Optimizing glycemic control: clinical utility of exenatide prolonged release injection

Giuseppe Derosa, Pamela MaffioliDepartment of Internal Medicine and Therapeutics, University of Pavia, Fondazione IRCCS Policlinico S Matteo, Pavia, ItalyAbstract: Despite the large variety of antidiabetic drugs currently available, reaching an adequate glycemic control is still difficult. Recently, a new exenatide long acting release (LAR) formulation, which can be administered once a week, has been released. We conducted a review analyzing the clinical utility of this new formulation and its place in antidiabetic therapy, and included the most important studies about exenatide LAR in the latest 10 years. A systematic search strategy was developed to identify randomized controlled trials in both MEDLINE and the Cochrane Register of Controlled Trials. The terms "exenatide," "exenatide long active release," "GLP-1 agonists," "incretins," and "glycemic control" were incorporated into an electronic search strategy that included the Dickersin filter for randomized controlled trials. We concluded that exenatide LAR can be a valid option for the treatment of type 2 diabetes mellitus because it showed to be effective in reducing HbA1c, and because of its pleiotropic effects, such as the reduction of blood pressure, the improvement of the patient's lipid profile, and the positive effects on body weight and β-cell function. Moreover, exenatide LAR has demonstrated a favorable cost/effectiveness ratio, and its once weekly administration may help to increase patient compliance.Keywords: β-cell, body weight, exenatide long acting release, glycemic contro

Optimizing glycemic control: clinical utility of exenatide prolonged release injection

Giuseppe Derosa, Pamela MaffioliDepartment of Internal Medicine and Therapeutics, University of Pavia, Fondazione IRCCS Policlinico S Matteo, Pavia, ItalyAbstract: Despite the large variety of antidiabetic drugs currently available, reaching an adequate glycemic control is still difficult. Recently, a new exenatide long acting release (LAR) formulation, which can be administered once a week, has been released. We conducted a review analyzing the clinical utility of this new formulation and its place in antidiabetic therapy, and included the most important studies about exenatide LAR in the latest 10 years. A systematic search strategy was developed to identify randomized controlled trials in both MEDLINE and the Cochrane Register of Controlled Trials. The terms “exenatide,” “exenatide long active release,” “GLP-1 agonists,” “incretins,” and “glycemic control” were incorporated into an electronic search strategy that included the Dickersin filter for randomized controlled trials. We concluded that exenatide LAR can be a valid option for the treatment of type 2 diabetes mellitus because it showed to be effective in reducing HbA1c, and because of its pleiotropic effects, such as the reduction of blood pressure, the improvement of the patient's lipid profile, and the positive effects on body weight and β-cell function. Moreover, exenatide LAR has demonstrated a favorable cost/effectiveness ratio, and its once weekly administration may help to increase patient compliance.Keywords: β-cell, body weight, exenatide long acting release, glycemic contro

The Influence of Spatial Resolution on Nonlinear Force-Free Modeling

The nonlinear force-free field (NLFFF) model is often used to describe the solar coronal magnetic field, however a series of earlier studies revealed difficulties in the numerical solution of the model in application to photospheric boundary data. We investigate the sensitivity of the modeling to the spatial resolution of the boundary data, by applying multiple codes that numerically solve the NLFFF model to a sequence of vector magnetogram data at different resolutions, prepared from a single Hinode/SOT-SP scan of NOAA Active Region 10978 on 2007 December 13. We analyze the resulting energies and relative magnetic helicities, employ a Helmholtz decomposition to characterize divergence errors, and quantify changes made by the codes to the vector magnetogram boundary data in order to be compatible with the force-free model. This study shows that NLFFF modeling results depend quantitatively on the spatial resolution of the input boundary data, and that using more highly resolved boundary data yields more self-consistent results. The free energies of the resulting solutions generally trend higher with increasing resolution, while relative magnetic helicity values vary significantly between resolutions for all methods. All methods require changing the horizontal components, and for some methods also the vertical components, of the vector magnetogram boundary field in excess of nominal uncertainties in the data. The solutions produced by the various methods are significantly different at each resolution level. We continue to recommend verifying agreement between the modeled field lines and corresponding coronal loop images before any NLFFF model is used in a scientific setting.Comment: Accepted to ApJ; comments/corrections to this article are welcome via e-mail, even after publicatio

Effect of manidipine-simvastatin combination on fibrinolysis, adhesion molecules and C-reactive protein in hypertensive hypercholesterolemic patients

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Rosiglitazone and glimeperide: review of clinical results supporting a fixed dose combination

Type 2 diabetes has become a major burden to the health care systems worldwide. Among the drugs approved for this indication, glimepiride and rosiglitazone have gained substantial importance in routine use. While glimepiride stimulates β-cell secretion and leads to reduction of blood glucose values, rosiglitazone activates PPARγ and improves insulin resistance, at the vascular and metabolically active cells. Therefore, the combination of the two drugs may be an interesting approach to improve glycemic control and lower cardiovascular risk. A fixed combination of both drugs has been approved for clinical use in the US and EU. The combination of glimepiride and rosiglitazone is generally well tolerated and the use of a fixed combination may lead to improved adherence of the patients to their therapy. The purpose of this review is to evaluate the clinical data that have been published on this combination, appearing to represent a convenient way to obtain therapeutic targets in patients with type 2 diabetes mellitus

Identification and visualization of multidimensional antigen-specific T-cell populations in polychromatic cytometry data.

An important aspect of immune monitoring for vaccine development, clinical trials, and research is the detection, measurement, and comparison of antigen-specific T-cells from subject samples under different conditions. Antigen-specific T-cells compose a very small fraction of total T-cells. Developments in cytometry technology over the past five years have enabled the measurement of single-cells in a multivariate and high-throughput manner. This growth in both dimensionality and quantity of data continues to pose a challenge for effective identification and visualization of rare cell subsets, such as antigen-specific T-cells. Dimension reduction and feature extraction play pivotal role in both identifying and visualizing cell populations of interest in large, multi-dimensional cytometry datasets. However, the automated identification and visualization of rare, high-dimensional cell subsets remains challenging. Here we demonstrate how a systematic and integrated approach combining targeted feature extraction with dimension reduction can be used to identify and visualize biological differences in rare, antigen-specific cell populations. By using OpenCyto to perform semi-automated gating and features extraction of flow cytometry data, followed by dimensionality reduction with t-SNE we are able to identify polyfunctional subpopulations of antigen-specific T-cells and visualize treatment-specific differences between them

Identification of IMDC intermediate-risk subgroups in patients with metastatic clear-cell renal cell carcinoma (ccRCC).

e16577Background: Majority of patients (pts) with ccRCC at first line (1L) treatment are classified in the IR subgroup according to International Metastatic Renal Cell Carcinoma Database Consortium..