Patient-level meta-analysis of the EDITION 1, 2 and 3 studies: glycaemic control and hypoglycaemia with new insulin glargine 300 U/ml versus glargine 100 U/ml in people with type 2 diabetes.

AIMS: To conduct a patient-level meta-analysis of the EDITION 1, 2 and 3 studies, which compared the efficacy and safety of new insulin glargine 300 U/ml (Gla-300) with insulin glargine 100 U/ml (Gla-100) in people with type 2 diabetes (T2DM) on basal and mealtime insulin, basal insulin and oral antihyperglycaemic drugs, or no prior insulin, respectively. METHODS: The EDITION studies were multicentre, randomized, open-label, parallel-group, phase IIIa studies, with similar designs and endpoints. A patient-level meta-analysis of the studies enabled these endpoints to be examined over 6 months in a large population with T2DM (Gla-300, n = 1247; Gla-100, n = 1249). RESULTS: No significant study-by-treatment interactions across studies were found, enabling them to be pooled. The mean change in glycated haemoglobin was comparable for Gla-300 and Gla-100 [each -1.02 (standard error 0.03)%; least squares (LS) mean difference 0.00 (95% confidence interval (CI) -0.08 to 0.07)%]. Annualized rates of confirmed (≤3.9 mmol/l) or severe hypoglycaemia were lower with Gla-300 than with Gla-100 during the night (31% difference in rate ratio over 6 months) and at any time (24 h, 14% difference). Consistent reductions were observed in percentage of participants with ≥1 hypoglycaemic event. Severe hypoglycaemia at any time (24 h) was rare (Gla-300: 2.3%; Gla-100: 2.6%). Weight gain was low (<1 kg) in both groups, with less gain with Gla-300 [LS mean difference -0.28 kg (95% CI -0.55 to -0.01); p = 0.039]. Both treatments were well tolerated, with similar rates of adverse events. CONCLUSION: Gla-300 provides comparable glycaemic control to Gla-100 in a large population with a broad clinical spectrum of T2DM, with consistently less hypoglycaemia at any time of day and less nocturnal hypoglycaemia.

[Regulating activity of plasma membranous Ca2+ channels in PC-12 pheochromocytoma cells with chemicals and pharmaceutic agents]. / Reguliatsiia aktivnosti Ca2+-kanalov plazmaticheskikh membran kletok feokhromotsitomy PC-12 s pomoshch'iu khimicheskikh soedinenii i farmakologicheskikh agentov.

The activity of the voltage-operated Ca2+ channels (VOC channels) and store-operated Ca(2+)-channels (SOC channels) was studied on rat pheochromatocytomic cells PC-12 by using the fluorescence calcium dye Fura-2. The VOC channels were transferred in their open state by depolarizing the plasma membranes of the cells through addition of high KCl concentrations (50 mM). The SOC channels were activated by treating the cells with tapsigargine, a special inhibitor of Ca2+ ATPase in the intracellular Ca2+ stores. Verapamil effectively inhibited the activity of the VOC channels (IC50 = 0.6 micron), but failed to affect the SOC channels. Arachidonic acid reduced the level of [Ca2+]-induced TG (200 nM) at a concentration of 3-10 microns). The movement of Ca2+ along the SOC channels was electrogenic. The depolarization of the plasma membrane of PC-12 cells caused no release of Ca(2+) from the intercellular Ca2+ stores. It is concluded that PC-12 cells are a suitable model to study the activity of different Ca2+ channels and search for chemical compounds that affect the potential-dependent and potential-independent Ca2+ channels.

[The effect of sodium nitroprusside and nitro-containing vasodilators on rat liver microsomal mono-oxygenases]. / Vliianie nitroprussida natriia i nitrosoderzhashchikh vazodilatatorov na mikrosomnye monooksigenazy pecheni krys.

It has been shown in vitro that sodium nitroprusside (SN) causes a concentration-dependent suppression of the enzymatic activity of aminopyridine demethylase-APDM(IC50 = 1.86 x 10(-4) M) and ethoxycoumarin O-deethylase-ECOD(IC50 = 1.46 x 10(-4) M) in hepatic microsomes of Wistar rats, which is related to different isoforms of cytochrome P-450. The inhibiting effect of other nitro compounds (nitroglycerin and isosorbide dinitrate) in relation to APDM is less marked than that of SN. These compounds have practically no effect on ECOD activity. It is assumed that the degree of the inhibiting effect of SN, nitroglycerin, and isosorbide dinitrate is connected with the mechanism of NO release.