Perforated gastric ulcer as the initial manifestation of hyperparathyroidism

Primary hyperparathyroidism is characterised by autonomous production of parathyroid hormone resulting in hypercalcaemia. It is estimated that 12% of these patients present with peptic ulcer-related symptoms. The pathophysiological mechanism is not well established, but studies reveal serum calcium activating gastrin cell calcium receptors ultimately resulting in increased gastric acid production leading to peptic ulcer disease. A patient presented acutely to our service with peptic ulcer perforation in the context of incidentally elevated serum calcium levels. Further inpatient investigations lead to the diagnosis of primary hyperparathyroidism as the first manifestation of this patient’s disease.

Manganese-enhanced MRI (MEMRI) in breast and prostate cancers: exploring the potential role of calcium receptors

ABSTRACTProceduresTo assess the relationship between Manganese Enhanced Magnetic Resonance Imaging (MEMRI) and the expression of calcium receptors in human prostate and breast cancer animal models.MethodsNOD/SCID mice were inoculated with MDA-MB-231 breast cancer cells and prostate PC3 cancer cells to develop orthotopic or pseudometastatic cancer animal models. Mice were studied on a clinical 3T scanner by using a prototype birdcage coil before and after intravenous injection of MnCl2. Assessment of receptor’s status was carried out after the MR images acquisition by immunohistochemistry on excised tumours.ResultsManganese contrast enhancement in breast or prostate cancer animal models well correlated with CaSR expression (p<0.01), whereas TRPV6 expression levels appeared not relevant to the Mn uptake.ConclusionMEMRI appears an efficient tool to characterize human breast and prostate cancer animal models in the presence of different expression level of CaSR.

Calcium receptors located in fibrotic septa: a new target to reduce portal pressure in liver cirrhosis

In rats with experimental liver cirrhosis, the kidney contains reduced amounts of membrane-bound CaRs (calcium-sensing receptors), and the specific stimulation of CaRs causes the generation of PGE2 (prostaglandin E2), renal vasodilation and increased natriuresis. CaR content and function in the liver of cirrhotic rats are unknown. To assess the activity of this Ca2+-dependent vasomotor system, we evaluated the effects of intravenous administration of PolyAg (poly-L-arginine), a selective CaR agonist, on hormonal status, portal haemodynamics, MAP (mean arterial pressure) in rats with liver cirrhosis induced by chronic CCl4 (carbon tetrachloride) administration. Two groups of eight control rats received intravenously 1 ml of 5% (w/v) glucose solution alone or containing 0.5 mg of PolyAg; two groups of ten cirrhotic rats were administered vehicle or PolyAg. Compared with controls, at baseline cirrhotic rats showed higher portal pressure (P<0.01), lower estimated functional liver plasma flow, measured as CICG (Indocyanine Green clearance) (P<0.03) and reduced hepatic protein content of CaRs (P<0.03), which were located mainly in sub-endothelial layers of portal venules and in myofibroblasts of fibrotic septa (immunohistochemistry and indirect immunofluorescence staining of liver sections). In cirrhotic animals, 0.5 mg of PolyAg decreased portal pressure (P<0.01) and increased CICG (P<0.05), without effects on arterial pressure and hormonal status. In conclusion, the present study provides evidence that in experimental cirrhosis agonists of liver CaRs elicit beneficial portal hypotensive effects by reducing intrahepatic resistance to portal flow. Moreover, these drugs are devoid of effects on systemic haemodynamics.

A case of severe neonatal hyperparathyroidism due to defect in calcium receptors

The first case of severe neonatal hyperparathyroidism in the Russian population verified by molecular-genetic testing is described. The patient presented with very high calcium and parathyroid hormone (PTH) levels and showed characteristic clinical symptoms of hyperparathyroidism in the absence of lesions in long tubular bones. Removal of all parathyroid glands resulted in normalization of laboratory parameters and general health status of the patient. Diagnosis of severe neonatal hyperparathyroidism was confirmed by sequencing the CASR gene while parents of the child were shown to suffer familial hypocalciuric hypercalcemia.