However, any drug with potential for treating diabetic complications must also have no adverse effects on the function of pancreatic islets. Thus, the goal of the current study was to assess the effect of KU-32 on the in vitro viability and function of human islets. Treating human islets with KU-32 for 24 hours showed no toxicity as assessed using the alamarBlue XL184 price assay. Confocal microscopy confirmed that with a minimum of 2-day exposure, KU-32 improved cellular viability by blocking apoptosis. Functionally, isolated human islets released
more glucose-stimulated insulin when preincubated in KU-32. However, diabetic BKS-db/db mice, a model for type 2 diabetes, administered KU-32 for 10 weeks did not show any significant changes in blood glucose and insulin
levels, despite having greater insulin staining/beta cell in the pancreas compared to untreated BKS-db/db mice. In summary, KU-32 did not harm isolated human islets and may even be protective. However, the effect does not appear significant enough to alter the in vivo metabolic parameters of diabetic mice.”
“Aims: We sought to determine the unknown effects of cardiac resynchronization therapy (CRT) in patients with a left ventricular mTOR inhibitor ejection fraction (LVEF) >35%. Because of its technical limitations, echocardiography (Echo) may underestimate LVEF, compared with cardiovascular magnetic resonance (CMR).
Methods: Of 157 patients undergoing CRT (New York Heart Association [NYHA] functional class III or IV, QRS >= 120 ms), all of whom had a preimplant Echo-LVEF HIF-1 pathway <= 35%, 130 had a CMR-LVEF <= 35% (Group A, 19.7 +/- 7.0% [mean +/- standard deviation]) and 27 had a CMR-LVEF >35% (Group B, 43.6 +/- 7.7%). All patients underwent a CMR scan at baseline and a clinical evaluation, including
a 6-minute walk test and a quality of life questionnaire, at baseline and after CRT.
Results: Both groups derived similar improvements in NYHA functional class (A = -1.3, B = -1.2, [mean]), quality of life scores (A = -21.6, B = -33.0; all P < 0.0001 for changes from baseline), and 6-minute walking distance (A = 64.5, B = 70.1 m; P < 0.001 and P < 0.0001, respectively). Symptomatic response rates (increase by >= 1 NYHA classes or 25% 6-minute walking distance) were 79% in group A and 92% in group B. Over a maxi. mum follow-up period of 5.9 years for events, patients in group A were at a higher risk of death from any cause, hospitalization for major cardiovascular events (P = 0.0232), or cardiovascular death (P = 0.0411). There were borderline differences in the risk of death from any cause (P = 0.0664) and cardiovascular death or hospitalization for heart failure (P = 0.0526).
Conclusions: This observational Study suggests that the benefits of CRT extend to patients with a LVEF >35%.