Novartis

About: Novartis is a company organization based out in Basel, Switzerland. It is known for research contribution in the topics: Alkyl & Population. The organization has 41930 authors who have published 50566 publications receiving 1978996 citations. The organization is also known as: Novartis International AG.

Dual bronchodilation with QVA149 versus single bronchodilator therapy: the SHINE study

Abstract: We investigated the efficacy and safety of dual bronchodilation with QVA149 versus its monocomponents indacaterol and glycopyrronium, tiotropium and placebo in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD). This was a multicentre, randomised, double-blind, placebo- and active-controlled, 26-week trial. Patients (n = 2144) were randomised (2:2:2:2:1) to receive once-daily QVA149 (indacaterol 110 μg/glycopyrronium 50 μg), indacaterol 150 μg, glycopyrronium 50 μg, open-label tiotropium 18 μg or placebo. The primary end-point was trough forced expiratory volume in 1 s (FEV1) at week 26 for QVA149 versus its monocomponents. Secondary end-points included dyspnoea, health status, rescue medication use and safety. Trough FEV1 at week 26 was significantly improved (p<0.001) with QVA149 compared with indacaterol and glycopyrronium (least squares mean (LSM) differences 0.07 L and 0.09 L, respectively), tiotropium and placebo (LSM differences 0.08 L and 0.20 L, respectively); these beneficial effects were sustained throughout the 26-week study. QVA149 significantly improved dyspnoea and health status versus placebo (p<0.001 and p = 0.002, respectively) and tiotropium (p = 0.007 and p = 0.009, respectively) at week 26. All treatments were well tolerated. Dual bronchodilation with once-daily QVA149 demonstrated superior and clinically meaningful outcomes versus placebo and superiority versus treatment with a single bronchodilator, with a safety and tolerability profile similar to placebo, supporting the concept of fixed-dose long-acting muscarinic antagonist/long-acting β2-agonist combinations for the treatment of COPD.

Vildagliptin, a Dipeptidyl Peptidase-IV Inhibitor, Improves Model-Assessed β-Cell Function in Patients with Type 2 Diabetes

Abstract: Aims/Hypothesis: The dipeptidyl peptidase IV inhibitor, vildagliptin, increases levels of intact glucagon-like peptide-1 (GLP-1) and improves glycemic control in patients with type 2 diabetes. Although GLP-1 is known to stimulate insulin secretion, vildagliptin does not affect plasma insulin levels in diabetic patients, suggesting that more sophisticated measures are necessary to ascertain the influence of vildagliptin on β-cell function. Methods: This study examined the effects of 28-d treatment with vildagliptin (100 mg, twice daily; n = 9) vs. placebo (n = 11) on β-cell function in diabetic patients using a mathematical model that describes the insulin secretory rate as a function of glucose levels (β-cell dose response), the change in glucose with time (derivative component), and a potentiation factor, which is a function of time and may reflect the actions of nonglucose secretagogues and other factors. Results: Vildagliptin significantly increased the insulin secretory rate at 7 mmol/liter glucose (s...

Prediction of the Localization of High-Risk Coronary Atherosclerotic Plaques on the Basis of Low Endothelial Shear Stress An Intravascular Ultrasound and Histopathology Natural History Study

Abstract: Background— Low endothelial shear stress (ESS) promotes the development of atherosclerosis; however, its role in the progression of atherosclerotic plaques and evolution to inflamed high-risk plaques has not been studied. Our hypothesis was that the lowest values of ESS are responsible for the development of high-risk coronary atherosclerotic plaques associated with excessive expansive remodeling. Methods and Results— Twenty-four swine, treated with streptozotocin to induce diabetes and fed a high-fat diet, were allocated into early (n=12) and late (n=12) atherosclerosis groups. Intima-media thickness was assessed by intravascular ultrasound in the coronary arteries at weeks 4 and 8 in the early group and weeks 23 and 30 in the late group. Plaques started to develop after week 8, leading to marked heterogeneity in plaque severity at week 30. ESS was calculated in plaque-free subsegments of interest (n=142) in the late group at week 23. Coronary arteries (n=31) of this group were harvested at week 30, and ...

Dynamic expression of de novo DNA methyltransferases Dnmt3a and Dnmt3b in the central nervous system

Abstract: To explore the role of DNA methylation in the brain, we examined the expression pattern of de novo DNA methyltransferases Dnmt3a and Dnmt3b in the mouse central nervous system (CNS). By comparing the levels of Dnmt3a and Dnmt3b mRNAs and proteins in the CNS, we showed that Dnmt3b is detected within a narrow window during early neurogenesis, whereas Dnmt3a is present in both embryonic and postnatal CNS tissues. To determine the precise pattern of Dnmt3a and Dnmt3b gene expression, we carried out X-gal histochemistry in transgenic mice in which the lacZ marker gene is knocked into the endogenous Dnmt3a or Dnmt3b gene locus (Okano et al. [1999] Cell 99:247-257). In Dnmt3b-lacZ transgenic mice, X-gal-positive cells are dispersed across the ventricular zone of the CNS between embryonic days (E) 10.5 and 13.5 but become virtually undetectable in the CNS after E15.5. In Dnmt3a-lacZ mice, X-gal signal is initially observed primarily in neural precursor cells within the ventricular and subventricular zones between E10.5 and E17.5. However, from the newborn stage to adulthood, Dnmt3a X-gal signal was detected predominantly in postmitotic CNS neurons across all the regions examined, including olfactory bulb, cortex, hippocampus, striatum, and cerebellum. Furthermore, Dnmt3a signals in CNS neurons increase during the first 3 weeks of postnatal development and then decline to a relatively low level in adulthood, suggesting that Dnmt3a may be of critical importance for CNS maturation. Immunocytochemistry experiments confirmed that Dnmt3a protein is strongly expressed in neural precursor cells, postmitotic CNS neurons, and oligodendrocytes. In contrast, glial fibrillary acidic protein-positive astrocytes exhibit relatively weak or no Dnmt3a immunoreactivity in vitro and in vivo. Our data suggest that whereas Dnmt3b may be important for the early phase of neurogenesis, Dnmt3a likely plays a dual role in regulating neurogenesis prenatally and CNS maturation and function postnatally.