A5021220986- Regulation of Appetite and Obesity
- Adipose Tissue and Metabolism
- Growth Hormone and Insulin-like Growth Factors
- Pituitary Gland Disorders and Treatments
- Biochemical Analysis and Sensing Techniques
- Neurogenesis and neuroplasticity mechanisms
- Diet and metabolism studies
- Adrenal and Paraganglionic Tumors
- Cardiovascular Health and Disease Prevention
- Hormonal and reproductive studies
- Circadian rhythm and melatonin
- Parkinson's Disease Mechanisms and Treatments
- Dietary Effects on Health
- RNA and protein synthesis mechanisms
- Adipokines, Inflammation, and Metabolic Diseases
- Birth, Development, and Health
- Immunotherapy and Immune Responses
- RNA Interference and Gene Delivery
- Cell Image Analysis Techniques
- Peroxisome Proliferator-Activated Receptors
- Chemical Synthesis and Analysis
- RNA regulation and disease
- Lipid metabolism and biosynthesis
- Cholesterol and Lipid Metabolism
- RNA Research and Splicing
Swansea University
2015-2024
Saint Joseph Hospital
2019
British Museum
2019
University Hospital of Wales
1997-2014
Cardiff University
2000-2011
Weatherford College
2005
University of Wales
2000-2002
Diabetes Australia
2000-2002
Sex hormones appear to play a pivotal role in determining cardiovascular risk. Androgen deprivation therapy for males with prostate cancer results hypogonadal state that may have important, but as yet undetermined, effects on the vasculature. We studied of androgen large artery stiffness 22 patients (mean age, 67 +/- 8 yr) over 6-month period. Arterial was assessed using pulse-wave analysis, technique measures peripheral arterial pressure waveforms and generates corresponding central aortic...
Summary objective Transsphenoidal selective adenomectomy (TSA) is widely accepted as the treatment of choice for Cushing’s disease but not all patients are cured by this procedure. The success surgery depends on skill and experience surgeon criteria used to define remission highly variable. We have analysed outcome following in our centre using stringent requirement a postoperative serum cortisol < 50 nmol/l definition assessed whether changes surgical policy, including greater emphasis...
Circulating ghrelin elevates abdominal adiposity by a mechanism independent of its central orexigenic activity. In this study we tested the hypothesis that peripheral induces depot-specific increase in white adipose tissue (WAT) mass vivo GH secretagogue receptor (GHS-R(1a))-mediated lipolysis. Chronic iv infusion acylated increased retroperitoneal and inguinal WAT volume rats without elevating superficial sc fat, food intake, or circulating lipids glucose. Increased resulted from adipocyte...
Calorie restriction (CR) is neuroprotective in Parkinson's disease (PD) although the mechanisms are unknown. In this study we hypothesized that elevated ghrelin, a gut hormone with properties, during CR prevents neurodegeneration an 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD. attenuated MPTP-induced loss substantia nigra (SN) dopamine neurons and striatal turnover ghrelin WT but not KO mice, demonstrating mediates CR's effect. phosphorylated AMPK ACC levels striatum mice...
The beneficial effects of calorie restriction (CR) have been described at both organismal and cellular levels in multiple organs. However, our understanding the causal mediators such hormesis is poorly understood, particularly context higher brain function. Here, we show that receptor for orexigenic hormone acyl-ghrelin, growth secretagogue (Ghsr), enriched neurogenic niche hippocampal dentate gyrus (DG). Acute elevation acyl-ghrelin by injection or overnight CR, increased DG transcription...
Ghrelin, the endogenous ligand of GH secretagogue receptor type 1a, has emerged as pleiotropic modulator diverse biological functions, including energy homeostasis and, recently, reproduction. Although inhibitory actions ghrelin on LH secretion and puberty onset have been reported previously, mechanisms mediating these actions, potential gonadotropic effects unacylated isoform (UAG), remain unclear. In this work, single repeated administration or UAG were compared in pubertal adult male...
We retrospectively analyzed 90 patients who underwent transsphenoidal surgery (performed by three surgeons) in our center as initial therapy for acromegaly. used a combination of modern, evidence-based remission criteria including mean day curve GH less than 2.5 micro g/liter (5 mU/liter), nadir 1.0 (2 mU/liter) after an oral glucose tolerance test, and normal age-related IGF-I levels (where available). Fifty-seven (63%) remained surgery. Seventy-nine percent with microadenomas but only 56%...
An important link exists between intact metabolic processes and normal cognitive functioning; however, the underlying mechanisms remain unknown. There is accumulating evidence that gut hormone ghrelin, an orexigenic peptide elevated during calorie restriction (CR) known primarily for stimulating growth release, has extra-hypothalamic functions, such as enhancing synaptic plasticity hippocampal neurogenesis. The present study was designed to evaluate long-term effects of elevating...
Metformin is a widely prescribed drug used to treat type-2 diabetes, although recent studies show it has wide ranging effects other diseases. Animal and retrospective human indicate that treatment neuroprotective in Parkinson's Disease (PD), the mechanism unknown, numerous suggest beneficial on glucose homeostasis may be through AMPK activation. In this study we tested whether or not activation dopamine neurons was required for of PD. We generated transgenic mice which activity ablated by...
Abstract Despite being unable to activate the cognate ghrelin receptor (GHS-R), unacylated (UAG) possesses a unique activity spectrum that includes promoting bone marrow adipogenesis. Since mediating this action has not been identified, we re-appraised potential interaction of UAG with GHS-R in regulation adiposity. Surprisingly, adipogenic effects intra-bone (ibm)-infused acylated (AG) and were abolished male GHS-R-null mice. Gas chromatography showed isolated tibial adipocytes contain...
Primary hyperparathyroidism (PHPT) is associated with increased cardiovascular risk, although the mechanisms involved remain unclear. Recent evidence has shown pulse pressure to be a powerful predictor of events. As increases in are due largely arterial stiffening, we measured stiffness 21 subjects PHPT (18 women and 3 men; 46–71 yr old) age- sex-matched healthy controls using wave analysis, technique that measures peripheral waveforms generates corresponding central aortic waveforms. This...
Summary Objective Reports suggest that up to 70% of patients with microprolactinomas treated dopamine agonist therapy may achieve long‐term normoprolactinaemic remission following drug withdrawal. Yet, there is no consensus on the duration nor therapeutic interruption universally practised. We have assessed rates in a large cohort treatment‐naive subjects microprolactinomas. Subjects received (DA) either cabergoline or bromocriptine for period 2 3 years majority cases, followed by trial...
OBJECTIVES: Controversy persists with regard to the atherogenic risk associated adult growth hormone deficiency (GHD). Endothelial dysfunction and enhanced oxidative stress are early features of atherogenesis. Therefore, we have studied effect three months low dose GH replacement therapy (0.03IU/kg/day) on these parameters in GHD adults. SUBJECTS AND METHODS: Eight hypopituitary adults (4 male, 4 female), who were receiving conventional therapy, before after 3 (0.03IU/kg/day). All...
Ghrelin is a metabolic hormone that has neuroprotective actions in number of neurological conditions, including Parkinson's disease (PD), stroke and traumatic brain injury. Acyl ghrelin treatment vivo vitro also shows protective capacity Alzheimer's (AD). In the present study, we used knockout (KO) their wild-type littermates to test whether or not endogenous mouse model AD, which human amyloid β peptide 1-40 (Aβ1-40 ) was injected into lateral ventricles i.c.v. Recognition memory, using...
Several studies have shown that using language is most suitable for the patient essential effective communication in healthcare. Using a patients second during health consultations can negatively impact patient, causing delays treatment and misdiagnosis. In Wales both Welsh English equal status public sector organisations, however, independent primary care providers such as General Practices (GPs), do not need to comply with all Language Standards. Thus, there inconsistency availability of...
The physiological impact of ultradian temporal feeding patterns remains a major unanswered question in nutritional science. We have employed automated and nasogastric to address this male rodents human volunteers. While grazing meal-feeding reduced food intake parallel (compared ad libitum-fed rodents), body length tibial epiphysial plate width were maintained meal-fed via the action ghrelin its receptor, GHS-R. Grazing initially suppressed elevated pre-prandial levels rats, followed by...
Anabolic androgenic steroids are used by some bodybuilders to enhance performance. While the cardiovascular implications of supraphysiological androgen levels requires further clarification, use is associated with sudden death, left ventricular hypertrophy, thrombo-embolism and cerebro-vascular events.To understand effect anabolic steroid abuse on vascular function, this study assessed stiffness (pulse-wave analysis) risk factors in 28 male, bodybuilding subjects, whom ten were actively...
Human startle disease, also known as hyperekplexia (OMIM 149400), is a paroxysmal neurological disorder caused by defects in glycinergic neurotransmission. Hyperekplexia characterised an exaggerated reflex response to tactile or acoustic stimuli which first presents neonatal hypertonia, followed some with episodes of life-threatening infantile apnoea. Genetic screening studies have demonstrated that genetically heterogeneous several missense and nonsense mutations the postsynaptic glycine...
Abstract Background Ghrelin is an orexigenic stomach hormone that acts centrally to increase mid-brain dopamine neurone activity, amplify signaling and protect against neurotoxin-induced cell death in the mouse substantia nigra pars compacta (SNpc). In addition, ghrelin inhibits lipopolysaccharide (LPS)-induced release of pro-inflammatory cytokines from peripheral macrophages, T-cells LPS stimulated microglia. Here we sought determine whether attenuates cytokine dopaminergic neurones....
Blood-borne factors regulate adult hippocampal neurogenesis and cognition in mammals. We report that elevating circulating unacylated-ghrelin (UAG), using both pharmacological genetic methods, reduced plasticity mice. Spatial memory impairments observed ghrelin-O-acyl transferase-null (GOAT-/-) mice lack acyl-ghrelin (AG) but have high levels of UAG were rescued by acyl-ghrelin. Acyl-ghrelin-mediated vitro was dependent on non-cell-autonomous BDNF signaling inhibited UAG. These findings...