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Pugh J.A.T.,University of Sheffield | Cox A.G.,University of Sheffield | McLeod C.W.,University of Sheffield | Bunch J.,University of Birmingham | And 5 more authors.
Analytical and Bioanalytical Chemistry | Year: 2012

Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) has been used to map the spatial distribution of magnetic resonance imaging (MRI) contrast agents (Gd-based) in histological sections in order to explore synergies with in vivo MRI. Images from respective techniques are presented for two separate studies namely (1) convection enhanced delivery of a Gd nanocomplex (developmental therapeutic) into rat brain and (2) convection enhanced delivery, with co-infusion ofMagnevist (commercial Gd contrast agent) and Carboplatin (chemotherapy drug), into pig brain. The LA technique was shown to be a powerful compliment to MRI not only in offering improved sensitivity, spatial resolution and signal quantitation but also in giving added value regarding the fate of administered agents (Gd and Pt agents). Furthermore simultaneous measurement of Fe enabled assignment of an anomalous contrast enhancement region in rat brain to haemorrhage at the infusion site. © Springer-Verlag 2012. Source


Goldstone A.P.,Metabolic and Molecular Imaging Group | Holland A.J.,University of Cambridge | Butler J.V.,University of Cambridge | Whittington J.E.,University of Cambridge
International Journal of Obesity | Year: 2012

Objective:Prader-Willi syndrome (PWS) is a genetic neurodevelopmental disorder with several nutritional phases during childhood proceeding from poor feeding, through normal eating without and with obesity, to hyperphagia and life-threatening obesity, with variable ages of onset. We investigated whether differences in appetite hormones may explain the development of abnormal eating behaviour in young children with PWS.Subjects:In this cross-sectional study, children with PWS (n=42) and controls (n=9) aged 7 months-5 years were recruited. Mothers were interviewed regarding eating behaviour, and body mass index (BMI) was calculated. Fasting plasma samples were assayed for insulin, leptin, glucose, peptide YY (PYY), ghrelin and pancreatic polypeptide (PP).Results:There was no significant relationship between eating behaviour in PWS subjects and the levels of any hormones or insulin resistance, independent of age. Fasting plasma leptin levels were significantly higher (mean±s.d.: 22.6±12.5 vs 1.97±0.79ngml-1, P=0.005), and PP levels were significantly lower (22.6±12.5 vs 69.8±43.8pmoll-1, P<0.001) in the PWS group compared with the controls, and this was independent of age, BMI, insulin resistance or IGF-1 levels. However, there was no significant difference in plasma insulin, insulin resistance or ghrelin levels between groups, though PYY declined more rapidly with age but not BMI in PWS subjects.Conclusion:Even under the age of 5 years, PWS is associated with low levels of anorexigenic PP, as in older children and adults. Hyperghrelinaemia or hypoinsulinaemia was not seen in these young children with PWS. Change in these appetite hormones was not associated with the timing of the transition to the characteristic hyperphagic phase. However, abnormal and/or delayed development or sensitivity of the effector pathways of these appetitive hormones (for example, parasympathetic and central nervous system) may interact with low PP levels, and later hyperghrelinaemia or hypoinsulinaemia, to contribute to hyperphagia in PWS. © 2012 Macmillan Publishers Limited. All rights reserved. Source


Johnston K.L.,University of Surrey | Thomas E.L.,Metabolic and Molecular Imaging Group | Bell J.D.,Metabolic and Molecular Imaging Group | Frost G.S.,Imperial College London | Robertson M.D.,University of Surrey
Diabetic Medicine | Year: 2010

Aims Diets rich in non-viscous fibre are linked to a reduced risk of both diabetes and cardiovascular disease; however, the mechanism of action remains unclear. This study was undertaken to assess whether chronic consumption of this type of fibre in individuals with the metabolic syndrome would improve insulin sensitivity via changes in ectopic fat storage. Methods The study was a single-blind, randomized, parallel nutritional intervention where 20 insulin resistant subjects consumed either the fibre supplement (resistant starch) (40 g/day) or placebo supplement (0 g/day) for 12 weeks. Insulin sensitivity was measured by euglycaemic-hyperinsulinaemic clamp and ectopic fat storage measured by whole-body magnetic resonance spectroscopy. Results Resistant starch consumption did not significantly affect body weight, fat storage in muscle, liver or visceral depots. There was also no change with resistant starch feeding on vascular function or markers of inflammation. However, in subjects randomized to consume the resistant starch, insulin sensitivity improved compared with the placebo group (P = 0.023). Insulin sensitivity correlated significantly with changes in waist circumference and fat storage in tibialis muscle and to a lesser extent to visceral-to-subcutaneous abdominal adipose tissue ratio. Conclusion Consumption of resistant starch improves insulin sensitivity in subjects with the metabolic syndrome. Unlike in animal models, diabetes prevention does not appear to be directly related to changes in body adiposity, blood lipids or inflammatory markers. Further research to elucidate the mechanisms behind this change in insulin sensitivity in human subjects is required. © 2010 Diabetes UK. Source


Hankir M.,Imperial College London | Hankir M.,Metabolic and Molecular Imaging Group | Bueter M.,Imperial College London | Bueter M.,University of Zurich | And 8 more authors.
Obesity Facts | Year: 2012

Objective: To investigate whether gastric bypass induces a higher activity of brown adipose tissue and greater levels of the brown adipose tissue-specific protein uncoupling protein-1 (UCP-1) in rats. Methods: Gastric bypass rats and sham-operated controls (each n = 8) underwent whole body 1H-MR spectroscopy for analysis of body composition and 18F- fluorodeoxyglucose positron emission tomography combined with computed tomography (18F-FDG PET/CT) imaging for measurement of the metabolic activity of brown adipose tissue. Brown adipose tissue was harvested and weighed, and UCP-1 mRNA content was measured by Northern Blot technique. Results: Gastric bypass rats had a significantly lower percentage of whole body adipose tissue mass compared to sham-operated rats (p = 0.001). There was no difference in brown adipose tissue activity between the two groups (standardised uptake value sham 2.81 ± 0.58 vs. bypass 2.56 ± 0.46 ; p = 0.73). Furthermore, there was no difference in the UCP-1 mRNA content of brown adipose tissue between the two groups (sham 49.5 ± 13.2 vs. bypass 43.7 ± 13.1; p = 0.77). Conclusion: Gastric bypass does not increase the activity of brown adipose tissue in rats suggesting that other mechanisms are involved to explain the increased energy expenditure after bypass surgery. Our results cannot justify the radiation dose of 18F-FDG PET/CT studies in humans to determine potential changes in brown adipose tissue after gastric bypass surgery. Copyright © 2012 S. Karger GmbH, Freiburg. Source


Arora T.,Hammersmith Hospital | Arora T.,National Dairy Research Institute | Anastasovska J.,Metabolic and Molecular Imaging Group | Gibson G.,University of Reading | And 4 more authors.
British Journal of Nutrition | Year: 2012

There is an increased interest in investigating the relationship between the gut microbiota and energy homeostasis. Probiotics are health beneficial microbes mainly categorised under the genus Lactobacillus and Bifidobacterium, which when administered in adequate amounts confer health benefits to the host, and have been implicated in various physiological functions. The potential role of probiotics in energy homeostasis is a current and an emerging area of research. In the present study, Lactobacillus acidophilus NCDC 13 was used to evaluate its anti-obesity potential in diet-induced obese (C57BL/6) mice. The probiotic bacterial culture was administered in Indian yogurt preparation called dahi, prepared using native starter cultures, and compared with control dahi containing only dahi starter cultures. The dietary intervention was followed for 8 weeks, and whole-body fat composition, and liver and muscle adiposity were measured using MRI. Changes in gut microbiota were assessed by fluorescent in situ hybridisation in faeces and caecal contents. The feeding of the probiotic brought no changes in body-weight gain, food and dahi intake when compared with the control dahi-fed animals. No significant changes in body fat composition, liver and muscle adiposity were also observed. At the end of the dietary intervention, a significant increase (P < 0•05) in the number of total Bifidobacterium was observed in both faeces and caecal contents of mice as a result of probiotic dahi administration. Thus, L. acidophilus NCDC 13 supplementation could be beneficial in shifting the gut microbiota balance positively. However, its anti-obesity potential could not be established in the present study and warrants further exploration. © 2011 The Authors. Source

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