impact of therapeutic substances, such as N-acetylcysteine (NAC), and preventive dietary components, such as the cruciferous vegetable constituent 3H-1,2-dithiole-3-thione (D3T), which is critically important for patient health. Previous studies in our lab have shown that when SH-SY5Y cells, a validated model for PN, are treated with advanced glycation end products (AGE), there is increased reactive oxygen species (ROS) generation, a significant decrease in glutathione (GSH) concentrations, and neurite loss. NAC was shown to protect against AGE-induced cell death, GSH depletion and neurite loss, indicating that maintaining GSH was important for neurite protection. Our lab has also shown that D3T, a potent inducer of nuclear factor (erythroid-derived 2)- like (Nrf2), can significantly increase SH-SY5Y cellular GSH concentrations and protect against H2O2 –induced cell death. Paradoxically, D3T conferred no protection against AGE-induced cell death or neurite degeneration. We report here follow up studies. The first aim of this study was to test whether NAC conferred protection through maintaining GSH, its intrinsic antioxidant properties, or both. Using buthionine sulfoximine (BSO) as a tool to evaluate the mechanistic role of NAC in neurite protection, we found that at high concentrations of NAC (2 mM) both intrinsic and GSH-maintaining properties were observed. At lower concentrations (1 mM), GSH-maintaining properties predominated. The second aim was to elucidate a mechanism for the paradoxical effect of D3T focusing on the role of NADPH-mediated ROS generation. NADPH is an electron donor for the oxidase enzyme that generates superoxide in response to the activation of the receptor for AGE (RAGE). D3T increased ROS generation and depleted GSH only in the presence of AGE, suggesting its role as a NADPH generating agent may promote oxidative stress rather than protect against it under these conditions. Inhibition of NADPH generation via glucose-6-phosphate dehydrogenase (G6PD), the protein product of a Nrf2-responsive gene, with dehydro-epiandrosterone (DHEA) was found to protect against AGE-induced loss of cell viability. These results suggest that the source of ROS is important to consider in evaluating the extent to which adaption to oxidative stress provides protection.

Artificial food colors (AFCs) have not been established as the main cause of attention-deficit hyperactivity disorder (ADHD), but accumulated evidence suggests that a subgroup shows significant symptom improvement when consuming an AFC-free diet and reacts with ADHD-type symptoms on challenge with AFCs. Of children with suspected sensitivities, 65% to 89% reacted when challenged with at least 100 mg of AFC. Oligoantigenic diet studies suggested that some children in addition to being sensitive to AFCs are also sensitive to common nonsalicylate foods (milk, chocolate, soy, eggs, wheat, corn, legumes) as well as salicylate-containing grapes, tomatoes, and orange. Some studies found “cosensitivity” to be more the rule than the exception. Recently, 2 large studies demonstrated behavioral sensitivity to AFCs and benzoate in children both with and without ADHD. A trial elimination diet is appropriate for children who have not responded satisfactorily to conventional treatment or whose parents wish to pursue a dietary investigation.

The objective was to determine the effects of natural- or synthetic-source vitamin E on reproductive efficiency in Angus-cross beef cows. In Exp. 1, one hundred fifty-two cows were fed hay and corn silage based diet and assigned to 1 of 3 dietary supplements (3 pens/treatment): 1) containing no additional vitamin E (CON), 2) formulated to provide 1,000 IU x d(-1) of synthetic-source vitamin E (SYN; all-rac or dl-alpha-tocopherol acetate), or 3) formulated to provide 1,000 IU x d(-1) of natural-source vitamin E (NAT; RRR or D-alpha-tocopherol acetate). In Exp. 2, seventy-five cows (2 reps/treatment) were assigned to similar treatments as Exp. 1; however, a vitamin-mineral supplement was offered for ad libitum intake and vitamin intake was calculated from predicted mineral intakes. Cows grazed pastures rather than being fed hay and corn silage as in Exp. 1. In Exp. 1 and 2, supplementation began 6 wk prepartum and continued until initiation of the breeding season. Blood samples were collected at calving (Exp. 1) or breeding (Exp. 2) to determine alpha-tocopherol concentration and weekly beginning 4 wk postpartum (Exp. 1) or 7 and 14 d before estrus synchronization (Exp. 2) to determine return to estrus via progesterone concentration. Cows were synchronized and bred by AI based on heat detection; nonresponding cows were time bred (AI) 66 h after PGF(2 alpha) injection, and cows returning to estrus after AI were bred by natural service. In Exp. 1, cows supplemented with NAT and SYN had greater (P0.001) serum concentrations of alpha-tocopherol at calving compared with CON cows. Dietary supplement did not affect (Por= 0.55) the percentage of cows cycling before synchronization or the number of days to return to estrus by cows that resumed estrus before synchronization. Cows supplemented with SYN tended to have greater first service conception rates compared with CON and NAT (P = 0.09); however, first plus second services combined and overall conception rates were not affected (Por= 0.23). In Exp. 2, NAT cows had greater (P = 0.002) concentrations of alpha-tocopherol at breeding, whereas there was no difference (P0.05) between SYN and CON. Supplementation of SYN or NAT did not affect (Por= 0.17) days to resumption of estrus before breeding, first service, first plus second services combined, or overall conception rates. These data suggest that supplementation of SYN or NAT source vitamin E increased alpha-tocopherol concentration in cows; however, effects on reproductive efficiency are minimal.

The objective of this study was to determine the effects of maternally supplemented natural- or synthetic-source vitamin E on suckling calf performance and immune response. In a 2-yr study, one hundred fifty-two 2- and 3-yr-old, spring-calving, Angus-cross beef cows were blocked by age, BW, and BCS into 1 of 3 isocaloric, corn-based dietary supplements containing 1) no additional vitamin E (CON), 2) 1,000 IU/d of synthetic-source vitamin E (SYN), or 3) 1,000 IU/d of natural-source vitamin E (NAT). Maternal supplementation began approximately 6 wk prepartum and continued until the breeding season. Colostrum from cows and blood from calves was collected 24 h postpartum for analysis of IgG concentration as an indicator of passive transfer and circulating alpha-tocopherol concentration. At 19 d of age, blood was collected from calves to determine the expression of CD14 and CD18 molecules on leukocytes. At 21 and 35 d of age, humoral immune response was measured by a subcutaneous injection, in the neck, with ovalbumin (20 mg; OVA) and blood samples collected weekly until d 63 of age to determine antibodies produced against OVA. At d 63 of age, calves were administered an intradermal injection of OVA (1 mg) in the neck to assess cell-mediated immunity, which was determined on d 65 of age by measuring nodule size with calipers. Circulating alpha-tocopherol concentrations were increased at both 24 h (P = 0.001) and at the day of initial OVA challenge (P0.001) in SYN and NAT compared with CON calves. No differences were detected (P0.05) for calf birth BW, ADG, or weaning BW. There were no differences (P0.05) in calf serum total IgG or cow colostrum total IgG at 24 h or presence of CD14 and CD18 receptors at d 19 of age. The NAT calves had a greater antigen response to OVA at d 63 than SYN calves (P = 0.01; treatment x day interaction). As an indicator of cell-mediated immunity to OVA, nodule size at 65 d of age was not affected (P = 0.92) by maternal dietary supplementation. In conclusion, calves suckling cows supplemented with natural- and synthetic-source vitamin E had increased circulating concentrations of alpha-tocopherol at 24 h, which appeared to continue throughout maternal supplementation; however, calf immune function and performance were not affected.

Diabetes is a disease characterized by poor glycemic control for which risk of the type 2 form increases with age. A rise in blood glucose concentration causes increased oxidative stress which contributes to the development and progression of diabetes-associated complications. Studies have shown that primary antioxidants or genetic manipulation of antioxidant defenses can at least partially ameliorate this oxidative stress and consequentially, reduce severity of diabetic complications in animal models. Data from humans is less clear and will be summarized in this review. We highlight results from studies performed to investigate the role of vitamin E in preventing diabetes-induced oxidative damage in cell culture, animal models, and human participants, and summarize evidence testing whether this nutrient has an effect on outcomes related to the diabetic complications of nephropathy, retinopathy, and neuropathy. The most compelling evidence for an effect of vitamin E in diabetes is on protection against lipid peroxidation, whereas effects on protein and DNA oxidation are less pronounced. More studies are required to make definitive conclusions about the effect of vitamin E treatment on diabetes complications in human subjects.

High vitamin D intake is associated with reduced insulin resistance. Expression of extra-renal 1α,25-dihydroxyvitamin D hydroxylase (1α-hydroxylase) has been reported in several tissues and contributes to local synthesis of 1α,25-dihydroxyvitamin D 3 (1,25(OH) 2 D) from the substrate 25-hydroxyvitamin D (25OHD). Expression and dietary regulation of 1α-hydroxylase in tissues associated with energy metabolism, including adipose tissue, has not been assessed. Male Wistar rats were fed a high calcium (1.5%) and high vitamin D (10,000 IU/kg) or a low calcium (0.25%), low vitamin D (400 IU/kg) with either a high fat (40% energy) or high sucrose (66% energy) dietary background for 14 weeks. Expression of 1α-hydroxylase, assessed by real time PCR, was detected in adipose tissue and did not differ with dietary level of calcium and vitamin D. 1α-Hydroxylase mRNA was also detected in 3T3-L1 preadipocytes and 25OHD treatment at 10 nM levels induced 1,25(OH) 2 D responsive gene, CYP24, and this response was reduced in the presence of the p450 inhibitor, ketoconazole. In addition, 3 H 25OHD was converted to 3 H 1,25(OH) 2 D in intact 3T3-L1 preadipocytes. Cumulatively, these results demonstrate that 1α-hydroxylase is expressed in adipose tissue and is functional in cultured adipocytes. Thus, the capacity for local production may play a role in regulating adipocyte growth and metabolism.

Quercetin (3,3',4',5,7-pentahydroxyflavone), a dietary flavonoid, is an inhibitor of phosphatidylinositol (PI) 3-kinase and potent antioxidant. We hypothesized that quercetin blocks airway epithelial cell chemokine expression via PI 3-kinase-dependent mechanisms. Pretreatment with quercetin and the PI 3-kinase inhibitor LY294002 each reduced TNF-alpha-induced IL-8 and monocyte chemoattractant protein (MCP)-1 (also called CCL2) expression in cultured human airway epithelial cells. Quercetin also inhibited TNF-alpha-induced PI 3-kinase activity, Akt phosphorylation, intracellular H(2)O(2) production, NF-kappaB transactivation, IL-8 promoter activity, and steady-state mRNA levels, consistent with the notion that quercetin inhibits chemokine expression by attenuating NF-kappaB transactivation via a PI 3-kinase/Akt-dependent pathway. Quercetin also reduced TNF-alpha-induced chemokine secretion in the presence of the transcriptional inhibitor actinomycin D, while inducing phosphorylation of eukaryotic translation initiation factor (eIF)-2alpha, suggesting that quercetin attenuates chemokine expression by post-transcriptional as well as transcriptional mechanisms. Finally, we tested the effects of quercetin in cockroach antigen-sensitized and -challenged mice. These mice show MCP-1-dependent airways hyperresponsiveness and inflammation. Quercetin significantly reduced lung MCP-1 and methacholine responsiveness. We conclude that quercetin blocks airway cell chemokine expression via transcriptional and post-transcriptional pathways.

Objective To investigate the effect of supplementation with different sources of oils rich in long chain fatty acids, ie, fish oil (FO) and safflower oil (SO), on the production of leukotriene B 4 (LTB 4 ) by polymorphonuclear leukocytes (PMNLs) in hemodialysis patients and the consequent effects on the symptoms of pruritus. Design Randomized, prospective, double-blind study for 2 treatment groups. Setting Three Medical Center—affiliated units. Patients Twenty-two patients on maintenance hemodialysis, of both sexes, age ≥ 20 years with complaint of dry and/or itchy skin. Intervention Two groups of patients receiving daily supplements of 6 g ethyl ester of FO or SO for 16 weeks. Main outcome measures Red blood cell (RBC) fatty acid profile, LTB 4 production by PMNLs, and pruritus symptoms at baseline and after supplementation. Results After supplementation, the FO group had a higher RBC 22:6n3, total n-3 fatty acids, and ratio of total n-3 to total n-6 fatty acids ( P 4 production (pg/mL) from baseline to week 16 was 240.7 ± 200.2 to 29.2 ± 14.6 in the FO group and from 171.1 ± 121.7 to 31.9 ± 14.7 in the SO group. The overall pruritus score change was 16.7 ± 11.4 to 8.9 ± 9.2 in the FO group and from 17.5 ± 8.8 to 13.1 ± 5.6 in the SO group. FO supplementation did not result in a significant specific effect on LTB 4 production by the PMNLs. There was a nonsignificant decrease in the pruritus scores that could be clinically significant and important to patients suffering with this condition. Conclusion Supplementation with FO results in significant incorporation of n-3 fatty acids in the RBCs. Intervention with both FO and SO resulted in a nonsignificant improvement of clinical symptoms of pruritus and a nonsignificant reduction in LTB 4 production by PMNLs in the hemodialysis patients. The percent decrease in total puritus score was greater for the FO group compared with the SO group.

Background: The Dietary Guidelines for Americans 2010 recommend that Americans age two years and older consume seafood, especially fish high in omega-3 polyunsaturated fatty acids, at least twice a week. Although fish is of particular importance during childhood to support proper brain and eye development, it is under-consumed in the US pediatric population. This study examined if substituting salmon for chicken would increase preschooler’s fish consumption. Methods: Two-to-five years old children (n = 45) were served eight lunches (four pairs of comparable chicken versus salmon dishes) twice, totaling sixteen lunches over a period of three months to test the hypothesis that children will consume fish at least once a week, thus increasing docosahexaenoic acid (DHA) intake. The plate waste method was used to collect intake data and consumption of total energy and DHA intake in the chicken and the fish dishes were compared using contrasts within a mixed effect ANOVA (significance at P < 0.05). Results: Dietary intake estimates showed that there were no significant differences in energy intake when the chicken and fish dishes looked similar (macaroni-and-cheese and wraps), but when the fish dishes looked new (nuggets and dumplings), energy intake on fish days was lower than on the chicken day. DHA intake increased significantly on all days the fish was served. Conclusions: This pilot study indicates that fish intake can meet recommendations if salmon is incorporated into familiar dishes such as salad wraps or macaroni-and-cheese, in the childcare setting. Although fish is more expensive, childcare centers may serve this highly nutritious protein once a week without experiencing undue amounts of food wastes if incorporated into well-accepted main dishes. Further studies in larger and more diverse samples of children, different experimental dishes, and longer exposure periods may elucidate additional venues to increase children’s diet quality by increasing consumption of fatty fish.

The purpose of this study was to investigate the effects of duck breeder age on liver lipid accumulation and yolk absorption and utilization in duck embryos (day 25 of incubation) and newly hatched ducklings. One breeder flock was monitored at 24 (young breeders), 31 (mature breeders and near peak egg production) and 47 (post peak egg production) weeks of age. Electron microscopy images of duck embryo liver slices revealed a significant change in hepatic lipid accumulation as a function of breeder age. More specifically, as breeder age increased both the relative number of liver lipid droplets as well as the size of the lipid droplets increased in duck embryos (day 25 of incubation). At hatch, however, newly hatched ducklings from 31-week-old breeders exhibited the lowest number as well as the smallest sized lipid droplets when compared to ducklings from 24 or 47-week-old breeders. The trend in yolk absorption at day 25 as a function of breeder age paralleled that in liver lipid accumulation. That is, day 25 maintained a higher percentage of unabsorbed yolk when compared to embryos from 31- or 47-week-old breeders. In contrast to breeder age, time of incubation (day 25 vs. day 28 or hatch) had little effect on yolk fatty acid profiles when compared to breeder age. Although there were no clear trends in yolk fatty acid usage among the various ages of breeders, newly hatched ducklings from 31-week-old breeders did have a significantly higher proportion of 18:2 n6 compared to those from breeders at 24 or 47 weeks of age. These data would suggest that breeder age subsequently affects the relative number and size of liver lipid droplets in embryos and newly hatched ducklings.

BACKGROUND Multiple endocrine neoplasia type 1 (MEN-1) is an autosomal dominant tumor syndrome associated with parathyroid, gastroenteropancreatic (GEP), and pituitary neoplasia. Gastrinoma and GEP malignancy are common life-threatening endocrine complications of MEN-1. An effective management strategy for these disorders remains to be determined. The authors attempted to determine the role of the somatostatin analogue, octreotide, in ameliorating features of hypergastrinemic GEP neoplasia associated with MEN-1. METHODS Five MEN-1 patients with hypergastrinemia and either symptoms of GEP neoplasia or hepatic metastases received a trial of octreotide, 100 μg subcutaneously, three times daily for 3 months. RESULTS Treatment with octreotide was associated with a rapid symptomatic and biochemical response. In all patients serum gastrin fell to < 25% of the pretreatment value. The serum glycoprotein-αsubunit (a marker of enterochromaffin-like [ECL] cell hyperplasia, gastric carcinoidosis, and disseminated enteropancreatic malignancy) was elevated at baseline in three patients. In each case the serum glycoprotein-αsubunit normalized after treatment with octreotide. Hepatic metastases were present in two patients at baseline. The size of the metastases diminished by up to 15% during the period of octreotide treatment. Four patients reported symptoms prior to treatment: lethargy, easy fatigability, and generalized musculoskeletal discomfort. A marked symptomatic improvement occurred in each case. No patient experienced side effects related to octreotide therapy and all elected to remain on treatment after completion of the trial. CONCLUSIONS Octreotide is a safe and effective adjunct to surgical strategies for the management of GEP neoplasia in hypergastrinemic MEN-1 patients. Cancer 1999;86:2154–9. © 1999 American Cancer Society.

In these studies, prostaglandin H synthase activity was increased in stably Harvey-ras transfected C3H10T1/2 cells. The level of total prostaglandin H synthase protein was two-fold higher in stably Harvey-ras transfected C3H10T1/2 cells than in control cells with no difference in prostaglandin H synthase-2 level. Prostaglandin H synthase-1 mRNA level was two-fold higher in transfected than in control cells, while prostaglandin H synthase-2 was not significantly different. Thus, prostaglandin H synthase-1, but not prostaglandin H synthase-2, expression was increased in Harvey-ras transfected C3H10T1/2 cells.

Glutathione redox balance ― defined as the ratio GSH/GSSG ― is a critical regulator of cellular redox state, and declines in this ratio are closely associated with oxidative stress and disease. However, little is known about the impact of genetic variation on this trait. Previous mouse studies suggest that tissue GSH/GSSG is regulated by genetic background and is therefore heritable. In this study, we measured glutathione concentrations and GSH/GSSG in liver and kidney of 30 genetically-diverse inbred mouse strains. Genetic background caused an approximately three-fold difference in hepatic and renal GSH/GSSG between the most disparate strains. Haplotype association mapping determined the loci associated with hepatic and renal glutathione phenotypes. We narrowed the number of significant loci by focusing on those located within protein-coding genes, which we now consider to be candidate genes for glutathione homeostasis. No candidate genes were associated with both hepatic and renal GSH/GSSG, suggesting that genetic regulation of GSH/GSSG occurs predominantly in a tissue-specific manner. This is the first quantitative trait loci study to examine the genetic regulation of glutathione concentrations and redox balance in mammals. We identified novel candidate genes that have the potential to redefine our knowledge of redox biochemistry, its regulation, and inform future therapeutic applications.

Several lines of evidence suggest that phospholipase A2 may play a role in the activated ras-mediated transformation process. In the present study, phospholipase A2 activity and expression were assessed in a murine fibroblast cell line (C3H10T1/2 cells) that was stably transfected with the Harvey ras oncogene, a cellular model used for studying multistage carcinogenesis. Reduced levels of fatty acids were released from the ras-transfected cells compared to untransfected controls. The in vitro phospholipase A2 activity apparent in the C3H10T1/2 showed preference for sn-2 arachidonyl phosphatidylcholine compared to dipalmitoyl phosphatidylcholine. The activity, as well as the cytosolic phospholipase A2 immunoreactive protein, was reduced by 50% in the ras-transfected cells compared to control cells. These results suggest that the cytosolic phospholipase A2 is the predominant form of this enzyme family expressed in C3H10T1/2 cells and that the activity and protein amount is reduced by 50% in these cells when stably transfected with the Harvey ras oncogene.

Long-Evans hooded rats maintained on vitamin E and selenium-deficient diets for 6 weeks from weaning exhibited a pattern of enhancement of calcium-independent phospholipase A2 activity in spleen cytosol similar to that previously reported for the lung and liver. The spleen cytosols from vitamin E and selenium deficient rats had approximately 5 fold higher activity than the samples from animals maintained on diets sufficient in these two nutrients (control) or deficient in either nutrient alone. The calcium-dependent PLA2 activity was about 6 fold higher in spleen cytosol of vitamin E and selenium deficient rats compared with cytosolic samples from animals on the other three diets. Time course studies indicated that in rats the calcium-independent phospholipase A2 activity in lung, liver, and spleen increased initially between 4 and 6 weeks of consuming the diets deficient in both vitamin E and selenium, and increased even further again at 7 weeks. This bi-phasic response to the deficiency occurred 1 week after indicators of vitamin E and Se status had reached minimum levels. When animals that were maintained on the deficient diet for 6 weeks consumed the control diet for 1 week the phospholipase A2 activity of lung, liver, and spleen was not different than the activity of the control animals. The malondialdehyde concentration of lung and spleen measured at 6 and 7 weeks correlated positively with the calcium-independent phospholipase A2 activity. These results indicate that deficiency of vitamin E and selenium in the rat leads to a bi-phasic increase in calcium-independent PLA2 activity in rat lung, liver, and spleen, and that the initial increase can be reversed by partial repletion of the two antioxidant nutrients.

Attention-deficit hyperactivity disorder (ADHD) is the term used to describe children who are inattentive, impulsive, and hyperactive. The cause is unknown and is thought to be multifactorial. Based on the work of others, we hypothesized that some children with ADHD have altered fatty acid metabolism. The present study found that 53 subjects with ADHD had significantly lower concentrations of key fatty acids in the plasma polar lipids (20:4n-6, 20:5n-3, and 22:6n-3) and in red blood cell total lipids (20:4n-6 and 22:4n-6) than did the 43 control subjects. Also, a subgroup of 21 subjects with ADHD exhibiting many symptoms of essential fatty acid (EFA) deficiency had significantly lower plasma concentrations of 20:4n-6 and 22:6n-3 than did 32 subjects with ADHD with few EFA-deficiency symptoms. The data are discussed with respect to cause, but the precise reason for lower fatty acid concentrations in some children with ADHD is not clear.

Oxidative stress is implicated as a major factor in the development of diabetes complications and is caused in part by advanced glycation end products (AGEs). AGEs ligate to the receptor for AGEs (RAGE), promoting protein kinase C (PKC)-dependent activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and superoxide radical generation. While scavenging antioxidants are protective against AGEs, it is unknown if induction of endogenous antioxidant defenses has the same effect. In this study, we confirmed that the compound 3H-1,2-dithiole-3-thione (D3T) increases reduced-state glutathione (GSH) concentrations and NADPH:quinone oxidoreductase 1 (NQO1) activity in SH-SY5Y cells and provides protection against H2O2. Surprisingly, D3T potentiated oxidative damage caused by AGEs. In comparison to vehicle controls, D3T caused greater AGE-induced cytotoxicity and depletion of intracellular GSH levels while offering no protection against neurite degeneration or protein carbonylation. D3T potentiated AGE-induced reactive oxygen species (ROS) formation, an effect abrogated by inhibitors of PKC and NADPH oxidase. This study suggests that chemical induction of endogenous antioxidant defenses requires further examination in models of diabetes.

Background Chronic obstructive pulmonary disease (COPD) is characterized by chronic bronchitis, emphysema and irreversible airflow limitation. These changes are thought to be due to oxidative stress and an imbalance of proteases and antiproteases. Quercetin, a plant flavonoid, is a potent antioxidant and anti-inflammatory agent. We hypothesized that quercetin reduces lung inflammation and improves lung function in elastase/lipopolysaccharide (LPS)-exposed mice which show typical features of COPD, including airways inflammation, goblet cell metaplasia, and emphysema. Methods Mice treated with elastase and LPS once a week for 4 weeks were subsequently administered 0.5 mg of quercetin dihydrate or 50% propylene glycol (vehicle) by gavage for 10 days. Lungs were examined for elastance, oxidative stress, inflammation, and matrix metalloproteinase (MMP) activity. Effects of quercetin on MMP transcription and activity were examined in LPS-exposed murine macrophages. Results Quercetin-treated, elastase/LPS-exposed mice showed improved elastic recoil and decreased alveolar chord length compared to vehicle-treated controls. Quercetin-treated mice showed decreased levels of thiobarbituric acid reactive substances, a measure of lipid peroxidation caused by oxidative stress. Quercetin also reduced lung inflammation, goblet cell metaplasia, and mRNA expression of pro-inflammatory cytokines and muc5AC. Quercetin treatment decreased the expression and activity of MMP9 and MMP12 in vivo and in vitro, while increasing expression of the histone deacetylase Sirt-1 and suppressing MMP promoter H4 acetylation. Finally, co-treatment with the Sirt-1 inhibitor sirtinol blocked the effects of quercetin on the lung phenotype. Conclusions Quercetin prevents progression of emphysema in elastase/LPS-treated mice by reducing oxidative stress, lung inflammation and expression of MMP9 and MMP12.

Naringenin, a flavonoid present in grapefruit, has recently been shown to exert hypolipidemic and hypocholesterolemic effects, which has a particular importance for protecting against chronic diseases. However, the lipid-lowering potential of naringenin at the concentrations in the dietary range and its underlying mechanisms have yet to be fully elucidated. The aim of the present study was (1) to investigate the effects of dietary naringenin on plasma and hepatic triglyceride and cholesterol levels and on adipose deposition in rat and (2) to determine the contribution of hepatic peroxisome proliferators–activated receptor α (PPARα) expression to fatty acid oxidation. Male Long-Evans hooded rats were fed a diet supplemented with naringenin (0.003, 0.006, and 0.012%) for 6 weeks. We analyzed plasma and hepatic lipid contents and determined the protein expression of PPARα, carnitine-palmitoyl transferase 1L (CPT-1), and uncoupling protein 2 (UCP2), all of which are critical genes for fatty acid oxidation. Naringenin supplementation caused a significant reduction in the amount of total triglyceride and cholesterol in plasma and liver. In addition, naringenin supplementation lowered adiposity and triglyceride contents in parametrial adipose tissue. Naringenin-fed animals showed a significant increase in PPARα protein expression in the liver. Furthermore, expression of CPT-1 and UCP2, both of which are known to be regulated by PPARα, was markedly enhanced by naringenin treatment. Our results indicate that the activation of PPARα transcription factor and upregulation of its fatty acid oxidation target genes by dietary naringenin may contribute to the hypolipidemic and anti-adiposity effects in vivo.

Aqueous extracts of the coralline red algaeBossiella orbigniana have been shown to catalyze the enzymatic oxidation of arachidonic acid to a previously unreported ω6 eicosapentaenoic acid product. This unique fatty acid contains a conjugated tetraene with absorption maxima at 293, 306, and 321 nm, and was identified by spectral methods as 5(Z),8(Z),10(E),12(E),14(Z)-eicosapentaenoic acid. The compound was given the trivial name bosseopentaenoic acid. Under experimental conditions, production of bosseopentaenoic acid was linear up to 2 hr and dioxygen was consumed. Bosseopentaenoic acid, along with several other conjugated tetraenes, was also present in the algae endogenously as revealed by a comparison of the ultraviolet (UV) spectra and the high-performance liquid chromatographic (HPLC) pattern of the purified product and the organic extract ofBossiella.

Genetic taste sensitivity to the bitterness of 6-n-propylthiouracil (PROP) is a potential marker for food selection. Compared with non-tasters, PROP tasters, especially super-tasters, are less accepting of cruciferous and other green vegetables, bitter citrus, added fats and chili pepper. If super-tasters avoid these foods, it may be hypothesized that they would have lower plasma antioxidant concentrations. Ninety-three healthy, non-smoking college women who did not use vitamins/supplements were classified by PROP-taster status using the paper disk method. Each participant provided a fasting blood sample that was assayed for vitamin C, beta-carotene, alpha-tocopherol, lycopene, uric acid and total peroxyl-trapping antioxidant capacity. Plasma alpha-tocopherol was lower in super-tasters than in non-tasters (P0.05), but no other indices differed among the groups. These findings suggest that PROP status does not associate with overall antioxidant status, but may be related to alpha-tocopherol intake derived principally from vegetable oils and green vegetables.

Dried corn distillers grains with sol- ubles (DDGS) fed to swine may adversely affect car- cass quality due to the high concentration of unsatu- rated fat. Feeding CLA enhances pork quality when unsaturated fat is contained in the diet. The effects of CLA on growth and pork quality were evaluated in pigs fed DDGS. Diets containing 0, 20, or 40% DDGS were fed to pigs beginning 30 d before slaughter. At 10 d before slaughter, one-half of each DDGS treatment group was fed 0.6% CLA or 1% choice white grease. Carcass data, liver- and backfat-samples were collected at slaughter. Longissimus muscle area, 10th-rib back- fat depth, last rib midline backfat depth, LM color, marbling, firmness and drip loss, and bacon collagen content were not altered by DDGS or CLA. Outer layer backfat iodine values were increased (P ≤ 0.05) with DDGS feeding and were 65.07, 69.75, and 74.25 for 0, 20, and 40% DDGS, respectively. Addition of CLA de- creased (P ≤ 0.05) outer layer backfat iodine values from 71.11 to 68.31. Diets containing DDGS decreased (P ≤ 0.05) percent lean tissue contained in bacon from 48% for controls to 38% for pigs fed 40%. Abundance of fatty acid synthase, carnitine palmitoyl transferase Ia, acetyl-CoA-carboxylase, stearoyl-CoA desaturase, and glycerol-3-phosphate dehydrogenase mRNA in adi- pose or liver were not different (P > 0.05) for pigs fed DDGS. Feeding CLA decreased (P ≤ 0.05) the ∆ 9 de- saturase index in adipose tissue. The data indicate that decreased carcass firmness with DDGS feeding is not reflected by changes in lipogenic gene expression. Feed- ing 20% or more DDGS to finishing swine decreases bacon leanness, but inclusion of 0.6% CLA in the fin- ishing diet can partially reverse these effects.

Managing stressors is essential for optimizing pig growth performance. To determine the effects of temperature and space allocation on growth performance and carcass characteristics, pigs were housed within their thermoneutral zone, at 23.9 degrees C, or above their thermoneutral zone, at 32.2 degrees C, and were provided either 0.66 or 0.93 m(2)/pig for the final 35 d of the grow-finish period. Individual BW were recorded on d 1, 10, 20, and 30. At slaughter, carcass measurements and samples of backfat and belly fat were collected. Final BW was decreased (P < or = 0.05) from 113 to 103 kg for pigs housed at 32.2 degrees C. The ADG was reduced (P < 0.05) for pigs housed at 32.2 degrees C (0.89 vs. 0.54 kg/d), as was G:F (0.28 vs. 0.24). Housing at 0.66 m(2)/pig resulted in pigs that were lighter (P < or = 0.05), at 106 compared with 110 kg, as a result of decreased (P < or = 0.05) ADG (0.78 to 0.65 kg/d) and decreased (P < or = 0.05) G:F (0.275 to 0.255) compared with pigs housed at 0.93 m(2)/pig. Pigs housed at a greater spatial allocation had elevated (P < or = 0.05) ADFI. The interaction of housing at 32.2 degrees C and decreasing spatial allocation increased (P < or = 0.05) the adipose iodine value from 66.8 to 70.4, decreased (P < or = 0.05) the saturated:unsaturated fatty acids ratio from 0.59 to 0.56, and increased (P < or = 0.05) the n-6:n-3 from 23.56 to 25.27. Decreased spatial allocation resulted in decreased (P < or = 0.05) belly weights. Although increased temperature did not affect belly weight, the 32.2 degrees C pigs had decreased (P < or = 0.05) raw and cooked slice weights, increased (P < or = 0.05) percentage lean of bacon, increased (P < or = 0.05) lean:fat ratio of bacon slices, increased (P < or = 0.05) raw slice scores, and increased (P < or = 0.05) quantity of collagen in belly fat. Some of these changes may have resulted from changes in lipid metabolism. Increasing spatial allocation in the 32.2 degrees C pigs decreased fatty acid synthase (P = 0.03) and stearoyl-CoA desaturase- 1 (P = 0.08) mRNA expression in adipose tissue. The results from this study demonstrated decreased growth, carcass lipid quality, and bacon quality in pigs housed at temperatures above the thermoneutral zone; however, increasing the spatial allocation for housing may be a means to ameliorate the negative effects of temperature stress.

We have reported previously that a dietary deficiency in selenium results in an increase in glutathione S-transferase (GST) activity of various rat tissues. In order to verify that the increased GST activity observed in a selenium deficiency results from increased synthesis of GST protein, cytosolic fractions of livers obtained from rats fed selenium-deficient and selenium-supplemented diets were analyzed by Western (protein) blots. Antisera raised against purified individual GST subunits (Ya, Yb, and Yc) were used to detect the corresponding subunits on the blots. The Ya subunit was induced 2.5-fold in the selenium-deficient state. The amount of Yc subunit also increased significantly (p less than 0.05) in selenium deficiency but not to the extent of the Ya subunit. The Yb subunit was not significantly affected by altered selenium nutritional status. A corresponding increase in poly(A) RNAs coding for the Ya and Yc subunits was also observed by Northern blot analysis. Transcriptional activity of GST YaYc genes was elevated by approximately 2-fold in purified nuclei isolated from selenium-deficient rat livers, which is sufficient to account for the increase in YaYc mRNA levels. Therefore, it appears that transcriptional activation of rat liver YaYc genes is the primary cause for the elevation of the corresponding gene products in the selenium-deficient state. Since the GSTs, especially the isozymes containing Ya subunit, have been implicated in the formation of prostaglandin (PG) F2 alpha, we investigated the effect of selenium deficiency on the PGF2 alpha-forming activity using a specific inhibitor of GSTs, S-decyl-GSH. In rats fed a nutritionally adequate diet, the activity inhibited by S-decyl-GSH accounted for at least half of the conversion of PGH2 to PGF2 alpha. During selenium deficiency, this GST-catalyzed activity was approximately doubled with no change in PGF2 alpha formation by other pathways, resulting in a 2-fold increase in overall synthesis of PGF2 alpha. These data strongly support a role of GSTs, especially those composed of the Ya size subunit, in the synthesis of PGF2 alpha from PGH2.

Accumulating evidence suggests dietary fatty acids (FAs) may be sensed in the oral cavity. However, the effective cues have not been characterized. In particular, influences from other sensory cues have hampered identification of an independent gustatory contribution. Experiment 1 examined techniques to minimize the formation of FA oxidation products and improve the homogeneity of water/lipid emulsions to be used as stimuli in Experiment 2, a psychophysical study to determine FA detection thresholds in humans. Through sonication of chilled samples held in polypropylene labware and the addition of 0.01% ethylenediaminetetraacetic acid, calcium disodium salt, homogenous emulsions of unoxidized linoleic and oleic FAs were obtained. Spectrophotometric analysis revealed no oxidation product formation over a 24-h period. Coupled with these techniques, a masking approach was used to minimize other sensory cues imparted from linoleic, oleic, and stearic FAs. Concentration ranges from 0.00028% to 5% (w/v) were prepared in mixtures with 5% mineral oil (w/v) and 5% gum acacia (w/v) to mask lubricity and viscosity effects, respectively. Testing was conducted under red light with nares blocked to eliminate visual and olfactory cues. Oral rinses with 20 ppm capsaicin were administered to desensitize participants to selected irritation effects prior to remeasuring linoleic acid detection thresholds. To determine if the effective stimulus was an oxidation product, oxidized linoleic acid was included among the test stimuli. Detection thresholds were obtained using a 3-alternative, forced-choice ascending-concentration presentation procedure. The mean detection threshold for linoleic acid pre-desensitization was 0.034 +/- 0.008%, for linoleic acid post-desensitization was 0.032 +/- 0.007%, for oleic 0.022 +/- 0.003%, for stearic 0.032 +/- 0.005%, and oxidized linoleic 0.025 +/- 0.005%. The results suggest that linoleic, oleic, stearic, and oxidized linoleic acids are detectable in the oral cavity of humans with minimal input from the olfactory, capsaicin, and viscosity-assessing tactile systems.

Flavonoids are non-nutrient plant phenolic compounds proposed to provide health benefits in humans. The antioxidant and prooxidant effects of the citrus flavanone naringenin have been tested only in vitro. The dose-response effect of naringenin consumption was tested in weanling rats (n=6-8/group) with a 2x4 factorial design using high or low oxidative stress (Hox or Lox, respectively) diets, created by adequate or deficient amounts of vitamin E and selenium, with three increasing naringenin concentrations (30, 60, or 120 mg/kg of diet). Hox compared to Lox rats exhibited reduced growth and liver hypertrophy, which was not prevented by naringenin consumption. Also, Hox rats exhibited severalfold higher liver NAD(P)H:quinone oxidoreductase-1 activity, which was further elevated in proportion to naringenin intake, but this was not sufficient to protect against oxidative stress indicated by higher liver total aldehydes. In addition, dietary naringenin did not affect antioxidant nutrient status or physiological markers of growth under Lox conditions. Thus, dietary naringenin did not exhibit antioxidant or prooxidant effects in vivo in this rat model.