Publications by authors named "Neele S Dellschaft"

6 Publications

  • Page 1 of 1

Postprandial changes in gastrointestinal function and transit in cystic fibrosis assessed by Magnetic Resonance Imaging.

J Cyst Fibros 2020 Jun 16. Epub 2020 Jun 16.

Division of Child Health, Obstetrics and Gynaecology, University of Nottingham, UK; NIHR Nottingham Biomedical Research Centre (BRC), Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, UK. Electronic address:

Background: Cystic fibrosis (CF) is a multi-system genetic disorder affecting >72,000 people worldwide. Most CF patients experience gastrointestinal symptoms and can develop complications. However, the mechanisms of CF gut disease are not well understood. We evaluated gut function and transit in CF using magnetic resonance imaging (MRI). We hypothesised oro-caecal transit time (OCTT) is longer in CF; with lower small bowel water content (SBWC).

Methods: Twelve CF patients aged 12-40 years and 12 age and sex-matched controls underwent serial MRIs over 1 day with standardised meals. The primary endpoint was OCTT, assessed by the appearance of a food bolus in the caecum. Other measures included corrected SBWC and corrected colonic volume (both area under the curve, AUC), gastric half-emptying time and gastrointestinal symptoms.

Results: OCTT was longer in CF (CF 330 mins [270, >360] vs. controls 210 mins [173, 315], p = 0.04), with no difference in gastric half-emptying times. Corrected SBWC was higher in CF (CF 62 L.min/m [36, 80] vs. controls 34 L.min/m [28, 41], p = 0.021); minimal postprandial decrease between T240 and T300 (CF 13 mL/m [-13, 57] vs. controls 102 mL/m [67, 108], p = 0.002) suggests impaired ileal emptying. Corrected colonic volumes were higher in CF (CF 186 L.min/m [167, 206] vs. controls 123 L.min/m [89, 146], p = 0.012). There were no differences in gastrointestinal symptoms.

Conclusions: MRI provides novel insights into CF pathophysiology. Sub-clinical ileal obstruction may be more prevalent than previously thought. Gastrointestinal MRI shows promise as an investigational tool in CF.
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http://dx.doi.org/10.1016/j.jcf.2020.06.004DOI Listing
June 2020

The haemodynamics of the human placenta in utero.

PLoS Biol 2020 05 28;18(5):e3000676. Epub 2020 May 28.

Sir Peter Mansfield Imaging Centre, School of Physics and Astronomy, University of Nottingham, Nottingham, United Kingdom.

We have used magnetic resonance imaging (MRI) to provide important new insights into the function of the human placenta in utero. We have measured slow net flow and high net oxygenation in the placenta in vivo, which are consistent with efficient delivery of oxygen from mother to fetus. Our experimental evidence substantiates previous hypotheses on the effects of spiral artery remodelling in utero and also indicates rapid venous drainage from the placenta, which is important because this outflow has been largely neglected in the past. Furthermore, beyond Braxton Hicks contractions, which involve the entire uterus, we have identified a new physiological phenomenon, the 'utero-placental pump', by which the placenta and underlying uterine wall contract independently of the rest of the uterus, expelling maternal blood from the intervillous space.
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http://dx.doi.org/10.1371/journal.pbio.3000676DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7255609PMC
May 2020

Tissue cell stress response to obesity and its interaction with late gestation diet.

Reprod Fertil Dev 2018 Mar;30(3):430-441

Early Life Research Unit, Academic Division of Child Health, Obstetrics and Gynaecology, School of Medicine, Queen's Medical Centre, University of Nottingham, Nottingham NG7 2UH, UK.

Intrauterine growth restriction in late pregnancy can contribute to adverse long-term metabolic health in the offspring. In the present study we used an animal (sheep) model of maternal dietary manipulation in late pregnancy, combined with exposure of the offspring to a low-activity, obesogenic environment after weaning, to characterise the effects on glucose homeostasis. Dizygotic twin-pregnant sheep were either fed to 60% of requirements (nutrient restriction (R)) or fed ad libitum (~140% of requirements (A)) from 110 days gestation until term (~147 days). After weaning (~3 months of age), the offspring were kept in either a standard (in order to remain lean) or low-activity, obesogenic environment. R mothers gained less weight and produced smaller offspring. As adults, obese offspring were heavier and fatter with reduced glucose tolerance, regardless of maternal diet. Molecular markers of stress and autophagy in liver and adipose tissue were increased with obesity, with gene expression of hepatic glucose-related protein 78 (Grp78) and omental activation transcription factor 6 (Atf6), Grp78 and ER stress degradation enhancer molecule 1 (Edem1) only being increased in R offspring. In conclusion, the adverse effect of juvenile-onset obesity on insulin-responsive tissues can be amplified by previous exposure to a suboptimal nutritional environment in utero, thereby contributing to earlier onset of insulin resistance.
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http://dx.doi.org/10.1071/RD16494DOI Listing
March 2018

The Form of Choline in the Maternal Diet Affects Immune Development in Suckled Rat Offspring.

J Nutr 2016 04 2;146(4):823-30. Epub 2016 Mar 2.

Department of Agricultural, Food and Nutritional Science, University of Alberta, Li Ka Shing Centre for Health Research Innovation, Edmonton, Alberta, Canada; and

Background: Lipid-soluble phosphatidylcholine (PC) and aqueous free choline are absorbed and metabolized differently, but the metabolic effects of feeding these 2 forms of choline have not been thoroughly investigated.

Objective: We sought to compare the effects of PC and free choline in the maternal diet on the development of the offspring's immune system.

Methods: During lactation, Sprague-Dawley dams (n= 10) were randomly assigned to 1 of 2 diet groups containing the same concentration of total choline (1 g/kg diet) as free choline (choline bitartrate) or PC (egg lecithin). The splenocytes of pups aged 21 d were isolated and stimulated ex vivo with concanavalin A (ConA) or lipopolysaccharide (LPS), and the choline concentrations of stomach content, plasma, and the spleen were measured.

Results: Pups from PC-fed dams had a lower proportion of cells involved in antigen presentation but produced 54% more interleukin (IL)-2, 163% more IL-6, and 107% more IFN-γ after ConA stimulation and 110% more IL-6 and 43% more tumor necrosis factor (TNF)-α after LPS stimulation (allP< 0.05). The PC concentrations were significantly higher in the plasma and spleen of pups from PC-fed dams (P< 0.05). Increasing the supply of PC in the form of lysophosphatidylcholine to splenocytes in vitro increased the rate of proliferation and IL-2 production and the surface expression of CD25, CD28, CD71, and CD152 on CD8+ T cells, suggesting 1 possible mechanism.

Conclusions: The results of this study demonstrate that providing choline to rats in the form of PC (compared to free choline), possibly by increasing the supply of PC to the suckling pups, promotes maturation and improves function of the offspring's immune system.
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http://dx.doi.org/10.3945/jn.115.225888DOI Listing
April 2016

Choline is required in the diet of lactating dams to maintain maternal immune function.

Br J Nutr 2015 Jun 23;113(11):1723-31. Epub 2015 Apr 23.

Department of Agricultural,Food and Nutritional Science, University of Alberta, 4-126A Li Ka Shing Centre for Health Research Innovation,Edmonton,AB,CanadaT6G 2E1.

Choline demands during lactation are high; however, detailed knowledge is lacking regarding the optimal dietary intake during this critical period. The present study was designed to determine the effects of varying intakes of choline on maternal immune function during lactation. Primiparous Sprague-Dawley rats (n 42) were randomised 24-48 h before birth and fed the following diets for 21 d: choline-devoid (0 g choline/kg diet; D, n 10); 1·0 g choline/kg diet (C1, n 11); 2·5 g choline/kg diet (C2·5, n 10); 6·2 g choline/kg diet (C6, n 11). Splenocytes were isolated and stimulated ex vivo with concanavalin A, lipopolysaccharide (LPS) or CD3/CD28. D and C6 dams had lower final body weight, spleen weight and average pup weight than C1 dams (P< 0·05). There was a linear relationship between free choline concentration in pup stomach contents with maternal dietary choline content (P< 0·001, r² 0·415). Compared with C1 and C2·5, D spleens had a lower proportion of mature T cells and activated suppressor cells, and this resulted in reduced cytokine production after stimulation (P< 0·05). Feeding 6·2 g choline/kg diet resulted in a higher cytokine production after stimulation with CD3/CD28 (P< 0·05). Except for a higher IL-6 production after LPS stimulation with cells from the C2·5 dams (P< 0·05), there were no differences between the C1 and C2·5 dams. For the first time, we show that feeding lactating mothers a diet free of choline has substantial effects on their immune function and on offspring growth. Additionally, excess dietary choline had adverse effects on maternal and offspring body weight but only minimal effects on maternal immune function.
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http://dx.doi.org/10.1017/S0007114515001221DOI Listing
June 2015

Effect of pre- and postnatal growth and post-weaning activity on glucose metabolism in the offspring.

J Endocrinol 2015 Feb 21;224(2):171-82. Epub 2014 Nov 21.

Early Life Research UnitAcademic Division of Child Health, Obstetrics and Gynaecology, School of Medicine, Queen's Medical Centre, The University of Nottingham, Nottingham NG7 2UH, UKINRA and University of NantesUMR-1280 Physiologie des Adaptations Nutritionnelles, CHU Hôtel Dieu, 44093 Nantes cedex 1, FranceSchool of Veterinary Medicine and ScienceThe University of Nottingham, Sutton Bonington Campus, Nottingham LE12 5RD, UKInstitute of Health SciencesCentre for Life-Course Epidemiology, and Biocentre Oulu, University of Oulu, Aapistie 5B, 90014 Oulu, FinlandOnirisLaboratoire d'Etude des Résidus et Contaminants dans les Aliments, LUNAM Université, USC INRA 1329, Nantes, FranceDepartment of Animal ScienceUniversity of Missouri, Columbia, Missouri 65211, USA Early Life Research UnitAcademic Division of Child Health, Obstetrics and Gynaecology, School of Medicine, Queen's Medical Centre, The University of Nottingham, Nottingham NG7 2UH, UKINRA and University of NantesUMR-1280 Physiologie des Adaptations Nutritionnelles, CHU Hôtel Dieu, 44093 Nantes cedex 1, FranceSchool of Veterinary Medicine and ScienceThe University of Nottingham, Sutton Bonington Campus, Nottingham LE12 5RD, UKInstitute of Health SciencesCentre for Life-Course Epidemiology, and Biocentre Oulu, University of Oulu, Aapistie 5B, 90014 Oulu, FinlandOnirisLaboratoire d'Etude des Résidus et Contaminants dans les Aliments, LUNAM Université, USC INRA 1329, Nantes, FranceDepartment of Animal ScienceUniversity of Missouri, Columbia, Missouri 65211, USA.

Maternal caloric restriction during late gestation reduces birth weight, but whether long-term adverse metabolic outcomes of intra-uterine growth retardation (IUGR) are dependent on either accelerated postnatal growth or exposure to an obesogenic environment after weaning is not established. We induced IUGR in twin-pregnant sheep using a 40% maternal caloric restriction commencing from 110 days of gestation until term (∼147 days), compared with mothers fed to 100% of requirements. Offspring were reared either as singletons to accelerate postnatal growth or as twins to achieve standard growth. To promote an adverse phenotype in young adulthood, after weaning, offspring were reared under a low-activity obesogenic environment with the exception of a subgroup of IUGR offspring, reared as twins, maintained in a standard activity environment. We assessed glucose tolerance together with leptin and cortisol responses to feeding in young adulthood when the hypothalamus was sampled for assessment of genes regulating appetite control, energy and endocrine sensitivity. Caloric restriction reduced maternal plasma glucose, raised non-esterified fatty acids, and changed the metabolomic profile, but had no effect on insulin, leptin, or cortisol. IUGR offspring whose postnatal growth was enhanced and were obese showed insulin and leptin resistance plus raised cortisol. This was accompanied by increased hypothalamic gene expression for energy and glucocorticoid sensitivity. These long-term adaptations were reduced but not normalized in IUGR offspring whose postnatal growth was not accelerated and remained lean in a standard post-weaning environment. IUGR results in an adverse metabolic phenotype, especially when postnatal growth is enhanced and offspring progress to juvenile-onset obesity.
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http://dx.doi.org/10.1530/JOE-14-0600DOI Listing
February 2015