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There is little information available about the relationship of newborn vitamin D status with pregnancy outcome and infant health. The purpose of this cross-sectional study was to estimate the prevalence of vitamin D deficiency and insufficiency in newborns in the Saskatoon Health Region, identify risk factors for low neonatal levels of vitamin D, and determine whether any association exists between low levels of vitamin D and adverse pregnancy and neonatal outcomes. The Newborn Vitamin D Study was conducted between December, 2011 and February, 2012. Sixty-five maternal-fetal dyads delivering in the Saskatoon Health Region were included in the study. Mean cord blood vitamin D level was 64.1 nmol/L (standard deviation = 19.8 nmol/L), which is in the insufficient range. Cord blood vitamin D level was deficient (<50 nmol/L) in 22% and insufficient (50-75 nmol/L) in 48% of the 65 newborns studied. Simple linear regression indicated that low weight gain during pregnancy is significantly associated with low vitamin D levels (p = 0.04). However, younger maternal age (p < 0.01) and urban area of residence (p = 0.09) were the strongest predictors of low cord blood vitamin D levels in a multiple linear regression model (R2 of 0.519, p = 0.003). Cord blood vitamin D levels were not significantly associated with any pregnancy or neonatal outcomes. Despite 85% of mothers reporting having taken a daily prenatal supplement, 70% of newborns in our study population had either an insufficient or deficient cord blood vitamin D status. This suggests that prenatal supplements, which typically contain 400 IU of vitamin D, contain an inadequate dose of vitamin D to produce sufficient cord blood vitamin D levels in most newborns. Further research is necessary to inform maternal vitamin D supplementation guidelines and to investigate the role of vitamin D in pregnancy outcomes and infant health.

Syftet med föreliggande studie var att identifiera lämplig aktivitetsfrekvens och aktivitetsduration för att upprätthålla en adekvat D-vitaminstatus hos postmenopausala kvinnor. Databasen PubMed har använts för litteratur- och informationssökning i syfte att söka fakta om teori, begrepp och metoder. Mesh-filter har använts för att begränsa området till fysisk aktivitet och dess effekter i terapeutiskt syfte. Sammanlagt sju artiklar, varav sex tvärsnittsstudier och en randomiserad kontroll/fallstudie valdes ut för vidare studium. Resultaten visar samband mellan D-vitaminstatus och god fysisk kondition, muskelstyrka, fall- och frakturfrekvens, bentäthet samt träningsduration, vilket även medför ökad solexponering. Tvärsittsstudierna tillåter dock inte utläsning av kausalitet, då observerade samband endast används till att förutsäga förväntad effekt av en viss parameter. Det vore lämpligt att undersöka träningens kortsiktiga effekter i form av epidemiologiska och kliniska metoder. Idag förefaller adekvat information om träningens relevans vad gäller kortsiktiga effekter på D-vitaminstatus otillräcklig för fullt ut uppnå undersökningens syfte. / The aim of this study was to investigate the frequency and duration of physical activity required to maintain adequate vitamin D status in postmenopausal women. PubMed was used as a search tool for assessing relevant information about theory, concept and methods. Mesh-filter was applied in order to narrow down the search area to physical activity and its use in a therapeutic purpose. Seven articles in total were considered relevant for evaluating the purpose of the study. Among the seven articles, six were analytical cross sectional studies and one study was a randomized control trial. The investigations present associations between vitamin D and physical function, muscle-strength, fall and fracture, BMD and duration of physical activity, which is also correlated to increased sun exposure. However, cross sectional study alone are limited in terms of their causality. The associations observed mainly predict the expected effect of a certain parameter. Based on these facts, it would be interesting to investigate the effects of physical activity on vitamin D assessing epidemiologic and clinical methods in order to acquire short-term results. Adequate information regarding the relevancy of physical activity on vitamin D status today appears inadequate to support distinct recommendations on this topic.

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Call number: LD2668 .T4 1951 W58 / Master of Science

In ständigem Kontakt mit zahlreichen Mikroorganismen benötigt unser Körper eine Vielzahl an Mechanismen zur Abwehr krankheitserregender Keime. Antimikrobielle Peptide unterstützen als Effektormoleküle die einzellige Epithelschicht des Darms, die als Mukosabarriere unseren Körper vor dem Eindringen pathogener Keime bewahrt. Die Expression des antimikrobiellen Peptids LL-37, auch Cathelicidin genannt, stellt eine Strategie des angeborenen Immunsystems zur Abwehr von Mikroorganismen im Kolon dar. Die Expression des Cathelicidin Gens camp kann, wie in der vorliegenden Arbeit untersucht wurde, durch exogene Faktoren, wie die biologisch aktive Form des Vitamin D3, das 1,25(OH)2D3, die kurzkettige Fettsäure Butyrat und das Ernährungssupplement Intestamin®, angeregt werden. Die Stimulation der Zellen mit den genannten Substanzen führte in allen gestesteten Zelllinien zeit- und dosisabhängig zu einer Steigerung der Expression des Cathelicidin Gens. Die Induktion der camp-Expression durch 1,25(OH)2D3 wird durch die Existenz eines Vitamin D Response Elements (VDRE) in der Promoterrregion des camp-Gens begründet, an das der Vitamin D-Rezeptor Komplex als ligandenabhängiger Transkriptionsfaktor bindet und die Genexpression vermittelt. Die Auswirkungen von Butyrat auf die Genexpression des Cathelicidins werden auf die Modifikation des Acetylierungsstatus der Histonproteine zurückgeführt. Butyrat bewirkt durch eine reversible Hemmung der Histondeacetylase die Hyperacetylierung bestimmter Kernhistone und greift auf diese Weise in die Regulation der Gentranskription ein. Das enterale Ernährungssupplement Intestamin®, das als Pharmakonutrition speziell für schwerkranke Patienten entwickelt wurde, ist reich an Glutamin-Dipeptiden, Tributyrin und Antioxidantien. Der Effekt, den Intestamin® auf die Expression des Cathelicidin Gens ausübt, ist wahrscheinlich auf Tributyrin zurückzuführen. Tributyrin, der Ester aus Glycerin und Butyrat, wird durch Hydrolyse zu Butyrat umgesetzt und bewirkt vermutlich die Steigerung der camp-Expression. Eine Co-Stimulation von GEKI 02 Zellen mit 1,25(OH)2D3 plus Butyrat erzielte nach 48 Stunden eine weitere Steigerung der Expression des Cathelicidin Gens gegenüber beiden Einzelsubstanzen. In allen anderen getesteten Zelllinien zeigte sich keine synergetische Wirkung der beiden Substanzen. Auch eine Co-Stimulation mit Intestamin® plus Butyrat konnte nicht zu einer stärkeren Zunahme der camp-Expression führen als eine Behandlung mit beiden Einzelsubstanzen. Eine synergetische Wirkung der Substanzen 1,25(OH)2D3 und Butyrat in GEKI 02 Zellen könnte durch die Acetylierung der Histone bedingt sein, die eine Auflockerung der Chromatinstruktur bewirkt, was wiederum die Bindung von Transkriptionsfaktoren wie dem Vitamin D-Rezeptor Komplex erleichtert. Die fehlende synergetische Wirkung in allen anderen getesteten Zelllinien könnte mit der Tatsache in Zusammenhang stehen, dass die Induktion der camp-Expression zeitabhängig ist: Vitamin D3 erzielte nach 24 Stunden, Butyrat nach 48 Stunden die deutlichsten Auswirkungen auf die Genexpression des Cathelicidins. Der Einfluss des MEK/ERK Signalweges auf die durch 1,25(OH)2D3, Butyrat und Intestamin® induzierte camp-Expression wurde in den durchgeführten Versuchen mittels des spezifischen MEK 1/2 Inhibitors U0126 untersucht. U0126 blockierte die Induktion des Cathelicidin Gens durch Intestamin® und Butyrat, was die Beteiligung des Signalweges MEK/ERK belegt. Vitamin D3 dagegen übt seinen Einfluss auf LL-37 nicht über den Signalweg MEK/ERK aus. Obwohl Vitamin D3 und Butyrat die Expression des Cathelicidin Gens camp induzieren, konnte die Inkubation der Zellen mit beiden Substanzen die antimikrobielle Aktivität der Kolonepithelzellen gegenüber E.coli im Vergleich zu unbehandelten Kontrollzellen nicht steigern. Ursächlich hierfür könnte neben der Wahl eines apathogenen Bakterienstammes das Mikromilieu der Umgebung sein. Außer der Konzentration des Peptids spielen insbesondere der pH-Wert und die Salzkonzentration des Kulturmediums eine wichtige Rolle, da sie die Ausbildung der Sekundärstruktur, nämlich der &#945;-helikalen Konformation, des LL-37 beeinflussen, die für die Interaktion mit Biomembranen erforderlich ist. Aufgrund der zunehmenden Resistenzentwicklung von Bakterien gegenüber herkömmlichen Antibiotika, wächst das Interesse an der Erforschung antimikrobieller Peptide. Exogene Faktoren wie 1,25(OH)2D3, Butyrat und Intestamin® können eine Steigerung der Expression des Cathelicidin Gens erzielen. Ob sich dieser Effekt allerdings auch in-vivo zeigt und eventuell therapeutischen Einsatz finden könnte, müssen weitere Studien klären. / Defence of mucosal and epithelial surfaces against microbial pathogens involves the innate and adaptive immune response. The single cell layer of the colonic epithelium produces an array of immune modulators, including antimicrobial peptides, such as cathelicidins, that participate in the innate immune system. The aim of the present study was to analyse the effect of calcitriol, the histon-deacetylase inhibitor butyrate and the enteral pharmaconutrition supplement Intestamin® on the expression of the cathlicidin gene camp. After exposure to these stimuli a time and dose dependent induction of the expression of the cathelicidin gene was found in all investigated colorectal cell lines. The effect of calcitriol, 1,25(OH)2D3, is mediated by the vitamin D response element (VDRE) in the camp promoter that was bound by the vitamin D receptor (VDR). The induction of cathelicidin expression after treatment with butyrate is attributed to a reversible inhibition of histone deacetylases resulting in modulation of core histone and non-histone proteins and subsequent regulation of the gene transcription. The enteral pharmaconutrition supplement Intestamin® contains glutamine, antioxidant vitamins and tributyrin. The increased cathelicidin level after treatment with Intestamin® are ascribed to tributyrin because tributyrin is a novel structured lipid composed of three molecules of butyrate esterified with glycerol that induces the cathelicidin gene camp after hydrolysis to butyrate. When colorectal cells GEKI 02 were stimulated with 1,25(OH)2D3 plus butyrate, a further increase of cathelicidin expression was seen after 48 hours. This effect was not seen for the incubation with Intestamin® plus butyrate. Changes in the acetylation status of core histone and non-histone proteins caused by butyrate that enhance binding of the vitamin D receptor complex as a transcription factor might be responsible for the synergistic effect of butyrate and calcitriol. To determine the influence of the MEK/ERK signalling pathway in the investigated cell lines the specific MEK/ERK inhibitor U0126 was utilized. Inhibition of the MEK/ERK pathway blocked butyrate- and Intestamin®-induced cathelicidin expression while no effect was observed for calcitriol. Although incubation with vitamin D3 and butyrate increased cathelicidin expression, the antimicrobial activity against E.coli could not be enhanced in the investigated colorectal cells. This might be caused by selection of a commensal bacterium and the absence of relevant microenvironmental stimuli because the antibacterial activity correlates with the extent of &#945;-helicity, which is influenced by ion composition, pH, and peptide concentration. Due to the fast development of bacterial resistance to traditional antibiotics, there is increasing interest in the research on antimicrobial peptides. Exogenic factors like 1,25(OH)2D3, butyrate and Intestamin® can enhance an expression of the cathelicidin gene. Further in vivo studies, however, are necessary to verify this effect for the potential future therapeutic application.

Three experiments were carried out to investigate dietary and genetic factors influencing the n-3 polyunsaturated fatty acid content of sheepmeat. In the first experiment, four isoenergetic and iso-nitrogenous diets, based on dried grass with similar fat levels (60 g/kg OM) from different sources; Megalac (control), linseed (a-linolenic acid, CI8:3n-3), fish oil (eicosapentaenoic, C20:5n-3 and docosahexaenoic, C22:6n-3 acids) and linseed plus fish oil were fed to four rumen and duodenal cannulated sheep in a 4x4 Latin square design. Biohydrogenation of C 18:3n-3 was, 80-92 % in all diets, while that of C20:5n-3 and C22:6n-3 was 58-74 %. Dietary n-3 PUFA decreased microbial efficiency (p < 0.05) measured using the total purine technique as a microbial marker, whilst fish oil depressed fibre digestion in the rumen (p < 0.01). In experiment two, the same four diets were randomly allocated to 72 lambs from three breeds; Suffolk, Soayand Friesland blocked on live weight. Muscle fatty acid content was 2.4-2.8 % of tissue weight. Compared to the control diet, linseed doubled the quantity of CI8:3n-3 in muscle and increased levels of C20:5n-3 and C22:6n-3 by 0.5 (p < 0.001). Fish oil alone increased C20:5n-3 and C22:6n-3 by 3-4 times (p < 0.001), whilst the mixed diet resulted in n-3 PUFA levels intermediate between the linseed and fish oil diets. Soay lambs deposited more PUF A on the control diet than Suffolk or Friesland lambs (p < 0.05). In the third experiment three iso-energetic and iso-nitrogenous diets, with different fat sources, Megalac or formaldehyde treated linseed (protected) with or without fish oil, and with two levels of vitamin E 100 (low) and 500 (high) mg/kg OM were randomly allocated to 96 lambs from two breeds; Suffolk and Scottish Blackface blocked on live weight. Muscle fatty acid content was 2.3-3.1 % of tissue weight but was lower in control fed lambs (p3 mg/kg muscle) in all lambs fed any of the diets. Overall, dietary modifications were more effective than genetic factors in increasing the n-3 PUF A in sheepmeat.

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