Plasma 25 hydroxyvitamin D level and blood gene expression profiles: a cross-sectional study of the Norwegian Women and Cancer Post-genome Cohort

Background/Objectives: Vitamin D deficiency has been associated with increased risk of developing several diseases, but much is unknown about the molecular effects involved. Gene expression technology is increasingly being used to elucidate molecular mechanisms related to nutritional factors, and in this study of free-living, middle-aged Norwegian women, we aimed at identifying gene expression pathways in the blood associated with vitamin D status. Subjects/Methods: Blood samples and questionnaires were collected as a part of the Norwegian Women and Cancer Post-genome Cohort (500 invited subjects, 218 included). Plasma 25 hydroxyvitamin D (25(OH)D) concentrations were measured using high-performance liquid chromatography, and we compared groups with sufficient versus deficient vitamin D status (25(OH)D >50 nmol/l (n=66) versus <37.5 nmol/l (n=83)), to identify differences in gene expression profiles obtained using full-genome microarrays. Results: In a targeted pathway-level analysis, several immunological processes, immune cell functions and major signaling pathways were differentially regulated according to vitamin D status (P<0.01). To a certain degree, results from in vitro studies reported in the literature were reflected in this population setting. Conclusions: We conclude that vitamin D status measured as 25(OH)D was associated with molecular pathways that may ultimately affect the potential onset of diseases. The use of gene expression analysis in a population setting may give valuable input to the study of effects of nutritional factors.publishedVersio

Dietary Vitamin D3 Supplements Reduce Demyelination in the Cuprizone Model

Vitamin D is emerging as a probably important environmental risk factor in multiple sclerosis, affecting both susceptibility and disease progression. It is not known to what extent this effect is due to a modulation of peripheral lymphocyte function, or to intrathecal effects of vitamin D. We investigated the effect of dietary vitamin D3 content on de/remyelination in the cuprizone model, which is a well established toxic model of demyelination, with no associated lymphocyte infiltration. The mice received diets either deficient of (<50 IU/kg), or supplemented with low (500 IU/kg), high (6200 IU/kg) or very high (12500 IU/kg) amounts of vit D3. Cuprizone (0.2%) was added to the diet for six weeks, starting two weeks after onset of the experimental diets. Mouse brain tissue was histopathologically evaluated for myelin and oligodendrocyte loss, microglia/macrophage activation, and lymphocyte infiltration after six weeks of cuprizone exposure, and two weeks after discontinuation of cuprizone exposure. High and very high doses of vitamin D3 significantly reduced the extent of white matter demyelination (p = 0.004) and attenuated microglia activation (p = 0.001). No differences in the density of oligodendrocytes were observed between the diet groups. Two weeks after discontinuation of cuprizone exposure, remyelination was only detectable in the white matter of mice receiving diets deficient of or with low vitamin D3 content. In conclusion, high dietary doses of vitamin D3 reduce the extent of demyelination, and attenuate microglia activation and macrophage infiltration in a toxic model of demyelination, independent of lymphocyte infiltration

Faecal calprotectin concentrations in apparently healthy children aged 0-12 years in urban Kampala, Uganda: a community-based survey

<p>Abstract</p> <p>Background</p> <p>Calprotectin is a calcium and zinc binding protein, abundant in neutrophils and is extremely stable in faeces. Faecal calprotectin is used as a non-specific marker for gastrointestinal inflammation. It has a good diagnostic precision to distinguish between irritable bowel syndrome and inflammatory bowel disease. Studies have established normal concentrations in healthy children; all these studies have been performed in high-income countries. The objective of this study was to determine the concentration of faecal calprotectin in apparently healthy children aged 0-12 years in urban Kampala, Uganda.</p> <p>Method</p> <p>We tested 302 apparently healthy children aged, age 0-12 years (162 female, 140 male) in urban Kampala, Uganda. The children were recruited consecutively by door-to-door visits. Faecal calprotectin was analyzed using a quantitative enzyme-linked immunosorbent assay. Faeces were also tested for <it>Helicobacter pylori (H. pylori) </it>antigen, for growth of enteropathogens and microscopy was performed to assess protozoa and helminths. A short standardized interview with socio-demographic information and medical history was obtained to assess health status of the children.</p> <p>Results</p> <p>In the different age groups the median faecal calprotectin concentrations were 249 mg/kg in 0 < 1 year (n = 54), 75 mg/kg in 1 < 4 years (n = 89) and 28 mg/kg in 4 < 12 years (n = 159). There was no significant difference in faecal calprotectin concentrations and education of female caretaker, wealth index, gender, habits of using mosquito nets, being colonized with <it>H. pylori </it>or having other pathogens in the stool.</p> <p>Conclusion</p> <p>Concentrations of faecal calprotectin among healthy children, living in urban Ugandan, a low-income country, are comparable to those in healthy children living in high-income countries. In children older than 4 years, the faecal calprotectin concentration is low. In healthy infants faecal calprotectin is high. The suggested cut-off concentrations in the literature can be used in apparently healthy Ugandan children. This finding also shows that healthy children living under poor circumstances do not have a constant inflammation in the gut. We see an opportunity to use this relatively inexpensive test for further understanding and investigations of gut inflammation in children living in low-income countries.</p

Diagnostic accuracy of a short endoscopic secretin test in patients with cystic fibrosis

Objective: Short endoscopic secretin tests for exocrine pancreatic function are not properly evaluated in cystic fibrosis (CF). Methods: Patients with CF and healthy controls (HCs) underwent endoscopic collection of duodenal juice between 30 and 45 minutes after secretin stimulation. Duodenal juice was analyzed for HCO3- concentration and pancreatic enzyme activities. Stool was analyzed for fecal elastase. Results: Thirty-one patients with CF and 25 HCs were tested. Patients were classified as exocrine pancreatic sufficient (n = 13) or insufficient (n = 18). Both bicarbonate concentrations and enzyme activities in duodenal juice differentiated patients with CFI from patients with CFS and HC (P < 0.001). The population displays strong correlation between severe CF genotype in both alleles and pancreatic insufficient phenotype (P < 0.001). Conclusions: Pancreatic exocrine insufficient CF patients could be differentiated from exocrine sufficient patients and HCs using short endoscopic secretin test

Plasma 25 hydroxyvitamin D level and blood gene expression profiles: a cross-sectional study of the Norwegian Women and Cancer Post-genome Cohort

Background/Objectives: Vitamin D deficiency has been associated with increased risk of developing several diseases, but much is unknown about the molecular effects involved. Gene expression technology is increasingly being used to elucidate molecular mechanisms related to nutritional factors, and in this study of free-living, middle-aged Norwegian women, we aimed at identifying gene expression pathways in the blood associated with vitamin D status. Subjects/Methods: Blood samples and questionnaires were collected as a part of the Norwegian Women and Cancer Post-genome Cohort (500 invited subjects, 218 included). Plasma 25 hydroxyvitamin D (25(OH)D) concentrations were measured using high-performance liquid chromatography, and we compared groups with sufficient versus deficient vitamin D status (25(OH)D >50 nmol/l (n=66) versus <37.5 nmol/l (n=83)), to identify differences in gene expression profiles obtained using full-genome microarrays. Results: In a targeted pathway-level analysis, several immunological processes, immune cell functions and major signaling pathways were differentially regulated according to vitamin D status (P<0.01). To a certain degree, results from in vitro studies reported in the literature were reflected in this population setting. Conclusions: We conclude that vitamin D status measured as 25(OH)D was associated with molecular pathways that may ultimately affect the potential onset of diseases. The use of gene expression analysis in a population setting may give valuable input to the study of effects of nutritional factors