Endocrine Abstracts

Background: The late effects of childhood cancer therapy include a higher risk of subsequent primary cancers, fertility issues, and other endocrine dysfunction.Case: A 47 year old woman was treated at age 9 for acute myeloid leukaemia with chemotherapy (DAT, MACE, and cyclophosphamide), total body irradiation (990 cGy) and allogeneic bone marrow transplantation. Aged 22, a rapidly enlarging right sided thyroid nodule developed in the context of a multino...

Rescuing neurons from death and promoting axon regeneration through the delivery of individual neurotrophic factors (NTF) to the CNS has proved disappointing. We evaluated in vitro the potency of FGF2, NT-3, and BDNF given singly, or in combination, to trophically support retinal ganglion cells (RGC) in the presence of inhibitory CNS myelin, and demonstrated increased survival and neurite outgrowth greater than the sum of the effects of each NTF given alone. We observed...

Glucocorticoids (Gc) are potent anti-inflammatory agents, but their clinical use is limited by their significant side effects. The effects of glucocorticoids are mediated by the cytosolic glucocorticoid receptor (GR), which regulates transcription by transactivation or transrepression. Independent of these genomic effects of the GR are other, very rapid non-genomic effects.The glucocorticoid receptor forms a complex with hsp90, FKBP51, FKBP52 and cyp40 i...

The application of exogenous neurotrophins (NT) has been widely proposed as a therapeutic strategy for the recovery of regeneration in axotomised CNS neurons. Results from this approach have, however, been disappointing since limited regenerative responses are elicited, we suggest due to limited neurotrophin receptor (NTR) expression. NT exert their trophic effects by signalling through the Trk/p75 receptors. Adequate receptor expression levels must, therefore, be central to t...

Background/aims: The transcription factor neurogenin 3 (NGN3) is required for pancreatic islet cell specification from multipotent progenitor cells; yet we have limited understanding of the downstream genetic program it directly initiates. A 3 Mb centromeric region on chromosome 20p contains a number of genes activated downstream of NGN3 including INSM1 and NKX2.2. We proposed that NGN3 alters the expression of other genes within this region as poten...

Chronic pancreatitis (CP) may lead to deficiency of fat soluble vitamins such as vitamin D; little is known of the extent of this in chronic pancreatitics.In order to assess the extent and severity of vitamin D deficiency in CP we examined the notes of 111 patients with CP. In addition to clinical information and calcium, vitamin D and PTH levels, exocrine function was evaluated using the PABA test to obtain a pancreatic excretion index (PEI: normal &#62...

Glucocorticoids (GCs) are potent anti-inflammatory agents, but a variable therapeutic response occurs. We have used microarray analysis to explore the basis for inter-individual differences in the GC sensitivity of a healthy volunteer population, and identified genes predictive of response to GCs. Three such discriminating genes were then selected to be investigated for their potential to interact with the Glucocorticoid Receptor (GR). These are the Bone Morphogenetic Protein ...

The promiscuous low affinity neurotrophin co-receptor p75NTR, a member of the nerve tumor necrosis factor (TNF) receptor superfamily, mediates neuronal survival as well as death, and interacts with Trk receptors to increase their affinity for neurotrophins. Furthermore, p75NTR is the transmembrane signalling moiety which associates with the NOGO binding receptor for all CNC myelin-derived axon growth inhibitors in the injured CNS. We have shown in rats that intravitreal implan...

Aim: To evaluate the outcomes of radioactive iodine therapy (RAI) in benign thyroid disease following implementation of 2007 Royal College of Physicians (RCP) guidelines in a large NHS foundation trust.Method: The medical records of patients referred for RAI therapy at Sheffield Teaching Hospitals (UK) between 2013 and 2015 were retrospectively reviewed. Patient data was collected from patients’ notes and electronic documents system. The data record...

The incretin hormone glucagon-like peptide-1 (GLP-1) has been proposed to increase beta cell mass, via effects on proliferation, apoptosis and neogenesis. However, the role of GLP-1 during normal human development is unclear. We have addressed this in human fetuses by quantifying GLP-1 secretion during fetal development and determining how GLP-1 signalling impacts on early human fetal pancreas in explant culture.GLP-1 is first secreted by the stomach, du...