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  1. Article ; Online: A pilot observational study measuring acute sarcopenia in older colorectal surgery patients

    Carly Welch / Carolyn A. Greig / Zaki K. Hassan-Smith / Thomas D. Pinkney / Janet M. Lord / Thomas A. Jackson

    BMC Research Notes, Vol 12, Iss 1, Pp 1-

    2019  Volume 7

    Abstract: Abstract Objective To explore variability in acute changes in muscle mass and function in older patients undergoing elective colorectal surgery, as well as feasibility of measures, in order to refine study processes to inform the protocol for a larger ... ...

    Abstract Abstract Objective To explore variability in acute changes in muscle mass and function in older patients undergoing elective colorectal surgery, as well as feasibility of measures, in order to refine study processes to inform the protocol for a larger study. Results Results are presented for seven participants recruited to this pilot study. It is possible to perform serial measurements of bilateral anterior thigh thickness (BATT) and handgrip strength prior to, within 24 h of surgery, and 1 week postoperatively. Gait speed can be reliably measured preoperatively and at 1 week postoperatively. In this pilot study, BATT and gait speed declined at 1 week postoperatively (median BATT 4.17 cm, 3.47 cm, p = 0.028; median gait speed 0.89 m/s, 0.83 m/s, p = 0.043). Baseline hsCRP correlated with change in BATT (τb = 0.73, p = 0.04) and baseline DHEA-S correlated with change in gait speed (τb = 0.87, p = 0.02). This pilot study has assisted to refine the protocol for our larger study, which will further characterise these changes.
    Keywords Acute sarcopenia ; Inflammation ; Biomarkers ; Aged ; Medicine ; R ; Biology (General) ; QH301-705.5 ; Science (General) ; Q1-390
    Language English
    Publishing date 2019-01-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 exert distinct effects on human skeletal muscle function and gene expression.

    Zaki K Hassan-Smith / Carl Jenkinson / David J Smith / Ivan Hernandez / Stuart A Morgan / Nicola J Crabtree / Neil J Gittoes / Brian G Keevil / Paul M Stewart / Martin Hewison

    PLoS ONE, Vol 12, Iss 2, p e

    2017  Volume 0170665

    Abstract: Age-associated decline in muscle function represents a significant public health burden. Vitamin D-deficiency is also prevalent in aging subjects, and has been linked to loss of muscle mass and strength (sarcopenia), but the precise role of specific ... ...

    Abstract Age-associated decline in muscle function represents a significant public health burden. Vitamin D-deficiency is also prevalent in aging subjects, and has been linked to loss of muscle mass and strength (sarcopenia), but the precise role of specific vitamin D metabolites in determining muscle phenotype and function is still unclear. To address this we quantified serum concentrations of multiple vitamin D metabolites, and assessed the impact of these metabolites on body composition/muscle function parameters, and muscle biopsy gene expression in a retrospective study of a cohort of healthy volunteers. Active serum 1,25-dihydroxyvitamin D3 (1α,25(OH)2D3), but not inactive 25-hydroxyvitamin D3 (25OHD3), correlated positively with measures of lower limb strength including power (rho = 0.42, p = 0.02), velocity (Vmax, rho = 0.40, p = 0.02) and jump height (rho = 0.36, p = 0.04). Lean mass correlated positively with 1α,25(OH)2D3 (rho = 0.47, p = 0.02), in women. Serum 25OHD3 and inactive 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) had an inverse relationship with body fat (rho = -0.30, p = 0.02 and rho = -0.33, p = 0.01, respectively). Serum 25OHD3 and 24,25(OH)2D3 were also correlated with urinary steroid metabolites, suggesting a link with glucocorticoid metabolism. PCR array analysis of 92 muscle genes identified vitamin D receptor (VDR) mRNA in all muscle biopsies, with this expression being negatively correlated with serum 25OHD3, and Vmax, and positively correlated with fat mass. Of the other 91 muscle genes analysed by PCR array, 24 were positively correlated with 25OHD3, but only 4 were correlated with active 1α,25(OH)2D3. These data show that although 25OHD3 has potent actions on muscle gene expression, the circulating concentrations of this metabolite are more closely linked to body fat mass, suggesting that 25OHD3 can influence muscle function via indirect effects on adipose tissue. By contrast, serum 1α,25(OH)2D3 has limited effects on muscle gene expression, but is associated with increased muscle strength and lean mass in women. These pleiotropic effects of the vitamin D 'metabolome' on muscle function indicate that future supplementation studies should not be restricted to conventional analysis of the major circulating form of vitamin D, 25OHD3.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article: High throughput LC–MS/MS method for the simultaneous analysis of multiple vitamin D analytes in serum

    Jenkinson, Carl / Angela E. Taylor / Brian G. Keevil / John S. Adams / Martin Hewison / Paul M. Stewart / Zaki K. Hassan-Smith

    Journal of chromatography. 2016 Mar. 01, v. 1014

    2016  

    Abstract: Recent studies suggest that vitamin D-deficiency is linked to increased risk of common human health problems. To define vitamin D ‘status’ most routine analytical methods quantify one particular vitamin D metabolite, 25-hydroxyvitamin D3 (25OHD3). ... ...

    Abstract Recent studies suggest that vitamin D-deficiency is linked to increased risk of common human health problems. To define vitamin D ‘status’ most routine analytical methods quantify one particular vitamin D metabolite, 25-hydroxyvitamin D3 (25OHD3). However, vitamin D is characterized by complex metabolic pathways, and simultaneous measurement of multiple vitamin D metabolites may provide a more accurate interpretation of vitamin D status.To address this we developed a high-throughput liquid chromatography-tandem mass spectrometry (LC–MS/MS) method to analyse multiple vitamin D analytes, with particular emphasis on the separation of epimer metabolites. A supportive liquid-liquid extraction (SLE) and LC–MS/MS method was developed to quantify 10 vitamin D metabolites as well as separation of an interfering 7α-hydroxy-4-cholesten-3-one (7αC4) isobar (precursor of bile acid), and validated by analysis of human serum samples.In a cohort of 116 healthy subjects, circulating concentrations of 25-hydroxyvitamin D3 (25OHD3), 3-epi-25-hydroxyvitamin D3 (3-epi-25OHD3), 24,25-dihydroxyvitamin D3 (24R,25(OH)2D3), 1,25-dihydroxyvitamin D3 (1α,25(OH)2D3), and 25-hydroxyvitamin D2 (25OHD2) were quantifiable using 220μL of serum, with 25OHD3 and 24R,25(OH)2D3 showing significant seasonal variations.This high-throughput LC–MS/MS method provides a novel strategy for assessing the impact of vitamin D on human health and disease.
    Keywords 24,25-dihydroxycholecalciferol ; 25-hydroxycholecalciferol ; 25-hydroxyergocalciferol ; bile acids ; biochemical pathways ; blood serum ; calcitriol ; human health ; humans ; liquid chromatography ; liquid-liquid extraction ; metabolites ; risk ; tandem mass spectrometry ; vitamin D deficiency
    Language English
    Dates of publication 2016-0301
    Size p. 56-63.
    Publishing place Elsevier B.V.
    Document type Article
    ISSN 1570-0232
    DOI 10.1016/j.jchromb.2016.01.049
    Database NAL-Catalogue (AGRICOLA)

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  4. Article ; Online: SFRP2 Is Associated with Increased Adiposity and VEGF Expression.

    Rachel K Crowley / Michael W O'Reilly / Iwona J Bujalska / Zaki K Hassan-Smith / Jonathan M Hazlehurst / Danielle R Foucault / Paul M Stewart / Jeremy W Tomlinson

    PLoS ONE, Vol 11, Iss 9, p e

    2016  Volume 0163777

    Abstract: Aims The aim of this study was to assess depot-specific expression and secretion of secreted frizzled-related protein 2 (sFRP2) by adipose tissue and its effect on adipocyte biology. We measured serum sFRP2 concentrations in 106 patients in vivo to ... ...

    Abstract Aims The aim of this study was to assess depot-specific expression and secretion of secreted frizzled-related protein 2 (sFRP2) by adipose tissue and its effect on adipocyte biology. We measured serum sFRP2 concentrations in 106 patients in vivo to explore its relationship to fat mass, glycaemia and insulin resistance. Methods Expression of sFRP2 in mouse and human tissues was assessed using polymerase chain reaction and Western blot. Western blot confirmed secretion of sFRP2 by adipose tissue into cell culture medium. Effects of recombinant sFRP2 on lipogenesis and preadipocyte proliferation were measured. Preadipocyte expression of the angiogenic genes vascular endothelial growth factor (VEGF) and nuclear factor of activated T-cells 3 (NFATC3) was measured after recombinant sFRP2 exposure. Complementary clinical studies correlating human serum sFRP2 with age, gender, adiposity and insulin secretion were also performed. Results sFRP2 messenger RNA (mRNA) was expressed in mouse and human adipose tissue. In humans, sFRP2 mRNA expression was 4.2-fold higher in omental than subcutaneous adipose. Omental adipose tissue secreted 63% more sFRP2 protein than subcutaneous. Treatment with recombinant sFRP2 did not impact on lipogenesis or preadipocyte proliferation but was associated with increased VEGF mRNA expression. In human subjects, circulating insulin levels positively correlated with serum sFRP2, and levels were higher in patients with abnormal glucose tolerance (34.2ng/ml) compared to controls (29.5ng/ml). A positive correlation between sFRP2 and BMI was also observed. Conclusions Circulating sFRP2 is associated with adipose tissue mass and has a potential role to drive adipose angiogenesis through enhanced VEGF expression.
    Keywords Medicine ; R ; Science ; Q
    Subject code 616 ; 610
    Language English
    Publishing date 2016-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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