Efficacy and safety of canagliflozin when used in conjunction with incretin-mimetic therapy in patients with type 2 diabetes

Aims: To assess the efficacy and safety of canagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, in patients with type 2 diabetes enrolled in the CANagliflozin cardioVascular Assessment Study (CANVAS) who were on an incretin mimetic [dipeptidyl peptidase-4 (DPP-4) inhibitor or glucagon-like peptide-1 (GLP-1) receptor agonist]. Methods: CANVAS is a double-blind, placebo-controlled study that randomized participants to canagliflozin 100 or 300 mg or placebo added to routine therapy. The present post hoc analysis assessed the efficacy and safety of canagliflozin 100 and 300 mg compared with placebo in subsets of patients from CANVAS who were taking background DPP-4 inhibitors or GLP-1 receptor agonists with or without other antihyperglycaemic agents at week 18. Results: Of the 4330 patients in CANVAS, 316 were taking DPP-4 inhibitors and 95 were taking GLP-1 receptor agonists. At 18 weeks, canagliflozin 100 and 300 mg provided larger placebo-subtracted reductions in glycated haemoglobin (HbA1c) in patients taking DPP-4 inhibitors [-0.56% (95% confidence interval [CI]: -0.77, -0.35), and -0.75% (95% CI: -0.95, -0.54), respectively] and GLP-1 receptor agonists [-1.00% (95% CI: -1.35, -0.65), and -1.06% (95% CI: -1.43, -0.69), respectively]. Body weight and blood pressure (BP) reductions were seen with canagliflozin versus placebo in both subsets. Higher incidences of genital mycotic infections and osmotic diuresis-related adverse events (AEs) were seen with canagliflozin compared with placebo. The incidence of hypoglycaemia was numerically higher with canagliflozin versus placebo; nearly all events occurred in patients on background insulin or insulin secretagogues. Conclusions: In patients on background incretin mimetics, canagliflozin improved HbA1c, body weight and BP, with an increased incidence of AEs related to SGLT2 inhibition

EFFECTS OF HELPER AND REGULATORY CELLS UPON PHENOTYPIC COMPOSITION OF BLOOD B LYMPHOCYTES AND THYROID GLAND IN GRAVES’ DISEASE

The aim of this work was a comparative study of the helper- (Th cells) and regulatory T cells (Treg) effects upon the phenotypic composition of B lymphocytes in blood and thyroid tissue in Graves’ disease (GD). 43 women with GD were examined. The diagnosis of GD was based on clinical and laboratory signs of the disease: complaints, clinical picture of the thyrotoxicosis with objective examination, characteristic sonographic changes in thyroid gland, as well as elevated titers of antibodies to thyroid-stimulating hormone receptor in blood serum, and corresponding changes in thyroid status. 67 practically healthy women were examined as a control. The studies of Th cells, Treg and B lymphocytes phenotypes in blood and thyroid tissue were carried out by flow cytometry using direct immunofluorescence, respectively, in whole peripheral blood and lymphocytes isolated from thyroid tissue. The relative amounts of Tregs in thyroid gland from the patients with GD corresponds to their level in the blood. We did not find any changes in the content of blood T helpers expressing vs. non-expressing CD25 receptors, as compared to the control values. In patients with GD, an increased B1 cells content was revealed in peripheral blood. The percentage of this B cell subpopulation in thyroid tissue is reduced when compared to the levels found in blood, but with increased memory B cells contents. The number of activated B lymphocytes (by CD23 marker) in blood of patients with GD is reduced when compared to control values. It was found that, in thyroid tissue, there is an even more pronounced decrease in the relative amount of activated B cells compared to the levels detected in blood from these patients. By means of correlation analysis, it was found that increase in activated B lymphocytes in blood from controls is accompanied by a co-directional reaction from Treg (the usual immunoregulatory process). In Graves’ disease, such a relationship was not found. The amounts of Treg and activated T helper cells in blood of the patients did positively correlate with common B lymphocytes, B2 cells and na ve B lymphocytes. Meanwhile, Treg’s in thyroid tissue, were completely excluded from the system of interactions with activated B lymphocytes. It is assumed that a decrease in Treg’s content in peripheral blood, along with altered functional activity is observed in patients with GD

Researches of the category in system of electrodes a needle – a plane at the raised pressure of air (cathode directional a streamer)

Была разработана и построена экспериментальная установка, выполнены научные исследования пространственно-временных характеристик стримера для различных газовых разрядов. Используя эту установку, выполнены экспериментальные исследования динамики стримера в неоднородном электрическом пространстве и при высоком давлении воздуха. В результате обработки компьютером экспериментальных данных были получены зависимости скорости распространения стримера по разрядному промежутку при различных давлениях в воздухе. Для этого использовались прикладные программы. Характер изменения скорости стримера по разрядному промежутку рассчитан для неустойчивого фронта стримера. Анализ экспериментальных результатов, где скорость стримера и ее максимальная длина были уменьшены с увеличением давления, позволяет сделать выводы, что для высоких давлений имеет место существенное уменьшение проводимости канала плазмы стримера.У результаті обробки комп'ютером експериментальних даних були отримані залежності швидкості поширення стримера по розрядному проміжку при різних тисках у повітрі. Характер зміни швидкості стримера по розрядному проміжку розрахований для нестійкого фронту стримераAs a result of the computer processing of the experimental data the dependence of streamer velocity during discharge gap from different gas pressures were obtained. The nature of streamer velocity modification in the discharge gap is accounted for the instability of streamer front