Lage Aksnes

Daily duration of vitamin D synthesis in human skin with relation to latitude, total ozone, altitude, ground cover, aerosols and cloud thickness.

Abstract Vitamin D production in human skin occurs only when incident UV radiation exceeds a certain threshold. From simulations of UV irradiances worldwide and throughout the year, we have studied the dependency of the extent and duration of cutaneous vitamin D production in terms of latitude, time, total ozone, clouds, aerosols, surface reflectivity and altitude. For clear atmospheric conditions, no cutaneous vitamin D production occurs at 51 degrees latitude and higher during some periods of the year. At 70 degrees latitude, vitamin D synthesis can be absent for 5 months. Clouds, aerosols and thick ozone events reduce the duration of vitamin D synthesis considerably, and can suppress vitamin D synthesis completely even at the equator. A web page allowing the computation of the duration of cutaneous vitamin D production worldwide throughout the year, for various atmospheric and surface conditions, is available on the Internet at http://zardoz.nilu.no/~olaeng/fastrt/VitD.html and http://zardoz.nilu.no/~olaeng/fastrt/VitD-ez.html. The computational methodology is outlined here.

Mutations in the CEL VNTR cause a syndrome of diabetes and pancreatic exocrine dysfunction.

Dysfunction of the exocrine pancreas is observed in diabetes, but links between concurrent exocrine and endocrine pancreatic disease and contributing genetic factors are poorly characterized. We studied two families with diabetes and exocrine pancreatic dysfunction by genetic, physiological and in vitro functional studies. A genome-wide screen in Family 1 linked diabetes to chromosome 9q34 (maximal lod score 5.07). Using fecal elastase deficiency as a marker of exocrine pancreatic dysfunction refined the critical chromosomal region to 1.16 Mb (maximal lod score 11.6). Here, we identified a single-base deletion in the variable number of tandem repeats (VNTR)-containing exon 11 of the carboxyl ester lipase (CEL) gene, a major component of pancreatic juice and responsible for the duodenal hydrolysis of cholesterol esters. Screening subjects with maturity-onset diabetes of the young identified Family 2, with another single-base deletion in CEL and a similar phenotype with beta-cell failure and pancreatic exocrine disease. The in vitro catalytic activities of wild-type and mutant CEL protein were comparable. The mutant enzyme was, however, less stable and secreted at a lower rate. Furthermore, we found some evidence for an association between common insertions in the CEL VNTR and exocrine dysfunction in a group of 182 unrelated subjects with diabetes (odds ratio 4.2 (1.6, 11.5)). Our findings link diabetes to the disrupted function of a lipase in the pancreatic acinar cells.

Vitamin D status of middle-aged women at 65–71°N in relation to dietary intake and exposure to ultraviolet radiation

Objective: To determine the vitamin D status of middle-aged women living in the Norwegian arctic and its relationship with vitamin D intake and exposure to ultraviolet (UV) radiation. Design: Cross-sectional study. Subjects and setting: This study is based on measurements of 25-hydroxyvitamin D (25(OH)D) levels in a sub-sample of the Norwegian component of the EPIC biological bank, which consists of blood samples from a random selection of participants in the Norwegian Women and Cancer Study. From November 2001 until June 2002, 309 blood samples were collected from a total of 443 invited middle-aged women (44–59 years) in northern Norway (65–718N) (crude response rate, 69.8%). Questionnaire data provided information on dietary sources of vitamin D and UV exposure. Results: Median plasma 25(OH)D concentration for the whole group was 55.0 nmol l 21 (range 8.1–142.8 nmol l 21 ). Vitamin D intake was a significant predictor of 25(OH)D status (P ¼ 0.0003). The time of the year when the blood sample was collected significantly predicted plasma 25(OH)D level (P ¼ 0.005). Levels of 25(OH)D were positively associated (P ¼ 0.0002) with estimated hours per day of exposure to UV-B radiation. Residing in northern Norway during the summer prior to blood sampling was negatively associated with 25(OH)D concentration (P ¼ 0.001). The prevalence of moderate hypovitaminosis D was highest in January–February, when a quarter of the participants had 25(OH)D concentrations #37.5 nmol l 21 . Conclusions: Increased ingestion of marine food items that provide vitamin D should be promoted and further studies should be carried out to investigate vitamin D status in arctic populations in relation to both UV exposure and traditional food sources.

Faecal calprotectin levels in infants with infantile colic, healthy infants, children with inflammatory bowel disease, children with recurrent abdominal pain and healthy children

This study investigated faecal calprotectin concentration, a measure of intestinal inflammation, in infants and children with abdominal pain. Faecal calprotectin was measured by an enzyme‐linked immunosorbent assay kit in spot stool samples in 76 infants with typical infantile colic, 7 infants with transient lactose intolerance and 27 healthy infants. All infants were 2‐10 wk of age. In addition, 19 children with recurrent abdominal pain (RAP; mean age 11.5 y), 17 with inflammatory bowel disease (IBD; mean age 11.1 y; 10 had Crohns disease and 7 ulcerative colitis) and 24 healthy children (mean age 5.3 y) were studied. In infants with infantile colic the mean faecal calprotectin concentration was not different from that in healthy infants (278 ± 105 vs 277 ± 109 mg kg−1, p= 0.97) or in infants with transient lactose intolerance (300.3 ± 124 mg kg−1, p= 0.60). The calprotectin level was similar in boys and girls and fell significantly with age (p = 0.04). Children with IBD had faecal calprotectin levels (293 ± 218 mgkg−1) much higher than healthy children (40 ± 28 mg kg−1, p < 0.0001) and children with RAP without identified organic disease (18 ± 24 mg kg−1, p < 0.0001).

Characteristics of asthma and airway hyper‐responsiveness after premature birth

Asthma‐like symptoms and airway hyper‐responsiveness (AHR) are frequently reported in children subsequent to premature birth and bronchopulmonary dysplasia (BPD). There is limited knowledge on the mechanisms underlying these respiratory manifestations. Generally, childhood asthma and AHR is described within a context of inheritance, allergy and eosinophilic airway inflammation, and often in relation to cigarette exposures. We investigated these factors in relation to current asthma and AHR in a population‐based cohort of 81 young people, born with gestational age ≤28 wk or birth weight ≤1000 g, and in a matched term‐born control population. In the pre‐term population, asthma and AHR were additionally studied in relation to neonatal respiratory morbidity. At follow up, more pre‐term than control subjects had asthma. Forced expiratory volume in first second (FEV1) was reduced, AHR was substantially increased, and the level of the urinary leukotriene metabolite E4 (U‐LTE4) was increased in the pre‐term population compared to the term‐born. In control subjects, asthma and AHR was associated with a pattern consistent with inheritance, allergy, airway inflammation, and cigarette exposures. In the pre‐terms, asthma and AHR was either unrelated or less related to these factors. Instead, AHR was strongly related to a neonatal history of BPD and prolonged requirement for oxygen treatment. In conclusion, asthma and AHR subsequent to extremely premature birth differed from typical childhood asthma with respect to important features, and AHR was best explained by neonatal variables. These respiratory manifestations thus seem to represent a separate clinical entity.

Self-Reported Dietary Supplement Use Is Confirmed by Biological Markers in the Norwegian Mother and Child Cohort Study (MoBa)

Background/Aims: A food frequency questionnaire (FFQ) and a database for dietary supplements were developed for use in the Norwegian Mother and Child Cohort Study (MoBa). The aim of the present study was to investigate the relation between reported use and biomarkers in supplement and nonsupplement users and to validate self-reported intake of dietary supplements in mid pregnancy. Method: 120 women were recruited from MoBa, and 119 subjects completed the MoBa FFQ and a 4-day weighed food diary. Information on supplement use was collected by both methods. Venous blood specimens and 24-hour urine samples were obtained for measurement of dietary biomarkers. Results: Biomarker concentration/excretion and intake differed significantly between supplement and nonsupplement users for vitamin D, carotenoids, folate, the n–6/n–3 fatty acid ratio and iodine (p < 0.05 for all variables). Flavonoid excretion was higher in flavonoid-supplement users (p < 0.05). Significant correlations between total dietary intake (food and supplements) and biomarker concentration/excretion were found for vitamin D (r = 0.45, p < 0.001), folate (r = 0.26, p = 0.005), the n–6/n–3 fatty acid ratio (r = 0.36, p < 0.001) and iodine (r = 0.42, p < 0.001). Conclusion: The biochemical indicators examined in this study confirmed differences in self-reported micronutrient intake between supplement and nonsupplement users for vitamin D, beta-carotene, folate, n–3 fatty acids, flavonoids and iodine.

Quantitation of the main metabolites of vitamin D in a single serum sample II. Determination by uv-absorption and competitive protein binding assays

The present report, together with extraction, separation and purification procedures described previously [1], constitutes a sensitive method for determination of vitamin D and its main metabolites in 2 ml of human serum. By omitting vitamin D itself, 25-OHD, 24,25-(OH)2D, 25,26-(OH)2D and 1,25-(OH)2D could be determined in less than 0.5 ml serum. The quantitation methods described have detection limits of 1.8 pmol for vitamin D, 20 fmol for 25-OHD, 24,25-(OH)2D and 25,26-(OH)2D, and 1 fmol for 1,25-(OH)2D.

High prevalence of asymptomatic coeliac disease in Norway: a study of blood donors.

OBJECTIVE The prevalence of symptomatic coeliac disease in Norway is 1:675. Coeliac disease has previously been reported in presumably healthy people. Our aim was to determine the prevalence of latent coeliac disease in apparently healthy (i.e. asymptomatic) Norwegian individuals. METHODS Blood donor sera were tested for gluten antibodies (IgA, IgG). Positive samples (IgA AGA > 0.35, IgG AGA > 0.90) were further tested for endomysium antibodies (IgA EMA). EMA positive individuals were offered gastroenterological investigation. RESULTS Of 2096 sera, 83 fulfilled the criteria for EMA testing (M/F = 55/28). Eight individuals were EMA positive. On biopsy, seven out of eight had villous atrophy (six subtotal, one partial). None of the patients had significant symptoms. Biochemical data showed iron deficiency (two), hypocalcaemia (one), and low serum zinc (five). All patients were treated with a gluten-free diet and followed up. CONCLUSION The study indicates a prevalence of 1:340 among asymptomatic and presumably healthy people. This is in keeping with studies from other countries. Lack of symptoms does not exclude secondary deficiency conditions.

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.

Quantitation of the main metabolites of vitamin D in a single serum sample I. Extraction, separation and purification of metabolites

A method for extraction, separation and purification of the main serum metabolites of vitamin D from a single serum sample is described. The method involved extraction of serum by diethylether and separation and purification of vitamin D, 25-OHD and the dihydroxymetabolites 24,25-(OH)2D, 25,26-(OH),2D and 1,25-(OH)2D by elution in three steps from a short open silicic acid column. The eluted vitamin D metabolites were further separated and purified by high pressure liquid chromatography (HPLC). The HPLC systems described separated the D2 and D3 forms of vitamin D, 25-OHD, 1,25-(OH)2D, and probably also 24,25-(OH)2D and 25,26-(OH)2D. The metabolites were purified by the methods described for further quantitation by UV-absorption or competitive protein binding assays, and were found to be homogenous on re-chromatography with different HPLC systems. Good recoveries were obtained for all the metabolites.