Endocrine Abstracts

Low testosterone levels in men are associated with increased atherosclerosis, and testosterone replacement therapy has been shown to reduce myocardial ischemia in men with coronary artery disease. Vascular smooth muscle cell (VSMC) apoptosis is proposed to reduce plaque stability, but the role of testosterone in this process is unknown. Testosterone causes vasodilatation via calcium channel antagonism and the calcium channel antagonist nifedipine induces VSMC apoptosis. We hav...

Atherosclerotic plaque smooth muscle cells (SMCs) are sensitive to apoptotic stimuli, increasing plaque instability. Testosterone replacement therapy is beneficial in men with coronary artery disease, although its effect upon plaque stability is unknown. We have utilised the rat A7r5 vascular SMC line to investigate the effects of testosterone on apoptosis induced by serum deprivation or the calcium channel antagonist nifedipine.Cells were plated at 1500...

The global epidemic of obesity has heightened the need to understand the mechanisms that underpin its pathogenesis. Clinical observations in patients with Cushing's syndrome have highlighted the link between cortisol and central obesity. However, whilst circulating cortisol levels are normal or reduced in obesity, local regeneration of cortisol, from inactive cortisone, by 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) has been postulated as a pathogenic mechanism. W...

SHOX has been implicated in the regulation of bone growth and modelling. Haploinsufficiency and heterozygous mutations of SHOX are associated with Lerri Weil Dyschondrosteosis (LWD). The cardinal features of LWD are mesomelic limb shortening and Madelung deformity. Histological studies demonstrate premature fusion of the ulna border of the radial epiphysis and disordered osteoblast maturation and orientation. In view of these observations we investigated the role of SHOX in th...

Pseudoexons resemble true exons by current bioinformatic criteria and may outnumber true exons by 10:1. They are, however, never spliced into mature mRNA. A point mutation in the GHR gene results in abnormal splicing of a pseudoexon, leading to Laron syndrome. The GHR pseudoexon lies between exons six and seven and the point mutation is adjacent to the pseudoexon 5' splice site.Our studies aimed to define the elements that normally prevent splicing of this pseudoexon.A...

Islet amyloid deposition is a characteristic feature of Type 2 diabetes. Accumulation of IAPP by abnormal intracellular peptide degradation in beta-cell could promote fibril formation. IAPP is present in high concentrations in beta-cell lysosomes. To determine if fibrils form in lysosomes and the pathway for the accumulation human islets were cultured under conditions of elevated production of insulin (11mM glucose) and inhibition of secretion (0.6mM diazoxide) and/or lysosoma...

The evolution of aquatic vertebrates to dry land required adaptation of physiological systems concerned with water and mineral ion homeostasis. Two factors, calcitonin (CT) and parathyroid hormone (PTH), have ultimately become the principal hypo- and hyper-calcaemic factors respectively, in terrestrial vertebrates. Fish CT has been isolated and shown to be hypocalcaemic in mammals; its role in fish physiology is less well defined, although it may control calcium influx via the...

Aim To describe the early outcomes of carcinoid patients undergoing surgical heart valve replacement.Methods In a retrospective study, records of patients with symptomatic carcinoid heart disease referred for valve surgery between 2012 and 2021 were reviewed. The perioperative and early postoperative outcomes were analyzed.Results Thirteen patients, with a mean age of 64 years (range 55-79 years) underwent cardiac surgery for carci...

Background: The National Paediatric Diabetes audit (NPDA) reports increasing number of children and young people with type 2 diabetes (CYP2D). CYP2D are less likely to receive all recommended health checks compared to those with type 1 diabetes (33% vs 59% respectively) and do not receive treatment for complications even when they are identified (T2D spotlight audit 2019/20). We assessed variation in care across different units against the national T2D guideli...

Malignancy-related hypercalcaemia occurs in over 20% of cancer patients. Most cases are due to enhanced production of parathyroid hormone-related peptide (PTHrP) by tumours and carry a poor prognosis of survival of weeks to months. A 74 year old man with a history of prostate cancer treated with radical radiotherapy in 2013 and androgen blockade until 2015 underwent CT and PET/CT scans in 2017, which showed liver and spleen abnormalities, suggestive of metastases, but unlikely...