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ABSTRACT: Nutrition and physiological state affect hepatic metabolism. Our objective was to determine whether feeding flaxseed oil (∼50% C18:3n-3 cis), high oleic soybean oil (∼70% C18:1 cis-9), or milk fat (∼50% C16:0) alters hepatic expression of PC, PCK1, and PCK2 and the flow of carbons from propionate and pyruvate into the tricarboxylic acid (TCA) cycle in preruminating calves. Male Holstein calves (n = 40) were assigned to a diet of skim milk with either: 3% milk fat (MF; n = 8), 3% flaxseed oil (Flax; n = 8), 3% high oleic soybean oil (HOSO; n = 8), 1.5% MF + 1.5% high oleic soybean oil (MF-HOSO; n = 8), or 1.5% MF + 1.5% flaxseed oil (MF-Flax; n = 8) from d 14 to d 21 postnatal. At d 21 postnatal, a liver biopsy was taken for gene expression and metabolic flux analysis. Liver explants were incubated in [U-13C] propionate and [U-13C] pyruvate to trace carbon flux through TCA cycle intermediates or with [U-14C] lactate, [1-14C] palmitic acid, or [2-14C] propionate to quantify substrate oxidation to CO2 and acid-soluble products. Compared with other treatments, plasma C18:3n-3 cis was 10 times higher and C18:1 cis-9 was 3 times lower in both Flax (Flax and MF-Flax) treatments. PC, PCK1, and PCK2 expression and flux of [U-13C] pyruvate as well as [U-13C] propionate were not different among treatments. PC expression was negatively correlated with the enrichment of citrate M+5 and malate M+3, and PCK2 was negatively correlated with citrate M+5, suggesting that when expression of these enzymes is increased, carbon from pyruvate enters the TCA cycle via PC-mediated carboxylation, and then oxaloacetate is converted to phosphoenolpyruvate via PCK2. Acid-soluble product formation and PC expression were reduced in HOSO (MF-HOSO and HOSO) treatments compared with Flax (MF-Flax and Flax), indicating that fatty acids regulate PC expression and carbon flux, but that fatty acid flux control points are not connected to PC, PCK1, or PCK2. In conclusion, fatty acids regulate hepatic expression of PC, PCK1, and PCK2, and carbon flux, but the point of control is distinct.

Citrus bioflavonoids are polyphenolic plant-derived pigments found in high levels in oranges, lemons, grapefruits and other citrus fruits. The three most abundant types of citrus bioflavonoids are hesperidin, naringenin and eriocitrin. Citrus bioflavonoids have long been known to possess powerful free radical-scavenging properties and cardioprotective effects. The study involved the analysis of 10 commercially available citrus bioflavonoid supplements from three different countries: Australia, the United States and Canada. The supplements were tested for their citrus bioflavonoid content which varied from 0.8 to 33.3% w/w. The daily bioflavonoid dose varied from 19 mg to 560 mg. Hesperidin was the major citrus bioflavonoid in nine out of ten supplements. One supplement was found to contain less than 10% of the quantity of rutin claimed to have been added. The DPP-4 inhibitory potential, compared through an estimation of rutin equivalence, ranged from 1.9 mg to 400 mg per day. This data highlights the variability between the supplements in their potential to inhibit DPP-4 for subsequent health benefits.

Diabetes mellitus is one of the most common chronic diseases in the United States and peripheral neuropathy (PN) affects at least 50% of diabetic patients. Medications available for patients ameliorate symptoms (pain), but do not protect against cellular damage and come with severe side effects, leading to discontinued use. Our research group uses differentiated SH-SY5Y cells treated with advanced glycation end products (AGE) as a model to mimic diabetic conditions and to study the mechanisms of oxidative stress mediated cell damage and antioxidant protection. N-acetylcysteine (NAC), a common antioxidant supplement, was previously shown by our group to fully protect against AGE-induced damage. We have also shown that 3H-1,2-dithiole-3-thione (D3T), a cruciferous vegetable constituent and potent inducer of nuclear factor (erythroid-derived 2)- like 2 (Nrf2), can significantly increase cellular GSH concentrations and protect against oxidant species–induced cell death. Paradoxically, D3T conferred no protection against AGE-induced cell death or neurite degeneration. In the present study we establish a mechanism for this paradox by showing that D3T in combination with AGE increased oxidant species generation and depleted GSH via inhibition of glutathione reductase (GR) activity and increased expression of the NADPH generating enzyme glucose-6-phosphate dehydrogenase (G6PD). Blocking NADPH generation with the G6PD inhibitor dehydroepiandrosterone was found to protect against AGE-induced oxidant species generation, loss of viability, and neurite degeneration. It further reversed the D3T potentiation effect under AGE-treated conditions. Collectively, these results suggest that strategies aimed at combating oxidative stress that rely on upregulation of the endogenous antioxidant defense system via Nrf2 may backfire and promote further damage in diabetic PN. Keywords: Peripheral neuropathy, Diabetes, D3T, NAC, Redox balance, Oxidative stress

Abstract Objective: To determine the adequacy of iodine nutrition of Tasmanian primary school‐aged children and to examine possible associations with socio‐economic status (SES), location and dietary factors. Methods: Urinary iodine levels and measures of SES, geographical information and dietary habits were surveyed in a population‐based sample of 170 children (4 to 12 years) at baseline (1998/99) and at follow‐up (2000/01). Results: Median urinary iodine concentration in 1989‐99 and 2000‐01 were 75 μg/L (range 15 μg/L to 240 μg/L) and 76 μg/L (range 18 μg/L to 480 μg/L) respectively. No significant associations with SES or geographical location were found. More frequent or recent intake of foods that are likely to be dietary sources of iodine tended to be associated with greater prevalence of adequate urinary iodine, particularly consumption of yoghurt and ‘fruche’ (p=0.04). Conclusions: After several decades of iodine sufficiency, Tasmanian primary school‐aged children are again mildly iodine‐deficient by WHO criteria. Despite reduction in iodophor use by the dairy industry in the past decade, consumption of dairy products continues to be associated with higher levels of iodine nutrition. Implications: The lack of association of iodine levels with SES and geographical location within Tasmania found in our study, and the results of studies of iodine levels in Melbourne and Sydney, suggest that inadequate iodine nutrition is a widespread problem in south‐eastern Australia. Our study suggests that milk‐containing products continue to be an important source of iodine for children.

Functional paragangliomas are rare neuroendocrine tumours that secrete catecholamines and are infrequently found in the mediastinum. We report a case of a young male with symptoms of catecholamine excess and a personal and family history of the paraganglioma predisposing succinate dehydrogenase subunit B mutation. The lesion had anatomical intrapericardial juxtaposition to important cardiac anatomy and posed the significant challenge of dissection at surgery. The lesion was successfully resected via sternotomy on cardiopulmonary bypass and confirmed histopathologically as paraganglioma. Intrapericardial paraganglioma is rare and treatment is difficult and time critical considering the proximity of cardiac anatomy as well as malignant potential.