Advanced glycation end products (AGEs), which are elevated in diabetic and uremic patients, may induce vascular dysfunctions, and calcitriol may improve the cardiovascular complications. Therefore, we examined whether calcitriol may modify the endothelial response to AGEs stimulation. Knowing the importance of nuclear factor-kappaB in endothelial inflammatory responses, the effect of AGEs and calcitriol on this pathway was also studied. Calcitriol was added to endothelial cells previously incubated with AGE-human serum albumin (HSA). AGE-HSA induced a decrease in endothelial nitric oxide synthase (eNOS) mRNA expression and enzyme activity. Addition of calcitriol to AGE-HSA-treated endothelial cells improved the decreased action of AGEs on the eNOS system. AGE-HSA increased the AGEs receptor mRNA and protein, which were both blunted by calcitriol. The parallel elevation of interleukin-6 mRNA in the presence of AGE-HSA was also blunted by calcitriol. The NF-kappaB-p65 DNA binding activity was enhanced and associated with a decrease in inhibitor kappaBalpha (IkappaBalpha) and an increase in phosphorylated (p)-IkappaBalpha levels. Addition of calcitriol blunted the AGEs-induced elevation of NF-kappaB-p65 DNA binding activity, a phenomenon related to an increased expression of IkappaBalpha. This increase was correlated to declined p-IkappaBalpha levels. The present results support the concept that calcitriol may act as a vascular protective agent counteracting the probable deleterious actions of AGEs on endothelial cell activities.

The decreased NFkappaB and p38 activities followed by calcitriol treatment may explain the anti-inflammatory/atherosclerotic properties of calcitriol that were observed previously and were emphasized in this study, demonstrating the inhibitory effect of calcitriol on the pro-inflammatory parameters: adhesion molecules, RAGE and IL-6.

Malignant insulinoma usually has a poor prognosis, as no efficient medical treatment is available. The somatostatin analogs octreotide and lanreotide have limited ability to control the hypoglycemic events. Pasireotide is a multi-receptor targeted somatostatin-analog with improved affinity for ssTR5. There is to date no reported treatment experience with this drug in such tumors. CAse DesCRIPTION: A 72-year-old patient with a g2 stage Iv insulinoma, who underwent excision of the primary pancreatic tumor and multiple hepatic metastases, required further treatment for recurrent hypoglycemic events. The glycemic control achieved with pasireotide LAR was better compared with lanreotide and everolimus. however, none of these treatments showed tumor anti-proliferative effects. CONCLUsIONs: Pasireotide monthly injections achieved improved glycemic control in a patient with malignant insulinoma and recurrent hypoglycemic events compared with other medical treatments.Key words: Hypoglycemia, Insulinoma, Neuroendocrine, Pasireotide Case report HORMONES 2016, 15(2):271-276 Address for correspondence: Ilan Shimon, MD, Institute of Endocrinology, Rabin Medical Centre, Beilinson Campus, Petah Tiqva, 4941492, Israel; Tel.: +972-54-5749044, Fax: +972-3-9211403, E-mail: ilanshi@clalit.org.il Received: 25-08-201525-08- , Accepted: 29-10-2015 CAse RePORTWe report a 72-year-old male presenting with recurrent fainting episodes. His medical history is unremarkable except for well-controlled hypertension and dyslipidemia. The patient had experienced recurrent fainting episodes, suspected as being syncope, between 2005 and 2010. After the patient complained of severe pre-lunch hunger, blood glucose monitoring was initiated, revealing recurrent hypoglycemia as low as 60 mg/dl (3.3 mmol/l). A subsequent inpatient 72-hour fasting test failed to reproduce the hypoglycemia.In July 2012, the patient fainted at home, at which point his capillary glucose level was 25 mg/dl (1.4 mmol/l). The patient regained consciousness following a bolus of 50% dextrose solution and was then hospitalized. C-peptide levels of 3.4 ng/ml and serum insulin of 14.4 mIU/ml were observed during an in-house hypoglycemic event (40 mg/dl, 2.2 mmol/l). The patient and his spouse denied use of insulin secretagogs and no serum anti-insulin antibodies were detected, thus a diagnosis of endogenous hyperinsulinism was made.

The addition of colchicine to prednisone in patients admitted for acute idiopathic pericarditis does not reduce the risk of recurrence. This finding suggests that prednisone blunts the salutary effects of colchicine.