Many anti-diabetic drugs with different mechanisms of action are now available for treatment of type 2 diabetes mellitus. Sulfonylureas have been extensively used for treatment of type 2 diabetes for nearly 50 years and, even in our times, are widely used for treatment of this devastating chronic illness. Here, we review some of the available data on sulfonylureas, evaluating their mechanism of action and their effects on glycemic control. We can conclude that sulfonylureas are still the most used anti-diabetic agents: maybe this is due to their lower cost, to the possibility of mono-dosing and to the presence of an association with metformin in the same tablet. However, sulfonylureas, especially the older ones, are linked to a greater prevalence of hypoglycemia, and cardiovascular risk; newer prolonged-release preparations of sulfonylureas are undoubtedly safer, mainly due to reducing hypoglycemia, and for this reason should be preferred.

GAS6 protein has been described to be involved in immune modulation in vitro and in vivo. Some of these effects are probably mediated through the involvement of monocytes/macrophages. To understand the role of GAS6 in modulating the immune response, we evaluated the effect on cytokine secretion by monocytes/ macrophages and the molecular pathways involved. GAS6 inhibits TNF-␣ and IL-6 secretion by LPS-stimulated U937 cells and monocytes/machrophages. We evidenced that among GAS6 receptors, only Mer (but not Axl or Tyro3) is expressed on differentiated U937 cells, and its activation is responsible for the reduction of cytokine expression. In immunoblot analysis, Mer was activated after GAS6 stimulation, giving rise to an increased phosphorylation of Akt. We also observed GSK3␤ phosphorylation and consequent inhibition of NF-B nuclear translocation. Therefore, GAS6 modulates macrophage cytokine secretion, triggering an "anti-inflammatory pathway" involving PI3K/Akt/GSK3␤ and NF-B.

BackgroundTransorbital sonography (TOS) has been proven to be able to non-invasively detect elevated intracranial pressure. In this condition TOS shows an increase in optic nerve sheath diameter (ONSD). It has been suggested that internal jugular vein valve insufficiency (IJVVI) may represent a factor contributing to the pathogenesis of idiopathic intracranial hypertension (IIH). The aim of this study was to investigate whether patients with IIH or secondary IH have higher ONSD values and higher frequency of IJVVI compared to subjects without IH.MethodsTwenty-one patients with newly diagnosed IIH or secondary IH were prospectively evaluated and compared with 21 age, gender and BMI-matched controls. Experienced vascular sonographers used B-mode TOS to evaluate ONSD, optic nerve diameter (OND) and IJVVI. CSF opening pressures were also measured.ResultsONSD values were significantly higher in patients (6.50 ± 0.67) than controls (5.73 ± 0.66; p < 0.0001). No differences were found in OND values between patients (2.99 ± 0.26) and controls (2.93 ± 0.41; p = 0.574). No correlation was demonstrated between ONSD and CSF opening pressure (r = 0,086) (p = 0.73). No difference in frequency of IJVVI between patients (11/42 valves, 26 %) and controls (9/42, 21 %) was observed (p = 0.777).ConclusionsIncreased ONSD values detected by TOS support the diagnosis of IH. Our results do not support the hypothesis of a venous congestion as a potential factor contributing to the pathogenesis of IIH.Trial registrationNot applicable. Observational, non-interventional study.Electronic supplementary materialThe online version of this article (doi:10.1186/s12883-016-0594-3) contains supplementary material, which is available to authorized users.

The association between cancer and immune-mediated rheumatic conditions is controversial, especially as far as polymyalgia rheumatica (PMR) is concerned. Furthermore, no clinical feature has been shown to be suggestive of a paraneoplastic rheumatic syndrome. With the present study, we aim to address both these issues. The study population comprised N = 1750 patients, including N = 100 with PMR, who attended our tertiary immuno-rheumatology clinic between January 1, 2005 and November 30, 2012. A rheumatic disease was deemed paraneoplastic if cancer had been diagnosed in the 2 years preceding or following its onset. The probability of a significant association between a specific rheumatic disease and cancer was evaluated by computing the odds ratio (OR): N = 702 patients with osteoarthritis serving as controls. Furthermore, clinical features distinguishing paraneoplastic rheumatic diseases were searched for by univariate and multivariate analysis. Sjogren's syndrome (SS) [OR 3.6 (CI 95% 1.7-7.5)], PMR (OR 5.1 CI 95% 2.9-8.9), dermatomyositis/polymyositis [OR 12.09 (CI 95% 2.6-55.8)] and vasculitis [OR 3.70 (CI 95% 1.81-7.52)] are associated with cancer. At multivariate analysis, older age is associated with cancer among SS patients (p = 0.03), while in the PMR group, older age, male gender, and ≥6 tender joints are independent predictors of paraneoplastic PMR (p < 0.0004). Cancer frequently either heralds or follows rheumatic manifestations, including PMR. Older age, male gender and a more extensive joint involvement should be considered red flags for paraneoplastic PMR.