184 results found
Abbara A, Clarke S, Islam R, et al., 2017, Reply: Clinical trial registry alone is not adequate: on the perception of possible endpoint switching and P-hacking., Hum Reprod, Pages: 1-3
Abbara A, Clarke S, Islam R, et al., 2017, A second dose of kisspeptin-54 improves oocyte maturation in women at high risk of ovarian hyperstimulation syndrome: a Phase 2 randomized controlled trial, HUMAN REPRODUCTION, Vol: 32, Pages: 1915-1924, ISSN: 0268-1161
Algeffari M, Jayasena CN, MacKeith P, et al., 2017, Testosterone therapy for sexual dysfunction in men with Type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials., Diabet Med
AIM: To evaluate the effectiveness of testosterone therapy on a range of sexual function domains in men with Type 2 diabetes. METHOD: Electronic databases were searched for studies investigating the effect of testosterone therapy on sexual function in men with Type 2 diabetes. All randomized controlled trials were considered for inclusion if they compared the efficacy of testosterone therapy with that of placebo and reported sexual function outcomes. Statistical analysis was performed using a random-effects model, and heterogeneity was expressed using the I(2) statistic. RESULTS: A total of 611 articles were screened. Six randomized control trials, in a total of 587 men with Type 2 diabetes, were eligible for inclusion. The pooled data suggested that testosterone therapy improves sexual desire (random-effects pooled effect size 0.314; 95% CI 0.082-0.546) and erectile function (random-effects pooled effect size 0.203; 95% CI 0.007-0.399) when compared with control groups. Testosterone therapy had no significant effect on constitutional symptoms or other sexual domains compared with control groups. No studies have investigated the incidence of prostate cancer, fertility and cardiovascular disease after testosterone therapy in men with Type 2 diabetes. CONCLUSION: Testosterone therapy may moderately improve sexual desire and erectile function in men with Type 2 diabetes; however, available data are limited, and the long-term risks of testosterone therapy are not known in this specific patient group. We conclude that testosterone therapy is a potential treatment for men with Type 2 diabetes non-responsive to phosphodiesterase-5 inhibitors. Testosterone therapy could be considered for men with Type 2 diabetes when potential risks and benefits of therapy are carefully considered and other therapeutic options are unsuitable. This article is protected by copyright. All rights reserved.
Bhatt PS, Dhillo WS, Salem V, 2017, Human brown adipose tissue-function and therapeutic potential in metabolic disease., Curr Opin Pharmacol, Vol: 37, Pages: 1-9
There has been a resurgence of interest in brown adipose tissue (BAT) over the last decade. Key to this has been our ability to accurately image it, which has improved significantly. The role of BAT in regulating energy expenditure is important, and its pharmacological manipulation may hold therapeutic potential in metabolic disease. There is ample evidence of BAT activation by cold exposure, and pharmacological utilisation of similar pathways, using B3 receptor agonists holds promise since the development of selective agonists with limited cross-reactivity has rekindled interest. Endogenous agents like irisin, FGF21 and certain gut hormones may hold value as BAT activators. Other agents such as steroid hormones may also hold therapeutic potential, although short-term worsening of metabolic profile remains problematic. Clearly, pharmacological manipulation of BAT is important, and thanks to recent advances we may one day be able to add such agents to our anti-obesity arsenal.
Comninos AN, Dhillo WS, 2017, Emerging Roles of Kisspeptin in Sexual and Emotional Brain Processing., Neuroendocrinology
<br>The emergence of kisspeptin as a crucial regulator of the hypothalamo-pituitary-gonadal (HPG) axis over the last 14 years has answered many questions as to the control of reproductive hormone secretion from the hypothalamus. More recently the role of kisspeptin outside the HPG axis has received increasing attention in the hope of delineating the pathways linking various sensory and social behaviours to reproduction. These studies, in a range of species from zebrafish to humans, have identified a role for kisspeptin in behavioural networks related to reproduction including olfaction, audition, fear, anxiety, mood and sexual arousal. The available evidence suggests that extrahypothalamic kisspeptin signalling encourages positive aspects of emotional and sexual brain processing in a presumed drive towards reproduction and ultimately maintenance of the species at a population level. In this review, we examine these studies, which collectively propose that kisspeptin may integrate sexual and emotional brain processing with the control of the HPG axis.<br>.
Comninos AN, Wall MB, Demetriou L, et al., 2017, Kisspeptin modulates sexual and emotional brain processing in humans, JOURNAL OF CLINICAL INVESTIGATION, Vol: 127, Pages: 709-719, ISSN: 0021-9738
Hameed S, Patterson M, Dhillo WS, et al., 2017, Thyroid Hormone Receptor Beta in the Ventromedial Hypothalamus Is Essential for the Physiological Regulation of Food Intake and Body Weight, CELL REPORTS, Vol: 19, Pages: 2202-2209, ISSN: 2211-1247
Katugampola H, King PJ, Chatterjee S, et al., 2017, Kisspeptin Is a Novel Regulator of Human Fetal Adrenocortical Development and Function: A Finding With Important Implications for the Human Fetoplacental Unit, JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, Vol: 102, Pages: 3349-3359, ISSN: 0021-972X
Law JM, Morris DE, Izzi-Engbeaya C, et al., 2017, Thermal imaging is a non-invasive alternative to PET-CT for measurement of brown adipose tissue activity in humans., J Nucl Med
Background: Obesity and its metabolic consequences are a major cause of morbidity and mortality. Brown adipose tissue (BAT) utilises glucose and free fatty acids to produce heat, thereby increasing energy expenditure. Effective evaluation of human BAT stimulators is constrained by current standard BAT assessment methods as positron emission tomography-computed tomography (PET-CT) requires exposure to high doses of ionising radiation. Infrared thermography (IRT) is a potential non-invasive, safe alternative, although direct corroboration with PET-CT has not previously been established. Methods: IRT and 18F-FDG PET-CT data from 8 healthy male participants subjected to water jacket cooling were directly compared. Thermal images (TIs) were geometrically transformed to overlay PET-CT-derived maximum intensity projection (MIP) images from each subject and the areas of greatest intensity of temperature and glucose-uptake within the supraclavicular regions compared. Relationships between supraclavicular temperatures from IRT (TSCR) and the maximum rate of glucose uptake (MR(gluc)) from PET-CT were determined. Results: Glucose uptake on MR(gluc)MIP was positively correlated with change in TSCR relative to a reference region (r2 = 0.721; P = 0.008). Spatial overlap between areas of maximal MR(gluc)MIP and maximal TSCR was 29.5±5.1%. Prolonged cooling to 60 minutes was associated with further TSCR rise compared with cooling to 10 minutes. Conclusion: The supraclavicular hotspot identified on IRT closely corresponds to the area of maximal uptake on PET-CT-derived MR(gluc)MIP images. Greater increases in relative TSCR were associated with raised glucose uptake. IRT should now be considered a suitable method for measuring BAT activation, especially in populations where PET-CT is not feasible, practical or repeatable. This work is licensed under a Creative Commons Attribution 4.0 International License http://creativecommons.org/licenses/by/4.0/.
Owens LA, Abbara A, Lerner A, et al., 2017, The direct and indirect effects of kisspeptin-54 on granulosa lutein cell function., Hum Reprod, Pages: 1-11
STUDY QUESTION: What are the in vivo and in vitro actions of kisspeptin-54 on the expression of genes involved in ovarian reproductive function, steroidogenesis and ovarian hyperstimulation syndrome (OHSS) in granulosa lutein (GL) cells when compared with traditional triggers of oocyte maturation? SUMMARY ANSWER: The use of kisspeptin-54 as an oocyte maturation trigger augmented expression of genes involved in ovarian steroidogenesis in human GL cells including, FSH receptor (FSHR), LH/hCG receptor (LHCGR), steroid acute regulatory protein (STAR), aromatase, estrogen receptors alpha and beta (ESR1, ESR2), 3-beta-hydroxysteroid dehydrogenase type 2 (3BHSD2) and inhibin A (INHBA), when compared to traditional maturation triggers, but did not alter markers of OHSS. WHAT IS KNOWN ALREADY: hCG is the most widely used trigger of oocyte maturation, but is associated with an increased risk of OHSS. The use of GnRH agonists to trigger oocyte maturation is a safer alternative to hCG. More recently, kisspeptin-54 has emerged as a novel therapeutic option that safely triggers oocyte maturation even in women at high risk of OHSS. Kisspeptin indirectly stimulates gonadotropin secretion by acting on hypothalamic GnRH neurons. Kisspeptin and its receptor are also expressed in the human ovary, but there is limited data on the direct action of kisspeptin on the ovary. STUDY DESIGN SIZE, DURATION: Forty-eight women undergoing IVF treatment for infertility consented to kisspeptin-54 triggering and/or granulosa cell collection and were included in the study. Twelve women received hCG, 12 received GnRH agonist and 24 received kisspeptin-54 to trigger oocyte maturation. In the kisspeptin-54 group, 12 received one injection of kisseptin-54 (9.6 nmol/kg) and 12 received two injections of kisspeptin-54 at a 10 h interval (9.6 nmol/kg × 2). PARTICIPANTS/MATERIALS, SETTING, METHODS: Follicular fluid was aspirated and pooled from follicles during the retrieval of oocytes for IVF/ICSI. GL
Prague JK, Dhillo WS, 2017, Neurokinin 3 receptor antagonism - the magic bullet for hot flushes?, CLIMACTERIC, Vol: 20, Pages: 505-509, ISSN: 1369-7137
Prague JK, Roberts RE, Comninos AN, et al., 2017, Neurokinin 3 receptor antagonism as a novel treatment for menopausal hot flushes: a phase 2, randomised, double-blind, placebo-controlled trial, LANCET, Vol: 389, Pages: 1809-1820, ISSN: 0140-6736
Vimalesvaran S, Narayanaswamy S, Yang L, et al., 2017, Using kisspeptin to assess GnRH function in an unusual case of primary amenorrhoea., Endocrinol Diabetes Metab Case Rep, Vol: 2017, ISSN: 2052-0573
SUMMARY: Primary amenorrhoea is defined as the failure to commence menstruation by the age of 15 years, in the presence of normal secondary sexual development. The potential causes of primary amenorrhoea extend from structural to chromosomal abnormalities. Polycystic ovarian syndrome (PCOS) is a common cause of secondary amenorrhoea but an uncommon cause of primary amenorrhoea. An early and prompt diagnosis of PCOS is important, as up to 30% of these women are predisposed to glucose intolerance and obesity, with the subgroup of women presenting with primary amenorrhoea and PCOS displaying a higher incidence of metabolic dysfunction. We describe a case of an 18-year-old female presenting with primary amenorrhoea of unknown aetiology. Although initial investigations did not demonstrate clinical or biochemical hyperandrogenism or any radiological evidence of polycystic ovaries, a raised luteinising hormone (LH) suggested a diagnosis of PCOS. If PCOS was the correct diagnosis, then one would expect intact hypothalamic GnRH and pituitary gonadotropin release. We used the novel hormone kisspeptin to confirm intact hypothalamic GnRH release and a GnRH stimulation test to confirm intact pituitary gonadotroph function. This case highlights that kisspeptin is a potential unique tool to test GnRH function in patients presenting with reproductive disorders. LEARNING POINTS: Polycystic ovarian syndrome (PCOS) can present with primary amenorrhoea, and therefore, should be considered in the differential diagnosis.PCOS is a heterogeneous condition that may present in lean women with few or absent signs of hyperandrogenism.GnRH stimulation tests are useful in evaluating pituitary function; however, to date, we do not have a viable test of GnRH function. Kisspeptin has the potential to form a novel diagnostic tool for assessing hypothalamic GnRH function by monitoring gonadotropin response as a surrogate marker of GnRH release.Confirmation of intact GnRH function helps consolidate a
Wernig F, Jayasena CN, Dhillo WS, 2017, Carcinoid syndrome and neuroendocrine tumours, Medicine (United Kingdom), Vol: 45, Pages: 543-546, ISSN: 1357-3039
© 2017 Neuroendocrine tumours (NETs) arise from the gastrointestinal tract, pancreas, bronchi or other rare primary sites and comprise a variety of different tumour types. Carcinoid tumours are the most common. NETs can be associated with a variety of clinical syndromes. For instance, classic symptoms of carcinoid syndrome, such as flushing and diarrhoea, occur because of the release of hormones, including serotonin, tachykinins and peptide hormones. However, most NETs are non-secretory in nature and are detected incidentally or through compression of surrounding structures. Liver metastasis has usually already occurred at the time of diagnosis. Surgery can be curative if disease is entirely localized. Injections of somatostatin analogues such as octreotide are the mainstay of non-surgical treatment for NETs. Surgical debulking and embolization techniques are useful to reduce tumour bulk in patients who remain symptomatic despite medical treatment. Peptide receptor radionucleotide therapy using radiolabelled somatostatin analogues has recently been shown to prolong progression-free survival. Furthermore, several novel agents, such as everolimus, have emerged in the treatment of patients with metastatic disease. This article aims to summarize the pathophysiology and clinical features of NETs, with a focus on carcinoid syndrome. It also discusses recent advances in clinical management of NETs.
de Tassigny XD, Jayasena C, Murphy KG, et al., 2017, Mechanistic insights into the more potent effect of KP-54 compared to KP-10 in vivo, PLOS ONE, Vol: 12, ISSN: 1932-6203
Comninos AN, Anastasovska J, Sahuri-Arisoylu M, et al., 2016, Kisspeptin signaling in the amygdala modulates reproductive hormone secretion, BRAIN STRUCTURE & FUNCTION, Vol: 221, Pages: 2035-2047, ISSN: 1863-2653
Hickson M, Moss C, Dhillo WS, et al., 2016, Increased peptide YY blood concentrations, not decreased acyl-ghrelin, are associated with reduced hunger and food intake in healthy older women: Preliminary evidence, APPETITE, Vol: 105, Pages: 320-327, ISSN: 0195-6663
Jayasena CN, Abbara A, Comninos AN, et al., 2016, Novel circulating placental markers prokineticin-1, soluble fms-like tyrosine kinase-1, soluble endoglin and placental growth factor and association with late miscarriage, HUMAN REPRODUCTION, Vol: 31, Pages: 2681-2688, ISSN: 0268-1161
Narayanaswamy S, Jayasena CN, Ng N, et al., 2016, Subcutaneous infusion of kisspeptin-54 stimulates gonadotrophin release in women and the response correlates with basal oestradiol levels, CLINICAL ENDOCRINOLOGY, Vol: 84, Pages: 939-945, ISSN: 0300-0664
Narayanaswamy S, Prague JK, Jayasena CN, et al., 2016, Investigating the KNDy Hypothesis in Humans by Coadministration of Kisspeptin, Neurokinin B, and Naltrexone in Men, JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, Vol: 101, Pages: 3429-3436, ISSN: 0021-972X
Polyviou T, MacDougall K, Chambers ES, et al., 2016, Randomised clinical study: inulin short-chain fatty acid esters for targeted delivery of short-chain fatty acids to the human colon, ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Vol: 44, Pages: 662-672, ISSN: 0269-2813
Salem V, Izzi-Engbeaya C, Coello C, et al., 2016, Glucagon increases energy expenditure independently of brown adipose tissue activation in humans, DIABETES OBESITY & METABOLISM, Vol: 18, Pages: 72-81, ISSN: 1462-8902
Abbara A, Jayasena CN, Christopoulos G, et al., 2015, Efficacy of Kisspeptin-54 to Trigger Oocyte Maturation in Women at High Risk of Ovarian Hyperstimulation Syndrome (OHSS) During In Vitro Fertilization (IVF) Therapy, JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, Vol: 100, Pages: 3322-3331, ISSN: 0021-972X
Chambers ES, Viardot A, Psichas A, et al., 2015, Effects of targeted delivery of propionate to the human colon on appetite regulation, body weight maintenance and adiposity in overweight adults, GUT, Vol: 64, Pages: 1744-1754, ISSN: 0017-5749
Chambers ES, Viardot A, Psichas A, et al., 2015, Effects of elevating colonic propionate on liver fat content in overweight adults with non-alcoholic fatty liver disease: a pilot study, PROCEEDINGS OF THE NUTRITION SOCIETY, Vol: 74, Pages: E30-E30, ISSN: 0029-6651
Clarke H, Dhillo WS, Jayasena CN, 2015, Comprehensive Review on Kisspeptin and Its Role in Reproductive Disorders, ENDOCRINOLOGY AND METABOLISM, Vol: 30, Pages: 124-141, ISSN: 2093-596X
Hussain S, Richardson E, Ma Y, et al., 2015, Glucokinase activity in the arcuate nucleus regulates glucose intake, JOURNAL OF CLINICAL INVESTIGATION, Vol: 125, Pages: 337-349, ISSN: 0021-9738
Izzi-Engbeaya C, Salem V, Atkar RS, et al., 2015, Insights into Brown Adipose Tissue Physiology as Revealed by Imaging Studies, ADIPOCYTE, Vol: 4, Pages: 1-12, ISSN: 2162-3945
Jayasena CN, Abbara A, Narayanaswamy S, et al., 2015, Direct comparison of the effects of intravenous kisspeptin-10, kisspeptin-54 and GnRH on gonadotrophin secretion in healthy men, HUMAN REPRODUCTION, Vol: 30, Pages: 1934-1941, ISSN: 0268-1161
Jayasena CN, Comninos AN, Narayanaswamy S, et al., 2015, The identification of elevated urinary kisspeptin-immunoreactivity during pregnancy, ANNALS OF CLINICAL BIOCHEMISTRY, Vol: 52, Pages: 395-398, ISSN: 0004-5632
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