Professor Sir Steve Bloom FMedSci, FRS

Bloom S, 2012, Peptides and obesity, 19th International Symposium on Regulatory Peptides, Publisher: ELSEVIER SCIENCE BV, Pages: S10-S10, ISSN: 0167-0115

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Sam AH, Gunner DJ, King A, Persaud SJ, Brooks L, Hostomska K, Ford HE, Liu B, Ghatei MA, Bloom SR, Bewick GAet al., 2012, Selective Ablation of Peptide YY Cells in Adult Mice Reveals Their Role in Beta Cell Survival, GASTROENTEROLOGY, Vol: 143, Pages: 459-468, ISSN: 0016-5085

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• Citations: 57

Pournaras DJ, Glicksman C, Vincent RP, Kuganolipava S, Alaghband-Zadeh J, Mahon D, Bekker JHR, Ghatei MA, Bloom SR, Walters JRF, Welbourn R, le Roux CWet al., 2012, The Role of Bile After Roux-en-Y Gastric Bypass in Promoting Weight Loss and Improving Glycaemic Control, ENDOCRINOLOGY, Vol: 153, Pages: 3613-3619, ISSN: 0013-7227

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• Citations: 284

Parker JA, Bloom SR, 2012, Hypothalamic neuropeptides and the regulation of appetite, NEUROPHARMACOLOGY, Vol: 63, Pages: 18-30, ISSN: 0028-3908

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• Citations: 165

Suzuki K, Jayasena CN, Bloom SR, 2012, Obesity and Appetite Control, Experimental Diabetes Research, Vol: 2012, ISSN: 1687-5214

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Hankir M, Bueter M, Gsell W, Seyfried F, Khalil M, Smith KL, Bloom SR, Bell JD, le Roux CWet al., 2012, Increased Energy Expenditure in Gastric Bypass Rats Is Not Caused by Activated Brown Adipose Tissue, OBESITY FACTS, Vol: 5, Pages: 349-358, ISSN: 1662-4025

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• Citations: 18

Ramachandran R, Bech P, Murphy KG, Dhillo WS, Meeran KM, Chapman RS, Caplin M, Ghatei MA, Bloom SR, Martin NMet al., 2012, Improved diagnostic accuracy for neuroendocrine neoplasms using two chromogranin A assays., Clin Endocrinol (Oxf), Vol: 76, Pages: 831-836

Chromogranin A (Cg A) is the best available diagnostic marker for neuroendocrine neoplasms (NENs). However, clinical interpretation of Cg A results may be limited by considerable heterogeneity between commonly available Cg A assays. Variation in diagnostic accuracy of these assays largely reflects differences in antibody specificities. We compared the diagnostic utility of four Cg A assays [Imperial Supra-regional Assay Service radioimmunoassay (SAS) and three commercial assays, Cisbio, DAKO and Eurodiagnostica].

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Jayasena CN, Comninos AN, Januszewski A, Gabra H, Taylor A, Harvey RA, Ghatei MA, Bloom SR, Dhillo WSet al., 2012, Plasma Kisspeptin: A Potential Biomarker of Tumor Metastasis in Patients with Ovarian Carcinoma, CLINICAL CHEMISTRY, Vol: 58, Pages: 1061-1063, ISSN: 0009-9147

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• Citations: 12

Hafeez R, Wagner CV, Smith S, Boulos P, Halligan S, Bloom S, Taylor SAet al., 2012, Patient experiences of MR colonography and colonoscopy: a qualitative study, BRITISH JOURNAL OF RADIOLOGY, Vol: 85, Pages: 765-769, ISSN: 0007-1285

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• Citations: 10

Bech PR, Ramachandran R, Dhillo WS, Martin NM, Bloom SRet al., 2012, Quantifying the Effects of Renal Impairment on Plasma Concentrations of the Neuroendocrine Neoplasia Biomarkers Chromogranin A, Chromogranin B, and Cocaine- and Amphetamine-Regulated Transcript, CLINICAL CHEMISTRY, Vol: 58, Pages: 941-943, ISSN: 0009-9147

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• Citations: 31

Abuirmeileh A, Harkavyi A, Rampersaud N, Lever R, Tadross JA, Bloom SR, Whitton PSet al., 2012, Exendin-4 treatment enhances L-DOPA evoked release of striatal dopamine and decreases dyskinetic movements in the 6-hydoxydopamine lesioned rat, JOURNAL OF PHARMACY AND PHARMACOLOGY, Vol: 64, Pages: 637-643, ISSN: 0022-3573

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• Citations: 24

Fenske WK, Bueter M, Miras AD, Ghatei MA, Bloom SR, le Roux CWet al., 2012, Exogenous peptide YY3-36 and Exendin-4 further decrease food intake, whereas octreotide increases food intake in rats after Roux-en-Y gastric bypass, INTERNATIONAL JOURNAL OF OBESITY, Vol: 36, Pages: 379-384, ISSN: 0307-0565

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• Citations: 42

Cummings DE, Bloom SR, Rubino F, 2012, At the heart of the benefits of bariatric surgery, NATURE MEDICINE, Vol: 18, Pages: 358-359, ISSN: 1078-8956

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• Citations: 1

Jones BJ, Tan T, Bloom SR, 2012, Minireview: Glucagon in Stress and Energy Homeostasis, ENDOCRINOLOGY, Vol: 153, Pages: 1049-1054, ISSN: 0013-7227

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• Citations: 81

Germain N, Galusca B, Feasson L, Grouselle D, Bloom SR, Laville M, Vidal H, Boirie Y, Estour Bet al., 2012, Absence of weight gain after 4 weeks of lipidic overnutrition and constitutional thinness: profile of hormines in appetite regulation, DIABETES & METABOLISM, Vol: 38, Pages: A13-A14, ISSN: 1262-3636

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Hankir MK, Parkinson JR, Bloom SR, Bell JDet al., 2012, The effects of glutamate receptor agonists and antagonists on mouse hypothalamic and hippocampal neuronal activity shown through manganese enhanced MRI, NEUROIMAGE, Vol: 59, Pages: 968-978, ISSN: 1053-8119

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• Citations: 17

Ashby D, Choi P, Bloom S, 2012, Ghrelin in cachexia associated with end-stage renal disease, Ghrelin in Health and Disease, Pages: 231-256, ISBN: 9781617799020

Much of the high mortality seen in chronic renal failure is due to a form of vascular disease which, unlike the overnutrition vascular disease of the general population, is closely associated with the development of malnutrition. Various micronutrient de fi ciencies occur, and are commonly treatment related, but a speci fi c syndrome of energy malnutrition associated with unexplained activation of in fl ammatory mediators, is a common and early feature of renal failure, which is frequently refractory to nutritional supplementation. Many abnormalities of appetite hormones have been found in renal failure, and like obesity, renal malnutrition is increasingly understood as a disorder of appetite homeostasis, which therefore would respond best to manipulation of the appetite regulatory system-for example by administration of ghrelin. Reduced clearance by failing kidneys leads to accumulation of ghrelin, with elevated circulating levels of total ghrelin; however, a reduction in the acyl fraction has been found. Acyl ghrelin administration has been shown to increase energy intake in animal models of renal failure, and promising results have also been found with daily subcutaneous injections in dialysis patients over the course of a week. In addition, ghrelin is thought to have an anti-in fl ammatory effect, which may be therapeutically relevant in a syndrome in which inappropriate in fl ammation is a prominent feature.

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• Citations: 1

De Silva A, Bloom SR, 2012, Gut Hormones and Appetite Control: A Focus on PYY and GLP-1 as Therapeutic Targets in Obesity, Gut and Liver, Vol: 6, Pages: 10-20, ISSN: 2005-1212

The global obesity epidemic has resulted in significant morbidity and mortality. However, the medical treatment of obesity is limited. Gastric bypass is an effective surgical treatment but carries signifi cant perioperative risks. The gut hormones, peptide tyrosine tyrosine (PYY) and glucagon-like peptide 1 (GLP-1), are elevated following gastric bypass and have been shown to reduce food intake. They may provide new therapeutic targets. This review article provides an overview of the central control of food intake and the role of PYY and GLP-1 in appetite control. Key translational animal and human studies are reviewed.

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Li JV, Ashrafian H, Bueter M, Kinross J, Sands C, le Roux CW, Bloom SR, Darzi A, Athanasiou T, Marchesi JR, Nicholson JK, Holmes Eet al., 2012, Metabolic surgery profoundly influences gut microbial-host metabolic cross-talk, Gut, Vol: 60, Pages: 1214-1223

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Cetkovic A, Miljic D, Ljubic A, Patterson M, Ghatei M, Stamenkovic J, Nikolic-Djurovic M, Pekic S, Doknic M, Glisic A, Bloom S, Popovic Vet al., 2012, Plasma Kisspeptin Levels in Pregnancies with Diabetes and Hypertensive Disease as a Potential Marker of Placental Dysfunction and Adverse Perinatal Outcome, ENDOCRINE RESEARCH, Vol: 37, Pages: 78-88, ISSN: 0743-5800

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• Citations: 46

Tan TM, Field BCT, Minnion JS, Cuenco Shillito J, Chambers ES, Zac-Varghese S, Brindley CJ, Mt-Isa S, Fiorentino F, Ashby D, Ward I, Ghatei MA, Bloom SRet al., 2012, Pharmacokinetics, adverse effects and tolerability of a novel analogue of human pancreatic polypeptide, PP 1420., British Journal of Clinical Pharmacology, Vol: 73, Pages: 232-239

AIMS: The objectives of this phase 1 study were to confirm the tolerability ofsingle ascending subcutaneous doses of PP 1420 in healthy subjects, to assess itsadverse effects and to investigate the drug's pharmacokinetics and doseproportionality.METHODS: This was a double-blind, placebo-controlled, randomized study. Therewere three dosing periods. Each subject (n= 12) was randomized to receive onedose of placebo and two ascending doses of PP 1420, given as a subcutaneousinjection. Blood samples were taken over 24 h to assess pharmacokinetics.Standard safety and laboratory data were collected. The primary endpoint was the tolerability of PP 1420. The secondary endpoint was exposure to PP 1420 asassessed by C(max) and AUC(0,∞).RESULTS: PP 1420 was well tolerated by all subjects with no serious adverseeffects. Following single subcutaneous doses of PP 1420 at 2, 4 and 8 mg to male subjects, C(max) was reached at a median t(max) of approximately 1 h post dose(range 0.32-2.00 h). Thereafter, plasma concentrations of PP 1420 declined withgeometric mean apparent terminal elimination t(1/2) ranging from 2.42-2.61 h(range 1.64-3.95 h) across all dose levels.CONCLUSIONS: Subcutaneous PP 1420 was well tolerated in healthy human subjects atsingle doses between 2-8 mg, with no tolerability issues arising. Where observed,adverse events were not serious, and there was no evidence of a dose-relationshipto frequency of adverse events. The results therefore support the conduct ofclinical trials to investigate efficacy, tolerability and pharmacokinetics duringrepeated dosing.

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Simpson K, Parker J, Plumer J, Bloom Set al., 2012, CCK, PYY and PP: the control of energy balance., Handb Exp Pharmacol, Pages: 209-230, ISSN: 0171-2004

The control of food intake consists of neural and hormonal signals between the gut and central nervous system (CNS). Gut hormones such as CCK, PYY and PP signal to important areas in the CNS involved in appetite regulation to terminate a meal. These hormones can act directly via the circulation and activate their respective receptors in the hypothalamus and brainstem. In addition, gut vagal afferents also exist, providing an alternative pathway through which gut hormones can communicate with higher centres through the brainstem. Animal and human studies have demonstrated that peripheral administration of certain gut hormones reduces food intake and leads to weight loss. Gut hormones are therefore potential targets in the development of novel treatments for obesity and analogue therapies are currently under investigation.

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Ghourab S, Beale KE, Semjonous NM, Simpson KA, Martin NM, Ghatei MA, Bloom SR, Smith KLet al., 2011, Intracerebroventricular administration of vasoactive intestinal peptide inhibits food intake, REGULATORY PEPTIDES, Vol: 172, Pages: 8-15, ISSN: 0167-0115

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• Citations: 15

Dixon AFR, le Roux CW, Ghatei MA, Bloom SR, McGee TL, Dixon JBet al., 2011, Pancreatic Polypeptide Meal Response May Predict Gastric Band-Induced Weight Loss, OBESITY SURGERY, Vol: 21, Pages: 1906-1913, ISSN: 0960-8923

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• Citations: 8

Addison ML, Minnion JS, Shillito JC, Suzuki K, Tan TM, Field BCT, Germain-Zito N, Becker-Pauly C, Ghatei MA, Bloom SR, Murphy KGet al., 2011, A Role for Metalloendopeptidases in the Breakdown of the Gut Hormone, PYY_3-36, ENDOCRINOLOGY, Vol: 152, Pages: 4630-4640, ISSN: 0013-7227

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• Citations: 19

Zac-Varghese S, De Silva A, Bloom SR, 2011, Translational studies on PYY as a novel target in obesity, CURRENT OPINION IN PHARMACOLOGY, Vol: 11, Pages: 582-585, ISSN: 1471-4892

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• Citations: 22

Jayasena CN, Nijher GMK, Comninos AN, Abbara A, Januszewki A, Vaal ML, Sriskandarajah L, Murphy KG, Farzad Z, Ghatei MA, Bloom SR, Dhillo WSet al., 2011, The Effects of Kisspeptin-10 on Reproductive Hormone Release Show Sexual Dimorphism in Humans, JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, Vol: 96, Pages: E1963-E1972, ISSN: 0021-972X

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• Citations: 89

De Silva A, Salem V, Long CJ, Makwana A, Newbould RD, Rabiner EA, Ghatei MA, Bloom SR, Matthews PM, Beaver JD, Dhillo WSet al., 2011, The Gut Hormones PYY_3-36 and GLP-1_7-36 amide Reduce Food Intake and Modulate Brain Activity in Appetite Centers in Humans, CELL METABOLISM, Vol: 14, Pages: 700-706, ISSN: 1550-4131

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• Citations: 236

Patterson M, Bloom SR, Gardiner JV, 2011, Ghrelin and appetite control in humans-Potential application in the treatment of obesity, PEPTIDES, Vol: 32, Pages: 2290-2294, ISSN: 0196-9781

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• Citations: 51

Bueter M, Miras AD, Chichger H, Fenske W, Ghatei MA, Bloom SR, Unwin RJ, Lutz TA, Spector AC, le Roux CWet al., 2011, Alterations of sucrose preference after Roux-en-Y gastric bypass, PHYSIOLOGY & BEHAVIOR, Vol: 104, Pages: 709-721, ISSN: 0031-9384

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• Citations: 141