Beneficial effects of combinatorial micronutrition on body fat and atherosclerosis in mice

Aims More than two billion people worldwide are deficient in key micronutrients. Single micronutrients have been used at high doses to prevent and treat dietary insufficiencies. Yet the impact of combinations of micronutrients in small doses aiming to improve lipid disorders and the corresponding metabolic pathways remains incompletely understood. Thus, we investigated whether a combination of micronutrients would reduce fat accumulation and atherosclerosis in mice. Methods and results Lipoprotein receptor-null mice fed with an original combination of micronutrients incorporated into the daily chow showed reduced weight gain, body fat, plasma triglycerides, and increased oxygen consumption. These effects were achieved through enhanced lipid utilization and reduced lipid accumulation in metabolic organs and were mediated, in part, by the nuclear receptor PPARα. Moreover, the micronutrients partially prevented atherogenesis when administered early in life to apolipoprotein E-null mice. When the micronutrient treatment was started before conception, the anti-atherosclerotic effect was stronger in the progeny. This finding correlated with decreased post-prandial triglyceridaemia and vascular inflammation, two major atherogenic factors. Conclusion Our data indicate beneficial effects of a combination of micronutritients on body weight gain, hypertriglyceridaemia, liver steatosis, and atherosclerosis in mice, and thus our findings suggest a novel cost-effective combinatorial micronutrient-based strategy worthy of being tested in human

Beneficial effects of combinatorial micronutrition on body fat and atherosclerosis in mice

AIMS: More than two billion people worldwide are deficient in key micronutrients. Single micronutrients have been used at high doses to prevent and treat dietary insufficiencies. Yet the impact of combinations of micronutrients in small doses aiming to improve lipid disorders and the corresponding metabolic pathways remains incompletely understood. Thus, we investigated whether a combination of micronutrients would reduce fat accumulation and atherosclerosis in mice. METHODS AND RESULTS: Lipoprotein receptor-null mice fed with an original combination of micronutrients incorporated into the daily chow showed reduced weight gain, body fat, plasma triglycerides, and increased oxygen consumption. These effects were achieved through enhanced lipid utilization and reduced lipid accumulation in metabolic organs and were mediated, in part, by the nuclear receptor PPARα. Moreover, the micronutrients partially prevented atherogenesis when administered early in life to apolipoprotein E-null mice. When the micronutrient treatment was started before conception, the anti-atherosclerotic effect was stronger in the progeny. This finding correlated with decreased post-prandial triglyceridaemia and vascular inflammation, two major atherogenic factors. CONCLUSION: Our data indicate beneficial effects of a combination of micronutritients on body weight gain, hypertriglyceridaemia, liver steatosis, and atherosclerosis in mice, and thus our findings suggest a novel cost-effective combinatorial micronutrient-based strategy worthy of being tested in humans

Current relevance of hypoxia in head and neck cancer

Head and Neck cancer (HNC) is a complex mix of cancers and one of the more common cancers with a relatively poor prognosis. One of the factors that may assist us in predicting survival and allow us to adjust our treatment strategies is the presence of tumor hypoxia. In this overview we aim to evaluate the current evidence and potential clinical relevance of tumor hypoxia in head and neck cancer according to an extensive search of current literature. An abundance of evidence and often contradictory evidence is found in the literature. Contradictions and comparisons are difficult to judge as criteria and methodologies differ greatly, furthermore few prospective observational studies exist for verification in pre-clinical studies. Despite these discrepancies there is clear evidence of associations between prognosis and poor tumor oxygenation biomarkers such as HIF-1α, GLUT-1 and lactate, though these associations are not exclusive. The use of genetic markers is expanding and will probably lead to significantly more and complex evidence. The lack of oxygenation in head and neck tumors is of paramount importance for the prediction of treatment outcomes and prognosis. Despite the wide array of conflicting evidence, the drive towards non-invasive prediction of tumor hypoxia should continue

Thyroid-stimulating immunoglobulins as measured in a reporter bioassay are not detected in patients with Hashimoto's thyroiditis and ophthalmopathy or isolated upper eyelid retraction

Although ophthalmopathy is mainly associated with Graves' hyperthyroidism, milder eye changes are also found in about 25% of patients with Hashimoto's thyroiditis (HT). The recent finding of negative thyrotropin receptor (TSHR) antibodies, as measured in the Thyretain™ thyroid-stimulating immunoglobulin (TSI) reporter bioassay, in patients with euthyroid Graves' disease raises the possibility that TSHR antibodies are not the cause of ophthalmopathy in all situations. Here, we have tested serum from patients with HT with and without ophthalmopathy or isolated upper eyelid retraction (UER) for TSHR antibodies, using the TSI reporter bioassay and collagen XIII as a marker of autoimmunity against the orbital fibroblast. Study groups were 23 patients with HT with ophthalmopathy, isolated UER, or both eye features and 17 patients without eye signs. Thyretain™ TSI results were expressed as a percentage of the sample-to-reference ratio, with a positive test being taken as a sample-to-reference ratio of more than 140%. Serum collagen XIII antibodies were measured in standard enzyme-linked immunosorbent assay. TSI tests were positive in 22% of patients with HT with no eye signs but in no patient with eye signs. In contrast, TSI tests were positive in 94% of patients with Graves' ophthalmopathy. Tests were negative in all normal subjects tested. Collagen XIII antibodies were detected in 83% of patients with ophthalmopathy, UER, or both eye features, but in only 30% of patients with no eye signs. Our findings suggest that TSHR antibodies do not play a major role in the pathogenesis of ophthalmopathy or isolated UER in patients with HT. Moreover, the role of TSHR antibodies in the development of ophthalmopathy in patients with Graves' disease remains to be proven. In contrast, collagen XIII antibodies appear to be a good marker of eye disease in patients with HT.6 page(s

Association of the CASQ1 gene SNP rs3838216 with Graves' ophthalmopathy and Hashimoto’s thyroiditis in patients with thyroid autoimmunity

The pathogenesis of Graves' ophthalmopathy is poorly understood, but there is evidence for the involvement of calsequestrin (CASQ1) as an autoantigen. Aim: To compare the frequency of the single nucleotide polymorphism (SNP) rs3838216 (located in intron 1 of CASQ1) in patients with autoimmune thyroid disease (ATD), Graves' Ophthalmopathy and controls. Methods: Germline DNA was assayed for rs3838216 by MassARRAY SNP analysis using iPLEX technology of SEQUENOM in 405 individuals (98 males, 307 females) with ATD (comprising Graves' Opthalmopathy (GO, N=74), Graves' Hyperthyroidism (GH, N=131), Hashimoto's thyroiditis (HT, N=92), and controls with no personal or family history of autoimmune thyroid disorders (N=108). Results: Genotypes for rs3838216 differed significantly across groups with minor allele frequencies as follows: GO 17%, GH 24%, HT 19% and controls 30% groups (P=0.0427). P of SNP rs3838216 was significant in GO vs. control (odds ratio 2.16, P=0.003), and HT vs control (odds ratio 1.87, P= 0.008). On pair wise analysis, homozygosity for the major allele was associated with GO vs. control (odds ratio = 2.42, P=0.0046), and HT vs control (odds ratio 2.07, P=0.0116); whereas heterozygosity was associated with GO vs. control (odds ratio = 0.52, P=0.039), and HT vs control (odds ratio 0.570, P=0.054). Conclusion: The CASQ1 gene SNP rs3838216 is associated with autoimmune thyroid disease and with GO in particular.13 page(s