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Advanced glycation end products (AGEs) are mediators in the process of cellular dysfunction in response to hyperglycemia. Numerous data indicate that the accumulation of AGEs in the extracellular matrix plays a key role in the development of obesity-related adipose tissue dysfunction. Through binding of their membrane receptor (RAGE), AGEs affect numerous intracellular pathways and impair adipocyte differentiation, metabolism, and secretory activity. Therefore, inhibiting the production and accumulation of AGEs, as well as interfering with the metabolic pathways they activate, may be a promising therapeutic strategy for restoring normal adipose tissue function and, thus, combating obesity-related comorbidities. This narrative review summarizes data on the involvement of the RAGE pathway in adipose tissue dysfunction in obesity and the development of its metabolic complications. The paper begins with a brief review of AGE synthesis and the RAGE signaling pathway. The effect of the RAGE pathway on adipose tissue development and activity is then presented. Next, data from animal and human studies on the involvement of the RAGE pathway in obesity, diabetes, and cardiovascular diseases are summarized. Finally, therapeutic perspectives based on interference with the RAGE pathway are discussed.

Background: Treatment with glucocorticoids (GCs) is associated with side effects. In contrast to the well-known negative impact on bone tissue exerted by oral GCs, few data are available regarding intravenous GCs. We investigated the influence of intravenous methylprednisolone (IVMP) on bone turnover markers (BTM): amino-terminal propeptide of type I procollagen (P1NP) and the C-terminal telopeptide of type I collagen (CTX), and on calcium metabolism parameters: 1,25-dihydroxyvitamin D (1,25(OH)2D), 25-hydroxyvitamin D (25(OH)D), calcium (Ca), phosphate (P), and intact parathormone (iPTH). Methods: In a prospective study, 23 consecutive subjects with Graves’ orbitopathy were included and treated with IVMP according to the European Group on Graves’ Orbitopathy recommendations. We evaluated effects on BTM occurring during the first 7 days after 0.5 g IVMP, and after the therapy with 12 IVMP pulses with a cumulative dose of 4.5 g. Results: We observed prompt but transient decrease of P1NP (p < 0.001) and the reduction of CTX (p = 0.02) after the first IVMP pulse. Following the full course of IVMP therapy, both P1NP and CTX were found decreased (p < 0.05 and p < 0.01, respectively). Conclusions: A single pulse of 0.5 g IVMP already decreases bone formation and resorption; however, this change is transient. The full therapy is associated with suppression of bone turnover.

ABSTRACT Background: Intravenous glucocorticoids pulses administration is the main therapeutic option in the treatment of Graves’ orbitopathy. Such therapy could relate to the multiple adverse effects. The aim of the study is evaluation the influence of intravenous methylprednisolone (IVMP) pulse therapy on the heart rhythm (HR) changes in patients with active, moderate-to-severe Graves’ Orbitopathy (GO). Methods: We studied 20 patients with moderate-to-severe GO. All patients received 12 IVMP pulses (6x500 mg plus 6x250mg) at equal time intervals in a weekly schedule. We performed Holter ECG monitoring for 3 consecutive days (the day before, the day of IVMP and day after IVMP) to monitor HR and arrhythmias. We compared changes in HR between these 3 days and set time interval when the alteration was significant. This evaluation was performed during the 1st, 6th and 12th IVMP pulse. Results: Increased HR, in comparison with the day before, was registered on the day of IVMP administration. The most significant increase in HR started 5 hours (h) after a pulse administration and lasted 12 h. There were no significant differences in HR between the day before and the day after IVMP. We did not notice any major adverse cardiac events including severe arrhythmias. Conclusions: IVMP therapy is associated with increased HR, that occurs a few hours after infusion, lasts several hours and is transient.  Keywords: Graves’ ophthalmopathy; Graves’ disease; glucocorticoids; heart rate

Introduction. Somatostatin analogs (SSA) are widely used in the treatment of patients with well-differentiated neuroendocrine tumors (NET). There are limited reports about the role of octreotide LAR in first-line therapy of advanced pancreatic NET (pan-NET). This study aimed to evaluate the antiproliferative effect of octreotide LAR in patients with sporadic, advanced, unresectable pan-NET, based on progression-free survival (PFS).Material and methods. This was a retrospective analysis of 374 patients with pan-NET; 41 treated subjects were included. The primary endpoint was PFS defined as the time to disease progression (Response Evaluation Criteria in Solid Tumors: RECIST). Univariate and multivariate analyses were used to identify predictors of PFS. Secondary endpoints included overall survival (OS) and second-line therapies after progression.Results. There were 13 (32%) patients with G1 pan-NET and 28 (68%) with pan-NET G2, 21 female and 20 male, with mean age 55.4 (range 29-87). Median PFS was 9.0 months (95% CI 4.7-24.0). Subgroup analysis revealed that G1 and no-bulky liver disease (< 25% liver volume) were associated with significantly longer PFS. Univariate analysis confirmed a correlation between G1 [0.34 hazard rate (HR) of progression or death (95% CI 0.16-0.72)] and no-bulky liver disease HR = 0.31 (95% CI 0.13-0.71). Multivariable analysis demonstrated that only functional (secretory) pan-NET was associated as an independent factor with shorter PFS HR = 2.97 (95% CI 1.0-8.74).Median OS was 105.4 months (95% CI 40.0-172.0). After relapse following initial systemic therapy, the second line was used in 34 subjects, 3rd line in 18th, and 4th line in 9 subjects. Conclusions.Octreotide LAR shows moderate antiproliferative activity in pan-NET. Prolonged PFS may be associated with G1 and low-volume metastatic liver disease. In patients with progressive disease, various treatment options were used, which resulted in median OS of 105.4 months.