Formulation, evaluation and optimization of stomach specific in situ gel of clarithromycin and metronidazole benzoate

The present investigation deals with the formulation, optimization and evaluation of sodium alginate based In situ gel of Clarithromycin and Metronidazole Benzoate. Sodium alginate used as a polymer and CaCO3 was used as a cross-linking agent. The In situ formulation exhibited well, viscosity, drug content and sustained drug release; this study reports that oral administration of aqueous solutions containing sodium alginate results in formation of In situ gel, such formulations are homogenous liquid when administered orally and become gel at the contact site. The results of a 32 full factorial design revealed that the concentration of sodium alginate and concentration of CaCO3 significantly affected the dependent variables Q1, Q12 and T80. These In situ gels are, thus, suitable for oral sustained release of Clarithromycin and Metronidazole Benzoate.Keywords: In situ gel; Stomach specific; Gastric residence time

Formulation, evaluation and optimization of stomach specific in situ gel of clarithromycin and metronidazole benzoate

The present investigation deals with the formulation, optimization and evaluation of sodium alginate based In situ gel of Clarithromycin and Metronidazole Benzoate. Sodium alginate used as a polymer and CaCO3 was used as a cross-linking agent. The In situ formulation exhibited well, viscosity, drug content and sustained drug release; this study reports that oral administration of aqueous solutions containing sodium alginate results in formation of In situ gel, such formulations are homogenous liquid when administered orally and become gel at the contact site. The results of a 32 full factorial design revealed that the concentration of sodium alginate and concentration of CaCO3 significantly affected the dependent variables Q1, Q12 and T80. These In situ gels are, thus, suitable for oral sustained release of Clarithromycin and Metronidazole Benzoate.Keywords: In situ gel; Stomach specific; Gastric residence time

Entanglement and Dynamic Stability of Nash Equilibria in a Symmetric Quantum Game

We study the evolutionary stability of Nash equilibria (NE) in a symmetric quantum game played by the recently proposed scheme of applying `identity' and `Pauli spin flip' operators on the initial state with classical probabilities. We show that in this symmetric game dynamic stability of a NE can be changed when the game changes its form, for example, from classical to quantum. It happens even when the NE remains intact in both forms.Comment: Latex,no figure,submitted to Physics Letters

Single and Double BFKL Pomeron Exchange and a Dipole Picture of High Energy Hard Processes

Onium-onium scattering at high energy is used to illustrate a dipole picture of high energy hard scattering in the large $N_c$ limit. Single and double BFKL pomeron exchanges are calculated in the leading logarithmic approximation. An expression is given for the triple pomeron coupling when one of the pomeron's momentum is zero while the other two have momentum transfer, t. This expression is explicit and could be evaluated numerically. It has a $(-t)^{-{1\over 2}}$ singularity at t=0.Comment: CU-TP-625, minor TeX problems of previous version have been fixe

Electrophysiological characterization of activation state-dependent Cav2 channel antagonist TROX-1 in spinal nerve injured rats

AbstractPrialt, a synthetic version of Cav2.2 antagonist ω-conotoxin MVIIA derived from Conus magus, is the first clinically approved voltage-gated calcium channel blocker for refractory chronic pain. However, due to the narrow therapeutic window and considerable side effects associated with systemic dosing, Prialt is only administered intrathecally. N-triazole oxindole (TROX-1) is a novel use-dependent and activation state-selective small-molecule inhibitor of Cav2.1, 2.2 and 2.3 calcium channels designed to overcome the limitations of Prialt. We have examined the neurophysiological and behavioral effects of blocking calcium channels with TROX-1. In vitro, TROX-1, in contrast to state-independent antagonist Prialt, preferentially inhibits Cav2.2 currents in rat dorsal root ganglia (DRG) neurons under depolarized conditions. In vivo electrophysiology was performed to record from deep dorsal horn lamina V/VI wide dynamic range neurons in non-sentient spinal nerve-ligated (SNL) and sham-operated rats. In SNL rats, spinal neurons exhibited reduced responses to innocuous and noxious punctate mechanical stimulation of the receptive field following subcutaneous administration of TROX-1, an effect that was absent in sham-operated animals. No effect was observed on neuronal responses evoked by dynamic brushing, heat or cold stimulation in SNL or sham rats. The wind-up response of spinal neurons following repeated electrical stimulation of the receptive field was also unaffected. Spinally applied TROX-1 dose dependently inhibited mechanically evoked neuronal responses in SNL but not sham-operated rats, consistent with behavioral observations. This study confirms the pathological state-dependent actions of TROX-1 through a likely spinal mechanism and reveals a modality selective change in calcium channel function following nerve injury

Baryon Density Correlations in High Temperature Hadronic Matter

As part of an ongoing effort to characterize the high temperature phase of QCD, in a numerical simulation using the staggered fermion scheme, we measure the quark baryon density in the vicinity of a fixed test quark at high temperature and compare it with similar measurements at low temperature and at the crossover temperature. We find an extremely weak correlation at high temperature, suggesting that small color singlet clusters are unimportant in the thermal ensemble. We also find that at $T = 0.75\ T_c$ the total induced quark number shows a surprisingly large component attributable to baryonic screening. A companion simulation of a simple flux tube model produces similar results and also suggests a plausible phenomenological scenario: As the crossover temperature is approached from below, baryonic states proliferate. Above the crossover temperature the mean size of color singlet clusters grows explosively, resulting in an effective electrostatic deconfinement.Comment: 26 pp, RevTeX, 12 postscript figures, combined in a single shell archive file. (Also available in 13 postscript files by anonymous ftp from einstein.physics.utah.edu, /pub/milc/paper.sh.Z.

A first estimate of triply heavy baryon masses from the pNRQCD perturbative static potential

Within pNRQCD we compute the masses of spin-averaged triply heavy baryons using the now-available NNLO pNRQCD potentials and three-body variational approach. We focus in particular on the role of the purely three-body interaction in perturbation theory. This we find to be reasonably small and of the order 25 MeV Our prediction for the Omega_ccc baryon mass is 4900(250) in keeping with other approaches. We propose to search for this hitherto unobserved state at B factories by examining the end point of the recoil spectrum against triple charm.Comment: 18 figures, 21 page

Plane-symmetric inhomogeneous magnetized viscous fluid universe with a variable Λ\Lambda

The behavior of magnetic field in plane symmetric inhomogeneous cosmological models for bulk viscous distribution is investigated. The coefficient of bulk viscosity is assumed to be a power function of mass density $(\xi =\xi_{0}\rho^{n})$. The values of cosmological constant for these models are found to be small and positive which are supported by the results from recent supernovae Ia observations. Some physical and geometric aspects of the models are also discussed.Comment: 18 pages, LaTex, no figur

Dupilumab reduces systemic corticosteroid use and sinonasal surgery rate in CRSwNP

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a type 2 inflammatory disease with a high symptom burden and poor quality of life. Treatment options include recurrent surgeries and/or frequent systemic corticosteroids (SCS). Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin-4 and interleukin-13, key drivers of type 2-mediated inflammation. We report results of pooled analyses from 2 randomised, double-blind, placebo-controlled phase 3 studies (SINUS 24 [NCT02912468]; SINUS-52 [NCT02898454]) to evaluate dupilumab effect versus placebo in adults with CRSwNP with/without SCS use and sinonasal surgery. METHODOLOGY: SINUS-24 patients were randomised 1:1 to subcutaneous dupilumab 300 mg (n=143) or placebo (n=133) every 2 weeks (q2w) for 24 weeks. SINUS-52 patients were randomised 1:1:1 to 52 weeks of subcutaneous dupilumab 300 mg q2w (n=150), 24 weeks q2w followed by 28 weeks of dupilumab 300 mg every 4 weeks (n=145) or 52 weeks of placebo q2w (n=153). RESULTS: Dupilumab reduced the number of patients undergoing sinonasal surgery (82.6%), the need for in-study SCS use (73.9%), and SCS courses (75.3%). Significant improvements were observed with dupilumab vs placebo regardless of prior sinonasal surgery or SCS use in nasal polyp, nasal congestion, Lund-MacKay, and Sinonasal Outcome Test (22-items) scores, and the University of Pennsylvania Smell Identification Test. CONCLUSIONS: Dupilumab demonstrated significant improvements in disease signs and symptoms and reduced the need for sino-nasal surgery and SCS use versus placebo in patients with severe CRSwNP, regardless of SCS use in the previous 2 years, or prior sinonasal surgery

Myocardial fibrosis in asymptomatic and symptomatic chronic severe primary mitral regurgitation and relationship to tissue characterisation and left ventricular function on cardiovascular magnetic resonance

Background: Myocardial fbrosis occurs in end-stage heart failure secondary to mitral regurgitation (MR), but it is not known whether this is present before onset of symptoms or myocardial dysfunction. This study aimed to characterise myocardial fbrosis in chronic severe primary MR on histology, compare this to tissue characterisation on cardiovascular magnetic resonance (CMR) imaging, and investigate associations with symptoms, left ventricular (LV) function, and exercise capacity. Methods: Patients with class I or IIa indications for surgery underwent CMR and cardiopulmonary exercise testing. LV biopsies were taken at surgery and the extent of fbrosis was quantifed on histology using collagen volume fraction (CVFmean) compared to autopsy controls without cardiac pathology. Results: 120 consecutive patients (64±13 years; 71% male) were recruited; 105 patients underwent MV repair while 15 chose conservative management. LV biopsies were obtained in 86 patients (234 biopsy samples in total). MR patients had more fbrosis compared to 8 autopsy controls (median: 14.6% [interquartile range 7.4–20.3] vs. 3.3% [2.6–6.1], P<0.001); this diference persisted in the asymptomatic patients (CVFmean 13.6% [6.3–18.8], P<0.001), but severity of fbrosis was not signifcantly higher in NYHA II-III symptomatic MR (CVFmean 15.7% [9.9–23.1] (P=0.083). Fibrosis was patchy across biopsy sites (intraclass correlation 0.23, 95% CI 0.08–0.39, P=0.001). No signifcant relationships were identifed between CVFmean and CMR tissue characterisation [native T1, extracellular volume (ECV) or late gadolinium enhancement] or measures of LV function [LV ejection fraction (LVEF), global longitudinal strain (GLS)]. Although the range of ECV was small (27.3±3.2%), ECV correlated with multiple measures of LV function (LVEF: Rho=−0.22, P=0.029, GLS: Rho=0.29, P=0.003), as well as NTproBNP (Rho=0.54, P<0.001) and exercise capacity (%PredVO2max: R=−0.22, P=0.030). Conclusions: Patients with chronic primary MR have increased fbrosis before the onset of symptoms. Due to the patchy nature of fbrosis, CMR derived ECV may be a better marker of global myocardial status. Clinical trial registration Mitral FINDER study; Clinical Trials NCT02355418, Registered 4 February 2015, https://clinicaltr ials.gov/ct2/show/NCT0235541