1,405 research outputs found
Effect of Oral Semaglutide Compared With Placebo and Subcutaneous Semaglutide on Glycemic Control in Patients With Type 2 Diabetes: A Randomized Clinical Trial.
Importance: Glucagon-like peptide-1 (GLP-1) receptor agonists are effective therapies for the treatment of type 2 diabetes and are all currently available as an injection.
Objectives: To compare the effects of oral semaglutide with placebo (primary) and open-label subcutaneous semaglutide (secondary) on glycemic control in patients with type 2 diabetes.
Design, Setting, and Patients: Phase 2, randomized, parallel-group, dosage-finding, 26-week trial with 5-week follow-up at 100 sites (hospital clinics, general practices, and clinical research centers) in 14 countries conducted between December 2013 and December 2014. Of 1106 participants assessed, 632 with type 2 diabetes and insufficient glycemic control using diet and exercise alone or a stable dose of metformin were randomized. Randomization was stratified by metformin use.
Interventions: Once-daily oral semaglutide of 2.5 mg (n = 70), 5 mg (n = 70), 10 mg (n = 70), 20 mg (n = 70), 40-mg 4-week dose escalation (standard escalation; n = 71), 40-mg 8-week dose escalation (slow escalation; n = 70), 40-mg 2-week dose escalation (fast escalation, n = 70), oral placebo (n = 71; double-blind) or once-weekly subcutaneous semaglutide of 1.0 mg (n = 70) for 26 weeks.
Main Outcomes and Measures: The primary end point was change in hemoglobin A1c (HbA1c) from baseline to week 26. Secondary end points included change from baseline in body weight and adverse events.
Results: Baseline characteristics were comparable across treatment groups. Of the 632 randomized patients (mean age, 57.1 years [SD, 10.6]; men, 395 (62.7%); diabetes duration, 6.3 years [SD, 5.2]; body weight, 92.3 kg [SD, 16.8]; BMI, 31.7 [SD, 4.3]), 583 (92%) completed the trial. Mean change in HbA1c level from baseline to week 26 decreased with oral semaglutide (dosage-dependent range, -0.7% to -1.9%) and subcutaneous semaglutide (-1.9%) and placebo (-0.3%); oral semaglutide reductions were significant vs placebo (dosage-dependent estimated treatment difference [ETD] range for oral semaglutide vs placebo, -0.4% to -1.6%; P = .01 for 2.5 mg,
Conclusions and Relevance: Among patients with type 2 diabetes, oral semaglutide resulted in better glycemic control than placebo over 26 weeks. These findings support phase 3 studies to assess longer-term and clinical outcomes, as well as safety.
Trial Registration: clinicaltrials.gov Identifier: NCT01923181
Medium-chain fatty acids released from polymeric electrospun patches inhibit Candida albicans growth and reduce the biofilm viability
Oral candidiasis is a very common oral condition among susceptible individuals, with the main causative organism being the fungus Candida albicans. Current drug delivery systems to the oral mucosa are often ineffective because of short drug/tissue contact times as well as increased prevalence of drug-resistant Candida strains. We evaluated the potency of saturated fatty acids as antifungal agents and investigated their delivery by novel electrospun mucoadhesive oral patches using agar disk diffusion and biofilm assays. Octanoic (C8) and nonanoic (C9) acids were the most effective at inhibiting C. albicans growth on disk diffusion assays, both in solution or when released from polycaprolactone (PCL) or polyvinylpyrrolidone/RS100 (PVP/RS100) electrospun patches. In contrast, dodecanoic acid (C12) displayed the most potent antifungal activity against pre-existing C. albicans biofilms in solution or when released by PCL or PVP/RS100 patches. Both free and patch-released saturated fatty acids displayed a significant toxicity to wild-type and azole-resistant strains of C. albicans. These data not only provide evidence that certain saturated fatty acids have the potential to be used as antifungal agents but also demonstrate that this therapy could be delivered directly to Candida-infected sites using electrospun mucoadhesive patches, demonstrating a potential new therapeutic approach to treat oral thrush
Saturn's icy satellites and rings investigated by Cassini - VIMS. III. Radial compositional variability
In the last few years Cassini-VIMS, the Visible and Infared Mapping
Spectrometer, returned to us a comprehensive view of the Saturn's icy
satellites and rings. After having analyzed the satellites' spectral properties
(Filacchione et al. (2007a)) and their distribution across the satellites'
hemispheres (Filacchione et al. (2010)), we proceed in this paper to
investigate the radial variability of icy satellites (principal and minor) and
main rings average spectral properties. This analysis is done by using 2,264
disk-integrated observations of the satellites and a 12x700 pixels-wide rings
radial mosaic acquired with a spatial resolution of about 125 km/pixel. The
comparative analysis of these data allows us to retrieve the amount of both
water ice and red contaminant materials distributed across Saturn's system and
the typical surface regolith grain sizes. These measurements highlight very
striking differences in the population here analyzed, which vary from the
almost uncontaminated and water ice-rich surfaces of Enceladus and Calypso to
the metal/organic-rich and red surfaces of Iapetus' leading hemisphere and
Phoebe. Rings spectra appear more red than the icy satellites in the visible
range but show more intense 1.5-2.0 micron band depths. The correlations among
spectral slopes, band depths, visual albedo and phase permit us to cluster the
saturnian population in different spectral classes which are detected not only
among the principal satellites and rings but among co-orbital minor moons as
well. Finally, we have applied Hapke's theory to retrieve the best spectral
fits to Saturn's inner regular satellites using the same methodology applied
previously for Rhea data discussed in Ciarniello et al. (2011).Comment: 44 pages, 27 figures, 7 tables. Submitted to Icaru
Two-Proton Correlations near Midrapidity in p+Pb and S+Pb Collisions at the CERN SPS
Correlations of two protons emitted near midrapidity in p+Pb collisions at
450 GeV/c and S+Pb collisions at 200A GeV/c are presented, as measured by the
NA44 Experiment. The correlation effect, which arises as a result of final
state interactions and Fermi-Dirac statistics, is related to the space-time
characteristics of proton emission. The measured source sizes are smaller than
the size of the target lead nucleus but larger than the sizes of the
projectiles. A dependence on the collision centrality is observed; the source
size increases with decreasing impact parameter. Proton source sizes near
midrapidity appear to be smaller than those of pions in the same interactions.
Quantitative agreement with the results of RQMD (v1.08) simulations is found
for p+Pb collisions. For S+Pb collisions the measured correlation effect is
somewhat weaker than that predicted by the model simulations, implying either a
larger source size or larger contribution of protons from long-lived particle
decays.Comment: 10 pages (LaTeX) text, 4 (EPS) figures; accepted for publication in
Phys. Lett.
Interatomic potentials for atomistic simulations of the Ti-Al system
Semi-empirical interatomic potentials have been developed for Al, alpha-Ti,
and gamma-TiAl within the embedded atomic method (EAM) by fitting to a large
database of experimental as well as ab-initio data. The ab-initio calculations
were performed by the linear augmented plane wave (LAPW) method within the
density functional theory to obtain the equations of state for a number of
crystal structures of the Ti-Al system. Some of the calculated LAPW energies
were used for fitting the potentials while others for examining their quality.
The potentials correctly predict the equilibrium crystal structures of the
phases and accurately reproduce their basic lattice properties. The potentials
are applied to calculate the energies of point defects, surfaces, planar faults
in the equilibrium structures. Unlike earlier EAM potentials for the Ti-Al
system, the proposed potentials provide reasonable description of the lattice
thermal expansion, demonstrating their usefulness in the molecular dynamics or
Monte Carlo studies at high temperatures. The energy along the tetragonal
deformation path (Bain transformation) in gamma-TiAl calculated with the EAM
potential is in a fairly good agreement with LAPW calculations. Equilibrium
point defect concentrations in gamma-TiAl are studied using the EAM potential.
It is found that antisite defects strongly dominate over vacancies at all
compositions around stoichiometry, indicating that gamm-TiAl is an antisite
disorder compound in agreement with experimental data.Comment: 46 pages, 6 figures (Physical Review B, in press
Forward K+ production in subthreshold pA collisions at 1.0 GeV
K+ meson production in pA (A = C, Cu, Au) collisions has been studied using
the ANKE spectrometer at an internal target position of the COSY-Juelich
accelerator. The complete momentum spectrum of kaons emitted at forward angles,
theta < 12 degrees, has been measured for a beam energy of T(p)=1.0 GeV, far
below the free NN threshold of 1.58 GeV. The spectrum does not follow a thermal
distribution at low kaon momenta and the larger momenta reflect a high degree
of collectivity in the target nucleus.Comment: 4 pages, 3 figure
The covalent reactivity of functionalized 5-hydroxy-butyrolactams is the basis for targeting of fatty acid binding protein 5 (FABP5) by the neurotrophic agent MT-21
Covalently acting compounds experience a strong interest within chemical biology both as molecular probes in studies of fundamental biological mechanisms and/or as novel drug candidates. In this context, the identification of new classes of reactive groups is particularly important as these can expose novel reactivity modes and, consequently, expand the ligandable proteome. Here, we investigated the electrophilic reactivity of the 3-acyl-5-hydroxy-1,5-dihydro-2H-pyrrole-2-one (AHPO) scaffold, a heterocyclic motif that is e.g. present in various bioactive natural products. Our investigations were focused on the compound MT-21 - a simplified structural analogue of the natural product epolactaene - which is known to have both neurotrophic activity and ability to trigger apoptotic cell death. We found that the central N-acyl hemiaminal group of MT-21 can function as an electrophilic centre enabling divergent reactivity with both amine- and thiokbased nucleophiles, which furthermore translated to reactivity with proteins in both cell lysates and live cells. We found that in live cells MT-21 strongly engaged the lipid transport protein fatty acid-binding protein 5 (FABP5) by direct binding to a cysteine residue in the bottom of the ligand binding pocket. Through preparation of a series of MT-21 derivatives, we probed the specificity of this interaction which was found to be strongly dependent on subtle structural changes. Our study suggests that MT-21 may be employed as a tool compound in future studies of the biology of FABP5, which remains incompletely understood. Furthermore, our study has also made dear that other natural products containing the AHPO-motif may likewise possess covalent reactivity and that this property may underlie their biological activity.Molecular Physiolog
Granulocytic sarcoma (chloroma) of the oral cavity: Report of a case and literature review
SummaryA case of granulocytic sarcoma (chloroma) of the palatal mucosa is reported. Granulocytic sarcomas are composed of a localized collection of immature myeloid cells and are considered to be specific lesions of AML or the onset of a blast crisis in chronic myelogenous leukemia (CML). Localization in the oral cavity is rare. A review of the literature showed only thirty-six cases of granulocytic sarcoma in the oral cavity. In this paper we present patient’s data and an overview of the literature
- …