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Sample records for nonoscillatory eno formulations

  1. WLS-ENO: Weighted-least-squares based essentially non-oscillatory schemes for finite volume methods on unstructured meshes

    Science.gov (United States)

    Liu, Hongxu; Jiao, Xiangmin

    2016-06-01

    ENO (Essentially Non-Oscillatory) and WENO (Weighted Essentially Non-Oscillatory) schemes are widely used high-order schemes for solving partial differential equations (PDEs), especially hyperbolic conservation laws with piecewise smooth solutions. For structured meshes, these techniques can achieve high order accuracy for smooth functions while being non-oscillatory near discontinuities. For unstructured meshes, which are needed for complex geometries, similar schemes are required but they are much more challenging. We propose a new family of non-oscillatory schemes, called WLS-ENO, in the context of solving hyperbolic conservation laws using finite-volume methods over unstructured meshes. WLS-ENO is derived based on Taylor series expansion and solved using a weighted least squares formulation. Unlike other non-oscillatory schemes, the WLS-ENO does not require constructing sub-stencils, and hence it provides a more flexible framework and is less sensitive to mesh quality. We present rigorous analysis of the accuracy and stability of WLS-ENO, and present numerical results in 1-D, 2-D, and 3-D for a number of benchmark problems, and also report some comparisons against WENO.

  2. High-order weighted essentially nonoscillatory finite-difference formulation of the lattice Boltzmann method in generalized curvilinear coordinates

    Science.gov (United States)

    Hejranfar, Kazem; Saadat, Mohammad Hossein; Taheri, Sina

    2017-02-01

    In this work, a high-order weighted essentially nonoscillatory (WENO) finite-difference lattice Boltzmann method (WENOLBM) is developed and assessed for an accurate simulation of incompressible flows. To handle curved geometries with nonuniform grids, the incompressible form of the discrete Boltzmann equation with the Bhatnagar-Gross-Krook (BGK) approximation is transformed into the generalized curvilinear coordinates and the spatial derivatives of the resulting lattice Boltzmann equation in the computational plane are solved using the fifth-order WENO scheme. The first-order implicit-explicit Runge-Kutta scheme and also the fourth-order Runge-Kutta explicit time integrating scheme are adopted for the discretization of the temporal term. To examine the accuracy and performance of the present solution procedure based on the WENOLBM developed, different benchmark test cases are simulated as follows: unsteady Taylor-Green vortex, unsteady doubly periodic shear layer flow, steady flow in a two-dimensional (2D) cavity, steady cylindrical Couette flow, steady flow over a 2D circular cylinder, and steady and unsteady flows over a NACA0012 hydrofoil at different flow conditions. Results of the present solution are compared with the existing numerical and experimental results which show good agreement. To show the efficiency and accuracy of the solution methodology, the results are also compared with the developed second-order central-difference finite-volume lattice Boltzmann method and the compact finite-difference lattice Boltzmann method. It is shown that the present numerical scheme is robust, efficient, and accurate for solving steady and unsteady incompressible flows even at high Reynolds number flows.

  3. High-order weighted essentially nonoscillatory finite-difference formulation of the lattice Boltzmann method in generalized curvilinear coordinates.

    Science.gov (United States)

    Hejranfar, Kazem; Saadat, Mohammad Hossein; Taheri, Sina

    2017-02-01

    In this work, a high-order weighted essentially nonoscillatory (WENO) finite-difference lattice Boltzmann method (WENOLBM) is developed and assessed for an accurate simulation of incompressible flows. To handle curved geometries with nonuniform grids, the incompressible form of the discrete Boltzmann equation with the Bhatnagar-Gross-Krook (BGK) approximation is transformed into the generalized curvilinear coordinates and the spatial derivatives of the resulting lattice Boltzmann equation in the computational plane are solved using the fifth-order WENO scheme. The first-order implicit-explicit Runge-Kutta scheme and also the fourth-order Runge-Kutta explicit time integrating scheme are adopted for the discretization of the temporal term. To examine the accuracy and performance of the present solution procedure based on the WENOLBM developed, different benchmark test cases are simulated as follows: unsteady Taylor-Green vortex, unsteady doubly periodic shear layer flow, steady flow in a two-dimensional (2D) cavity, steady cylindrical Couette flow, steady flow over a 2D circular cylinder, and steady and unsteady flows over a NACA0012 hydrofoil at different flow conditions. Results of the present solution are compared with the existing numerical and experimental results which show good agreement. To show the efficiency and accuracy of the solution methodology, the results are also compared with the developed second-order central-difference finite-volume lattice Boltzmann method and the compact finite-difference lattice Boltzmann method. It is shown that the present numerical scheme is robust, efficient, and accurate for solving steady and unsteady incompressible flows even at high Reynolds number flows.

  4. Application of essentially nonoscillatory methods to aeroacoustic flow problems

    Science.gov (United States)

    Atkins, Harold L.

    1995-01-01

    A finite-difference essentially nonoscillatory (ENO) method has been applied to several of the problems prescribed for the workshop sponsored jointly by the Institute for Computer Applications in Science and Engineering and by NASA Langley Research Center entitled 'Benchmark Problems in Computational Aeroacoustics'. The workshop focused on computational challenges specific to aeroacoustics. Among these are long-distance propagation of a short-wavelength disturbance, propagation of small-amplitude disturbances, and nonreflective boundary conditions. The shock capturing-capability inherent to the ENO method effectively eliminates oscillations near shock waves without the need to add and tune dissipation or filter terms. The method-of-lines approach allows the temporal and spatial operators to be chosen separately in accordance with the demands of a particular problem. The ENO method was robust and accurate for all problems in which the propagating wave was resolved with 8 or more points per wavelength. The finite-wave-model boundary condition, a local nonlinear acoustic boundary condition, performed well for the one-dimensional problems. The buffer-domain approach performed well for the two-dimensional test problem. The amplitude of nonphysical reflections were less than 1 percent of the exiting wave's amplitude.

  5. ENO reconstruction and ENO interpolation are stable

    CERN Document Server

    Fjordholm, Ulrik S; Tadmor, Eitan

    2011-01-01

    We prove stability estimates for the ENO reconstruction and ENO interpolation procedures. In particular, we show that the jump of the reconstructed ENO pointvalues at each cell interface has the same sign as the jump of the underlying cell averages across that interface. We also prove that the jump of the reconstructed values can be upper-bounded in terms of the jump of the underlying cell averages. Similar sign properties hold for the ENO interpolation procedure. These estimates, which are shown to hold for ENO reconstruction and interpolation of arbitrary order of accuracy and on non-uniform meshes, indicate a remarkable rigidity of the piecewise-polynomial ENO procedure.

  6. Non-polynomial ENO and WENO finite volume methods for hyperbolic conservation laws

    OpenAIRE

    Guo, Jingyang; Jung, Jae-Hun

    2016-01-01

    The essentially non-oscillatory (ENO) method is an efficient high order numerical method for solving hyperbolic conservation laws designed to reduce the Gibbs oscillations, if existent, by adaptively choosing the local stencil for the interpolation. The original ENO method is constructed based on the polynomial interpolation and the overall rate of convergence provided by the method is uniquely determined by the total number of interpolation points involved for the approximation. In this pape...

  7. Third-order modified coefficient scheme based on essentially non-oscillatory scheme

    Institute of Scientific and Technical Information of China (English)

    LI Ming-jun; YANG Yu-yue; SHU Shi

    2008-01-01

    A third-order numerical scheme is presented to give approximate solutions to multi-dimensional hyperbolic conservation laws only using modified coefficients of an essentially non-oscillatory (MCENO) scheme without increasing the base points during construction of the scheme.The construction process shows that the modified coefficient approach preserves favourable properties inherent in the original essentially non oscillatory (ENO) scheme for its essential non-oscillation,total variation bounded (TVB),etc.The new scheme improves accuracy by one order compared to the original one.The proposed MCENO scheme is applied to simulate two-dimensional Rayleigh-Taylor (RT) instability with densities 1:3 and 1:100,and solve the Lax shock-wave tube numerically.The ratio of CPU time used to implement MCENO,the third-order ENO and fifth-order weighed ENO (WENO) schemes is 0.62:1:2.19.This indicates that MCENO improves accuracy in smooth regions and has higher accuracy and better efficiency compared to the original ENO scheme.

  8. Multi-Dimensional High Order Essentially Non-Oscillatory Finite Difference Methods in Generalized Coordinates

    Science.gov (United States)

    Shu, Chi-Wang

    1998-01-01

    This project is about the development of high order, non-oscillatory type schemes for computational fluid dynamics. Algorithm analysis, implementation, and applications are performed. Collaborations with NASA scientists have been carried out to ensure that the research is relevant to NASA objectives. The combination of ENO finite difference method with spectral method in two space dimension is considered, jointly with Cai [3]. The resulting scheme behaves nicely for the two dimensional test problems with or without shocks. Jointly with Cai and Gottlieb, we have also considered one-sided filters for spectral approximations to discontinuous functions [2]. We proved theoretically the existence of filters to recover spectral accuracy up to the discontinuity. We also constructed such filters for practical calculations.

  9. On the application of ENO scheme with subcell resolution to conservation laws with stiff source terms

    Science.gov (United States)

    Chang, Shih-Hung

    1991-01-01

    Two approaches are used to extend the essentially non-oscillatory (ENO) schemes to treat conservation laws with stiff source terms. One approach is the application of the Strang time-splitting method. Here the basic ENO scheme and the Harten modification using subcell resolution (SR), ENO/SR scheme, are extended this way. The other approach is a direct method and a modification of the ENO/SR. Here the technique of ENO reconstruction with subcell resolution is used to locate the discontinuity within a cell and the time evolution is then accomplished by solving the differential equation along characteristics locally and advancing in the characteristic direction. This scheme is denoted ENO/SRCD (subcell resolution - characteristic direction). All the schemes are tested on the equation of LeVeque and Yee (NASA-TM-100075, 1988) modeling reacting flow problems. Numerical results show that these schemes handle this intriguing model problem very well, especially with ENO/SRCD which produces perfect resolution at the discontinuity.

  10. On the Growth of Nonoscillatory Solutions for Difference Equations with Deviating Argument

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    Došlá Z

    2008-01-01

    Full Text Available Abstract The half-linear difference equations with the deviating argument , are considered. We study the role of the deviating argument , especially as regards the growth of the nonoscillatory solutions and the oscillation. Moreover, the problem of the existence of the intermediate solutions is completely resolved for the classical half-linear equation ( = 1. Some analogies or discrepancies on the growth of the nonoscillatory solutions for the delayed and advanced equations are presented; and the coexistence with different types of nonoscillatory solutions is studied.

  11. On the Growth of Nonoscillatory Solutions for Difference Equations with Deviating Argument

    Directory of Open Access Journals (Sweden)

    M. Marini

    2008-08-01

    Full Text Available The half-linear difference equations with the deviating argument Δ(an|Δxn|αsgn Δxn+bn|xn+q|αsgn xn+q=0 , q ∈ ℤ are considered. We study the role of the deviating argument q, especially as regards the growth of the nonoscillatory solutions and the oscillation. Moreover, the problem of the existence of the intermediate solutions is completely resolved for the classical half-linear equation (q = 1. Some analogies or discrepancies on the growth of the nonoscillatory solutions for the delayed and advanced equations are presented; and the coexistence with different types of nonoscillatory solutions is studied.

  12. Electromyographic activity of shoulder muscles during exercises performed with oscillatory and non-oscillatory poles.

    Science.gov (United States)

    Hallal, Camilla Z; Marques, Nise R; Silva, Sarah R D; Dieën, Jaap V; Gonçalves, Mauro

    2011-01-01

    Pain and dysfunction of the shoulder complex are commonly found physiotherapy practice. These musculoskeletal abnormalities are related to instability and inadequate kinematic function, that depend on the integrity of the muscle tissues. Thus, to enhance the results of exercise therapies, and prevent and attenuate pain and dynfunction, the use of oscillatory pole has been implemented in clinical practice. The purpose of this study was to analyze the electromyographic (EMG) activity of shoulder stabilizing muscles during exercises performed with an oscillatory and a non-oscillatory pole. Twelve female volunteers, aged 20.4 years±1.9, participated in this study. EMG data were collected from upper trapezius (UT), lower trapezius (LT) and middle deltoid (MD) during three different exercises with an oscillatory and a non-oscillatory pole. The EMG signals were analyzed in the time domain through the calculation of Root Mean Square (RMS). The RMS values were normalized by the peak value obtained over all trials for each muscle. Statistical analysis was performed with repeated measures ANOVA and post-hoc of Bonferroni tests. The EMG activity of UT, LT and MD muscles were significantly higher with the oscillatory pole than the non-oscillatory pole (all pmuscles between exercises. The results of the present study indicated that the oscillatory pole does require higher activation of the shoulder muscles and therefore, may be useful in the training of the shoulder complex.

  13. Birth of oscillation in coupled non-oscillatory Rayleigh-Duffing oscillators

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    Guin, A.; Dandapathak, M.; Sarkar, S.; Sarkar, B. C.

    2017-01-01

    We have studied the dynamics of two bilaterally-coupled non-oscillatory Rayleigh-Duffing oscillators (RDOs). With the increase of coupling factor (CF) between RDOs, birth of periodic oscillations observed. For increased values of CF, dynamics becomes chaotic through a quasi-periodicroute but for even higher CF, synchronized stable periodic oscillations in RDOs are found. Taking direct and anti-diffusive coupling cases into consideration, we derive conditions for periodic bifurcation in parameter space analytically and verified them through numerical solution of system equations. Numerical simulation is also used to predict system states in two parameter space involving CF and linear damping parameter of RDOs. It indicates non-oscillatory, periodic, quasi-periodic and chaotic zones of system dynamics. Qualitative explanation of the simulated dynamics is given using homoclinic perturbation theory. Hardware experiment is performed on analog circuits simulating RDO model and obtained results confirm the predictions regarding birth of periodic oscillation and other features of system dynamics. Experimental results examining onset of oscillations in two under-biased bi-laterally coupled X-band Gunn oscillators (which are modelled as RDOs) is presented in support of the analysis.

  14. Regulation of eNOS enzyme activity by posttranslational modification.

    Science.gov (United States)

    Heiss, Elke H; Dirsch, Verena M

    2014-01-01

    The regulation of endothelial NO synthase (eNOS) employs multiple different cellular control mechanisms impinging on level and activity of the enzyme. This review aims at summarizing the current knowledge on the posttranslational modifications of eNOS, including acylation, nitrosylation, phosphorylation, acetylation, glycosylation and glutathionylation. Sites, mediators and impact on enzyme localization and activity of the single modifications will be discussed. Moreover, interdependence, cooperativity and competition between the different posttranslational modifications will be elaborated with special emphasis on the susceptibility of eNOS to metabolic cues.

  15. Solving 3D relativistic hydrodynamical problems with weighted essentially nonoscillatory discontinuous Galerkin methods

    Science.gov (United States)

    Bugner, Marcus; Dietrich, Tim; Bernuzzi, Sebastiano; Weyhausen, Andreas; Brügmann, Bernd

    2016-10-01

    Discontinuous Galerkin (DG) methods coupled to weighted essentially nonoscillatory (WENO) algorithms allow high order convergence for smooth problems and for the simulation of discontinuities and shocks. In this work, we investigate WENO-DG algorithms in the context of numerical general relativity, in particular for general relativistic hydrodynamics. We implement the standard WENO method at different orders, a compact (simple) WENO scheme, as well as an alternative subcell evolution algorithm. To evaluate the performance of the different numerical schemes, we study nonrelativistic, special relativistic, and general relativistic test beds. We present the first three-dimensional simulations of general relativistic hydrodynamics, albeit for a fixed spacetime background, within the framework of WENO-DG methods. The most important test bed is a single Tolman-Oppenheimer-Volkoff star in three dimensions, showing that long term stable simulations of single isolated neutron stars can be obtained with WENO-DG methods.

  16. Brian Eno Hollandi Festivali peakülaliseks

    Index Scriptorium Estoniae

    1999-01-01

    Inglise helilooja, videokunstnik ja muusikaprodutsent Brian Eno on 5.-26. juunini Amsterdamis toimuva avangardse Hollandi Festivali peakülaline, kelle videoinstallatsioon seatakse üles Stedelijki Muuseumis. Festivali programmist

  17. A family of fourth-order entropy stable nonoscillatory spectral collocation schemes for the 1-D Navier-Stokes equations

    Science.gov (United States)

    Yamaleev, Nail K.; Carpenter, Mark H.

    2017-02-01

    High-order numerical methods that satisfy a discrete analog of the entropy inequality are uncommon. Indeed, no proofs of nonlinear entropy stability currently exist for high-order weighted essentially nonoscillatory (WENO) finite volume or weak-form finite element methods. Herein, a new family of fourth-order WENO spectral collocation schemes is developed, that are nonlinearly entropy stable for the one-dimensional compressible Navier-Stokes equations. Individual spectral elements are coupled using penalty type interface conditions. The resulting entropy stable WENO spectral collocation scheme achieves design order accuracy, maintains the WENO stencil biasing properties across element interfaces, and satisfies the summation-by-parts (SBP) operator convention, thereby ensuring nonlinear entropy stability in a diagonal norm. Numerical results demonstrating accuracy and nonoscillatory properties of the new scheme are presented for the one-dimensional Euler and Navier-Stokes equations for both continuous and discontinuous compressible flows.

  18. Finite Difference Weighted Essentially Non-Oscillatory Schemes with Constrained Transport for Ideal Magnetohydrodynamics

    CERN Document Server

    Christlieb, Andrew J; Tang, Qi

    2013-01-01

    In this work we develop a class of high-order finite difference weighted essentially non-oscillatory (FD-WENO) schemes for solving the ideal magnetohydrodynamic (MHD) equations in 2D and 3D. The philosophy of this work is to use efficient high-order WENO spatial discretizations with high-order strong stability-preserving Runge-Kutta (SSP-RK) time-stepping schemes. Numerical results have shown that with such methods we are able to resolve solution structures that are only visible at much higher grid resolutions with lower-order schemes. The key challenge in applying such methods to ideal MHD is to control divergence errors in the magnetic field. We achieve this by augmenting the base scheme with a novel high-order constrained transport approach that updates the magnetic vector potential. The predicted magnetic field from the base scheme is replaced by a divergence-free magnetic field that is obtained from the curl of this magnetic potential. The non-conservative weakly hyperbolic system that the magnetic vecto...

  19. Finite difference weighted essentially non-oscillatory schemes with constrained transport for ideal magnetohydrodynamics

    Science.gov (United States)

    Christlieb, Andrew J.; Rossmanith, James A.; Tang, Qi

    2014-07-01

    In this work we develop a class of high-order finite difference weighted essentially non-oscillatory (FD-WENO) schemes for solving the ideal magnetohydrodynamic (MHD) equations in 2D and 3D. The philosophy of this work is to use efficient high-order WENO spatial discretizations with high-order strong stability-preserving Runge-Kutta (SSP-RK) time-stepping schemes. Numerical results have shown that with such methods we are able to resolve solution structures that are only visible at much higher grid resolutions with lower-order schemes. The key challenge in applying such methods to ideal MHD is to control divergence errors in the magnetic field. We achieve this by augmenting the base scheme with a novel high-order constrained transport approach that updates the magnetic vector potential. The predicted magnetic field from the base scheme is replaced by a divergence-free magnetic field that is obtained from the curl of this magnetic potential. The non-conservative weakly hyperbolic system that the magnetic vector potential satisfies is solved using a version of FD-WENO developed for Hamilton-Jacobi equations. The resulting numerical method is endowed with several important properties: (1) all quantities, including all components of the magnetic field and magnetic potential, are treated as point values on the same mesh (i.e., there is no mesh staggering); (2) both the spatial and temporal orders of accuracy are fourth-order; (3) no spatial integration or multidimensional reconstructions are needed in any step; and (4) special limiters in the magnetic vector potential update are used to control unphysical oscillations in the magnetic field. Several 2D and 3D numerical examples are presented to verify the order of accuracy on smooth test problems and to show high-resolution on test problems that involve shocks.

  20. The Characteristics and Regulatory Mechanisms of Superoxide Generation from eNOS Reductase Domain.

    Directory of Open Access Journals (Sweden)

    Hu Peng

    Full Text Available In addition to superoxide (O2.- generation from nitric oxide synthase (NOS oxygenase domain, a new O2.- generation site has been identified in the reductase domain of inducible NOS (iNOS and neuronal NOS (nNOS. Cysteine S-glutathionylation in eNOS reductase domain also induces O2.- generation from eNOS reductase domain. However, the characteristics and regulatory mechanism of the O2.- generation from NOS reductase domain remain unclear. We cloned and purified the wild type bovine eNOS (WT eNOS, a mutant of Serine 1179 replaced with aspartic acid eNOS (S1179D eNOS, which mimics the negative charge caused by phosphorylationand truncated eNOS reductase domain (eNOS RD. Both WT eNOS and S1179D eNOS generated significant amount of O2.- in the absence of BH4 and L-arginine. The capacity of O2.- generation from S1179D eNOS was significantly higher than that of WT eNOS (1.74:1. O2.- generation from both WT eNOS and S1179D eNOS were not completely inhibited by 100nM tetrahydrobiopterin(BH4. This BH4 un-inhibited O2.- generation from eNOS was blocked by 10mM flavoprotein inhibitor, diphenyleneiodonium (DPI. Purified eNOS reductase domain protein confirmed that this BH4 un-inhibited O2.- generation originates at the FMN or FAD/NADPH binding site of eNOS reductase domain. DEPMPO-OOH adduct EPR signals and NADPH consumptions analyses showed that O2.- generation from eNOS reductase domain was regulated by Serine 1179 phosphorylation and DPI, but not by L-arginine, BH4 or calmodulin (CaM. In addition to the heme center of eNOS oxygenase domain, we confirmed another O2.- generation site in the eNOS reductase domain and characterized its regulatory properties.

  1. Gravitational waveforms from binary neutron star mergers with high-order weighted-essentially-nonoscillatory schemes in numerical relativity

    Science.gov (United States)

    Bernuzzi, Sebastiano; Dietrich, Tim

    2016-09-01

    The theoretical modeling of gravitational waveforms from binary neutron star mergers requires precise numerical relativity simulations. Assessing convergence of the numerical data and building the error budget is currently challenging due to the low accuracy of general-relativistic hydrodynamics schemes and to the grid resolutions that can be employed in (3 +1 )-dimensional simulations. In this work, we explore the use of high-order weighted-essentially-nonoscillatory (WENO) schemes in neutron star merger simulations and investigate the accuracy of the waveforms obtained with such methods. We find that high-order WENO schemes can be robustly employed for simulating the inspiral-merger phase and they significantly improve the assessment of the waveform's error budget with respect to finite-volume methods. High-order WENO schemes can be thus efficiently used for high-quality waveform production, and in future large-scale investigations of the binary parameter space.

  2. Identification of chicken eNOS gene and differential expression in highland versus lowland chicken breeds.

    Science.gov (United States)

    Peng, J F; Ling, Y; Gou, W Y; Zhang, H; Wu, C X

    2012-09-01

    Nitric oxide (NO), an endothelium-derived relaxing factor, is synthesized from l-arginine by endothelial nitric oxide synthase (eNOS) in the endothelium. The objective of the present study was to preliminarily illuminate the expression of the eNOS gene in hypoxic adaptation of chicken embryonic development. The eNOS expression profiles between the Tibet and Shouguang chickens incubated under both normoxic and hypoxic conditions were detected by TaqMan real-time PCR. In this study, the chicken eNOS gene was found by both in silico cloning and RACE approaches. From the eNOS gene, we obtained a 3,310-bp mRNA sequence and a 10,666-bp DNA sequence and discovered that it was located on chicken chromosome 2 and had 7 unique transcripts. eNOS mRNA was detected in abundant amounts in some chick embryo organs (i.e., heart, liver, chorio-allantoic membrane, and lung), and expressed stably with the lowest levels in the brain. We observed that when exposed to hypoxia (13% O(2)) different embryo organ tissues had various sensitivities to hypoxia as determined by their eNOS expression profiles. Compared with the Shouguang chicken, the eNOS expression in the Tibet chicken was higher in the lung and liver, lower in the heart, and similar in the brain. In chorio-allantoic membranes, eNOS expression was higher in the Shouguang chicken than the Tibet chicken under hypoxic conditions, but not markedly different under normoxic conditions. The differences of eNOS expression between the 2 breeds may be relative to the hypoxic adaptation ability in Tibet chickens during embryonic development. This work will provide reference for future studies on the role of eNOS in hypoxic adaptation and response.

  3. Role of SIRT1 and FOXO factors in eNOS transcriptional activation by resveratrol.

    Science.gov (United States)

    Xia, Ning; Strand, Susanne; Schlufter, Frank; Siuda, Daniel; Reifenberg, Gisela; Kleinert, Hartmut; Förstermann, Ulrich; Li, Huige

    2013-08-01

    Many of the cardiovascular protective effects of resveratrol are attributable to an enhanced production of nitric oxide (NO) by the endothelial NO synthase (eNOS). Resveratrol has been shown to enhance eNOS gene expression as well as eNOS enzymatic activity. The aim of the present study was to analyze the molecular mechanisms of eNOS transcriptional activation by resveratrol. Treatment of human EA.hy 926 endothelial cells with resveratrol led to a concentration-dependent upregulation of eNOS expression. In luciferase reporter gene assay, resveratrol enhanced the activity of human eNOS promoter fragments (3500, 1600, 633 and 263bp in length, respectively), indicating that the proximal promoter region is required for resveratrol-induced eNOS transcriptional activation. Knockdown of the NAD(+)-dependent protein deacetylase sirtuin 1 (SIRT1) by siRNA prevented the upregulation of eNOS mRNA and protein by resveratrol. Forkhead box O (FOXO) transcription factors are established downstream targets of SIRT1. siRNA-mediated knockdown of FOXO1 and FOXO3a abolished the effect of resveratrol on eNOS expression, indicating the involvement of these factors. Resveratrol treatment enhanced the expression of FOXO1 and FOXO3a in EA.hy 926 cells. Reporter gene assay using promoter containing forkhead response elements showed increased FOXO factor activity by resveratrol. In electrophoretic mobility shift assay, the enhanced binding of nuclear proteins to the eNOS promoter regions by resveratrol could be blocked by antibodies against FOXO1 and FOXO3a. In conclusion, resveratrol enhances the expression and activity of FOXO transcription factors. The SIRT1/FOXO factor axis is involved in resveratrol-induced eNOS transcriptional activation.

  4. Arsenic, cadmium and neuron specific enolase (ENO2, γ-enolase expression in breast cancer

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    Soh Maureen A

    2011-11-01

    Full Text Available Abstract Background Neuron specific enolase (ENO2, γ-enolase has been used as a biomarker to help identify neuroendocrine differentiation in breast cancer. The goal of the present study was to determine if ENO2 expression in the breast epithelial cell is influenced by the environmental pollutants, arsenite and cadmium. Acute and chronic exposure of MCF-10A cells to As+3 and Cd+2 sufficient to allow colony formation in soft agar, was used to determine if ENO2 expression was altered by these pollutants. Results It was shown that both As+3 and Cd+2 exposure caused significant increases in ENO2 expression under conditions of both acute and chronic exposure. In contrast, ENO1, the major glycolytic enolase in non-muscle and neuronal cells, was largely unaffected by exposure to either As+3 or Cd+2. Localization studies showed that ENO2 in the MCF-10A cells transformed by As+3 or Cd+2 had both a cytoplasmic and nuclear localization. In contrast, ENO1 was localized to the cytoplasm. ENO2 localized to the cytoplasm was found to co-localized with ENO1. Conclusion The results are the first to show that ENO2 expression in breast epithelial cells is induced by acute and chronic exposure to As+3 or Cd+2. The findings also suggest a possible link between As+3 and Cd+2 exposure and neuroendocrine differentiation in tumors. Overall, the results suggest that ENO2 might be developed as a biomarker indicating acute and/or chronic environmental exposure of the breast epithelial cell to As+3 and Cd+2.

  5. Endothelin-1 Overexpression Improves Renal Function in eNOS Knockout Mice

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    Oleg Tsuprykov

    2015-10-01

    Full Text Available Background/Aims: To investigate the renal phenotype under conditions of an activated renal ET-1 system in the status of nitric oxide deficiency, we compared kidney function and morphology in wild-type, ET-1 transgenic (ET+/+, endothelial nitric oxide synthase knockout (eNOS-/- and ET+/+eNOS-/- mice. Methods: We assessed blood pressure, parameters of renal morphology, plasma cystatin C, urinary protein excretion, expression of genes associated with glomerular filtration barrier and tissue remodeling, and plasma metabolites using metabolomics. Results: eNOS-/- and ET+/+eNOS-/- mice developed hypertension. Osteopontin, albumin and protein excretion were increased in eNOS-/- and restored in ET+/+eNOS-/- animals. All genetically modified mice developed renal interstitial fibrosis and glomerulosclerosis. Genes involved in tissue remodeling (serpine1, TIMP1, Col1a1, CCL2 were up-regulated in eNOS-/-, but not in ET+/+eNOS-/- mice. Plasma levels of free carnitine and acylcarnitines, amino acids, diacyl phosphatidylcholines, lysophosphatidylcholines and hexoses were descreased in eNOS-/- and were in the normal range in ET+/+eNOS-/- mice. Conclusion: eNOS-/- mice developed renal dysfunction, which was partially rescued by ET-1 overexpression in eNOS-/- mice. The metabolomics results suggest that ET-1 overexpression on top of eNOS knockout is associated with a functional recovery of mitochondria (rescue effect in β-oxidation of fatty acids and an increase in antioxidative properties (normalization of monounsaturated fatty acids levels.

  6. Exercise-induced cardioprotection: a role for eNOS uncoupling and NO metabolites.

    Science.gov (United States)

    Farah, C; Kleindienst, A; Bolea, G; Meyer, G; Gayrard, S; Geny, B; Obert, P; Cazorla, O; Tanguy, S; Reboul, Cyril

    2013-11-01

    Exercise is an efficient strategy for myocardial protection against ischemia-reperfusion (IR) injury. Although endothelial nitric oxide synthase (eNOS) is phosphorylated and activated during exercise, its role in exercise-induced cardioprotection remains unknown. This study investigated whether modulation of eNOS activation during IR could participate in the exercise-induced cardioprotection against IR injury. Hearts isolated from sedentary or exercised rats (5 weeks training) were perfused with a Langendorff apparatus and IR performed in the presence or absence of NOS inhibitors [N-nitro-L-arginine methyl ester, L-NAME or N5-(1-iminoethyl)-L-ornithine, L-NIO] or tetrahydrobiopterin (BH₄). Exercise training protected hearts against IR injury and this effect was abolished by L-NAME or by L-NIO treatment, indicating that exercise-induced cardioprotection is eNOS dependent. However, a strong reduction of eNOS phosphorylation at Ser1177 (eNOS-PSer1177) and of eNOS coupling during early reperfusion was observed in hearts from exercised rats (which showed higher eNOS-PSer1177 and eNOS dimerization at baseline) in comparison to sedentary rats. Despite eNOS uncoupling, exercised hearts had more S-nitrosylated proteins after early reperfusion and also less nitro-oxidative stress, indexed by lower malondialdehyde content and protein nitrotyrosination compared to sedentary hearts. Moreover, in exercised hearts, stabilization of eNOS dimers by BH4 treatment increased nitro-oxidative stress and then abolished the exercise-induced cardioprotection, indicating that eNOS uncoupling during IR is required for exercise-induced myocardial cardioprotection. Based on these results, we hypothesize that in the hearts of exercised animals, eNOS uncoupling associated with the improved myocardial antioxidant capacity prevents excessive NO synthesis and limits the reaction between NO and O₂·- to form peroxynitrite (ONOO⁻), which is cytotoxic.

  7. On the Existence of Non-Oscillatory Phase Functions for Second Order Ordinary Differential Equations in the High-Frequency Regime

    Science.gov (United States)

    2014-08-04

    trigonometric functions of large arguments. 11. Conclusions We have shown that the solutions of a large class of second order differential equations can be...nonoscillatory phase functions . In addition, we describe numerical experiments which illustrate com- putational implications of this fact. For example, many...special functions of interest — such as the Bessel functions Jν and Yν — can be evaluated accurately using a number of operations which is Op1q in

  8. PGE1 analog alprostadil induces VEGF and eNOS expression in endothelial cells.

    Science.gov (United States)

    Haider, Dominik G; Bucek, Robert A; Giurgea, Aura G; Maurer, Gerald; Glogar, Helmut; Minar, Erich; Wolzt, Michael; Mehrabi, Mohammad R; Baghestanian, Mehrdad

    2005-11-01

    Endothelial nitric oxide synthase (eNOS), VEGF, and hypoxia-inducible factor 1-alpha (HIF-1alpha) are important regulators of endothelial function, which plays a role in the pathophysiology of heart failure (HF). PGE1 analog treatment in patients with HF elicits beneficial hemodynamic effects, but the precise mechanisms have not been investigated. We have investigated the effects of the PGE1 analog alprostadil on eNOS, VEGF, and HIF-1alpha expression in human umbilical vein endothelial cells (HUVEC) using RT-PCR and immunoblotting under normoxic and hypoxic conditions. In addition, we studied protein expression by immunohistochemical staining in explanted hearts from patients with end-stage HF, treated or untreated with systemic alprostadil. Alprostadil causes an upregulation of eNOS and VEGF protein and mRNA expression in HUVEC and decreases HIF-1alpha. Hypoxia potently increased eNOS, VEGF, and HIF-1alpha synthesis. The alprostadil-induced upregulation of eNOS and VEGF was prevented by inhibition of MAPKs with PD-98056 or U-0126. Consistently, the expression of eNOS and VEGF was increased, and HIF-1alpha was reduced in failing hearts treated with alprostadil. The potent effects of alprostadil on endothelial VEGF and eNOS synthesis may be useful for patients with HF where endothelial dysfunction is involved in the disease process.

  9. A non-oscillatory balanced scheme for an idealized tropical climate model. Part II. Nonlinear coupling and moisture effects

    Energy Technology Data Exchange (ETDEWEB)

    Khouider, Boualem [University of Victoria, Mathematics and Statistics, Victoria, B.C. (Canada); Majda, Andrew J. [New York University, Department of Mathematics and Center for Atmosphere/Ocean Sciences, NY (United States); Courant Institute, New York, NY (United States)

    2005-10-01

    We use the non-oscillatory balanced numerical scheme developed in Part I to track the dynamics of a dry highly nonlinear barotropic/baroclinic coupled solitary wave, as introduced by Biello and Majda (2004), and of the moisture fronts of Frierson et al. (2004) in the presence of dry gravity waves, a barotropic trade wind, and the beta effect. It is demonstrated that, for the barotropic/baroclinic solitary wave, except for a little numerical dissipation, the scheme utilized here preserves total energy despite the strong interactions and exchange of energy between the baroclinic and barotropic components of the flow. After a short transient period where the numerical solution stays close to the asymptotic predictions, the flow develops small scale eddies and ultimately becomes highly turbulent. It is found here that the interaction of a dry gravity wave with a moisture front can either result in a reflection of a fast moistening front or the pure extinction of the precipitation. The barotropic trade wind stretches the precipitation patches and increases the lifetime of the moisture fronts which decay naturally by the effects of dissipation through precipitation while the Coriolis effect makes the moving precipitation patches disappear and appear at other times and places. (orig.)

  10. Activation of Endothelial Nitric Oxide (eNOS Occurs through Different Membrane Domains in Endothelial Cells.

    Directory of Open Access Journals (Sweden)

    Jason Tran

    Full Text Available Endothelial cells respond to a large range of stimuli including circulating lipoproteins, growth factors and changes in haemodynamic mechanical forces to regulate the activity of endothelial nitric oxide synthase (eNOS and maintain blood pressure. While many signalling pathways have been mapped, the identities of membrane domains through which these signals are transmitted are less well characterized. Here, we manipulated bovine aortic endothelial cells (BAEC with cholesterol and the oxysterol 7-ketocholesterol (7KC. Using a range of microscopy techniques including confocal, 2-photon, super-resolution and electron microscopy, we found that sterol enrichment had differential effects on eNOS and caveolin-1 (Cav1 colocalisation, membrane order of the plasma membrane, caveolae numbers and Cav1 clustering. We found a correlation between cholesterol-induced condensation of the plasma membrane and enhanced high density lipoprotein (HDL-induced eNOS activity and phosphorylation suggesting that cholesterol domains, but not individual caveolae, mediate HDL stimulation of eNOS. Vascular endothelial growth factor (VEGF-induced and shear stress-induced eNOS activity was relatively independent of membrane order and may be predominantly controlled by the number of caveolae on the cell surface. Taken together, our data suggest that signals that activate and phosphorylate eNOS are transmitted through distinct membrane domains in endothelial cells.

  11. The role of eNOS phosphorylation in causing drug-induced vascular injury.

    Science.gov (United States)

    Tobin, Grainne A McMahon; Zhang, Jun; Goodwin, David; Stewart, Sharron; Xu, Lin; Knapton, Alan; González, Carlos; Bancos, Simona; Zhang, Leshuai; Lawton, Michael P; Enerson, Bradley E; Weaver, James L

    2014-06-01

    Previously we found that regulation of eNOS is an important part of the pathogenic process of Drug-induced vascular injury (DIVI) for PDE4i. The aims of the current study were to examine the phosphorylation of eNOS in mesentery versus aorta at known regulatory sites across DIVI-inducing drug classes and to compare changes across species. We found that phosphorylation at S615 in rats was elevated 35-fold 2 hr after the last dose of CI-1044 in mesentery versus 3-fold in aorta. Immunoprecipitation studies revealed that many of the upstream regulators of eNOS activation were associated with eNOS in 1 or more signalosome complexes. Next rats were treated with drugs from 4 other classes known to cause DIVI. Each drug was given alone and in combination with SIN-1 (NO donor) or L-NAME (eNOS inhibitor), and the level of eNOS phosphorylation in mesentery and aorta tissue was correlated with the extent of vascular injury and measured serum nitrite. Drugs or combinations produced altered serum nitrite levels as well as vascular injury score in the mesentery. The results suggested that phosphorylation of S615 may be associated with DIVI activity. Studies with the species-specific A2A adenosine agonist CI-947 in rats versus primates showed a similar pattern.

  12. Nitric Oxide and eNOS Gene in Essential Hypertension

    Directory of Open Access Journals (Sweden)

    Kamna Srivastava

    2009-04-01

    Full Text Available Background: Currently hypertension grips around 25% of the entire world population. More than 90% of the hypertensive patients suffer from essential hypertension. In Asian Indians hypertension is the predominant risk factor for Coronary Artery Disease among others. Nitric Oxide (NO is synonymous with endothelial derived relaxation factor. Acting via cGMP (cyclic guanosine monophosphate it causes smooth muscle relaxation, prevents platelet aggregation and acts as an anti-inflammatory agent. iNOS (inducible Nitric oxide synthase, nNOS(neuronal nitric oxide synthase and eNOS (endothelial nitric oxide synthase are the three enzymes producing the gas nitric oxide in the human body. eNOS is the main source of NO under physiological conditions. It is known to have a number of polymorphisms. The most well known ones being the G to T polymorphism in exon 7, the T to C polymorphism in the promoter region and the a/b polymorphism in the intron 4. While the G to T polymorphism has been associated with hypertension in many races including the north Indian population, the association of other polymorphisms has been more of a controversy. Not much study has been done on the Asians especially those in India regarding these polymorphisms. Aims: To elucidate the association between the intron4a/b polymorphism in the eNOS gene and nitric oxide levels and essential hypertension. Objectives: 1. To determine the genotype frequencies of the above mentioned polymorphism in patients and controls2. To study the levels of NO in the plasma of the patients and controls3. To find out correlation if any between this polymorphism and plasma NO levels4. To find a correlation if any between this polymorphism and essential hypertension Materials and Methods: The study design was a case control study. 10 ml of venous blood was taken from 45 patients (selected from the department of Cardiology All India Institute of Medical Sciences, ages between 25 to 55 yrs and not on any

  13. (−)-Epicatechin activation of endothelial cell eNOS, NO and related signaling pathways

    Science.gov (United States)

    Ramirez-Sanchez, Israel; Maya, Lisandro; Ceballos, Guillermo; Villarreal, Francisco

    2010-01-01

    Recent reports indicate that (−)-epicatechin can exert cardioprotective actions, which may involve eNOS-mediated nitric oxide production in endothelial cells. However, the mechanism by which (−)-epicatechin activates eNOS remains unclear. In this study, we proposed to identify the intracellular pathways involved in (−)-epicatechin-induced effects on eNOS, utilizing human coronary artery endothelial cells in culture. Treatment of cells with (−)-epicatechin leads to time- and dose-dependent effects, which peaked at 10 min at 1 μmol/L. (−)-Epicatechin treatment activates eNOS via serine-633 and serine-1177 phosphorylation and threonine-495 dephosphorylation. Using specific inhibitors, we have established the participation of the PI3K pathway in eNOS activation. (−)-Epicatechin induces eNOS uncoupling from caveolin-1 and its association with calmodulin-1, suggesting the involvement of intracellular calcium. These results allowed us to propose that (−) epicatechin effects may be dependent on actions exerted at the cell membrane level. To test this hypothesis, cells were treated with the phospholipase C inhibitor U73122, which blocked (−)-epicatechin-induced eNOS activation. We also demonstrated inositol phosphate accumulation in (−)-epicatechin-treated cells. The inhibitory effects of the pre-incubation of cells with the CaMKII inhibitor KN-93 indicate that (−)-epicatechin-induced eNOS activation is at least partially mediated via the Ca2+/CaMKII pathway. The (−)-epicatechin stereoisomer catechin was only able to partially stimulate nitric oxide production in cells. Altogether, these results strongly suggest the presence of a cell surface acceptor-effector for the cacao flavanol (−)-epicatechin, which may mediate its cardiovascular effects. PMID:20404222

  14. Mild mitochondrial uncoupling and calorie restriction increase fasting eNOS, akt and mitochondrial biogenesis.

    Directory of Open Access Journals (Sweden)

    Fernanda M Cerqueira

    Full Text Available Enhanced mitochondrial biogenesis promoted by eNOS activation is believed to play a central role in the beneficial effects of calorie restriction (CR. Since treatment of mice with dinitrophenol (DNP promotes health and lifespan benefits similar to those observed in CR, we hypothesized that it could also impact biogenesis. We found that DNP and CR increase citrate synthase activity, PGC-1α, cytochrome c oxidase and mitofusin-2 expression, as well as fasting plasma levels of NO• products. In addition, eNOS and Akt phosphorylation in skeletal muscle and visceral adipose tissue was activated in fasting CR and DNP animals. Overall, our results indicate that systemic mild uncoupling activates eNOS and Akt-dependent pathways leading to mitochondrial biogenesis.

  15. A Two-dimensional Genetic Algorithm Based on the Eno-Haar Wavelet Transform%一种基于Eno-Haar小波变换二维遗传算法

    Institute of Scientific and Technical Information of China (English)

    宋锦萍; 赵晨萍; 李登峰

    2007-01-01

    A two-dimensional genetic algorithm of wavelet coefficient is presented by using the ENO wavelet transform and the decomposed characterization of the two-dimensional Haar wavelet. And simulated by the ENO interpolation the article shows the affectivity and the superiority of this algorithm.

  16. eNOS uncoupling in the cerebellum after BBB disruption by exposure to Phoneutria nigriventer spider venom.

    Science.gov (United States)

    Soares, Edilene Siqueira; Mendonça, Monique Culturato Padilha; da Cruz-Höfling, Maria Alice

    2015-09-15

    Numerous studies have shown that the venom of Phoneutria nigriventer (PNV) armed-spider causes excitotoxic signals and blood-brain barrier breakdown (BBBb) in rats. Nitric oxide (NO) is a signaling molecule which has a role in endothelium homeostasis and vascular health. The present study investigated the relevance of endothelial NO synthase (eNOS) uncoupling to clinical neurotoxic evolution induced by PNV. eNOS immunoblotting of cerebellum lysates processed through low-temperature SDS-PAGE revealed significant increased monomerization of the enzyme at critical periods of severe envenoming (1-2 h), whereas eNOS dimerization reversal paralleled to amelioration of animals condition (5-72 h). Moreover, eNOS uncoupling was accompanied by increased expression in calcium-sensing calmodulin protein and calcium-binding calbindin-D28 protein in cerebellar neurons. It is known that greater eNOS monomers than dimers implies the inability of eNOS to produce NO leading to superoxide production and endothelial/vascular barrier dysfunction. We suggest that transient eNOS deactivation and disturbances in calcium handling reduce NO production and enhance production of free radicals thus contributing to endothelial dysfunction in the cerebellum of envenomed rats. In addition, eNOS uncoupling compromises the enzyme capacity to respond to shear stress contributing to perivascular edema and it is one of the mechanisms involved in the BBBb promoted by PNV.

  17. CD151 gene delivery increases eNOS activity and induces ECV304 migration, proliferation and tube formation

    Institute of Scientific and Technical Information of China (English)

    Zhen-zhong ZHENO; Zheng-xiang LIU

    2007-01-01

    Aim: To investigate the effects of CD151 on the activity of endothelial NO syn-thase (eNOS), and ECV304 migration, proliferation and tube formation. Methods:pAAV-CD151 and pAAV-anti-CD151 were constructed and used to transiently transfect ECV304 mediated with Lipofectamine 2000. After transfection, the ex-pression of CD151 was measured by Western blotting. Cell migration assay was performed using Boyden transwell; proliferation assay was evaluated using the 3-[4,5-dimethylthiazol-2-yl]-2,5, diphenyltetrazolium bromide (MTT) method, and tube formation test was examined on matrigel, eNOS activity was assayed by L-[3H]citrulline production from L-[3H]arginine. The involvement of eNOS was ex-plored using an eNOS inhibitor (L-NAME) and the effects in the process were observed. Results: CD151 promotes cell migration, proliferation and tube formation.In addition, CD151 increases eNOS activity. Moreover, cell migration, prolifera-tion and tube formation induced by CD151 are inhibited when L-NAME is used,which indicates that there is an involvement of eNOS in CD151-induced cell migration, cell proliferation and tube formation. Conclusion: CD151 promotes ECV304 migration, proliferation and tube formation. The mechanism is that CD151 increases eNOS activity. This result also suggests that eNOS is involved in the angiogenic effects of CD151.

  18. ENO1 Protein Levels in the Tumor Tissues and Circulating Plasma Samples of Non-small Cell Lung Cancer Patients

    Directory of Open Access Journals (Sweden)

    Ying ZHANG

    2010-12-01

    Full Text Available Background and objective Proper tumor markers are useful to diagnosis, prognosis and treatment for lung cancer. The aim of this study is to examine the levels of alpha-enolase (ENO1 protein in the tumor tissues and peripheral plasma samples obtained from non-small cell lung cancer (NSCLC patients, and evaluate its potential clinical significance. Methods The ENO1 protein levels in the tumor tissues and corresponding normal tissues from 16 cases of lung squamous cell carcinoma were analyzed by Western blot. The ENO1 protein levels in the plasma samples from 42 healthy individuals, 34 patients with lung benign disease and 84 patients with NSCLC were measured by double antibody sandwich enzyme-linked immunosorbent assay. Results For 87.5% (14/16 of the patients with lung squamous cell carcinoma, the ENO1 protein level in the tumor tissues was higher than that in the corresponding normal lung tissues. The ENO1 protein level in the plasma of NSCLC patients was significantly higher than that in the plasma of healthy individuals (P=0.031 and patients with lung benign disease (P=0.019. Furthermore, the ENO1 protein level was significantly higher in the plasma of patients with lung adenocarcinoma than that of patients with lung squamous cell carcinoma. Conclusion The elevated levels of ENO1 protein in the tumor tissues and the plasma samples from NSCLC patients indicate ENO1 may be a candidate biomarker of lung cancer.

  19. Effects of Dietary Decosahexaenoic Acid (Dha) on eNOS in Human Coronary Artery Endothelial Cells

    Science.gov (United States)

    Stebbins, Charles L.; Stice, James P.; Hart, C. Michael; Mbai, Fiona N.; Knowlton, Anne A.

    2015-01-01

    Endothelial dysfunction occurs in heart disease, and may reduce functional capacity via attenuations in peripheral blood flow. Dietary DHA may improve this dysfunction, but the mechanism is unknown. We determined if DHA enhances expression and activity of eNOS in cultured human coronary artery endothelial cells (HCAEC). HCAEC from 4 donors were treated with 5 nM, 50 nM, or 1 μM DHA for 7 days to model chronic DHA exposure. A trend for increased expression of eNOS and phospho-eNOS was observed with 5 and 50 nM DHA. DHA also enhanced expression of two proteins instrumental in activation of eNOS; phospho-Akt (5 and 50 nM) and HSP90 (50 nM and 1 μM). VEGF-induced activation of Akt increased NOx in treated (50 nM DHA) vs. untreated HCAEC (9.2±1.0 vs. 3.3±1.1 μmols/μg protein/μl). Findings suggest that DHA enhances eNOS and Akt activity, augments HSP90 expression, and increases NO bioavailability in response to Akt kinase activation PMID:18682551

  20. Characterization of porcine ENO3: genomic and cDNA structure, polymorphism and expression

    Directory of Open Access Journals (Sweden)

    Xiong Yuanzhu

    2008-09-01

    Full Text Available Abstract In this study, a full-length cDNA of the porcine ENO3 gene encoding a 434 amino acid protein was isolated. It contains 12 exons over approximately 5.4 kb. Differential splicing in the 5'-untranslated sequence generates two forms of mRNA that differ from each other in the presence or absence of a 142-nucleotide fragment. Expression analysis showed that transcript 1 of ENO3 is highly expressed in liver and lung, while transcript 2 is highly expressed in skeletal muscle and heart. We provide the first evidence that in skeletal muscle expression of ENO3 is different between Yorkshire and Meishan pig breeds. Furthermore, real-time polymerase chain reaction revealed that, in Yorkshire pigs, skeletal muscle expression of transcript 1 is identical at postnatal day-1 and at other stages while that of transcript 2 is higher. Moreover, expression of transcript 1 is lower in skeletal muscle and all other tissue samples than that of transcript 2, with the exception of liver and kidney. Statistical analysis showed the existence of a polymorphism in the ENO3 gene between Chinese indigenous and introduced commercial western pig breeds and that it is associated with fat percentage, average backfat thickness, meat marbling and intramuscular fat in two different populations.

  1. enos informací po síti Ethernet

    OpenAIRE

    Kutílek, Miloš

    2013-01-01

    Tato diplomová práce se zabývá přenosem informací po síti Ethernet. V této práci byl vybrán vhodný mikrokontrolér a komunikační modul, který zajištuje přenos dat z Ethernetu na SPI sběrnici, dále bylo zvoleno optimální digitální teplotní čidlo DS1820. Teoreticky popisuje model TCP/IP a síť typu Ethernet. V práci je vytvořeno blokové schéma zapojení, dále bylo vytvořeno elektrické schéma zapojení a deska plošných spojů. V prostředí BascomAVR je naprogramován program, který slouží pro přenos in...

  2. Adenovirus-mediated eNOS expression augments liver injury after ischemia/reperfusion in mice.

    Directory of Open Access Journals (Sweden)

    Arun P Palanisamy

    Full Text Available Hepatic ischemia/reperfusion (l/R injury continues to be a critical problem. The role of nitric oxide in liver I/R injury is still controversial. This study examines the effect of endothelial nitric oxide synthase (eNOS over-expression on hepatic function following I/R. Adenovirus expressing human eNOS (Ad-eNOS was administered by tail vein injection into C57BL/6 mice. Control mice received either adenovirus expressing LacZ or vehicle only. Sixty minutes of total hepatic ischemia was performed 3 days after adenovirus treatment, and mice were sacrificed after 6 or 24 hrs of reperfusion to assess hepatic injury. eNOS over expression caused increased liver injury as evidenced by elevated AST and ALT levels and decreased hepatic ATP content. While necrosis was not pervasive in any group, TUNEL demonstrated significantly increased apoptosis in Ad-eNOS infected livers. Western blotting demonstrated increased levels of protein nitration and upregulation of the pro-apoptotic proteins bax and p53. Our data suggest that over-expression of eNOS is detrimental in the setting of hepatic I/R.

  3. Functional link between ETB receptors and eNOS maintain tissue oxygenation in the normal liver.

    Science.gov (United States)

    Paxian, Markus; Keller, Steve A; Baveja, Rajiv; Korneszczuk, Katarzyna; Huynh, Toan T; Clemens, Mark G

    2004-01-01

    Endothelins and their receptors play a crucial role in regulating liver microcirculation in pathophysiological conditions. The authors investigated the functional significance of the coupling of ET(B) receptors and eNOS in maintaining regional perfusion and tissue oxygenation in the normal liver. The effect of endothelin-1 or the ET(B) agonist IRL1620 on oxygen consumption was determined in isolated perfused liver and isolated hepatocytes. Oxygen delivery to the liver tissue was determined in vivo. Following eNOS or iNOS blockade, either ET-1 or IRL1620 was infused via the portal vein. Hepatic tissue oxygenation, redox state, and microcirculation were investigated by intravital microscopy. Injury was estimated by serum LDH. Although IRL1620 and endothelin-1 increased oxygen consumption in isolated hepatocytes, in intact liver, endothelin decreased oxygen consumption while IRL1620 produced no change. In vivo, ET(B) stimulation modestly altered hepatic tissue P(O(2)), redox potential, and microcirculation. eNOS inhibition and ET(B) activation dramatically reduced microcirculatory blood flow, oxygen supply, and increased LDH release. Inhibition of iNOS resulted in small but not significant changes in these parameters. Concomitant ET(A)/ET(B) receptor activation increased microcirculatory failure and decreased tissue oxygen even without NOS inhibition. In contrast, hepatocellular injury was significantly increased following eNOS inhibition. Coupling between ET(B) receptor stimulation and eNOS activation decreases sinusoidal constriction and plays a functionally important role in maintaining microcirculation and tissue oxygenation in the normal liver.

  4. Phosphomimetic modulation of eNOS improves myocardial reperfusion and mimics cardiac postconditioning in mice.

    Directory of Open Access Journals (Sweden)

    Terrence Pong

    Full Text Available OBJECTIVE: Myocardial infarction resulting from ischemia-reperfusion injury can be reduced by cardiac postconditioning, in which blood flow is restored intermittently prior to full reperfusion. Although key molecular mechanisms and prosurvival pathways involved in postconditioning have been identified, a direct role for eNOS-derived NO in improving regional myocardial perfusion has not been shown. The objective of this study is to measure, with high temporal and spatial resolution, regional myocardial perfusion during ischemia-reperfusion and postconditioning, in order to determine the contribution of regional blood flow effects of NO to infarct size and protection. METHODS AND RESULTS: We used myocardial contrast echocardiography to measure regional myocardial blood flow in mice over time. Reperfusion after myocardial ischemia-reperfusion injury is improved by postconditioning, as well as by phosphomimetic eNOS modulation. Knock-in mice expressing a phosphomimetic S1176D form of eNOS showed improved myocardial reperfusion and significantly reduced infarct size. eNOS knock-out mice failed to show cardioprotection from postconditioning. The size of the no-reflow zone following ischemia-reperfusion is substantially reduced by postconditioning and by the phosphomimetic eNOS mutation. CONCLUSIONS AND SIGNIFICANCE: Using myocardial contrast echocardiography, we show that temporal dynamics of regional myocardial perfusion restoration contribute to reduced infarct size after postconditioning. eNOS has direct effects on myocardial blood flow following ischemia-reperfusion, with reduction in the size of the no-reflow zone. These results have important implications for ongoing clinical trials on cardioprotection, because the degree of protective benefit may be significantly influenced by the regional hemodynamic effects of eNOS-derived NO.

  5. VEGF and eNOS Expression in Umbilical Cord from Pregnancy Complicated by Hypertensive Disorder with Different Severity

    Directory of Open Access Journals (Sweden)

    K. Bhavina

    2014-01-01

    Full Text Available Background. Reduced blood flow in hypertensive pregnancy may influence the production vasoconstrictors; subsequently the vessel remains in highly contracted state. NO is a vasodilator; VEGF influences its synthesis by regulating eNOS production. Aim of our study was to evaluate the expression of VEGF and eNOS in different severity of hypertensive pregnancy. Methods. Study was conducted in 4 groups with 40 members: group 1—control, group 2—gestational hypertension, group 3—mild preeclampsia, and group 4—severe preeclampsia. Fetal end of umbilical cord was taken and follows IHC staining protocol for VEGF and eNOS antibody. Staining intensity were measured by semiquantitative scoring method. Mann Whitney U test was used to compare each group. Results. Decreased expression of both VEGF and eNOS was found in hypertensive condition than in normal condition. Among hypertensive group, severe preeclamptic group showed more intensity in staining than gestational hypertension and mild preeclampsia. Conclusion. Reduction of VEGF and eNOS in gestational hypertension may lead to hypoperfusion and subsequent hypoxia of fetus in hypertensive pregnancy. The developed hypoxic state may upregulate the synthesis of VEGF and thereby eNOS. Increased expression of VEGF and eNOS in severe group may be a compensatory mechanism to dilate the blood vessels and to improve blood flow of fetus.

  6. Liposomal tetrahydrobiopterin preserves eNOS coupling in the post-ischemic heart conferring in vivo cardioprotection.

    Science.gov (United States)

    Xie, Lin; Talukder, M A Hassan; Sun, Jian; Varadharaj, Saradhadevi; Zweier, Jay L

    2015-09-01

    Tetrahydrobiopterin (BH4) is an essential cofactor of nitric oxide synthase (NOS), and reduced BH4 availability leads to endothelial NOS (eNOS) uncoupling and increased reactive oxygen species (ROS) generation. Questions remain regarding the functional state of eNOS and role of BH4 availability in the process of in vivo myocardial ischemia-reperfusion (I/R) injury. Rats were subjected to 60min of in vivo left coronary artery occlusion and varying periods of reperfusion with or without pre-ischemic liposomal BH4 supplementation (1mg/kg, iv). Myocardial infarction was correlated with cardiac BH4 content, eNOS protein level, NOS enzyme activity, and ROS generation. In the vehicle group, 60-min ischemia drastically reduced myocardial BH4 content in the area at risk (AAR) compared to non-ischemic (NI) area and the level remained lower during early reperfusion followed by recovery after 24-h reperfusion. Total eNOS, activated eNOS protein level (eNOS Ser1177 phosphorylation) and NOS activity were also significantly reduced during ischemia and/or early reperfusion, but recovered after 24-h reperfusion. With liposomal BH4 treatment, BH4 levels were identical in the AAR and NI area during ischemia and/or early reperfusion, and were significantly higher than with vehicle. BH4 pre-treatment preserved eNOS Ser1177 phosphorylation and NOS activity in the AAR, and significantly reduced myocardial ROS generation and infarction compared to vehicle. These findings provide direct evidence that in vivo I/R induces eNOS dysfunction secondary to BH4 depletion, and that pre-ischemic liposomal BH4 administration preserves eNOS function conferring cardioprotection with reduced oxidative stress. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Clustering of cardiovascular risk factors mimicking the human metabolic syndrome X in eNOS null mice.

    OpenAIRE

    Cook, S; Hugli, O; Egli, M; Vollenweider, P.; Burcelin, R.; Nicod, P; Thorens, B.; Scherrer, U

    2003-01-01

    AIMS/HYPOTHESIS: The metabolic syndrome comprises a clustering of cardiovascular risk factors but the underlying mechanism is not known. Mice with targeted disruption of endothelial nitric oxide synthase (eNOS) are hypertensive and insulin resistant. We wondered, whether eNOS deficiency in mice is associated with a phenotype mimicking the human metabolic syndrome. METHODS AND RESULTS: In addition to arterial pressure and insulin sensitivity (euglycaemic hyperinsulinaemic clamp), we measured t...

  8. Role of Endothelial Nitric Oxide Synthase in Diabetic Nephropathy: Lessons from Diabetic eNOS Knockout Mice

    OpenAIRE

    Takamune Takahashi; Harris, Raymond C.

    2014-01-01

    Diabetic nephropathy (DN) is the leading cause of end-stage renal disease in many countries. The animal models that recapitulate human DN undoubtedly facilitate our understanding of this disease and promote the development of new diagnostic markers and therapeutic interventions. Based on the clinical evidence showing the association of eNOS dysfunction with advanced DN, we and others have created diabetic mice that lack eNOS expression and shown that eNOS-deficient diabetic mice exhibit advan...

  9. Activation of eNOS in endothelial cells exposed to ionizing radiation involves components of the DNA damage response pathway

    Energy Technology Data Exchange (ETDEWEB)

    Nagane, Masaki; Yasui, Hironobu; Sakai, Yuri; Yamamori, Tohru [Laboratory of Radiation Biology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818 (Japan); Niwa, Koichi [Laboratory of Biochemistry, Department of Food and Cosmetic Science, Faculty of Bioindustry, Tokyo University of Agriculture, Abashiri 099-2493 (Japan); Hattori, Yuichi [Department of Molecular and Medical Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194 (Japan); Kondo, Takashi [Department of Radiological Sciences, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194 (Japan); Inanami, Osamu, E-mail: inanami@vetmed.hokudai.ac.jp [Laboratory of Radiation Biology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818 (Japan)

    2015-01-02

    Highlights: • eNOS activity is increased in BAECs exposed to X-rays. • ATM is involved in this increased eNOS activity. • HSP90 modulates the radiation-induced activation of ATM and eNOS. - Abstract: In this study, the involvement of ataxia telangiectasia mutated (ATM) kinase and heat shock protein 90 (HSP90) in endothelial nitric oxide synthase (eNOS) activation was investigated in X-irradiated bovine aortic endothelial cells. The activity of nitric oxide synthase (NOS) and the phosphorylation of serine 1179 of eNOS (eNOS-Ser1179) were significantly increased in irradiated cells. The radiation-induced increases in NOS activity and eNOS-Ser1179 phosphorylation levels were significantly reduced by treatment with either an ATM inhibitor (Ku-60019) or an HSP90 inhibitor (geldanamycin). Geldanamycin was furthermore found to suppress the radiation-induced phosphorylation of ATM-Ser1181. Our results indicate that the radiation-induced eNOS activation in bovine aortic endothelial cells is regulated by ATM and HSP90.

  10. Correlation between pulmonary gas exchange and basal and nitroglycerin (GTN)-induced exhaled nitric oxide (eNO) in patients undergoing cardiac surgery.

    Science.gov (United States)

    Kövesi, Tamás; Szabo, Anita; Royston, David; Marczin, Nándor

    2005-12-01

    The relationship between eNO and events in the alveolar-capillary unit in acute lung injury remains to be established. Since endogenous eNO largely originates from the airway epithelium, but nitroglycerin (GTN)-induced eNO is due to microvascular/alveolar metabolism, we have proposed to use basal and GTN-induced eNO as metabolic markers of the airway--and microvascular/alveolar function, respectively. The current work investigates the relationship between basal and GTN-induced eNO and oxygenation parameters (PaO(2)/FiO(2) ratio) in patients undergoing cardiac surgery utilising cardiopulmonary bypass (CPB). Breath by breath eNO measurements were made in 10 patients before, and 1 and 3 h after CPB either under basal conditions or following intravenous administration of GTN (1, 2 and 3 microg/kg). Basal eNO remained unchanged, whereas GTN-induced eNO was reduced following CPB. Also, there was a transient reduction in PaO(2)/FiO(2) ratio 1 h after CPB (32+/-4 vs. 44+/-3 kPa). A negative correlation was found between oxygenation and basal eNO by Pearson's correlation test and linear regression analysis suggesting that decreased oxygenation was associated with increased basal eNO. In contrast, a decrease in GTN-induced eNO positively correlated with reduced oxygenation index (R=0.533, p=0.002). These data suggest that differential relationships exist between basal and nitrovasodilator-induced eNO and oxygenation indices during subclinical lung injury in patients following CPB and that GTN-induced eNO evolution may reflect better microvascular events and injury.

  11. ENDOTHELIAL NITRIC OXIDE SYNTHASE (ENOS GENE POLYMORPHISM IS ASSOCIATED WITH AGE ONSET OF MENARCHE IN SICKLE CELL DISEASE FEMALES OF INDIA

    Directory of Open Access Journals (Sweden)

    Sudhansu Sekhar Nishank

    2013-06-01

    Full Text Available ABSTRACT   Background and Objective :  Females with sickle cell disease (SCD often show late onset of menarche. In transgenic sickle cell mouse, deficiency of gene encoding endothelial nitric oxide synthase (eNOS has been reported to be associated with late onset of menarche. Thus to explore the possible association of eNOS gene polymorphism with age of onset of menarche in SCD females, 3 important eNOS gene polymorphism- eNOS 4a/b, eNOS 894G>T and eNOS-786 T>C  and  plasma nitrite levels were tested among three groups of females- SCD late menarche, SCD early menarche and control females. Methods : PCR-RFLP method for genotyping eNOS gene polymorphisms and quantification of plasma nitrite level by ELISA based commercial kits were used Results: SCD late menarche females showed significantly higher prevalence and higher association of heterozygous genotypes, higher frequency of mutant alleles ‘4a’, ‘T’ and ‘C’ as compared to that of control group and SCD early menarche group. The frequency of haplotype  ‘4a-G-C’ and haplotype’ 4b-G-C’ (alleles in order of  eNOS 4a/b, eNOS 894G>T and eNOS-786 T>C respectively were found to be significantly high in SCD late menarche compared to combined groups of SCD early menarche and controls. SCD late menarche group had significantly low level of plasma nitrite concentration for all 3 eNOS gene polymorphisms as compared to controls and SCD early menarche females. Conclusion: eNOS gene polymorphism may influence age of onset of menarche in SCD females.   Key words : eNOS gene, sickle cell disease, menarche, haplotype, nitric oxide

  12. A novel multiplex PCR-RFLP method for simultaneous detection of the MTHFR 677 C > T, eNOS +894 G > T and - eNOS -786 T > C variants among Malaysian Malays

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    Loo Keat

    2012-05-01

    Full Text Available Abstract Background Hyperhomocysteinemia as a consequence of the MTHFR 677 C > T variant is associated with cardiovascular disease and stroke. Another factor that can potentially contribute to these disorders is a depleted nitric oxide level, which can be due to the presence of eNOS +894 G > T and eNOS −786 T > C variants that make an individual more susceptible to endothelial dysfunction. A number of genotyping methods have been developed to investigate these variants. However, simultaneous detection methods using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP analysis are still lacking. In this study, a novel multiplex PCR-RFLP method for the simultaneous detection of MTHFR 677 C > T and eNOS +894 G > T and eNOS −786 T > C variants was developed. A total of 114 healthy Malay subjects were recruited. The MTHFR 677 C > T and eNOS +894 G > T and eNOS −786 T > C variants were genotyped using the novel multiplex PCR-RFLP and confirmed by DNA sequencing as well as snpBLAST. Allele frequencies of MTHFR 677 C > T and eNOS +894 G > T and eNOS −786 T > C were calculated using the Hardy Weinberg equation. Methods The 114 healthy volunteers were recruited for this study, and their DNA was extracted. Primer pair was designed using Primer 3 Software version 0.4.0 and validated against the BLAST database. The primer specificity, functionality and annealing temperature were tested using uniplex PCR methods that were later combined into a single multiplex PCR. Restriction Fragment Length Polymorphism (RFLP was performed in three separate tubes followed by agarose gel electrophoresis. PCR product residual was purified and sent for DNA sequencing. Results The allele frequencies for MTHFR 677 C > T were 0.89 (C allele and 0.11 (T allele; for eNOS +894 G > T, the allele frequencies were 0.58 (G allele and 0.43 (T allele; and for eNOS −786 T > C, the allele

  13. Non-oscillatory Central Differencing (Noc) Scheme to Solve the Shallow Water Equations Coupled with Sediment Transport and Bed Evolution in Two Dimensions

    Science.gov (United States)

    Zia, H.; Simpson, G.

    2013-12-01

    The interaction between flowing surface water and sediment transport has numerous important applications in Earth science, including controls on river patterns, drainage basin evolution and morphological changes induced by extreme events such as tsunamis and dam breaks. Many of these problems can be investigated with the mathematical model of the shallow water equations coupled to conservation of sediment concentration and empirical functions for bed friction, substrate erosion and deposition. However, this system of equations is highly nonlinear, requiring fast and robust numerical methods. In this study, we investigate the solution of the shallow water equations coupled to sediment transports via the Non-oscillatory Central Differencing (NOC ) method, a second order scheme based on a predictor-corrector method. The scheme is chosen for its relative stability and robustness. The NOC scheme is especially favorable in situations where the water depth approaches zero and for steady flow conditions, both of which cause problems with more naive schemes. The model is verified by comparing computed results with documented solutions. We are currently using the model to investigate coupling between flow and sediment transport in alluvial rivers.

  14. KONSUMSI MIKRONUTRIEN DAN EKSPRESI GEN eNOS3 ALEL INTRO 4a4b PADA PENDERITA HIPERTENSI ETNIK MINANGKABAU

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    Delmi Sulastri

    2011-05-01

    Full Text Available AbstrakGen eNOS3 varian intron 4a4b merupakan salah satu gen yang berhubungan dengan kejadian hipertensi esensial. Kemampuan Gen eNOS3 varian ini untuk mensintesis enzim nitric oxide synthase (NOS berkurang sehingga sintesis Nitric oxide (NO menurun. Senyawa NO adalah suatu senyawa vasoaktif yang menyebabkan vasodilatasi pembuluh darah.Penelitian pada subjek hipertensi dan normotensi berusia 30-65 tahun bertujuan untuk melihat pengaruh mikronutrien terhadap ekspresi gen eNOS3 alel intron 4a4b. 130 subjek, diwawancara pola makannya lalu dilakukan analisis asupan mikronutrien, gen eNOS3, serta kadar NO plasma. Data yang diperoleh dianalisis menggunakan uji T dan chi-square.Kadar NO plasma penderita hipertensi adalah 26.91 + 15.40 μM/L dan normotensi 25.79 + 15.04 μM/L. 55.5% subjek hipertensi memiliki gen eNOS3 varian intron 4b dan 69% subjek normotensi mempunyai varian intron 4a4b. Kadar NO plasma rendah, (66.7% ditemukan pada subjek hipertensi dengan varian intron 4b. Tidak terdapat hubungan bermakna asupan mikronutrien dengan kadar NO plasma pada subjek hipertensi.Hasil ini tidak mendukung pengaruh konsumsi mikronutrien terhadap kadar NO plasma pada penderita hipertensi dengan gen eNOS3 varian intron 4a4b.Kata Kunci : hipertensi esensial, gen eNOS3, kadar NO plasmaAbstracteNOS 3 gene intron 4a4b allel is one of the important genes which is related to hypertesion essensial. This gene expresses the nitric oxide synthase (NOS enzyme which regulates the synthesis of Nitric oxide (NO in human body. NO causes vasodilatation, which decreases peripheral resistant and blood pressure.A research has been done based on cross sectional study on hypertension patients and those with normal blood pressure in the range of 30-65 years old. The main of this research is to evaluate the influence of micronutrient consumption on eNOS3 gene intron 4a4b allel expression in hypertension subjects in Minangkabau ethnicity. 130 subjects interviewed about micronutrient

  15. ENO1 promotes tumor proliferation and cell adhesion mediated drug resistance (CAM-DR) in Non-Hodgkin's Lymphomas

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Xinghua; Miao, Xiaobing; Wu, Yaxun; Li, Chunsun; Guo, Yan; Liu, Yushan; Chen, Yali; Lu, Xiaoyun [Department of Pathology, Affiliated Cancer Hospital of Nantong University, 30 North Tongyang Road, Pingchao, Nantong 226361, Jiangsu (China); Wang, Yuchan, E-mail: wangyuchannt@126.com [Department of Pathogen and Immunology, Medical College, Nantong University, 19 Qixiu Road, Nantong 226001, Jiangsu (China); He, Song, E-mail: hesongnt@126.com [Department of Pathology, Affiliated Cancer Hospital of Nantong University, 30 North Tongyang Road, Pingchao, Nantong 226361, Jiangsu (China)

    2015-07-15

    Enolases are glycolytic enzymes responsible for the ATP-generated conversion of 2-phosphoglycerate to phosphoenolpyruvate. In addition to the glycolytic function, Enolase 1 (ENO1) has been reported up-regulation in several tumor tissues. In this study, we investigated the expression and biologic function of ENO1 in Non-Hodgkin's Lymphomas (NHLs). Clinically, by western blot analysis we observed that ENO1 expression was apparently higher in diffuse large B-cell lymphoma than in the reactive lymphoid tissues. Subsequently, immunohistochemical staining of 144 NHLs suggested that the expression of ENO1 was significantly lower in the indolent lymphomas compared with the progressive lymphomas. Further, we identified ENO1 as an independent prognostic factor, and it was significantly correlated with overall survival of NHL patients. In addition, we found that ENO1 could promote cell proliferation, regulate cell cycle associated gene and PI3K/AKT signaling pathway in NHLs. Finally, we verified that ENO1 participated in the process of lymphoma cell adhesion mediated drug resistance (CAM-DR). Adhesion to FN or HS5 cells significantly protected OCI-Ly8 and Daudi cells from cytotoxicity compared with those cultured in suspension, and these effects were attenuated when transfected with ENO1-siRNA. Based on the study, we propose that inhibition of ENO1 expression may be a novel strategy for therapy for NHLs patients, and it may be a target for drug resistance. - Highlights: • ENO1 expression is reversely correlated with clinical outcomes of patients with NHLs. • ENO1 promotes the proliferation of NHL cells. • ENO1 regulates cell adhesion mediated drug resistance.

  16. Effects of rat urotensin II on coronary flow and myocardial eNOS protein expression in isolated rat heart

    Institute of Scientific and Technical Information of China (English)

    LingLI; Wen-junYUAN; Ding-fengSU

    2004-01-01

    AIM: To examine the effects of urotensin Ⅱ, a recently discovered endogenous peptide, on coronary flow (CF),cardiac function, and endothelial nitric oxide synthase (eNOS) expression in isolated rat hearts. METHODS: Heart was isolated and perfused retrogradely via the aorta in Langendorff mode. Rat urotensin Ⅱ was administered in the perfusion solution. The eNOS content in myocardium was determined by Western blot. RESULTS: Rat urotensin Ⅱ had no effect on the heart rate, left ventricular systolic pressure, left ventricular end-diastolic pressure, or±dp/dt max. While rat urotensin Ⅱ dose-dependently increased CF. CF was increased by 11.43%, 6.67%, 6.62%,6.56%, 6.36%, and 5.86% respectively in a time-dependent manner at 5, 10, 15, 20, 25, and 30 min after injection of rat urotensin Ⅱ 6.66×10-2μg. The maximal effect on CF was found at 5 min following urotensin Ⅱ administration.NG-nitro-L-arginine methyl ester (L-NAME) did not prevent the increased CF in response to urotensin Ⅱ. Rat urotensin Ⅱ dose-dependently increased the cardiac eNOS protein expression and this effect was not inhibited by L-NAME. CONCLUSION: Rat urotensin Ⅱ did not alter cardiac function but increased CF and the amount of myocardial eNOS protein in the isolated rat heart. The increased CF was independent of the involvement of eNOS.

  17. Role of Endothelial Nitric Oxide Synthase in Diabetic Nephropathy: Lessons from Diabetic eNOS Knockout Mice

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    Takamune Takahashi

    2014-01-01

    Full Text Available Diabetic nephropathy (DN is the leading cause of end-stage renal disease in many countries. The animal models that recapitulate human DN undoubtedly facilitate our understanding of this disease and promote the development of new diagnostic markers and therapeutic interventions. Based on the clinical evidence showing the association of eNOS dysfunction with advanced DN, we and others have created diabetic mice that lack eNOS expression and shown that eNOS-deficient diabetic mice exhibit advanced nephropathic changes with distinct features of progressive DN, including pronounced albuminuria, nodular glomerulosclerosis, mesangiolysis, and arteriolar hyalinosis. These studies clearly defined a critical role of eNOS in DN and developed a robust animal model of this disease, which enables us to study the pathogenic mechanisms of progressive DN. Further, recent studies with this animal model have explored the novel mechanisms by which eNOS deficiency causes advanced DN and provided many new insights into the pathogenesis of DN. Therefore, here we summarize the findings obtained with this animal model and discuss the roles of eNOS in DN, unresolved issues, and future investigations of this animal model study.

  18. Effect of Exercise Training on Enos Expression, NO Production and Oxygen Metabolism in Human Placenta

    Science.gov (United States)

    Ramírez-Vélez, Robinson; Bustamante, Juanita; Czerniczyniec, Analia; Aguilar de Plata, Ana C.; Lores-Arnaiz, Silvia

    2013-01-01

    Objective To determine the effects of combined aerobic and resistance exercise training during the second half of pregnancy on endothelial NOS expression (eNOS), nitric oxide (NO) production and oxygen metabolism in human placenta. Methods The study included 20 nulliparous in gestational week 16–20, attending prenatal care at three tertiary hospitals in Colombia who were randomly assigned into one of two groups: The exercise group (n = 10) took part in an exercise session three times a week for 12 weeks which consisted of: aerobic exercise at an intensity of 55–75% of their maximum heart rate for 60 min and 25 mins. Resistance exercise included 5 exercise groups circuit training (50 repetitions of each) using barbells (1–3 kg/exercise) and low-to-medium resistance bands. The control group (n = 10) undertook their usual physical activity. Mitochondrial and cytosol fractions were isolated from human placental tissue by differential centrifugation. A spectrophotometric assay was used to measure NO production in cytosolic samples from placental tissue and Western Blot technique to determine eNOS expression. Mitochondrial superoxide levels and hydrogen peroxide were measured to determine oxygen metabolism. Results Combined aerobic and resistance exercise training during pregnancy leads to a 2-fold increase in eNOS expression and 4-fold increase in NO production in placental cytosol (p = 0.05). Mitochondrial superoxide levels and hydrogen peroxide production rate were decreased by 8% and 37% respectively in the placental mitochondria of exercising women (p = 0.05). Conclusion Regular exercise training during the second half of pregnancy increases eNOS expression and NO production and decreases reactive oxygen species generation in human placenta. Collectively, these data demonstrate that chronic exercise increases eNOS/NO production, presumably by increasing endothelial shear stress. This adaptation may contribute to the beneficial effects of

  19. 胃癌组织中ENO1、M2-PK蛋白表达及其临床意义%Expressions and Clinical Significances of ENO1 and M2-PK in Gastric Cancer

    Institute of Scientific and Technical Information of China (English)

    倪田根; 祝秉东; 周欣; 王娜; 曾峰; 关泉林

    2011-01-01

    目的:探讨胃癌组织中烯醇化酶-α(enolase-α,ENO1)、肿瘤型丙酮酸激酶(tumor M2 pyruvate kinase,M2-PK)的表达、相互关系及临床病理学意义.方法:应用免疫组织化学SP染色方法分别对55例胃癌组织和23例胃良性病变组织切片染色,观察胃癌组织和良性病变组织ENO1、M2-PK的表达情况及分析两者临床病理关系.结果:胃癌组织中ENO1阳性表达率为67.3% (37/55),明显高于胃良性病变组30.4%(7/23)(P<0.01),其表达与胃癌分化程度、浸润深度、淋巴结转移及TNM分期均显著相关(均P<0.05).M2-PK在胃癌组织中的阳性表达率为78.2%(43/55),明显高于胃良性病变组织39.1%(9/23) (P<0.01),其表达与胃癌分化程度、浸润深度均显著相关(均P<0.05).胃癌组织中ENO1与M2-PK的表达呈正相关(r=0.5729,P<0.05).结论:ENO1和M2-PK的表达上调与胃癌的发生、发展可能有关,联合检测两种蛋白在肿瘤组织中的表达,对临床判断胃癌的预后有一定的指导意义.%Objective: To investigate the expression and clinicopathotogical significance of enolase-a (ENO1) and tumor M2 pyruvate kinase (M2-PK) in gastric cancer. Methods: The expression of ENO1 and M2-PK in 55 paraffin-embedded specimens of gastric cancer and 23 paraffin-embedded specimens of benign gastric tissue was detected by S-P immunohistochemistry. The correlation of ENO1 expression to M2-PK. Expression, and their correlations to the clinicophathologic features of gastric cancer were analyzed. Results: The positive rate of ENO1 was significantly higher in gastric cancer than in benign gastric tissue (67.3% vs . 30.4%, P<0.01) , and closely related to differentiation grade ( P<0.01) , depth of invasion (P<0.01), lymph node metastasis (P<0.05) and TNM staging( P<0. 05),The positive rate of M2-PK. Was significantly higher in gastric cancer than in benign gastric tissue (78.2%vs . 39,1%, P<0.01) , and closely related to differentiation grade ( P0

  20. Alpha-enolase (ENO1 controls alpha v/beta 3 integrin expression and regulates pancreatic cancer adhesion, invasion, and metastasis

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    Moitza Principe

    2017-01-01

    Full Text Available Abstract Background We have previously shown that in pancreatic ductal adenocarcinoma (PDA cells, the glycolytic enzyme alpha-enolase (ENO1 also acts as a plasminogen receptor and promotes invasion and metastasis formation. Moreover, ENO1 silencing in PDA cells induces oxidative stress, senescence and profoundly modifies PDA cell metabolism. Although anti-ENO1 antibody inhibits PDA cell migration and invasion, little is known about the role of ENO1 in regulating cell-cell and cell-matrix contacts. We therefore investigated the effect of ENO1 silencing on the modulation of cell morphology, adhesion to matrix substrates, cell invasiveness, and metastatic ability. Methods The membrane and cytoskeleton modifications that occurred in ENO1-silenced (shENO1 PDA cells were investigated by a combination of confocal microscopy and atomic force microscopy (AFM. The effect of ENO1 silencing was then evaluated by phenotypic and functional experiments to identify the role of ENO1 in adhesion, migration, and invasion, as well as in senescence and apoptosis. The experimental results were then validated in a mouse model. Results We observed a significant increase in the roughness of the cell membrane due to ENO1 silencing, a feature associated with an impaired ability to migrate and invade, along with a significant downregulation of proteins involved in cell-cell and cell-matrix adhesion, including alpha v/beta 3 integrin in shENO1 PDA cells. These changes impaired the ability of shENO1 cells to adhere to Collagen I and IV and Fibronectin and caused an increase in RGD-independent adhesion to vitronectin (VN via urokinase plasminogen activator receptor (uPAR. Binding of uPAR to VN triggers integrin-mediated signals, which result in ERK1-2 and RAC activation, accumulation of ROS, and senescence. In shENO1 cancer cells, the use of an anti-uPAR antibody caused significant reduction of ROS production and senescence. Overall, a decrease of in vitro and in vivo cell

  1. eNOS polymorphisms and clinical outcome in advanced HCC patients receiving sorafenib: final results of the ePHAS study.

    Science.gov (United States)

    Casadei Gardini, Andrea; Marisi, Giorgia; Faloppi, Luca; Scarpi, Emanuela; Foschi, Francesco Giuseppe; Iavarone, Massimo; Lauletta, Gianfranco; Corbelli, Jody; Valgiusti, Martina; Facchetti, Floriana; Della Corte, Cristina; Neri, Luca Maria; Tamberi, Stefano; Cascinu, Stefano; Scartozzi, Mario; Amadori, Dino; Nanni, Oriana; Tenti, Elena; Ulivi, Paola; Frassineti, Giovanni Luca

    2016-05-10

    Sorafenib may reduce endothelial nitric oxide synthase (eNOS) activity by inhibiting vascular endothelial growth factor receptors (VEGF-R), leading to a decrease in nitric oxide production. In the Italian multicenter ePHAS (eNOS polymorphisms in HCC and sorafenib) study, we analyzed the role of eNOS polymorphisms in relation to clinical outcome in patients with hepatocellular carcinoma (HCC) receiving sorafenib. Our retrospective study included a training cohort of 41 HCC patients and a validation cohort of 87 HCC patients, all undergoing sorafenib treatment. Three eNOS polymorphisms (eNOS -786T>C, eNOS VNTR 27bp 4a/b and eNOS+894G>T) were analyzed by direct sequencing or Real Time PCR in relation to progression-free survival (PFS) and overall survival (OS) (log-rank test). In univariate analysis, training cohort patients homozygous for eNOS haplotype (HT1:T-4b at eNOS-786/eNOS VNTR) had a lower median PFS (2.6 vs. 5.8 months, P < 0.0001) and OS (3.2 vs.14.6 months, P = 0.024) than those with other haplotypes. In the validation set, patients homozygous for HT1 had a lower median PFS (2.0 vs. 6.7 months, P < 0.0001) and OS (6.4 vs.18.0 months, P < 0.0001) than those with other haplotypes. Multivariate analysis confirmed this haplotype as the only independent prognostic factor. Our results suggest that haplotype HT1 in the eNOS gene may be capable of identifying a subset of HCC patients who are resistant to sorafenib.

  2. Environmental Aspects as Assessment Criteria in Municipal Heat Energy Decisions - Case of Eno Energy Cooperative

    Energy Technology Data Exchange (ETDEWEB)

    Puhakka, Asko [North Karelia Univ. of Applied Sciences, Joensuu (Finland)

    2006-07-15

    The aim of this paper is to provide information whether it is possible to consider the sustainable development perspectives in the decision making of the district energy decision. The new EU-directives concerning public procurements allow the use of environmental aspects as selection criteria. The focus here is on small-scale district heating systems and their fuel-supply chains. The comparable fuels included the analysis are forest chips, heavy fuel oil, light fuel oil and peat. The paper focuses to the concept of the sustainable development and establishes the indicators for ecological-, social- and economical aspects of the district heating. The indicators are utilized in the case study on the Eno Energy Cooperative. The equivalent CO{sub 2} emissions from the production and the combustion of the fuel, the employment impacts of the fuel production and the formation of the price of energy for the consumers are considered. After presenting the sustainable development indicators in the case of Eno Energy Cooperative, the investment models of heat entrepreneurship business are discussed. Finally, we also raise an attention into important aspects to be considered when establishing a local district heating scheme. The indicators used in this presentation show that the use of forest chips in energy production has positive effect through the reduced greenhouse gases. The use of wood in energy production also provides employment opportunities and is more favourable to consumers, because of the steady fuel price when compared to other alternative fuels.

  3. miR-222 contributes to sex-dimorphic cardiac eNOS expression via ets-1.

    Science.gov (United States)

    Evangelista, Alicia M; Deschamps, Anne M; Liu, Delong; Raghavachari, Nalini; Murphy, Elizabeth

    2013-06-17

    It is well recognized that there is sex-dimorphic expression of mRNA and protein in the heart; however, the underlying mechanism is poorly understood. Endothelial nitric oxide synthase (eNOS) is an important regulator of cardiac function, and the expression levels of eNOS differ between male and female hearts. The aim of this study was to examine whether expression of specific microRNA (miRNA, miR) in males and females contributes to changes in the expression of eNOS. miRNA was extracted from the myocardium of male and female C57BL/6 mice and subjected to an Affymetrix miRNA array. Decreased expression of miR-222 was discovered in females and confirmed by qRT-PCR from whole heart or isolated cardiomyocytes. The transcription factor V-ets erythroblastosis virus E26 oncogene homolog-1 (ets-1) was identified as a potential target of miR-222 using TargetScan, and fivefold increased ets-1 protein expression in females was confirmed by Western blot. Targeting of ets-1 by miR-222 was determined in HEK293 cells overexpressing luciferase under regulation of either the ets-1 3'-UTR, a null 3'-UTR control, or a scrambled ets-1 3'-UTR and treated with a small molecule miR-222 mimic or inhibitor. Additionally qRT-PCR confirmed that mRNA levels of the ets-1 transcriptional target, eNOS, were 25% higher in females. Compared with untreated myocyte controls, 50% inhibition of eNOS expression was achieved by treatment with a miR-222 mimic, compared with a 25% increase due to miR-222 inhibitor. Our findings indicate that sex-dependent miR-222 regulation alters the expression of the cardiac regulatory protein eNOS.

  4. eNOS protects from atherosclerosis despite relevant superoxide production by the enzyme in apoE mice.

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    Padmapriya Ponnuswamy

    Full Text Available BACKGROUND: All three nitric oxide synthase (NOS isoforms are expressed in atherosclerotic plaques. NOS enzymes in general catalyse NO production. However, under conditions of substrate and cofactor deficiency, the enzyme directly catalyse superoxide formation. Considering this alternative chemistry, the effects of NOS on key events in spontaneous hyperlipidemia driven atherosclerosis have not been investigated yet. Here, we evaluate how endothelial nitric oxide synthase (eNOS modulates leukocyte/endothelial- (L/E and platelet/endothelial- (P/E interactions in atherosclerosis and the production of nitric oxide (NO and superoxide by the enzyme. PRINCIPAL FINDINGS: Intravital microscopy (IVM of carotid arteries revealed significantly increased L/E-interactions in apolipoproteinE/eNOS double knockout mice (apoE(-/-/eNOS(-/-, while P/E-interactions did not differ, compared to apoE(-/-. eNOS deficiency increased macrophage infiltration in carotid arteries and vascular cell adhesion molecule-1 (VCAM-1 expression, both in endothelial and smooth muscle cells. Despite the expression of other NOS isoforms (inducible NOS, iNOS and neuronal NOS, nNOS in plaques, Electron Spin Resonance (ESR measurements of NO showed significant contribution of eNOS to total circulating and vascular wall NO production. Pharmacological inhibition and genetic deletion of eNOS reduced vascular superoxide production, indicating uncoupling of the enzyme in apoE(-/- vessels. CONCLUSION: Overt plaque formation, increased vascular inflammation and L/E- interactions are associated with significant reduction of superoxide production in apoE(-/-/eNOS(-/- vessels. Therefore, lack of eNOS does not cause an automatic increase in oxidative stress. Uncoupling of eNOS occurs in apoE(-/- atherosclerosis but does not negate the enzyme's strong protective effects.

  5. Partial deletion of eNOS gene causes hyperinsulinemic state, unbalance of cardiac insulin signaling pathways and coronary dysfunction independently of high fat diet.

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    Cecilia Vecoli

    Full Text Available Abnormalities in eNOS gene, possibly interacting with high fat diet (HFD, affect peripheral vascular function and glucose metabolism. The relative role of eNOS gene, HFD and metabolic derangement on coronary function has not been fully elucidated. We test whether eNOS gene deficiency per se or in association with HFD modulates coronary function through mechanisms involving molecular pathways related to insulin signaling. Wild type (WT, eNOS-/- and eNOS+/- mice were studied. WT and eNOS+/- mice were fed with either standard or HF diet for 16 weeks and compared with standard diet fed eNOS-/-. Glucose and insulin tolerance tests were performed during the last week of diet. Coronary resistance (CR was measured at baseline and during infusions of acetylcholine (Ach or sodium-nitroprusside (SNP to evaluate endothelium-dependent or independent vasodilation, in the Langendorff isolated hearts. Cardiac expression of Akt and ERK genes as evaluation of two major insulin-regulated signaling pathways involved in the control of vascular tone were assessed by western blot. HFD-fed mice developed an overt diabetic state. Conversely, chow-fed genetically modified mice (in particular eNOS-/- showed a metabolic pattern characterized by normoglycemia and hyperinsulinemia with a limited degree of insulin resistance. CR was significantly higher in animals with eNOS gene deletions than in WT, independently of diet. Percent decrease in CR, during Ach infusion, was significantly lower in both eNOS-/- and eNOS+/- mice than in WT, independently of diet. SNP reduced CR in all groups except eNOS-/-. The cardiac ERK1-2/Akt ratio, increased in animals with eNOS gene deletions compared with WT, independently of diet. These results suggest that the eNOS genetic deficiency, associated or not with HFD, has a relevant effect on coronary vascular function, possibly mediated by increase in blood insulin levels and unbalance in insulin-dependent signaling in coronary vessels

  6. Crystallization Formulation Lab

    Data.gov (United States)

    Federal Laboratory Consortium — The Crystallization Formulation Lab fills a critical need in the process development and optimization of current and new explosives and energetic formulations. The...

  7. Single nucleotide polymorphism (SNP) of the endothelial nitric oxide synthase (eNOS) gene (Glu298Asp variant) in infertile men with asthenozoospermia.

    Science.gov (United States)

    Buldreghini, Eddi; Mahfouz, Reda Z; Vignini, Arianna; Mazzanti, Laura; Ricciardo-Lamonica, Giuseppe; Lenzi, Andrea; Agarwal, Ashok; Balercia, Giancarlo

    2010-01-01

    The objective of this study was to elucidate the missense Glu298Asp polymorphism within exon 7 of the endothelial nitric oxide synthase (eNOS) gene in infertile men with asthenozoospermia and its potential role in sperm motility. In this prospective controlled study conducted in our andrology unit, we investigated the frequency of the 894G>T polymorphism (Glu298Asp variant) within exon 7 of the eNOS gene in 70 infertile men and 60 healthy men. Sperm motion kinetics were assessed with computer-assisted semen analysis. The presence of G>T, a single nucleotide polymorphism (SNP) in exon 7 of the eNOS gene (NCBI SNP cluster rs1799983; GenBank accession number NG_011992; protein accession number NP_000594) was determined by allelespecific polymerase chain reaction followed by restriction fragment length polymorphism analysis. Sequencing analysis was used to confirm the specific genotype. The 894G>T eNOS allele (T) was found at a higher frequency in the patients with asthenozoospermia (60% vs 22.5% in the control group; P = .02). The percentage of progressive motile sperm (grade a + b) was lower in the asthenozoospermic infertile men with the homozygous eNOS (TT) genotype than in the wild-type eNOS (GG) (P = .02) and heterozygous eNOS (GT) genotypes (P = .01). However, the percentage of progressive motile sperm (grade a + b) was higher in the wild-type vs mutant eNOS (TT) (P = .03) and heterozygous eNOS (GT) genotypes (P = .04). Our findings suggest that the T allele encoding for aspartic acid of the eNOS (Glu298Asp) gene may contribute to poor sperm motility.

  8. Vasoinhibins Prevent Bradykinin-Stimulated Endothelial Cell Proliferation by Inactivating eNOS via Reduction of both Intracellular Ca2+ Levels and eNOS Phosphorylation at Ser1179

    Directory of Open Access Journals (Sweden)

    Carmen Clapp

    2011-07-01

    Full Text Available Vasoinhibins, a family of antiangiogenic peptides derived from prolactin proteolysis, inhibit the vascular effects of several proangiogenic factors, including bradykinin (BK. Here, we report that vasoinhibins block the BK-induced proliferation of bovine umbilical vein endothelial cells. This effect is mediated by the inactivation of endothelial nitric oxide synthase (eNOS, as the NO donor DETA-NONOate reverted vasoinhibin action. It is an experimentally proven fact that the elevation of intracellular Ca2+ levels ([Ca2+]i upon BK stimulation activates eNOS, and vasoinhibins blocked the BK-mediated activation of phospholipase C and the formation of inositol 1,4,5-triphosphate leading to a reduced release of Ca2+ from intracellular stores. The [Ca2+]i rise evoked by BK also involves the influx of extracellular Ca2+ via canonical transient receptor potential (TRPC channels. Vasoinhibins likely interfere with TRPC-mediated Ca2+ entry since La3+, which is an enhancer of TRPC4 and TRPC5 channel activity, prevented vasoinhibins from blocking the stimulation by BK of endothelial cell NO production and proliferation, and vasoinhibins reduced the BK-induced increase of TRPC5 mRNA expression. Finally, vasoinhibins prevented the BK-induced phosphorylation of eNOS at Ser1179, a post-translational modification that facilitates Ca2+-calmodulin activation of eNOS. Together, our data show that vasoinhibins, by lowering NO production through the inhibition of both [Ca2+]i mobilization and eNOS phosphorylation, prevent the BK-induced stimulation of endothelial cell proliferation. Thus, vasoinhibins help to regulate BK effects on angiogenesis and vascular homeostasis.

  9. Vasoinhibins Prevent Bradykinin-Stimulated Endothelial Cell Proliferation by Inactivating eNOS via Reduction of both Intracellular Ca2+ Levels and eNOS Phosphorylation at Ser1179

    Science.gov (United States)

    Thebault, Stéphanie; González, Carmen; García, Celina; Zamarripa, David Arredondo; Nava, Gabriel; Vaca, Luis; López-Casillas, Fernando; de la Escalera, Gonzalo Martínez; Clapp, Carmen

    2011-01-01

    Vasoinhibins, a family of antiangiogenic peptides derived from prolactin proteolysis, inhibit the vascular effects of several proangiogenic factors, including bradykinin (BK). Here, we report that vasoinhibins block the BK-induced proliferation of bovine umbilical vein endothelial cells. This effect is mediated by the inactivation of endothelial nitric oxide synthase (eNOS), as the NO donor DETA-NONOate reverted vasoinhibin action. It is an experimentally proven fact that the elevation of intracellular Ca2+ levels ([Ca2+]i) upon BK stimulation activates eNOS, and vasoinhibins blocked the BK-mediated activation of phospholipase C and the formation of inositol 1,4,5-triphosphate leading to a reduced release of Ca2+ from intracellular stores. The [Ca2+]i rise evoked by BK also involves the influx of extracellular Ca2+ via canonical transient receptor potential (TRPC) channels. Vasoinhibins likely interfere with TRPC-mediated Ca2+ entry since La3+, which is an enhancer of TRPC4 and TRPC5 channel activity, prevented vasoinhibins from blocking the stimulation by BK of endothelial cell NO production and proliferation, and vasoinhibins reduced the BK-induced increase of TRPC5 mRNA expression. Finally, vasoinhibins prevented the BK-induced phosphorylation of eNOS at Ser1179, a post-translational modification that facilitates Ca2+-calmodulin activation of eNOS. Together, our data show that vasoinhibins, by lowering NO production through the inhibition of both [Ca2+]i mobilization and eNOS phosphorylation, prevent the BK-induced stimulation of endothelial cell proliferation. Thus, vasoinhibins help to regulate BK effects on angiogenesis and vascular homeostasis.

  10. Association between the eNOS gene polymorphisms and rheumatoid arthritis risk in a northern Chinese population

    Institute of Scientific and Technical Information of China (English)

    AN Jin-dan; LI Xin-yuan; YU Jian-bo; ZHAO Yu; JIN Zai-shun

    2012-01-01

    Background Several genetic polymorphisms in the endothelial nitric oxide synthase (eNOS) gene are associated with the pathogenesis of rheumatoid arthritis (RA).The objective of the present study was to investigate whether the two SNPs (T-786C and G894T) of the eNOS gene are associated with rheumatoid arthritis risk in a northern Chinese population.Methods In this study,the eNOS genes T-786C and G894T were studied in 196 cases with rheumatoid arthritis and 201 healthy controls with gender,age and ethnicity matched.The two SNPs were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).The analyses of association were statistically compared using the chi-square test with SPSS software for Windows.Results The frequency of the -786C allele was significantly higher in the rheumatoid arthritis patients than in the healthy controls (19.64% vs.14.18%,P <0.05).However,the 894T allele of the eNOS gene was not increased in the rheumatoid arthritis patients compared to the healthy controls.Conclusions Individuals with the -786CC genotype have an increased risk of rheumatoid arthritis.Further study with an increased samole size is necessary for the studv of the role of this SNP in rheumatoid arthritis.

  11. Ginsenoside Rb1 Preconditioning Enhances eNOS Expression and Attenuates Myocardial Ischemia/Reperfusion Injury in Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Rui Xia

    2011-01-01

    Full Text Available Diabetes mellitus is associated with decreased NO bioavailability in the myocardium. Ginsenoside Rb1 has been shown to confer cardioprotection against ischemia reperfusion injury. The aim of this study was to investigate whether Ginsenoside Rb1 exerts cardioprotective effects during myocardial ischemia-reperfusion in diabetic rats and whether this effect is related to increase the production of NO via enhancing eNOS expression in the myocardium. The myocardial I/R injury were induced by occluding the left anterior descending artery for 30 min followed by 120 min reperfusion. An eNOS inhibitor L-NAME or Rb1 were respectively administered 25 min or 10 min before inducing ischemia. Ginsenoside Rb1 preconditioning reduced myocardial infarct size when compared with I/R group. Ginsenoside Rb1 induced myocardial protection was accompanied with increased eNOS expression and NO concentration and reduced plasma CK and LDH (P<0.05. Moreover, the myocardial oxidative stress and tissue histological damage was attenuated by Ginsenoside Rb1 (P<0.05. L-NAME abolished the protective effects of Ginsenoside Rb1. It is concluded that Ginsenoside Rb1 protects against myocardium ischemia/reperfusion injury in diabetic rat by enhancing the expression of eNOS and increasing the content of NO as well as inhibiting oxidative stress.

  12. Impact of Lifestyle Intervention on HDL-Induced eNOS Activation and Cholesterol Efflux Capacity in Obese Adolescent

    Directory of Open Access Journals (Sweden)

    Jenny Wesnigk

    2016-01-01

    Full Text Available Background. Endothelial dysfunction occurs in obese children and adolescent and is regarded as a key step in the development of atherosclerosis. Important components for the development of endothelial dysfunction are reduced activity of endothelial nitric oxide synthase (eNOS and an increase in cholesterol deposition in the vessel wall, due to reduced reverse cholesterol transport (RCT activity. High density lipoprotein (HDL exhibits antiatherosclerotic properties including modulation of eNOS activity and cholesterol efflux capacity. Lifestyle intervention programs can modify endothelial dysfunction in obese adolescents, but their impact on HDL-mediated eNOS activation and RCT is unknown so far. Methods. Obese adolescents (15±1 years, BMI > 35 kg/m2 where randomized either to an intervention group (IG, n=8; restricted diet and exercise or to a usual care group (UC, n=8. At the beginning and after 10 months of treatment HDL-mediated eNOS phosphorylation and cholesterol efflux capacity were evaluated. Results. Ten months of treatment resulted in a substantial weight loss (−31%, an improvement of endothelial function, and an increase in HDL-mediated eNOS-Ser1177 phosphorylation and RCT. A correlation between change in eNOS-Ser1177 phosphorylation or RCT and change in endothelial function was noted. Conclusion. A structured lifestyle intervention program improves antiatherosclerotic HDL functions, thereby positively influencing endothelial function.

  13. Mesenchymal Stem Cells with eNOS Over-Expression Enhance Cardiac Repair in Rats with Myocardial Infarction.

    Science.gov (United States)

    Chen, Leilei; Zhang, Yuan; Tao, Liangliang; Yang, Zhijian; Wang, Liansheng

    2017-02-01

    Transplantation of mesenchymal stem cells (MSCs) is a promising therapeutic option for patients with acute myocardial infarction. We show here that the ectopic overexpression of endothelial nitric oxide synthases (eNOS), an endothelial form of NOS, could enhance the ability of MSCs in treating ischemic heart damage after the occlusion of the coronary artery. Adenoviral delivery of human eNOS gene into mouse bone marrow-derived MSCs (BM-MSCs) conferred resistance to oxygen glucose deprivation (OGD)-induced cell death in vitro, and elevated the bioavailability of nitric oxide when injected into the myocardium in vivo. In a rat model of acute myocardial infarction, the transplantation of eNOS-overexpressing BM-MSCs significantly reduced myocardial infarct size, corrected hemodynamic parameters and increased capillary density. We also found that the synergistic effects were consistently better than either treatment alone. These findings reveal a positive role of elevated eNOS expression in cardiac repair, and suggest the combination of eNOS and MSC transplant therapy as a potential approach for treating myocardial infarction.

  14. Effects of hyperbaric oxygen therapy in enhancing expressions of e-NOS, TNF-α and VEGF in wound healing

    Science.gov (United States)

    Susilo, Imam; Devi, Anita; Purwandhono, Azham; Hadi Warsito, Sunaryo

    2017-05-01

    Wound healing is a physiological process that occurs progressively through overlapping phases. Tissue oxygenation is an important part of the complex regulation for wound healing. Hyperbaric Oxygen (HBO) therapy is a method of increasing oxygen delivery to tissues. The therapy improves tissue oxygenation and stimulates the formation of H2O2 as a secondary messenger for Tumour Necrosis Factor alpha (TNF α), e-NOS, VEGF and Nuclear Factor Kappa Beta phosphorylation (NF-Kb) which play an important role in the rapid transcription of a wide variety of genes in response to extracellular stimuli. This study aims to determine the effects of Hyperbaric Oxygen therapy in enhancing the expressions of e-NOS, TNF-α, VEGF and wound healing. This study is an animal study with a ‘randomized control group of pre-test and post test design’ on 28 Wistar rats. Randomly, the rats were divided into 4 groups with 7 rats in each group. The HBO treatment group 1 received 5 sessions of HBO 2.4 ATA in 3 × 30 minutes; the HBO treatment group 2 received 10 sessions of HBO 2.4 ATA in 3 × 30 minutes; and each of the control groups were without HBO. Each of the 28 male rats were given a full thickness excisional wound of 1 × 1cm. Examinations of e-NOS, TNF-α, VEGF expressions and wound healing were performed on day-0 (pre-HBO) and day-5 HBO or on day-0 (pre-HBO) and day-10 HBO. The resultsshowthat the Hyperbaric Oxygen therapy can improve e-NOS (p=0.02), TNF-α (p= 0.02), VEGF expression (p=0.02) and wound healing (p=0.002) significantly in the provision of HBO 2.4 ATA for 3 × 30 minutes in 5 sessions over 5 consecutive days. While the 10 sessions of HBO 2.4 ATA for 3 × 30 minutes over 10 consecutive days only increase e-NOS (p=0.02), TNF-α (p=0.04), VEGF expression significantly (p=0.03) but do not improve wound healing significantly (p=0.3) compared with no HBO. The study concludes that HBO can improve the expressions of e-NOS, TNF-α, VEGF and wound healing in the provision of HBO

  15. Protective effects of Rho kinase inhibitor on rats’ vascular endothelium and its effects on the expression of eNO

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    Qiao WU

    2012-11-01

    Full Text Available Objective  To explore the protective effects of Rho kinase inhibitor (fasudil on rats' vascular endothelial cells and the effects on the expression of endothelial nitric oxide synthase (eNOS. Methods  Thirty male SD rats were randomly divided into 5 groups (6 each: control group (intraperitoneal injection with 0.9% normal saline, hyperhomocysteinemia (HHcy group, low-dose fasudil group [L -treatment group, intraperitoneal injection with 1mg/(kg•d fasudil], middle-dose fasudil group [M-treatment group, intraperitoneal injection with 5mg/(kg•d fasudil], and high-dose fasudil group [H-treatment group, intraperitoneal injection with 15mg/(kg•d fasudil]. Animals in HHcy group and fasudil groups were administered continuously with water containing 1.5% methionine for 4 weeks to establish HHcy damaged vascular endothelium model, and those in control group were only fed drinking water. After successful reproduction of model, the enzymatic method was applied to measure the serum level of nitric oxide (NO. The expressions of eNOS, Rho-associated coiled-coil protein kinase 2 (ROCK2 and RhoA protein in aorta were assessed by immunohistochemistry and Western blotting. Results  Compared with control group, the serum NO level and expression of eNOS protein in aorta decreased significantly in HHcy group (P 0.05. The aortic endothelial eNOS positive cells increased significantly in H-treatment group compared with that in HHcy group and L -treatment group (P 0.05. Compared with HHcy group, the expressions of RhoA and ROCK2 decreased significantly in H-treatment group (P 0.05. Conclusions  High-dose fasudil can protect vascular endothelia by inhibiting Rho/ROCK pathway to increase the expression of eNOS and NO.

  16. Acute mechanical stretch promotes eNOS activation in venous endothelial cells mainly via PKA and Akt pathways.

    Directory of Open Access Journals (Sweden)

    Zhenqian Hu

    Full Text Available In the vasculature, physiological levels of nitric oxide (NO protect against various stressors, including mechanical stretch. While endothelial NO production in response to various stimuli has been studied extensively, the precise mechanism underlying stretch-induced NO production in venous endothelial cells remains incompletely understood. Using a model of continuous cellular stretch, we found that stretch promoted phosphorylation of endothelial NO synthase (eNOS at Ser¹¹⁷⁷, Ser⁶³³ and Ser⁶¹⁵ and NO production in human umbilical vein endothelial cells. Although stretch activated the kinases AMPKα, PKA, Akt, and ERK1/2, stretch-induced eNOS activation was only inhibited by kinase-specific inhibitors of PKA and PI3K/Akt, but not of AMPKα and Erk1/2. Similar results were obtained with knockdown by shRNAs targeting the PKA and Akt genes. Furthermore, inhibition of PKA preferentially attenuated eNOS activation in the early phase, while inhibition of the PI3K/Akt pathway reduced eNOS activation in the late phase, suggesting that the PKA and PI3K/Akt pathways play distinct roles in a time-dependent manner. Finally, we investigated the role of these pathways in stretch-induced endothelial exocytosis and leukocyte adhesion. Interestingly, we found that inhibition of the PI3K/Akt pathway increased stretch-induced Weibel-Palade body exocytosis and leukocyte adhesion, while inhibition of the PKA pathway had the opposite effects, suggesting that the exocytosis-promoting effect of PKA overwhelms the inhibitory effect of PKA-mediated NO production. Taken together, the results suggest that PKA and Akt are important regulators of eNOS activation in venous endothelial cells under mechanical stretch, while playing different roles in the regulation of stretch-induced endothelial exocytosis and leukocyte adhesion.

  17. Nonoscillatory Solutions for First-Order Nonlinear Neutral Delay Differential Equations%一阶非线性中立型时滞微分方程的非振动解

    Institute of Scientific and Technical Information of China (English)

    袁丽芳; 刘桂荣

    2011-01-01

    Using the Bananch contraction mapping theorem,the class of firet-order nonlinear neutral delay differential equation are studied d/(dt)+c(t)x(t-τ1)+d(t)x(t-τ2)]+ h(t)f(t,x(t-σ1(t)),x(t-σ2(t)),…,x(t-σk(t)))=g(t) and the sufficieut conditions for the existence of nonoscillatory solutions.In addition,iterative approximation sequences of corresponding nonoscillatory soultions are obtained.%利用Banach压缩映象原理,研究下列一阶非线性中立型时滞微分方程d/(dt)[x(t)]+c(t)x(t-τ1)+d(t)x(t-τ2)]+h(t)f(t,x(t-σ1(t)),x(t-σ2(t)),…,x(t-σk(t)))=g(t)的非振动解的存在性,并获得了相应非振动解的迭代逼近序列.

  18. Mutation at the tomato excessive number of floral organs (ENO) locus impairs floral meristem development, thus promoting an increased number of floral organs and fruit size.

    Science.gov (United States)

    Fernández-Lozano, Antonia; Yuste-Lisbona, Fernando J; Pérez-Martín, Fernando; Pineda, Benito; Moreno, Vicente; Lozano, Rafael; Angosto, Trinidad

    2015-03-01

    A novel tomato (Solanum lycopersicum L.) mutant affected in reproductive development, excessive number of floral organs (eno), is described in this study. The eno plants yielded flowers with a higher number of floral organs in the three innermost floral whorls and larger fruits than those found in wild-type plants. Scanning-electron microscopy study indicated that the rise in floral organ number and fruit size correlates with an increased size of floral meristem at early developmental stages. It has been reported that mutation at the FASCIATED (FAS) gene causes the development of flowers with supernumerary organs; however, complementation test and genetic mapping analyses proved that ENO is not an allele of the FAS locus. Furthermore, expression of WUSCHEL (SlWUS) and INHIBITOR OF MERISTEM ACTIVITY (IMA), the two main regulators of floral meristem activity in tomato, is altered in eno but not in fas flowers indicating that ENO could exert its function in the floral meristem independently of FAS. Interestingly, the eno mutation delayed the expression of IMA leading to a prolonged expression of SlWUS, which would explain the greater size of floral meristem. Taken together, results showed that ENO plays a significant role in the genetic pathway regulating tomato floral meristem development. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  19. AB037. Icariside II improves human cavernous endothelial cells function by regulating miR-155/eNOS signal pathway

    Science.gov (United States)

    Guan, Ruili; Lei, Hongen; Yang, Bicheng; Li, Huixi; Wang, Lin; Guo, Yinglu; Xin, Zhongcheng

    2016-01-01

    Background To investigate the changes of miR-155/endothelial nitric oxide synthase (eNOS) signal pathway under the stimulation of age-BSA and glucose with or without icariside II (ICAII) intervention inhuman cavernous endothelial cells (HCECs). Methods Purified HCECs were first divided into three groups randomly: normal group + BSA (NC group), age-BSA + glucose group (DM group), ICAII treatment group (DM + ICAII group with different concentrations at 0.1, 1, 10 µM). Western Blot to detect the protein expression of eNOS and RAGE; real time PCR to detect the expression of miR-155 and eNOS; DAF-FM DA fluorescent probes assay and NaNO3/NaNO2 assay to detect the NO concentration. Lentivirus mediated miR-155 over-expression was constructed to observe the changes of eNOS and NO. Results The eNOS and RAGE expression in DM group is significantly reduced and increased respectively compared with that of NC group (P<0.05), while ICAII intervention could reverse this change effectively. The 10 µM of ICAII has the most powerful effect. MiR-155 has the highest fold changes among candidate miRNAs in diabetic like HCECs (P<0.05). MiR-155 increased and eNOS decreased remarkably in DM group, while ICAII intervention could inhibit the miR-155 expression, which led to the significantly higher eNOS expression and NO concentration (P<0.05). In lentivirus mediated miR-155 overexpression with or without ICAII intervention model, we found the similar trend with the above diabetic model. Conclusions MiR-155/eNOS signal pathway may be involved in the process of diabetic HCECs dysfunction. ICAII could promote the recovery of the endothelial dysfunction by regulating the miR-155/eNOS signal pathway.

  20. Negligible effect of eNOS palmitoylation on fatty acid regulation of contraction in ventricular myocytes from healthy and hypertensive rats.

    Science.gov (United States)

    Jin, Chun Li; Wu, Yu Na; Jang, Ji Hyun; Zhao, Zai Hao; Oh, Goo Taeg; Kim, Sung Joon; Zhang, Yin Hua

    2017-04-25

    S-palmitoylation is an important post-translational modification that affects the translocation and the activity of target proteins in a variety of cell types including cardiomyocytes. Since endothelial nitric oxide synthase (eNOS) is known to be palmitoylated and the activity of eNOS is essential in fatty acid-dependent β-oxidation in muscle, we aimed to test whether palmitoylation of eNOS is involved in palmitic acid (PA) regulation of left ventricular (LV) myocyte contraction from healthy (sham) and hypertensive (HTN) rats. Our results showed that PA, a predominant metabolic substrate for cardiac β-oxidation, significantly increased contraction and oxygen consumption rate (OCR) in LV myocytes from sham. Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME) or eNOS gene deletion prevented PA regulation of the myocyte contraction or OCR, indicating the pivotal role of eNOS in mediating the effects of PA in cardiac myocytes. PA increased the palmitoylation of eNOS in LV myocytes and depalmitoylation with 2-bromopalmitate (2BP; 100 μM) abolished the increment. Furthermore, although PA did not increase eNOS-Ser(1177), 2BP reduced eNOS-Ser(1177) with and without PA. Intriguingly, PA-induced increases in contraction and OCR were unaffected by 2BP treatment. In HTN, PA did not affect eNOS palmitoylation, eNOS-Ser(1177), or myocyte contraction. However, 2BP diminished eNOS palmitoylation and eNOS-Ser(1177) in the presence and absence of PA but did not change myocyte contraction. Collectively, our results confirm eNOS palmitoylation in LV myocytes from sham and HTN rats and its upregulation by PA in sham. However, such post-transcriptional modification plays negligible role in PA regulation of myocyte contraction and mitochondrial activity in sham and HTN.

  1. Entropy Stable Summation-by-Parts Formulations for Compressible Computational Fluid Dynamics

    KAUST Repository

    Carpenter, M.H.

    2016-11-09

    A systematic approach based on a diagonal-norm summation-by-parts (SBP) framework is presented for implementing entropy stable (SS) formulations of any order for the compressible Navier–Stokes equations (NSE). These SS formulations discretely conserve mass, momentum, energy and satisfy a mathematical entropy equality for smooth problems. They are also valid for discontinuous flows provided sufficient dissipation is added at shocks and discontinuities to satisfy an entropy inequality. Admissible SBP operators include all centred diagonal-norm finite-difference (FD) operators and Legendre spectral collocation-finite element methods (LSC-FEM). Entropy stable multiblock FD and FEM operators follows immediately via nonlinear coupling operators that ensure conservation, accuracy and preserve the interior entropy estimates. Nonlinearly stable solid wall boundary conditions are also available. Existing SBP operators that lack a stability proof (e.g. weighted essentially nonoscillatory) may be combined with an entropy stable operator using a comparison technique to guarantee nonlinear stability of the pair. All capabilities extend naturally to a curvilinear form of the NSE provided that the coordinate mappings satisfy a geometric conservation law constraint. Examples are presented that demonstrate the robustness of current state-of-the-art entropy stable SBP formulations.

  2. IT Supporting Strategy Formulation

    NARCIS (Netherlands)

    Achterbergh, J.M.I.M.

    2005-01-01

    This overview approaches information and communication technology (ICT) for competitive intelligence from the perspective of strategy formulation. It provides an ICT architecture for supporting the knowledge processes producing relevant knowledge for strategy formulation. To determine what this arch

  3. IT Supporting Strategy Formulation

    NARCIS (Netherlands)

    Achterbergh, J.M.I.M.

    2005-01-01

    This overview approaches information and communication technology (ICT) for competitive intelligence from the perspective of strategy formulation. It provides an ICT architecture for supporting the knowledge processes producing relevant knowledge for strategy formulation. To determine what this arch

  4. Torsion formulation of gravity

    Energy Technology Data Exchange (ETDEWEB)

    Lledo, M A; Sommovigo, L, E-mail: Maria.Lledo@ific.uv.e, E-mail: Luca.Sommovigo@mfn.unipmn.i [Departament de Fisica Teorica, Universitat de Valencia, and IFIC (Centro mixto CSIC-UVEG) C/Dr Moliner, 50, E-46100 Burjassot (Valencia) (Spain)

    2010-03-21

    We explain precisely what it means to have a connection with torsion as a solution of the Einstein equations. While locally the theory remains the same, the new formulation allows for topologies that would have been excluded in the standard formulation of gravity. In this formulation it is possible to couple arbitrary torsion to gauge fields without breaking the gauge invariance.

  5. Ketamine upregulates eNOS expression in human astroglial A172 cells: Possible role in its antidepressive properties.

    Science.gov (United States)

    Yuhas, Yael; Ashkenazi, Shai; Berent, Eva; Weizman, Abraham

    2017-04-15

    Ketamine is a potent anti-depressive agent. Nitric oxide plays an essential role in neuronal transmission and cerebral blood flow and has been implicated in the pathophysiology of major depressive disorder as well as cardiovascular functioning. We investigated the effect of ketamine on eNOS expression in human A172 astroglial cells. Ketamine (50-500μM) increased eNOS expression at 4-24h in a concentration-dependent manner. This effect was mediated by NMDA receptor, Akt inhibition and ERK1/2 activation and was synergistically augmented by rapamycin. The combined effect on the vascular, immune and neuronal systems may be relevant to the rapid antidepressive effect of ketamine. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Endothelial function does not improve with high-intensity continuous exercise training in SHR: implications of eNOS uncoupling.

    Science.gov (United States)

    Battault, Sylvain; Singh, François; Gayrard, Sandrine; Zoll, Joffrey; Reboul, Cyril; Meyer, Grégory

    2016-02-01

    Exercise training is a well-recognized way to improve vascular endothelial function by increasing nitric oxide (NO) bioavailability. However, in hypertensive subjects, unlike low- and moderate-intensity exercise training, the beneficial effects of continuous high-intensity exercise on endothelial function are not clear, and the underlying mechanisms remain unknown. The aim of this study was to investigate the impact of high-intensity exercise on vascular function, especially on the NO pathway, in spontaneous hypertensive rats (SHR). These effects were studied on WKY, sedentary SHR and SHR that exercised at moderate (SHR-MOD) and high intensity (SHR-HI) on a treadmill (1 h per day; 5 days per week for 6 weeks at 55% and 80% of their maximal aerobic velocity, respectively). Endothelial function and specific NO contributions to acetylcholine-mediated relaxation were evaluated by measuring the aortic ring isometric forces. Endothelial nitric oxide synthase (eNOS) expression and phosphorylation (ser1177) were evaluated by western blotting. The total aortic and eNOS-dependent reactive oxygen species (ROS) production was assessed using electron paramagnetic resonance in aortic tissue. Although the aortas of SHR-HI had increased eNOS levels without alteration of eNOS phosphorylation, high-intensity exercise had no beneficial effect on endothelium-dependent vasorelaxation, unlike moderate exercise. This result was associated with increased eNOS-dependent ROS production in the aortas of SHR-HI. Notably, the use of the recoupling agent BH4 or a thiol-reducing agent blunted eNOS-dependent ROS production in the aortas of SHR-HI. In conclusion, the lack of a positive effect of high-intensity exercise on endothelial function in SHR was mainly explained by redox-dependent eNOS uncoupling, resulting in a switch from NO to O2(-) generation.

  7. eNOS gene haplotype is indirectly associated with the recovery of cardiovascular autonomic modulation from exercise.

    Science.gov (United States)

    Silva, Bruno M; Barbosa, Thales C; Neves, Fabricia J; Sales, Allan K; Rocha, Natalia G; Medeiros, Renata F; Pereira, Felipe S; Garcia, Vinicius P; Cardoso, Fabiane T; Nobrega, Antonio C L

    2014-12-01

    Polymorphisms in the endothelial nitric oxide synthase (eNOS) gene decrease expression and activation of eNOS in vitro, which is associated with lower post-exercise increase in vasodilator reactivity in vivo. However, it is unknown whether such polymorphisms are associated with other eNOS-related phenotypes during recovery from exercise. Therefore, we investigated the impact of an eNOS haplotype containing polymorphic alleles at loci -786 and 894 on the recovery of cardiovascular autonomic function from exercise. Sedentary, non-obese, healthy subjects were enrolled [n = 107, age 32 ± 1 years (mean ± SEM)]. Resting autonomic modulation (heart rate variability, systolic blood pressure variability, and spontaneous baroreflex sensitivity) and vascular reactivity (forearm hyperemic response post-ischemia) were assessed at baseline, 10, 60, and 120 min after a maximal cardiopulmonary exercise test. Besides, autonomic function was assessed by heart rate recovery (HRR) immediately after peak exercise. Haplotype analysis showed that vagal modulation (i.e., HF n.u.) was significantly higher, combined sympathetic and vagal modulation (i.e., LF/HF) was significantly lower and total blood pressure variability was significantly lower post-exercise in a haplotype containing polymorphic alleles (H2) compared to a haplotype with wild type alleles (H1). HRR was similar between groups. Corroborating previous evidence, H2 had significantly lower post-exercise increase in vasodilator reactivity than H1. In conclusion, a haplotype containing polymorphic alleles at loci -786 and 894 had enhanced recovery of autonomic modulation from exercise, along with unchanged HRR, and attenuated vasodilator reactivity. Then, these results suggest an autonomic compensatory response of a direct deleterious effect of eNOS polymorphisms on the vascular function. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. FEATURES OF THE CLINICAL SIGNIFICANCE OF POLYMORPHIC VARIANTS OF ENOS AND AGTR2 GENES IN PATIENTS WITH CAD

    Directory of Open Access Journals (Sweden)

    A. L. Khokhlov

    2016-01-01

    Full Text Available Coronary heart disease (CHD is a major cause of mortality. Morphological substrate of CHD in most cases is atherosclerosis, which is based on structural genes polymorphism eNOS and AGTR2. The aim of the study was to study the prevalence of eNOS and AGTR2 genes in patients with coronary artery disease and the association of these genes with coronary heart disease. The study involved 187 patients aged 36 to 86 years (62,2±11,2 with different forms of CHD: stable and unstable angina, myocardial infarction and 45 people without CHD. Determination of gene polymorphisms was performed by real-time PCR analyzer of nucleic acids IQ 5 Bio-Rad. Statistical analysis was performed using Statistica 10.0. The study revealed a significant difference between the incidence of homozygous AA allelic variant gene AGTR2 group of patients with myocardial infarction and the comparison group; polymorphic variant AA AGTR2 gene is associated with earlier onset of coronary artery disease; It found that carriers of the polymorphic variant gene GA AGTR2 beginning statistically CHD occurred significantly later than in carriers of alleles GG and AA; age CHD debut TT allele carriers of the eNOS gene is associated with an earlier onset of the disease and statistically significantly different from the age of first CHD in carriers of alleles of polymorphic variants of GG and GT; revealed a positive correlation between the polymorphic allele AGTR2 gene with the presence of arterial hypertension in patients with coronary artery disease; It determined that the T allele carriers of the polymorphic gene eNOS is associated more early onset of hypertension, found the association of the polymorphic allele gene AGTR2 the need to use higher doses of ACE inhibitor — perindopril.

  9. Immunomodulatory effects of royal jelly on aorta CD3, CD68 and eNOS expression in hypercholesterolaemic rats

    Directory of Open Access Journals (Sweden)

    Amal Attia El-Morsy Ibrahim

    2014-08-01

    RJ administration (300 mg/kg/day with CH, produced a counteractive effect, represented in recompense of biochemical alteration, CD4 and CD8 expression. RJ intake also amended the histological picture. The immunohistochemical picture revealed a decrease in CD3, CD86 and eNOS in the aortic tissue. These findings attributed to the significant immunomodulatory effect of RJ remedy suppress deleterious effects of hypercholesterolaemia.

  10. Resveratrol Prevented Lipopolysaccharide-Induced Endothelial Dysfunction in Rat Thoracic Aorta Through Increased eNOS Expression

    Science.gov (United States)

    Uğurel, Seda Sultan; Kuşçu, Nilay; Özenci, Çiler Çelik; Dalaklıoğlu, Selvinaz; Taşatargil, Arda

    2016-01-01

    Background: The cardiovascular benefits of Resveratrol (RVT) have been well established by previous experimental and clinical studies. Aims: The goal of this study was to test the effectiveness of RVT administration on the impaired endothelial function induced by lipopolysaccharide (LPS), and to elucidate the role of endothelial nitric oxide synthase (eNOS)/Sirtuin 1 (SIRT1) pathway. Study Design: Animal experiment. Methods: Endotoxemia was induced by intraperitoneal injection of 10 mg/kg LPS, and the thoracic aorta was isolated six hours later. RVT was injected intraperitoneally 15 minutes before LPS administration. Six hours after LPS injection, potassium chloride (KCl), phenylephrine (Phe), acetylcholine (ACh), and sodium nitroprusside (SNP) were used to examine to vascular reactivity and endothelial function. eNOS, phospho-eNOS (p-eNOS) (Ser 1177), and SIRT1 expressions in thoracic aorta were evaluated by Western blot. Results: LPS administration significantly inhibited the relaxation response induced by ACh, while the relaxation to SNP was not significantly altered. Phe- and KCl-induced contractile responses in the thoracic aorta significantly decreased in LPS-injected group. eNOS and p-eNOS expression decreased significantly in arteries obtained from LPS group rats. The impaired vasoreactivity as well as decreased expressions of eNOS, p-eNOS, and SIRT1 in vessels from LPS-injected rats were improved by RVT treatment. Conclusion: The endothelium-dependent vasodilatation of the thoracic aorta was significantly inhibited by LPS administration, and RVT treatment may improve vascular endothelial function. The protective effect of RVT might be associated with increased eNOS expression and activity. PMID:27403381

  11. Effect of exercise training on eNOS expression, NO production and oxygen metabolism in human placenta.

    Directory of Open Access Journals (Sweden)

    Robinson Ramírez-Vélez

    Full Text Available OBJECTIVE: To determine the effects of combined aerobic and resistance exercise training during the second half of pregnancy on endothelial NOS expression (eNOS, nitric oxide (NO production and oxygen metabolism in human placenta. METHODS: The study included 20 nulliparous in gestational week 16-20, attending prenatal care at three tertiary hospitals in Colombia who were randomly assigned into one of two groups: The exercise group (n = 10 took part in an exercise session three times a week for 12 weeks which consisted of: aerobic exercise at an intensity of 55-75% of their maximum heart rate for 60 min and 25 mins. Resistance exercise included 5 exercise groups circuit training (50 repetitions of each using barbells (1-3 kg/exercise and low-to-medium resistance bands. The control group (n = 10 undertook their usual physical activity. Mitochondrial and cytosol fractions were isolated from human placental tissue by differential centrifugation. A spectrophotometric assay was used to measure NO production in cytosolic samples from placental tissue and Western Blot technique to determine eNOS expression. Mitochondrial superoxide levels and hydrogen peroxide were measured to determine oxygen metabolism. RESULTS: Combined aerobic and resistance exercise training during pregnancy leads to a 2-fold increase in eNOS expression and 4-fold increase in NO production in placental cytosol (p = 0.05. Mitochondrial superoxide levels and hydrogen peroxide production rate were decreased by 8% and 37% respectively in the placental mitochondria of exercising women (p = 0.05. CONCLUSION: Regular exercise training during the second half of pregnancy increases eNOS expression and NO production and decreases reactive oxygen species generation in human placenta. Collectively, these data demonstrate that chronic exercise increases eNOS/NO production, presumably by increasing endothelial shear stress. This adaptation may contribute to the beneficial effects of exercise on

  12. Alteration in cardiac uncoupling proteins and eNOS gene expression following high-intensity interval training in favor of increasing mechanical efficiency

    OpenAIRE

    Ali Asghar Fallahi; Shahnaz Shekarfroush; Mostafa Rahimi; Amirhossain Jalali; Ali Khoshbaten

    2016-01-01

    Objective(s): High-intensity interval training (HIIT) increases energy expenditure and mechanical energy efficiency. Although both uncoupling proteins (UCPs) and endothelial nitric oxide synthase (eNOS) affect the mechanical efficiency and antioxidant capacity, their effects are inverse. The aim of this study was to determine whether the alterations of cardiac UCP2, UCP3, and eNOS mRNA expression following HIIT are in favor of increased mechanical efficiency or decreased oxidative stress. Mat...

  13. Human red blood cells at work: identification and visualization of erythrocytic eNOS activity in health and disease.

    Science.gov (United States)

    Cortese-Krott, Miriam M; Rodriguez-Mateos, Ana; Sansone, Roberto; Kuhnle, Gunter G C; Thasian-Sivarajah, Sivatharsini; Krenz, Thomas; Horn, Patrick; Krisp, Christoph; Wolters, Dirk; Heiß, Christian; Kröncke, Klaus-Dietrich; Hogg, Neil; Feelisch, Martin; Kelm, Malte

    2012-11-15

    A nitric oxide synthase (NOS)-like activity has been demonstrated in human red blood cells (RBCs), but doubts about its functional significance, isoform identity and disease relevance remain. Using flow cytometry in combination with the nitric oxide (NO)-imaging probe DAF-FM we find that all blood cells form NO intracellularly, with a rank order of monocytes > neutrophils > lymphocytes > RBCs > platelets. The observation of a NO-related fluorescence within RBCs was unexpected given the abundance of the NO-scavenger oxyhemoglobin. Constitutive normoxic NO formation was abolished by NOS inhibition and intracellular NO scavenging, confirmed by laser-scanning microscopy and unequivocally validated by detection of the DAF-FM reaction product with NO using HPLC and LC-MS/MS. Using immunoprecipitation, ESI-MS/MS-based peptide sequencing and enzymatic assay we further demonstrate that human RBCs contain an endothelial NOS (eNOS) that converts L-(3)H-arginine to L-(3)H-citrulline in a Ca(2+)/calmodulin-dependent fashion. Moreover, in patients with coronary artery disease, red cell eNOS expression and activity are both lower than in age-matched healthy individuals and correlate with the degree of endothelial dysfunction. Thus, human RBCs constitutively produce NO under normoxic conditions via an active eNOS isoform, the activity of which is compromised in patients with coronary artery disease.

  14. Efectos ecológicos del fenómeno ENOS en Colombia

    Directory of Open Access Journals (Sweden)

    Yesid Carvajal

    2014-06-01

    Full Text Available El fenómeno ENOS, tiene un sustancial efecto sobre las variaciones del clima a nivel mundial; por lo tanto, no sorprende que sus efectos tengan un impacto ecológico y socioeconómico fuerte, alterando la seguridad alimentaria de los países a nivel mundial. Ante este panorama, es comprensible que haya despertado el mayor interés mundial, no sólo en los especialistas en meteorología y oceanografía sino también entre biólogos, ecólogos, físicos, matemáticos, agrónomos, hidrólogos, economistas, sociólogos y planificadores, entre otros. En el presente documento, se muestra algunos de los principales efectos ecológicos en Colombia durante las fases extremas cálida (El Niño y fría (La Niña, indicando que es una necesidad urgente, orientar la investigación en sus causas, consecuencias e impactos.

  15. Recoupling of eNOS with folic acid prevents abdominal aortic aneurysm formation in angiotensin II-infused apolipoprotein E null mice.

    Directory of Open Access Journals (Sweden)

    Kin Lung Siu

    Full Text Available We have previously shown that eNOS uncoupling mediates abdominal aortic aneurysm (AAA formation in hph-1 mice. In the present study we examined whether recoupling of eNOS prevents AAA formation in a well-established model of Angiotensin II-infused apolipoprotein E (apoE null mice by targeting some common pathologies of AAA. Infusion of Ang II resulted in a 92% incidence rate of AAA in the apoE null animals. In a separate group, animals were treated orally with folic acid (FA, which is known to recouple eNOS through augmentation of dihydrofolate reductase (DHFR function. This resulted in a reduction of AAA rate to 19.5%. Imaging with ultrasound showed that FA markedly inhibited expansion of abdominal aorta. FA also abolished elastin breakdown and macrophage infiltration in the AAA animals. The eNOS uncoupling activity, assessed by L-NAME-sensitive superoxide production, was minimal at baseline but greatly exaggerated with Ang II infusion, which was completely attenuated by FA. This was accompanied by markedly improved tetrahydrobiopterin and nitric oxide bioavailability. Furthermore, the expression and activity of DHFR was decreased in Ang II-infused apoE null mice specifically in the endothelial cells, while FA administration resulted in its recovery. Taken together, these data further establish a significant role of uncoupled eNOS in mediating AAA formation, and a universal efficacy of FA in preventing AAA formation via restoration of DHFR to restore eNOS function.

  16. ENO2 activity is required for the development and reproductive success of plants, and is feedback-repressed by AtMBP-1.

    Science.gov (United States)

    Eremina, Marina; Rozhon, Wilfried; Yang, Saiqi; Poppenberger, Brigitte

    2015-03-01

    Enolases are key glycolytic enzymes that are highly conserved in prokaryotic and eukaryotic organisms, and are among the most abundant cytosolic proteins. In this study we provide evidence that activity of the enolase ENO2 is essential for the growth and development of plants. We show that Arabidopsis plants with compromised ENO2 function, which were generated by mutating the LOS2/ENO2 locus, have severe cellular defects, including reduced cell size and defective cell differentiation with restricted lignification. At the tissue and organ level LOS2/ENO2-deficient plants are characterized by the reduced growth of shoots and roots, altered vascular development and defective secondary growth of stems, impaired floral organogenesis and defective male gametophyte function, resulting in embryo lethality as well as delayed senescence. These phenotypes correlate with reduced lignin and increased salicylic acid contents as well as altered fatty acid and soluble sugar composition. In addition to an enolase the LOS2/ENO2 locus encodes the transcription factor AtMBP-1, and here we reveal that this bifunctionality serves to maintain the homeostasis of ENO2 activity. In summary, we show that in plants enolase function is required for the formation of chorismate-dependent secondary metabolites, and that this activity is feedback-inhibited by AtMBP-1 to enable the normal development and reproductive success of plants.

  17. Explosive Formulation Pilot Plant

    Data.gov (United States)

    Federal Laboratory Consortium — The Pilot Plant for Explosive Formulation supports the development of new explosives that are comprised of several components. This system is particularly beneficial...

  18. The role of eNOS on the compensatory regulation of vascular tonus by H2S in mouse carotid arteries.

    Science.gov (United States)

    Ertuna, Elif; Loot, Annemarieke E; Fleming, Ingrid; Yetik-Anacak, Gunay

    2017-09-30

    The gasotransmitter nitric oxide (NO) has an important role in vascular function and a decrease in its bioavailability is accepted as a main pathological mechanism for cardiovascular diseases. However, other gasotransmitters such as hydrogen sulfide (H2S) are also generated by the endothelium and can also affect vascular tone and a crosstalk may exist between H2S and NO. We therefore investigated the consequences of deficiency, replacement or overexpression of endothelial nitric oxide synthase (eNOS) on H2S-induced vascular responses in murine carotid arteries. In pre-contracted carotid arteries from wild-type (WT) mice, l-cysteine elicited relaxation that was inhibited by the H2S synthesis inhibitor amino-oxyacetic acid (AOAA). Genetic deletion of eNOS increased l-cysteine-induced relaxation compared to WT, but the replacement of eNOS by adenoviral transfection or H2S synthesis inhibition by AOAA reversed it. Furthermore, eNOS deletion did not alter NaHS-induced relaxation in carotid arteries while eNOS overexpression/replacement increased NaHS-induced relaxation responses in carotid arteries from WT or eNOS(-/-). We suggest that, endogenously produced H2S can compensate for impaired vasodilatory responses in the absence of NO to maintain vascular patency; while, eNOS abundance can limit endogenous H2S-induced vascular responses in mice carotid arteries. Our result suggests that endogenous vs. exogenous H2S-induced relaxation are reciprocally regulated by NO in mice carotid arteries. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Formulations in first encounters

    NARCIS (Netherlands)

    A. Hak (Tony); F. de Boer (Fijgje)

    1994-01-01

    markdownabstractThe paper describes and compares the use and function of the formulation--decision pair in three types of diagnostic interviewing. The investigatory type of interviewing, which typically occurs in the medical interview, is characterized by the absence of formulations. In the explora

  20. Investigating the effects of perturbations to pgi and eno gene expression on central carbon metabolism in Escherichia coli using 13 C metabolic flux analysis

    Directory of Open Access Journals (Sweden)

    Usui Yuki

    2012-06-01

    Full Text Available Abstract Background It has long been recognized that analyzing the behaviour of the complex intracellular biological networks is important for breeding industrially useful microorganisms. However, because of the complexity of these biological networks, it is currently not possible to obtain all the desired microorganisms. In this study, we constructed a system for analyzing the effect of gene expression perturbations on the behavior of biological networks in Escherichia coli. Specifically, we utilized 13 C metabolic flux analysis (13 C-MFA to analyze the effect of perturbations to the expression levels of pgi and eno genes encoding phosphoglucose isomerase and enolase, respectively on metabolic fluxes. Results We constructed gene expression-controllable E. coli strains using a single-copy mini F plasmid. Using the pgi expression-controllable strain, we found that the specific growth rate correlated with the pgi expression level. 13 C-MFA of this strain revealed that the fluxes for the pentose phosphate pathway and Entner-Doudoroff pathway decreased, as the pgi expression lelvel increased. In addition, the glyoxylate shunt became active when the pgi expression level was almost zero. Moreover, the flux for the glyoxylate shunt increased when the pgi expression level decreased, but was significantly reduced in the pgi-knockout cells. Comparatively, eno expression could not be decreased compared to the parent strain, but we found that increased eno expression resulted in a decreased specific growth rate. 13 C-MFA revealed that the metabolic flux distribution was not altered by an increased eno expression level, but the overall metabolic activity of the central metabolism decreased. Furthermore, to evaluate the impact of perturbed expression of pgi and eno genes on changes in metabolic fluxes in E. coli quantitatively, metabolic sensitivity analysis was performed. As a result, the perturbed expression of pgi gene had a great impact to the

  1. The Role of e-NOS in Chronic Cholestasis-Induced Liver and Renal Injury in Rats: The Effect of N-Acetyl Cysteine

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    Yusuf Gunay

    2014-01-01

    Full Text Available Introduction. The role of chronic cholestasis (CC in liver injury and fibrosis remains unclear. The aims of this study were to define the role of endothelial nitric oxide synthase (e-NOS in CC and the protective effect of N-acetyl-L-cysteine (NAC in liver and kidney injury. Materials and Methods. Group A (sham group; Group B (CBDL; and Group C (CBDL + NAC. Group C received daily dosage of NAC (100 mg/kg intraperitoneally for up to 4 weeks. Results. The rate of bridging fibrosis was higher (100% versus 20%, P=.025, but the intensity of e-NOS in liver was lower in rats that received NAC (1.3 versus 2.7, P=.046. The necrotic area in the kidneys among rats that received NAC was lower at week 4 (48% versus 57%; P<.001. The numbers of e-NOS stained cells in kidney were similar in sham group and the two groups with CBDL. Discussion. NAC reduced the stimulus for liver fibrosis in this rat model of CC and attenuated liver and kidney injury. Our study showed that e-NOS expression increased in liver tissue of rats with CC and that this was reversed by NAC. Treatment with NAC might restore e-NOS protein expression and prevent liver injury in CC.

  2. Mutation of the gene promoter synthase nitric oxide eNOS T786С in patients with pseudarthrosis of long bones: relationship with lipid levels and endothelial function

    Directory of Open Access Journals (Sweden)

    Bezsmertnyi Yu.O.

    2013-06-01

    Full Text Available Objective: The prevalence of gene promoter polymorphism eNOS T786С and its relationship with the level of lipids and vascular endothelial function in patients with pseudoarthrosis of long bones was investigated. Materials and methods. In 118 patients with pseudoarthrosis of long bones frequency of mutation of gene promoter eNOS T786C was studied and its relationship to lipid levels and vascular endothelial function was determined. The control group consisted of 48 patients with consolidated diaphyseal fractures, representative by age, gender and location of the damage. Results and discussion. Pathological homozygotes eNOS 786-CC accumulate predominantly in patients with hypoplastic and atrophic type of pseudoarthrosis. The frequency of genotypes distribution in patients with normoplastic type of pseudoarthrosis corresponded to the same in people with consolidated fractures. In patients with genotype eNOS 786-CC more often individuals with aberrant lipid levels and structural and functional changes in the common carotid, brachial and femoral arteries are identified. Conclusions. In patients with pseudarthrosis of long bones tendency to decrease in the proportion of normal homozygotes (786-CT, increase in heterozygotes (786-CT and the proportion of individuals with abnormal genotype 786-CC is observed. The mutation in gene T786C eNOS was associated with the development of hypoplastic and aplastic types of pseudarthrosis, increasing the proportion of persons with aberrant lipid levels, endothelial dysfunction of the central and peripheral vessels.

  3. Target sequencing, cell experiments, and a population study establish endothelial nitric oxide synthase (eNOS) gene as hypertension susceptibility gene.

    Science.gov (United States)

    Salvi, Erika; Kuznetsova, Tatiana; Thijs, Lutgarde; Lupoli, Sara; Stolarz-Skrzypek, Katarzyna; D'Avila, Francesca; Tikhonoff, Valerie; De Astis, Silvia; Barcella, Matteo; Seidlerová, Jitka; Benaglio, Paola; Malyutina, Sofia; Frau, Francesca; Velayutham, Dinesh; Benfante, Roberta; Zagato, Laura; Title, Alexandra; Braga, Daniele; Marek, Diana; Kawecka-Jaszcz, Kalina; Casiglia, Edoardo; Filipovsky, Jan; Nikitin, Yuri; Rivolta, Carlo; Manunta, Paolo; Beckmann, Jacques S; Barlassina, Cristina; Cusi, Daniele; Staessen, Jan A

    2013-11-01

    A case-control study revealed association between hypertension and rs3918226 in the endothelial nitric oxide synthase (eNOS) gene promoter (minor/major allele, T/C allele). We aimed at substantiating these preliminary findings by target sequencing, cell experiments, and a population study. We sequenced the 140-kb genomic area encompassing the eNOS gene. In HeLa and HEK293T cells transfected with the eNOS promoter carrying either the T or the C allele, we quantified transcription by luciferase assay. In 2722 randomly recruited Europeans (53.0% women; mean age 40.1 years), we studied blood pressure change and incidence of hypertension in relation to rs3918226, using multivariable-adjusted models. Sequencing confirmed rs3918226, a binding site of E-twenty six transcription factors, as the single nucleotide polymorphism most closely associated with hypertension. In T compared with C transfected cells, eNOS promoter activity was from 20% to 40% (Phypertension. The hazard ratio and attributable risk associated with TT homozygosity were 2.04 (CI, 1.24-3.37; P=0.0054) and 51.0%, respectively. In conclusion, rs3918226 in the eNOS promoter tags a hypertension susceptibility locus, TT homozygosity being associated with lesser transcription and higher risk of hypertension.

  4. HMG-CoA reductase inhibitor rosuvastatin improves abnormal brain electrical activity via mechanisms involving eNOS.

    Science.gov (United States)

    Seker, F B; Kilic, U; Caglayan, B; Ethemoglu, M S; Caglayan, A B; Ekimci, N; Demirci, S; Dogan, A; Oztezcan, S; Sahin, F; Yilmaz, B; Kilic, E

    2015-01-22

    Apart from its repressing effect on plasma lipid levels, 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase inhibitors exert neuroprotective functions in animal models of neurodegenerative disorders. In view of these promising observations, we were interested in whether HMG-CoA reductase inhibition would affect epileptiform activity in the brain. To elucidate this issue, atorvastatin, simvastatin and rosuvastatin were administered orally at a dose of 20 mg/kg each for 3 days and their anti-epileptic activities were tested and compared in rats. Epileptiform activity in the brain was induced by an intracortical penicillin G injection. Among HMG-CoA reductase inhibitors, simvastatin-treatment was less effective in terms of spike frequency as compared with atorvastatin- and rosuvastatin-treated animals. Atorvastatin treatment reduced spike frequencies and amplitudes significantly throughout the experiment. However, the most pronounced anti-epileptic effect was observed in rosuvastatin-treated animals, which was associated with improved blood-brain barrier (BBB) integrity, increased expression of endothelial nitric oxide synthase (eNOS) mRNA and decreased expressions of pro-apoptotic p53, Bax and caspase-3 mRNAs. Inhibition of eNOS activity with L-NG-Nitroarginine Methyl Ester (L-NAME) reversed the anti-epileptic effect of rosuvastatin significantly. However, L-NAME did not alter the effect of rosuvastatin on the levels of p53, Bax and caspase-3 mRNA expression. Here, we provide evidence that among HMG-CoA reductase inhibitors, rosuvastatin was the most effective statin on the reduction of epileptiform activity, which was associated with improved BBB permeability, increased expression of eNOS and decreased expressions of pro-apoptotic p53, Bax and caspase-3. Our observation also revealed that the anti-epileptic effect of rosuvastatin was dependent on the increased expression level of eNOS. The robust anti-epileptic effect encourages proof-of-concept studies with

  5. Formulation techniques for nanofluids.

    Science.gov (United States)

    Rivera-Solorio, Carlos I; Payán-Rodríguez, Luis A; García-Cuéllar, Alejandro J; Ramón-Raygoza, E D; L Cadena-de-la-Peña, Natalia; Medina-Carreón, David

    2013-11-01

    Fluids with suspended nanoparticles, commonly known as nanofluids, may be formulated to improve the thermal performance of industrial heat transfer systems and applications. Nanofluids may show enhanced thermal and electrical properties such as thermal conductivity, viscosity, heat transfer coefficient, dielectric strength, etc. However, stability problems may arise as nanoparticles usually have the tendency to agglomerate and sediment producing deterioration in the increment of these properties. In this review, we discuss patents that report advances in the formulation of nanofluids including: production methods, selection of components (nanoparticles, base fluid and surfactants), their chemical compositions and morphologies, and characterization techniques. Finally, current and future directions in the development of nanofluid formulation are discussed.

  6. Assessment of strategy formulation

    DEFF Research Database (Denmark)

    Acur, Nuran; Englyst, Linda

    2006-01-01

    . Practical implications – The integration of three different strategy assessment approaches has been made to obtain a holistic, multi-perspective reflection on strategy formulation. Such reflection is assumed to enable managers to proactively evaluate the potential outcome and performance of their chosen......Purpose – Today, industrial firms need to cope with competitive challenges related to innovation, dynamic responses, knowledge sharing, etc. by means of effective and dynamic strategy formulation. In light of these challenges, the purpose of the paper is to present and evaluate an assessment tool...... for strategy formulation processes that ensures high quality in process and outcome. Design/methodology/approach – A literature review was conducted to identify success criteria for strategy formulation processes. Then, a simple questionnaire and assessment tool was developed and used to test the validity...

  7. Effect of Troglitazone on Expression of Adhesion Molecules and eNOS in Human Saphenous Vein Gaft

    Institute of Scientific and Technical Information of China (English)

    CHEN Shu; HU Zhiwei; ZHANG Kailun; SU Wei; SUN Zongquan

    2007-01-01

    To investigate whether peroxisome proliferators-activated receptor-y (PPARγ) ligand Troglitazone can reduce endothelial injury and activation during storage of harvested saphenous vein grafts. Segments of human saphenous vein graft were collected from 9 patients undergoing coronary bypass surgery and then divided into two equal parts of control and test specimens, were stored in ei-ther heparinized blood (control group) or heparinized blood containing 20 μmol/L troglitazone (test group) for 1 h at room temperature. Tissue distribution and protein expression of VCAM-1, ICAM-1, and endothelial nitric oxide synthase (eNOS) were compared using immunohistochemistry and West-ern blot analysis. Myeloperoxidase (MPO) activity, a marker of neutrophil sequestration in human saphenous vein grafts, was also measured in each group. The expression of ICAM-1 (753±132 versus 7201±934; P<0.01) , VCAM-1 (3731±294 versus 8292±793; P<0.01), and MPO activity (1.52±0.42 U/g, 5.04±1.26 U/g P<0.01) were significantly lower in test group. In contract, eNOS expression (7983±834 versus 3989±1008; P<0.01) was significantly higher in test group. PPARγ ligand troglita- zone might reduce endothelial injury during the storage period of human saphenous vein grafts.

  8. Association of Common Variants in eNOS Gene with Primary Open Angle Glaucoma: A Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Yang Xiang

    2016-01-01

    Full Text Available Purpose. To clarify the association of endothelial nitric oxide synthase (eNOS polymorphisms and primary open angle glaucoma (POAG. Methods. After a systematic literature search in the MEDLINE, EMBASE, and ISI Web of Science databases, all relevant studies evaluating the association between the polymorphisms (rs2070744 and rs1799983 of eNOS gene and POAG were screened and included. The pooled odds ratios (ORs and the 95% confidence interval (CI of each single-nucleotide polymorphism (SNP in five genetic models were estimated using fixed-effect model if I2<50% in the test for heterogeneity; otherwise the random-effects model was used. Results. Thirty-one records were obtained, with five being suitable for meta-analysis. The overall results showed that both TT genotype in rs2070744 and GG genotype in rs1799983 are associated with decreased risk of POAG susceptibility. Stratified analysis based on ethnicity showed that the association of rs2070744 with POAG remained only in Caucasians. Results of subgroup analysis by sex indicated association between both polymorphisms and POAG in female group, but not in male group. Conclusions. TT genotype and/or T-allele in rs2070744, as well as GG genotype and/or G-allele in rs1799983, was associated with decreased risk for POAG overall and in female group.

  9. Prunella vulgaris Suppresses HG-Induced Vascular Inflammation via Nrf2/HO-1/eNOS Activation

    Directory of Open Access Journals (Sweden)

    Ho Sub Lee

    2012-01-01

    Full Text Available Vascular inflammation is an important factor which can promote diabetic complications. In this study, the inhibitory effects of aqueous extract from Prunella vulgaris (APV on high glucose (HG-induced expression of cell adhesion molecules in human umbilical vein endothelial cells (HUVEC are reported. APV decreased HG-induced expression of intercellular adhesion molecule-1 (ICAM-1, vascular cell adhesion molecule-1 (VCAM-1, and E-selectin. APV also dose-dependently inhibited HG-induced adhesion of HL-60 monocytic cells. APV suppressed p65 NF-κB activation in HG-treated cells. APV significantly inhibited the formation of intracellular reactive oxygen species (ROS. HG-stimulated HUVEC secreted gelatinases, however, APV inhibited it. APV induced Akt phosphorylation as well as activation of heme oxygenase-1 (HO-1, eNOS, and nuclear factor E2-related factor 2 (Nrf2, which may protect vascular inflammation caused by HG. In conclusion, APV exerts anti-inflammatory effect via inhibition of ROS/NF-κB pathway by inducing HO-1 and eNOS expression mediated by Nrf2, thereby suggesting that Prunella vulgaris may be a possible therapeutic approach to the inhibition of diabetic vascular diseases.

  10. Sildenafil Ameliorates Gentamicin-Induced Nephrotoxicity in Rats: Role of iNOS and eNOS

    Directory of Open Access Journals (Sweden)

    Mohamed A. Morsy

    2014-01-01

    Full Text Available Gentamicin, an aminoglycoside antibiotic, is used for the treatment of serious Gram-negative infections. However, its usefulness is limited by its nephrotoxicity. Sildenafil, a selective phosphodiesterase-5 inhibitor, was reported to prevent or decrease tissue injury. The aim of this study is to evaluate the potential protective effects of sildenafil on gentamicin-induced nephrotoxicity in rats. Male Wistar rats were injected with gentamicin (100 mg/kg/day, i.p. for 6 days with and without sildenafil. Sildenafil administration resulted in nephroprotective effect in gentamicin-intoxicated rats as it significantly decreased serum creatinine and urea, urinary albumin, and renal malondialdehyde and nitrite/nitrate levels, with a concomitant increase in renal catalase and superoxide dismutase activities compared to gentamicin-treated rats. Moreover, immunohistochemical examination revealed that sildenafil treatment markedly reduced inducible nitric oxide synthase (iNOS expression, while expression of endothelial nitric oxide synthase (eNOS was markedly enhanced. The protective effects of sildenafil were verified histopathologically. In conclusion, sildenafil protects rats against gentamicin-induced nephrotoxicity possibly, in part, through its antioxidant activity, inhibition of iNOS expression, and induction of eNOS production.

  11. Cigarette Smoke Extract Changes Expression of Endothelial Nitric Oxide Synthase (eNOS) and p16(INK4a) and is Related to Endothelial Progenitor Cell Dysfunction.

    Science.gov (United States)

    He, Zhihui; Chen, Yan; Hou, Can; He, Wenfang; Chen, Ping

    2017-07-02

    BACKGROUND Endothelial dysfunction is an important pathophysiologic feature in many smoke-related diseases. Endothelial progenitor cells (EPCs) are the precursors of endothelial cells and play a fundamental role in the maintenance of endothelial integrity and function. Endothelial nitric oxide synthase (eNOS) is the dominant NOS isoform in the vasculature and plays a central role in the maintenance of endothelial homeostasis. p16(INK4a) is a cyclin-dependent kinase inhibitor and could be regarded as a major dominant senescence gene. The present study aimed to determine whether the expression of eNOS and p16(INK4a) in EPCs is related to EPCs function and the possible epigenetic mechanism, if any. MATERIAL AND METHODS We investigated EPCs capacity for proliferation, adhesion, and secretion, and the expression of eNOS and p16(INK4a) in EPCs which were altered by cigarette smoke extract (CSE) in vitro. Furthermore, Decitabine (Dec), an agent of demethylation, was used to examine whether it could alter the changes induced by CSE. RESULTS The present study demonstrated that EPCs altered by CSE in vitro displayed decreased capacities of proliferation, adhesion, and secretion, which was accompanied by decreased eNOS expression and increased p16(INK4a) expression in EPCs. Furthermore, Dec could alleviate the changes in the expression of eNOS and p16(INK4a), and protect against the EPCs dysfunction caused by CSE. CONCLUSIONS The decreased eNOS expression and increased p16(INK4a) expression was associated with dysfunction of EPCs caused by CSE. The mechanism of methylation, one of the most common epigenetic mechanism, may be involved in the EPCs dysfunction caused by CSE.

  12. Formulations and nebulizer performance.

    Science.gov (United States)

    O'Riordan, Thomas G

    2002-11-01

    To deliver a drug by nebulization, the drug must first be dispersed in a liquid (usually aqueous) medium. After application of a dispersing force (either a jet of gas or ultrasonic waves), the drug particles are contained within the aerosol droplets, which are then inhaled. Some drugs readily dissolve in water, whereas others need a cosolvent such as ethanol or propylene glycol. Some drugs are delivered as suspensions, and the efficiency of nebulizers can be different for solutions and suspensions. Solutions are delivered more efficiently with most devices. In general, conventional ultrasonic nebulizers should not be used to aerosolize suspensions, because of low efficiency. Newer strategies to improve the delivery of non-water-soluble drugs include the use of liposomes and the milling of the drug into very small "nanoparticles." In addition to the active therapeutic ingredient and solvents, drug formulations may include buffers (the solubility of some medications is influenced by pH), stabilizers, and, in the case of multi-dose preparations, antibacterial agents. Though formulations are designed to optimize drug solubility and stability, changes in formulation can also affect inhaled mass, particle size, and treatment time, though the differences between nebulizer brands probably have a greater impact than differences in formulation. Ultrasonic and jet nebulizers may damage protein and other complex agents through heat or shear stress. Additives to multi-dose formulations, especially antimicrobial and chelating agents, may cause adverse events, so there is a trend towards single-use, preservative-free vials.

  13. 面神经电图与瞬目反射在Bell麻痹中的应用比较%Comparison of ENoG and Blink reflex in patients with Bell paralysis

    Institute of Scientific and Technical Information of China (English)

    刘英; 杨友松

    2003-01-01

    目的:比较面神经电图(ENoG)与瞬目反射(BR)在Bell麻痹中的应用价值.方法:50例Bell麻痹患者在发病后1~3天(A组)和8~14天(B组)分别作面神经ENoG与BR检查.结果:BR在1~3天患侧就表现出明显异常,但1~3天及8~14天检查无明显差异.面神经ENoG在8~14天才表现明显异常.结论:对于Bell麻痹患者早期诊断作BR优于面神经ENoG,面神经ENoG在发病后8~14天对预后评价优于BR.

  14. Lubrication in tablet formulations.

    Science.gov (United States)

    Wang, Jennifer; Wen, Hong; Desai, Divyakant

    2010-05-01

    Theoretical aspects and practical considerations of lubrication in tablet compression are reviewed in this paper. Properties of the materials that are often used as lubricants, such as magnesium stearate, in tablet dosage form are summarized. The manufacturing process factors that may affect tablet lubrication are discussed. As important as the lubricants in tablet formulations are, their presence can cause some changes to the tablet physical and chemical properties. Furthermore, a detailed review is provided on the methodologies used to characterize lubrication process during tablet compression with relevant process analytical technologies. Finally, the Quality-by-Design considerations for tablet formulation and process development in terms of lubrication are discussed.

  15. An alternative smooth particle hydrodynamics formulation to simulate chemotaxis in porous media.

    Science.gov (United States)

    Avesani, Diego; Dumbser, Michael; Chiogna, Gabriele; Bellin, Alberto

    2016-08-27

    Chemotaxis, the microorganisms autonomous motility along or against the concentration gradients of a chemical species, is an important, yet often neglected factor controlling the transport of bacteria through saturated porous media. For example, chemotactic bacteria could enhance bioremediation by directing their own motion to residual contaminants trapped in low hydraulic conductive zones of contaminated aquifers. The aim of the present work is to develop an accurate numerical scheme to model chemotaxis in saturated porous media and other advective dominating flow systems. We propose to model chemotaxis by using a new class of meshless Lagrangian particle methods we recently developed for applications in fluid mechanics. The method is based on the Smooth Particle Hydrodynamics (SPH) formulation of (Ben Moussa et al., Int Ser Numer Math, 13(1):29-62, 2006), combined with a new Weighted Essentially Non-Oscillatory (WENO) reconstruction technique on moving point clouds in multiple space dimensions. The purpose of this new numerical scheme is to fully exploit the advantages of SPH among traditional mesh-based and mesh-free schemes and to overcome drawbacks related to the use of standard SPH for modeling chemotaxis in porous media. First, we test the new scheme against analytical reference solutions. Then, under the assumption of complete mixing at the Darcy scale, we perform two-dimensional conservative solute transport simulations under steady-state flow conditions, to show the capability of the proposed new scheme to model chemotaxis.

  16. Growth hormone receptor deficiency in mice results in reduced systolic blood pressure and plasma renin, increased aortic eNOS expression, and altered cardiovascular structure and function

    DEFF Research Database (Denmark)

    Egecioglu, E; Andersson, I J; Bollano, E

    2007-01-01

    .05) and increased aortic endothelial NO synthase (eNOS) expression (146%, P pressure (BP, 110 +/- 4 vs. 147 +/- 3 mmHg, P ....05) in GHR KO. Relative left ventricular weight was 14% lower in GHR KO mice (P ... to acetylcholine (P causes functional and morphological changes in both heart and vasculature that are beyond the observed alterations in body size...

  17. Common 894G>T single nucleotide polymorphism in the gene coding for endothelial nitric oxide synthase (eNOS) and risk of congenital heart defects

    NARCIS (Netherlands)

    Beynum, van I.M.; Mooij, C.; Kapusta, L.; Heil, S.G.; Heijer, den M.

    2008-01-01

    BACKGROUND: Endothelial nitric oxide synthase (eNOS) produces nitric oxide, which plays a role in vasodilatation and in the regulation of cell growth and apoptosis. eNOS-deficient mice have impaired cardiac development resulting in congenital heart defects (CHDs). In humans, a single nucleotide

  18. Antiphospholipid antibodies promote leukocyte-endothelial cell adhesion and thrombosis in mice by antagonizing eNOS via beta 2GPI and apoER2

    NARCIS (Netherlands)

    Ramesh, Sangeetha; Morrell, Craig N.; Tarango, Cristina; Thomas, Gail D.; Yuhanna, Ivan S.; Girardi, Guillermina; Herz, Joachim; Urbanus, Rolf T.; de Groot, Philip G.; Thorpe, Philip E.; Salmon, Jane E.; Shaul, Philip W.; Mineo, Chieko

    2011-01-01

    In antiphospholipid syndrome (APS), antiphospholipid antibodies (aPL) binding to beta 2 glycoprotein I (beta 2GPI) induce endothelial cell-leukocyte adhesion and thrombus formation via unknown mechanisms Here we show that in mice both of these processes are caused by the inhibition of eNOS In studie

  19. Disruption of COX-2 and eNOS does not confer protection from cardiovascular failure in lipopolysaccharide-treated conscious mice and isolated vascular rings

    DEFF Research Database (Denmark)

    Stæhr, Mette; Madsen, Kirsten; Vanhoutte, Paul M

    2011-01-01

    It was hypothesized that a serial stimulation of vascular cyclooxygenase-2 (COX-2) with subsequent activation of endothelial nitric oxide synthase (eNOS) is responsible for decrease in blood pressure, cardiac performance, and vascular reactivity in endotoxemia caused by LPS. The hypothesis was te...

  20. Passive leg movement enhances interstitial VEGF protein, endothelial cell proliferation, and eNOS mRNA content in human skeletal muscle

    DEFF Research Database (Denmark)

    Hellsten, Ylva; Rufener, Nora; Nielsen, Jens J

    2008-01-01

    were analyzed for mRNA content of VEGF, endothelial nitric oxide synthase (eNOS), and matrix metalloproteinase-2 (MMP-2). The passive leg movement caused an increase (P dialysate...... to cultured endothelial cells revealed that dialysate obtained during leg movement induced a 3.2-fold higher proliferation rate (P dialysate obtained at rest. Passive movement also enhanced (P

  1. Chronic aerobic exercise associated to dietary modification improve endothelial function and eNOS expression in high fat fed hamsters.

    Directory of Open Access Journals (Sweden)

    Beatriz C S Boa

    Full Text Available Obesity is epidemic in the western world and central adipose tissue deposition points to increased cardiovascular morbidity and mortality, independently of any association between obesity and other cardiovascular risk factors. Physical exercise has been used as non-pharmacological treatment to significantly reverse/attenuate obesity comorbidities. In this study we have investigated effects of exercise and/or dietary modification on microcirculatory function, body composition, serum glucose, iNOS and eNOS expression on 120 male hamsters treated for 12 weeks with high fat chow (HF, n = 30 starting on the 21st day of birth. From week 12 to 20, animals were randomly separated in HF (no treatment change, return to standard chow (HFSC, n = 30, high fat chow associated to an aerobic exercise training program (AET (HFEX, n = 30 and return to standard chow+AET (HFSCEX, n = 30. Microvascular reactivity in response to acetylcholine and sodium nitroprusside and macromolecular permeability increase induced by 30 minutes ischemia followed by reperfusion were assessed on the cheek pouch preparation. Total body fat and aorta eNOS and iNOS expression by immunoblotting assay were evaluated on the experimental day. Compared to HFSC and HFSCEX groups, HF and HFEX ones presented increased visceral fat [(mean±SEM (HF4.9±1.5 g and (HFEX4.7±0.9 g vs. (HFSC*3.0±0.7 g and (HFSCEX*1.9±0.4 g/100 g BW]; impaired endothelial-dependent vasodilatation [Ach 10(-8 M (HF87.9±2.7%; (HFSC*116.7±5.9%; (HFEX*109.1±4.6%; (HFSCEX*105±2.8%; Ach10(-6 M (HF95.3±3.1%; (HFSC*126±6.2%; (HFEX*122.5±2.8%; (HFSCEX*118.1±4.3% and Ach10(-4 M (HF109.5±4.8%; (HFSC*149.6±6.6%; (HFEX*143.5±5.4% and (HFSCEX*139.4±5.2%], macromolecular permeability increase after ischemia/reperfusion [(HF40.5±4.2; (HFSC*19.0±1.6; (HFEX*18.6±2.1 and (HFSCEX* 21.5±3.7 leaks/cm2, decreased eNOS expression, increased leptin and glycaemic levels. Endothelial-independent microvascular

  2. Sesamol alleviates diet-induced cardiometabolic syndrome in rats via up-regulating PPARγ, PPARα and e-NOS.

    Science.gov (United States)

    Sharma, Ashok Kumar; Bharti, Saurabh; Bhatia, Jagriti; Nepal, Saroj; Malik, Salma; Ray, Ruma; Kumari, Santosh; Arya, Dharamvir Singh

    2012-11-01

    Increased oxidative stress and inflammation in obesity are the central and causal components in the pathogenesis and progression of cardiometabolic syndrome (CMetS). The aim of the study was to determine the potential role of sesamol (a natural powerful antioxidant and anti-inflammatory phenol derivative of sesame oil) in chronic high-cholesterol/high-fat diet (HFD)-induced CMetS in rats and to explore the molecular mechanism driving this activity. Rats were fed with HFD (55% calorie from fat and 2% cholesterol) for 60 days to induce obesity, dyslipidemia, insulin resistance (IR), hepatic steatosis and hypertension. On the 30th day, rats with total cholesterol >150 mg/dl were considered hypercholesterolemic and administered sesamol 2, 4 and 8 mg/kg per day for the next 30 days. Sesamol treatment decreased IR, hyperinsulinemia, hyperglycemia, dyslipidemia, TNF-α, IL-6, leptin, resistin, highly sensitive C-reactive protein (hs-CRP), hepatic transaminases and alkaline phosphatase, along with normalization of adiponectin, nitric oxide and arterial pressures in a dose-dependent fashion. Increased TBARS, nitrotyrosine and decreased antioxidant enzyme activities were also amended in HFD rats. Similarly, sesamol normalized hepatic steatosis and ultrastructural pathological alteration in hepatocytes, although the effect was more pronounced at 8 mg/kg. Furthermore, hepatic PPARγ, PPARα and e-NOS protein expressions were increased, whereas LXRα, SERBP-1c, P-JNK and NF-κB expression were decreased by sesamol treatment. These results suggest that sesamol attenuates oxidative stress, inflammation, IR, hepatic steatosis and hypertension in HFD-fed rats via modulating PPARγ, NF-κB, P-JNK, PPARα, LXRα, SREBP-1c and e-NOS protein expressions, thereby preventing CMetS. Thus, the present study demonstrates the therapeutic potential of sesamol in alleviating CMetS.

  3. Alteration in cardiac uncoupling proteins and eNOS gene expression following high-intensity interval training in favor of increasing mechanical efficiency

    Science.gov (United States)

    Fallahi, Ali Asghar; Shekarfroush, Shahnaz; Rahimi, Mostafa; Jalali, Amirhossain; Khoshbaten, Ali

    2016-01-01

    Objective(s): High-intensity interval training (HIIT) increases energy expenditure and mechanical energy efficiency. Although both uncoupling proteins (UCPs) and endothelial nitric oxide synthase (eNOS) affect the mechanical efficiency and antioxidant capacity, their effects are inverse. The aim of this study was to determine whether the alterations of cardiac UCP2, UCP3, and eNOS mRNA expression following HIIT are in favor of increased mechanical efficiency or decreased oxidative stress. Materials and Methods: Wistar rats were divided into five groups: control group (n=12), HIIT for an acute bout (AT1), short term HIIT for 3 and 5 sessions (ST3 and ST5), long-term training for 8 weeks (LT) (6 in each group). The rats of the training groups were made to run on a treadmill for 60 min in three stages: 6 min running for warm-up, 7 intervals of 7 min running on treadmill with a slope of 5° to 20° (4 min with an intensity of 80-110% VO2max and 3 min at 50-60% VO2max), and 5-min running for cool-down. The control group did not participate in any exercise program. Rats were sacrificed and the hearts were extracted to analyze the levels of UCP2, UCP3 and eNOS mRNA by RT-PCR. Results: UCP3 expression was increased significantly following an acute training bout. Repeated HIIT for 8 weeks resulted in a significant decrease in UCPs mRNA and a significant increase in eNOS expression in cardiac muscle. Conclusion: This study indicates that Long term HIIT through decreasing UCPs mRNA and increasing eNOS mRNA expression may enhance energy efficiency and physical performance. PMID:27114795

  4. Nebivolol alleviates aortic remodeling through eNOS upregulation and inhibition of oxidative stress in L-NAME-induced hypertensive rats.

    Science.gov (United States)

    Wang, Yan; Zhang, Fei; Liu, Yu; Yin, Sha; Pang, Xuefen; Li, Zhidong; Wei, Zehui

    2017-06-22

    To investigate the effect and mechanism of nebivolol on aortic remodeling in N-nitro-l-arginine methyl ester (l-NAME)-induced hypertension. Male Sprague-Dawley rats were treated with equal volumes of drinking water or l-NAME (60 mg/kg/day), alone or in combination with nebivolol (8 mg/kg/day) or atenolol (80 mg/kg/day) by gavage for 8 weeks. Systolic blood pressure (SBP), aortic morphometry, plasma nitric oxide (NO) levels, nitric oxide synthase (NOS) activity, and relaxation of aorta to acetylcholine were determined. Protein expression of endothelial NOS (eNOS), Akt, and NADPH oxidase (Nox) was evaluated. l-NAME-treated rats showed an elevated SBP associated with aortic remodeling. l-NAME-treated rats showed reduced plasma NO levels and NOS activity and increased reactive oxygen species (ROS). Protein expression of eNOS, eNOS phosphorylated at Ser(1177) (p-eNOS), Akt, and Akt phosphorylated at Ser(473) (p-Akt) decreased, whereas that of Nox2, Nox4, and p22(phox) increased in the aortas from l-NAME-treated rats. Nebivolol treatment reduced SBP and ameliorated aortic remodeling. The effects of nebivolol were accompanied by increasing NO levels, NOS activity, and expression of eNOS, p-eNOS, Akt, and p-Akt, as well as reduction of ROS generation and Nox2, Nox4, and p22(phox) expression. These effects of nebivolol were not reproduced by atenolol. Our data indicate a protective role of nebivolol on the high blood pressure and vascular remodeling induced by l-NAME. The beneficial vascular effect of nebivolol is mediated by the upregulation of eNOS and inhibition of oxidative stress.

  5. Hypercholesterolemia-induced erectile dysfunction: endothelial nitric oxide synthase (eNOS) uncoupling in the mouse penis by NAD(P)H oxidase

    Science.gov (United States)

    Musicki, Biljana; Liu, Tongyun; Lagoda, Gwen A.; Strong, Travis D.; Sezen, Sena F.; Johnson, Justin M.; Burnett, Arthur L.

    2010-01-01

    INTRODUCTION Hypercholesterolemia induces erectile dysfunction (ED) mostly by increasing oxidative stress and impairing endothelial function in the penis, but the mechanisms regulating reactive oxygen species (ROS) production in the penis are not understood. AIMS We evaluated whether hypercholesterolemia activates nicotinamide adenine dinucleotide phosphate (NAD[P]H) oxidase in the penis, providing an initial source of ROS to induce endothelial nitric oxide synthase (eNOS) uncoupling and endothelial dysfunction resulting in ED. METHODS Low-density-lipoprotein receptor (LDLR)–null mice were fed Western diet for 4 weeks to induce early-stage hyperlipidemia. Wild type (WT) mice fed regular chow served as controls. Mice received NAD(P)H oxidase inhibitor apocynin (10 mM in drinking water) or vehicle. Erectile function was assessed in response to cavernous nerve electrical stimulation. Markers of endothelial function (phospho [P]-vasodilator-stimulated-protein [VASP]-Ser-239), oxidative stress (4-hydroxy-2-nonenal [HNE]), sources of ROS (eNOS uncoupling and NAD[P]H oxidase subunits p67phox, p47phox, and gp91phox), P-eNOS-Ser-1177, and eNOS were measured by Western blot in penes. MAIN OUTCOME MEASURES Molecular mechanisms of ROS generation and endothelial dysfunction in hypercholesterolemia-induced ED. RESULTS Erectile response was significantly (Phypercholesterolemia increased (Phypercholesterolemia. CONCLUSION Activated NAD(P)H oxidase in the penis is an initial source of oxidative stress resulting in eNOS uncoupling, thus providing a mechanism of eNOS uncoupling and endothelial dysfunction in hypercholesterolemia-induced ED. PMID:20626609

  6. Liposomal paclitaxel formulations.

    Science.gov (United States)

    Koudelka, Stěpán; Turánek, Jaroslav

    2012-11-10

    Over the past three decades, taxanes represent one of the most important new classes of drugs approved in oncology. Paclitaxel (PTX), the prototype of this class, is an anti-cancer drug approved for the treatment of breast and ovarian cancer. However, notwithstanding a suitable premedication, present-day chemotherapy employing a commercial preparation of PTX (Taxol®) is associated with serious side effects and hypersensitivity reactions. Liposomes represent advanced and versatile delivery systems for drugs. Generally, both in vivo mice tumor models and human clinical trials demonstrated that liposomal PTX formulations significantly increase a maximum tolerated dose (MTD) of PTX which outperform that for Taxol®. Liposomal PTX formulations are in various stages of clinical trials. LEP-ETU (NeoPharm) and EndoTAG®-1 (Medigene) have reached the phase II of the clinical trials; Lipusu® (Luye Pharma Group) has already been commercialized. Present achievements in the preparation of various liposomal formulations of PTX, the development of targeted liposomal PTX systems and the progress in clinical testing of liposomal PTX are discussed in this review summarizing about 30 years of liposomal PTX development.

  7. Evaluation of Protective Immune Responses Induced by Recombinant TrxLp and ENO2 Proteins against Toxoplasma gondii Infection in BALB/c Mice

    Directory of Open Access Journals (Sweden)

    Meng Wang

    2016-01-01

    Full Text Available Toxoplasma gondii is an obligate intracellular parasitic protozoan that can infect almost all species of warm-blooded animals. As any chemical-based drugs could not act against the tissue cyst stage of T. gondii, vaccination may be one of the ideal control strategies. In the present study, two new vaccine candidates, named TgENO2 and TgTrxLp, were purified from Escherichia coli with pET-30a(+ expression system and then were injected into BALB/c mice to evaluate the protective efficacy against acute and chronic toxoplasmosis. The results showed that both the recombinant proteins, either alone or in combination, could elicit strong humoral and cellular immune responses with a higher level of IgG antibodies, IFN-γ, IL-2, CD4+, and CD8+ T cells as compared to those in mice from control groups. After acute challenge with tachyzoites of the GJS strain, mice immunized with rTgTrxLp (8±2.77 d, rTgENO2 (7.4±1.81 d, and rTgTrxLp + rTgENO2 (8.38±4.57 d proteins showed significantly longer survival time than those that received Freund’s adjuvant (6.78±2.08 d and PBS (6.38±4.65 d (χ2 = 9.687, df = 4, P=0.046. The protective immunity of rTgTrxLp, rTgENO2, and rTgTrxLp + rTgENO2 proteins against chronic T. gondii infection showed 69.77%, 58.14%, and 20.93% brain cyst reduction as compared to mice that received PBS. The present study suggested that both TgENO2 and TgTrxLp were potential candidates for the development of multicomponent vaccines against toxoplasmosis.

  8. Formulations of entomopathogens as bioinsecticides

    Science.gov (United States)

    Developing a proper formulation is a necessary component for commercialization of entomopathogenic microbes as biological insecticides. The objective of this chapter is to present broad-ranging information about formulations to foster research toward developing commercial microbial-based insecticide...

  9. Systematic Equation Formulation

    DEFF Research Database (Denmark)

    Lindberg, Erik

    2007-01-01

    A tutorial giving a very simple introduction to the set-up of the equations used as a model for an electrical/electronic circuit. The aim is to find a method which is as simple and general as possible with respect to implementation in a computer program. The “Modified Nodal Approach”, MNA, and th......, and the “Controlled Source Approach”, CSA, for systematic equation formulation are investigated. It is suggested that the kernel of the P Spice program based on MNA is reprogrammed....

  10. Estrogen and phytoestrogens: Effect on eNOS expression and in vitro vasodilation in cerebral arteries in ovariectomized Watanabe heritable hyperlipidemic rabbits

    DEFF Research Database (Denmark)

    Lund, Claus Otto; Mortensen, A; Nilas, Lisbeth

    2007-01-01

    -six female ovariectomized Watanabe heritable hyperlipidemic (WHHL) rabbits were randomised to treatment with 17beta-estradiol (17beta-E(2)), SoyLife 150 or control for 16 weeks. Ring segments of basilar artery (BA) and posterior cerebral artery (PCA) were mounted in myographs for isometric tension recordings......OBJECTIVES: To evaluate the effect of estrogen replacement therapy or soy isoflavones supplement on endothelium-dependent relaxation in vitro and gene expression of endothelial nitric oxide synthase (eNOS) in cerebral arteries in a rabbit model of human hypercholesterolemia. STUDY DESIGN: Thirty...... in any of the arteries. Correspondingly, eNOS mRNA was similarly expressed in all treatment groups in both arteries. CONCLUSIONS: Improvement of cerebral endothelial function by estrogen or soy isoflavones in ovariectomized WHHL rabbits is not supported by the present data. The findings may be unique...

  11. Estrogen and phytoestrogens: Effect on eNOS expression and in vitro vasodilation in cerebral arteries in ovariectomized Watanabe heritable hyperlipidemic rabbits

    DEFF Research Database (Denmark)

    Lund, Claus O.; Mortensen, Alicja; Nilas, Lisbeth

    2007-01-01

    -six female ovariectomized Watanabe heritable hyperlipidemic (WHHL) rabbits were randomised to treatment with 17 beta-estradiol (17 beta-E-2), SoyLife 150(R) or control for 16 weeks. Ring segments of basilar artery (BA) and posterior cerebral artery (PCA) were mounted in myographs for isometric tension......Objectives: To evaluate the effect of estrogen replacement therapy or soy isoflavones supplement on endothelium-dependent relaxation in vitro and gene expression of endothelial nitric oxide synthase (eNOS) in cerebral arteries in a rabbit model of human hypercholesterolemia. Study design: Thirty......-independent response to SNP in any of the arteries. Correspondingly, eNOS mRNA was similarly expressed in all treatment groups in both arteries. Conclusions: Improvement of cerebral endothelial function by estrogen or soy isoflavones in ovariectomized WHHL rabbits is not supported by the present data. The findings may...

  12. Estrogen and phytoestrogens: Effect on eNOS expression and in vitro vasodilation in cerebral arteries in ovariectomized Watanabe heritable hyperlipidemic rabbits

    DEFF Research Database (Denmark)

    Lund, Claus Otto; Mortensen, A; Nilas, Lisbeth

    2007-01-01

    OBJECTIVES: To evaluate the effect of estrogen replacement therapy or soy isoflavones supplement on endothelium-dependent relaxation in vitro and gene expression of endothelial nitric oxide synthase (eNOS) in cerebral arteries in a rabbit model of human hypercholesterolemia. STUDY DESIGN: Thirty......-six female ovariectomized Watanabe heritable hyperlipidemic (WHHL) rabbits were randomised to treatment with 17beta-estradiol (17beta-E(2)), SoyLife 150 or control for 16 weeks. Ring segments of basilar artery (BA) and posterior cerebral artery (PCA) were mounted in myographs for isometric tension recordings...... in any of the arteries. Correspondingly, eNOS mRNA was similarly expressed in all treatment groups in both arteries. CONCLUSIONS: Improvement of cerebral endothelial function by estrogen or soy isoflavones in ovariectomized WHHL rabbits is not supported by the present data. The findings may be unique...

  13. Problematika nozokomiálních nákaz v Domově seniorů Mšeno

    OpenAIRE

    Procházková, Barbora

    2012-01-01

    Autor: Barbora Procházková Institution: Institute of social medicine Medical faculty Charles univerzity of Hradec Králové Department of nursing Title: Problems of nosocomiale infections in the House seniors Mšeno. Supervizor: Jaroslava Pečenková Pagens: 127 Addenda: 1 Year: 2012 Key words: nosocomial infections, transmission and source infection, preventiv nosocomial infections, MRSA, disinfection, sterilisation, clearing, barier care, client

  14. Relación entre malaria y el fenómeno de El Niño - Oscilación del Sur (ENOS. Fase II. Impacto de ENOS sobre la calidad de larvas y adultos y métodos alternativos de captura

    Directory of Open Access Journals (Sweden)

    Daniel Ruiz

    2001-04-01

    Full Text Available

    En diferentes partes del mundo se ha encontrado una asociación
    entre ENOS y brotes epidémicos de enfermedades tales como:
    malaria, dengue y otras transmitidas por vectores. En Colombia Poveda y Rojas presentan evidencias de la asociación entre brotes epidémicos de malaria y ENOS entre 1959 y 1994. El propósito de esta investigación es tratar de explicar la asociación entre brotes epidémicos de malaria y ENOS. En la primera fase (1998-2000 se encontró una correlación significativa entre los casos de malaria y la temperatura, pero no se hallaron asociaciones entre factores entomológicos (densidad y paridad con malaria o con clima. En esta segunda fase se medirá el efecto del clima, particularmente la temperatura sobre la calidad de los estadios larval y adulto. Además, se evaluarán métodos que sustituyan las capturas con cebo humano y se continuarán los estudios de campo sobre el efecto de ENOS en la densidad de la población de larvas y adultos y las tasas de picadura.

     

     

  15. Exercise Training Could Improve Age-Related Changes in Cerebral Blood Flow and Capillary Vascularity through the Upregulation of VEGF and eNOS

    Directory of Open Access Journals (Sweden)

    Sheepsumon Viboolvorakul

    2014-01-01

    Full Text Available This study aimed to investigate the effect of exercise training on age-induced microvascular alterations in the brain. Additionally, the association with the protein levels of vascular endothelial growth factor (VEGF and endothelial nitric oxide synthase (eNOS was also assessed. Male Wistar rats were divided into four groups: sedentary-young (SE-Young, n=5, sedentary aged (SE-Aged, n=8, immersed-aged (IM-Aged, n=5, and exercise trained-aged (ET-Aged, 60 minutes/day and 5 days/week for 8 weeks, n=8 rats. The MAPs of all aged groups, SE-Aged, IM-Aged, and ET-Aged, were significantly higher than that of the SE-Young group. The regional cerebral blood flow (rCBF in the SE-Aged and IM-Aged was significantly decreased as compared to SE-Young groups. However, rCBF of ET-Aged group was significantly higher than that in the IM-Aged group (P<0.05. Moreover, the percentage of capillary vascularity (%CV and the levels of VEGF and eNOS in the ET-Aged group were significantly increased compared to the IM-Aged group (P<0.05. These results imply that exercise training could improve age-induced microvascular changes and hypoperfusion closely associated with the upregulation of VEGF and eNOS.

  16. Marine Compound Catunaregin Inhibits Angiogenesis through the Modulation of Phosphorylation of Akt and eNOS in vivo and in vitro

    Directory of Open Access Journals (Sweden)

    Jun-Xiu Liu

    2014-05-01

    Full Text Available Angiogenesis is the formation of blood vessels from pre-existing vasculature. Excessive or uncontrolled angiogenesis is a major contributor to many pathological conditions whereas inhibition of aberrant angiogenesis is beneficial to patients with pathological angiogenesis. Catunaregin is a core of novel marine compound isolated from mangrove associate. The potential anti-angiogenesis of catunaregin was investigated in human umbilical vein endothelial cells (HUVECs and zebrafish. HUVECs were treated with different concentrations of catunaregin in the presence or absence of VEGF. The angiogenic phenotypes including cell invasion cell migration and tube formation were evaluated following catunaregin treatment in HUVECs. The possible involvement of AKT, eNOS and ERK1/2 in catunaregin-induced anti-angiogenesis was explored using Western blotting. The anti-angiogenesis of catunaregin was further tested in the zebrafish embryo neovascularization and caudal fin regeneration assays. We found that catunaregin dose-dependently inhibited angiogenesis in both HUVECs and zebrafish embryo neovascularization and zebrafish caudal fin regeneration assays. In addition, catunaregin significantly decreased the phosphorylation of Akt and eNOS, but not the phosphorylation of ERK1/2. The present work demonstrates that catunaregin exerts the anti-angiogenic activity at least in part through the regulation of the Akt and eNOS signaling pathways.

  17. Marine compound catunaregin inhibits angiogenesis through the modulation of phosphorylation of akt and eNOS in vivo and in vitro.

    Science.gov (United States)

    Liu, Jun-Xiu; Luo, Min-Qi; Xia, Meng; Wu, Qi; Long, Si-Mei; Hu, Yaohua; Gao, Guang-Chun; Yao, Xiao-Li; He, Mian; Su, Huanxing; Luo, Xiong-Ming; Yao, Shu-Zhong

    2014-05-12

    Angiogenesis is the formation of blood vessels from pre-existing vasculature. Excessive or uncontrolled angiogenesis is a major contributor to many pathological conditions whereas inhibition of aberrant angiogenesis is beneficial to patients with pathological angiogenesis. Catunaregin is a core of novel marine compound isolated from mangrove associate. The potential anti-angiogenesis of catunaregin was investigated in human umbilical vein endothelial cells (HUVECs) and zebrafish. HUVECs were treated with different concentrations of catunaregin in the presence or absence of VEGF. The angiogenic phenotypes including cell invasion cell migration and tube formation were evaluated following catunaregin treatment in HUVECs. The possible involvement of AKT, eNOS and ERK1/2 in catunaregin-induced anti-angiogenesis was explored using Western blotting. The anti-angiogenesis of catunaregin was further tested in the zebrafish embryo neovascularization and caudal fin regeneration assays. We found that catunaregin dose-dependently inhibited angiogenesis in both HUVECs and zebrafish embryo neovascularization and zebrafish caudal fin regeneration assays. In addition, catunaregin significantly decreased the phosphorylation of Akt and eNOS, but not the phosphorylation of ERK1/2. The present work demonstrates that catunaregin exerts the anti-angiogenic activity at least in part through the regulation of the Akt and eNOS signaling pathways.

  18. Diesel Particulate Exposed Macrophages Alter Endothelial Cell Expression of eNOS, iNOS, MCP1, and Glutathione Synthesis Genes

    Science.gov (United States)

    Weldy, Chad S.; Wilkerson, Hui-Wen; Larson, Timothy V.; Stewart, James A.; Kavanagh, Terrance J.

    2011-01-01

    There is considerable debate regarding inhaled diesel exhaust particulate (DEP) causing impairments in vascular reactivity. Although there is evidence that inhaled particles can translocate from the lung into the systemic circulation, it has been suggested that inflammatory factors produced in the lung following macrophage particle engulfment also pass into the circulation. To investigate these differing hypotheses, we used in vitro systems to model each exposure. By using a direct exposure system and a macrophage-endothelial cell co-culture model, we compared the effects of direct DEP exposure and exposure to inflammatory factors produced by DEP-treated macrophages, on endothelial cell mRNA levels for eNOS, iNOS, endothelin-1, and endothelin-converting-enzyme-1. As markers of oxidative stress, we measured the effects of DEP treatment on glutathione (GSH) synthesis genes and on total GSH. In addition, we analyzed the effect of DEP treatment on monocyte chemo-attractant protein-1. Direct DEP exposure increased endothelial GCLC and GCLM as well as total GSH in addition to increased eNOS, iNOS and Mcp1 mRNA. Alternatively, inflammatory factors released from DEP-exposed macrophages markedly up-regulated endothelial iNOS and Mcp1 while modestly down-regulating eNOS. These data support both direct exposure to DEP and the release of inflammatory cytokines as explanations for DEP-induced impairments in vascular reactivity. PMID:21920430

  19. Association between eNOS 4b/a Polymorphism and the Risk of Diabetic Retinopathy in Type 2 Diabetes Mellitus: A Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Ze-jun Ma

    2014-01-01

    Full Text Available Many studies have assessed the association between eNOS-4b/a polymorphism and the risk of diabetic retinopathy (DR among type 2 diabetic subjects. However, the results are inconsistent. In order to derive a more precise estimation of the association, a meta-analysis was conducted. Fifteen studies with 3, 183 cases and 3, 410 controls were enrolled by searching the databases of Pubmed, Embase, China National Knowledge Infrastructure (CNKI, and Chinese Wanfang Database. Summary odds ratios (ORs with 95% confidence intervals (CIs were calculated. The main analysis indicated no significant association between eNOS-4b/a polymorphism and the risk of DR in overall population [allelic model: OR=0.94 (0.79–1.11; additive model: OR=0.91 (0.73–1.14; recessive model: OR=1.01 (0.81–1.25; dominant model: OR=0.91 (0.75–1.09]. Subgroup analysis by ethnicity also indicated no significant association. In conclusion, the current meta-analysis did not observe any association between the polymorphism of eNOS 4b/a and the risk of DR among type 2 diabetic subjects. However, larger well-designed studies are required to confirm this finding.

  20. A new mouse model resembling human diabetic nephropathy: uncoupling of VEGF with eNOS as a novel pathogenic mechanism.

    Science.gov (United States)

    Nakagawa, T

    2009-02-01

    Diabetics develop a variety of histological abnormalities in the kidney. Early features include glomerular hypertrophy, glomerular basement membrane thickening, and mesangial expansion, whereas mesangiolysis, glomerular capillary aneurysm and nodular lesions develop in late phase. The goal of preventing diabetic nephropathy is important, but its achievement has been difficult due in part to a lack of an animal model for human diabetic nephropathy. Most animal models develop mild lesions in early phase diabetes, but not advanced lesions in late phase. Vascular endothelial growth factor (VEGF) mediates diabetic nephropathy, but its precise role remains to be determined. A complexity of VEGF function is that it is protective in nondiabetic renal diseases but is deleterious in diabetic nephropathy. Because diabetes is associated with endothelial dysfunction, we hypothesized that VEGF is deleterious in the setting of endothelial dysfunction. To test this hypothesis, we recently developed a new model of diabetic nephropathy in mice deficient in endothelial nitric oxide synthase (eNOS). Importantly, these mice developed the advanced lesions of diabetic nephropathy resembling to those in human diabetic nephropathy. In addition, these models also exhibit an uncoupling condition of VEGF with NO. In this review, we discuss our hypothesis which is that uncoupling of VEGF with NO causes advanced diabetic nephropathy.

  1. Olaparib tablet formulation

    DEFF Research Database (Denmark)

    Plummer, Ruth; Swaisland, Helen; Leunen, Karin

    2015-01-01

    BACKGROUND: The oral PARP inhibitor olaparib has shown efficacy in patients with BRCA-mutated cancer. This Phase I, open-label, three-part study (Parts A-C) in patients with advanced solid tumours evaluated the effect of food on the pharmacokinetics (PK) of olaparib when administered in tablet...... formulation. METHODS: PK data were obtained in Part A using a two-treatment period crossover design; single-dose olaparib 300 mg (two 150 mg tablets) was administered in two prandial states: fasted and fed. In Part B, patients received olaparib tablets (300 mg bid) for 5 days under fasting conditions; in Part...... exposure to olaparib 300 mg tablets, although in the absence of an effect on the extent of olaparib absorption....

  2. Impact of Rosuvastatin Treatment on HDL-Induced PKC-βII and eNOS Phosphorylation in Endothelial Cells and Its Relation to Flow-Mediated Dilatation in Patients with Chronic Heart Failure

    Directory of Open Access Journals (Sweden)

    Ephraim B. Winzer

    2016-01-01

    Full Text Available Background. Endothelial function is impaired in chronic heart failure (CHF. Statins upregulate endothelial NO synthase (eNOS and improve endothelial function. Recent studies demonstrated that HDL stimulates NO production due to eNOS phosphorylation at Ser1177, dephosphorylation at Thr495, and diminished phosphorylation of PKC-βII at Ser660. The aim of this study was to elucidate the impact of rosuvastatin on HDL mediated eNOS and PKC-βII phosphorylation and its relation to endothelial function. Methods. 18 CHF patients were randomized to 12 weeks of rosuvastatin or placebo. At baseline, 12 weeks, and 4 weeks after treatment cessation we determined lipid levels and isolated HDL. Human aortic endothelial cells (HAEC were incubated with isolated HDL and phosphorylation of eNOS and PKC-βII was evaluated. Flow-mediated dilatation (FMD was measured at the radial artery. Results. Rosuvastatin improved FMD significantly. This effect was blunted after treatment cessation. LDL plasma levels were reduced after rosuvastatin treatment whereas drug withdrawal resulted in significant increase. HDL levels remained unaffected. Incubation of HAEC with HDL had no impact on phosphorylation of eNOS or PKC-βII. Conclusion. HDL mediated eNOS and PKC-βII phosphorylation levels in endothelial cells do not change with rosuvastatin in CHF patients and do not mediate the marked improvement in endothelial function.

  3. Plutonium Immobilization Project Baseline Formulation

    Energy Technology Data Exchange (ETDEWEB)

    Ebbinghaus, B.

    1999-02-01

    A key milestone for the Immobilization Project (AOP Milestone 3.2a) in Fiscal Year 1998 (FY98) is the definition of the baseline composition or formulation for the plutonium ceramic form. The baseline formulation for the plutonium ceramic product must be finalized before the repository- and plant-related process specifications can be determined. The baseline formulation that is currently specified is given in Table 1.1. In addition to the baseline formulation specification, this report provides specifications for two alternative formulations, related compositional specifications (e.g., precursor compositions and mixing recipes), and other preliminary form and process specifications that are linked to the baseline formulation. The preliminary specifications, when finalized, are not expected to vary tremendously from the preliminary values given.

  4. Baseline LAW Glass Formulation Testing

    Energy Technology Data Exchange (ETDEWEB)

    Kruger, Albert A. [USDOE Office of River Protection, Richland, WA (United States); Mooers, Cavin [The Catholic University of America, Washington, DC (United States). Vitreous State Lab.; Bazemore, Gina [The Catholic University of America, Washington, DC (United States). Vitreous State Lab; Pegg, Ian L. [The Catholic University of America, Washington, DC (United States). Vitreous State Lab; Hight, Kenneth [The Catholic University of America, Washington, DC (United States). Vitreous State Lab; Lai, Shan Tao [The Catholic University of America, Washington, DC (United States). Vitreous State Lab; Buechele, Andrew [The Catholic University of America, Washington, DC (United States). Vitreous State Lab; Rielley, Elizabeth [The Catholic University of America, Washington, DC (United States). Vitreous State Lab; Gan, Hao [The Catholic University of America, Washington, DC (United States). Vitreous State Lab; Muller, Isabelle S. [The Catholic University of America, Washington, DC (United States). Vitreous State Lab; Cecil, Richard [The Catholic University of America, Washington, DC (United States). Vitreous State Lab

    2013-06-13

    The major objective of the baseline glass formulation work was to develop and select glass formulations that are compliant with contractual and processing requirements for each of the LAW waste streams. Other objectives of the work included preparation and characterization of glasses with respect to the properties of interest, optimization of sulfate loading in the glasses, evaluation of ability to achieve waste loading limits, testing to demonstrate compatibility of glass melts with melter materials of construction, development of glass formulations to support ILAW qualification activities, and identification of glass formulation issues with respect to contract specifications and processing requirements.

  5. Saltstone Clean Cap Formulation

    Energy Technology Data Exchange (ETDEWEB)

    Langton, C

    2005-04-22

    The current operation strategy for using Saltstone Vault 4 to receive 0.2 Ci/gallon salt solution waste involves pouring a clean grout layer over the radioactive grout prior to initiating pour into another cell. This will minimize the radiating surface area and reduce the dose rate at the vault and surrounding area. The Clean Cap will be used to shield about four feet of Saltstone poured into a Z-Area vault cell prior to moving to another cell. The minimum thickness of the Clean Cap layer will be determined by the cesium concentration and resulting dose levels and it is expected to be about one foot thick based on current calculations for 0.1 Ci Saltstone that is produced in the Saltstone process by stabilization of 0.2 Ci salt solution. This report documents experiments performed to identify a formulation for the Clean Cap. Thermal transient calculations, adiabatic temperature rise measurements, pour height, time between pour calculations and shielding calculations were beyond the scope and time limitations of this study. However, data required for shielding calculations (composition and specific gravity) are provided for shielding calculations. The approach used to design a Clean Cap formulation was to produce a slurry from the reference premix (10/45/45 weight percent cement/slag/fly ash) and domestic water that resembled as closely as possible the properties of the Saltstone slurry. In addition, options were investigated that may offer advantages such as less bleed water and less heat generation. The options with less bleed water required addition of dispersants. The options with lower heat contained more fly ash and less slag. A mix containing 10/45/45 weight percent cement/slag/fly ash with a water to premix ratio of 0.60 is recommended for the Clean Cap. Although this mix may generate more than 3 volume percent standing water (bleed water), it has rheological, mixing and flow properties that are similar to previously processed Saltstone. The recommended

  6. Endothelial nitric oxide synthase (eNOS) T-786C, 4a4b, and G894T polymorphisms and male infertility: study for idiopathic asthenozoospermia and meta-analysis.

    Science.gov (United States)

    Song, Pingping; Zou, Shasha; Chen, Tingting; Chen, Jianhua; Wang, Yanan; Yang, Juanjuan; Song, Zhijian; Jiang, Huayu; Shi, Huijuan; Huang, Yiran; Li, Zheng; Shi, Yongyong; Hu, Hongliang

    2015-02-01

    Recent studies on the eNOS gene and male infertility show that expression of eNOS regulates normal spermatogenesis in the testis, and the eNOS gene variants (T-786C, 4a4b, and G894T) are potentially involved in impairment of spermatogenesis and sperm function. Thus, we conducted this association and meta-analysis study to further validate whether variants of those three loci affected the risk of idiopathic asthenozoospermia (AZS) and male infertility. Approximately 340 Chinese idiopathic AZS patients and 342 healthy men were included for this case-control study, genotyped by gel electrophoresis analysis or direct sequencing of PCR products. The eNOS mRNA isolated from the semen of patients was further examined by quantitative real-time PCR. Also, a meta-analysis of association between eNOS gene polymorphisms and male infertility was performed. A significant association was identified on allelic level between 4a4b variant and AZS in our study (chi-squared = 7.53, corrected P = 0.018, odds ratio (OR) = 1.808), while there were no significant difference of T-786C and G894T for asthenozoospermia in both genotype and allele distributions. In addition, expression of eNOS was up-regulated in patients compared with controls (about 2.4-fold, P infertility in both Asian and Caucasian populations. Our study provides genetic evidence for the eNOS gene being a risk factor for idiopathic AZS and male infertility. Considering genetic differences among populations and complex pathogenesis of male infertility, more validating studies using independent samples are suggested in the future. © 2015 by the Society for the Study of Reproduction, Inc.

  7. Operator Formulation of Classical Mechanics.

    Science.gov (United States)

    Cohn, Jack

    1980-01-01

    Discusses the construction of an operator formulation of classical mechanics which is directly concerned with wave packets in configuration space and is more similar to that of convential quantum theory than other extant operator formulations of classical mechanics. (Author/HM)

  8. Formulation of supergravity without superspace

    CERN Document Server

    Ferrara, S

    1979-01-01

    Supergravity, the particle theory which unifies under a unique gauge principle the quantum-mechanical concept of spin and space-time geometry, is formulated in terms of quantities defined over Minkowski space-time. 'l'he relation between this formulation and the fonnulation which uses superspace, the space-time supplemented by spinning degrees of freedom, is also briefly discussed.

  9. Strategic Targets To induce Neovascularization By Resveratrol In Hypercholesterolemic Rat Myocardium: Role of Caveolin-1, eNOS, HO-1 and VEGF

    Science.gov (United States)

    Penumathsa, Suresh Varma; Koneru, Srikanth; Samuel, Samson Mathews; Maulik, Gautam; Bagchi, Debasis; Yet, Shaw-Fang; Menon, Venogopal P.; Maulik, Nilanjana

    2008-01-01

    Endothelial dysfunction and impaired angiogenesis is a hallmark of hypercholesterolemia (HC). This study was designed to examine the effects of resveratrol (R), an antioxidant with lipid lowering properties like statin, on neovascularization along with caveolar interaction with proangiogenic molecules in hypercholesterolemic (HC) rats. Animals were divided into: control (C), maintained on normal diet; rats maintained on 5% high cholesterol diet for 8 weeks (HC); & HC + R (20mg/kg) orally for 2 weeks (HCR). Myocardial infarction was induced by ligating the left anterior descending artery (LAD). Herein we examined a novel method of stimulating myocardial angiogenesis by pharmacological preconditioning with resveratrol at both capillary and arteriolar levels and the potential role of hemeoxygenase-1 (HO-1), e-NOS and Caveolin-1(Cav-1) in mediating such a response. We also investigated the functional relevance of such treatment by assessing whether the induced neovascularization can help preserve LV–contractile functional reserve in the setting of chronic hypercholesterolemic condition. Four weeks after sham surgery and LAD occlusion, rats underwent echocardiographic evaluation which revealed improvement in ejection fraction and fractional shortening in HCR compared to HC. Left ventricular tissue sections displayed increased capillary and arteriolar density in HCR compared to HC. Western blot analysis displayed downregulation of VEGF, HO-1 and increased association of Cav-1 along with eNOS in HC, preventing availability of eNOS to the system which was reversed with resveratrol treatment in HCR. This study was further validated in cardiac specific HO-1 overexpressed mice assuming molecular cross talk between the targets. Hence, our data identified potential regulators that primarily attenuate and blunt endothelial dysfunction by resveratrol therapy in hypercholesterolemic myocardium. PMID:18694817

  10. Association of the genetic polymorphisms of the ACE gene and the eNOS gene with lupus nephropathy in northern Chinese population

    Directory of Open Access Journals (Sweden)

    Lian H

    2010-06-01

    Full Text Available Abstract Background It has been reported that some single nucleotide polymorphisms (SNPs of the angiotensin converting enzyme (ACE gene and the endothelial nitric oxide synthase (eNOS gene are associated with the development of systemic lupus erythematosus (SLE and the progression of nephropathy. The aim of this study was to evaluate the possible association between six SNPs (A-5466C, T-3892C, A-240T, C1237T, G2215A and A2350G of the ACE gene and two SNPs (T-786C and G894T of the eNOS gene with lupus nephropathy in a northern Chinese population. Methods In this study, 225 patients with lupus nephropathy were compared to 232 healthy controls, matched by gender, age and ethnicity. Following the extraction of genomic DNA from the leukocytes in the peripheral blood, the genotypes of the eight selected SNPs were determined by the method of PCR-RFLP; the haplotypes were inferred using PHASE 2.1. The associations between the SNPs and the risk of lupus nephropathy were analyzed using Chi-square test and Logistic regression with SPSS13.0 software. Results Statistically significant differences of the allele frequency distribution of three SNPs (A-5466C, A2350G and G894T were observed between cases and controls (P P Conclusions Our study indicated an association between the risk of lupus nephropathy and the sequence variations of both the ACE gene and the eNOS gene, which may play an important role in the pathogenesis of lupus nephropathy in the northern Chinese population. Further studies are warranted to validate our findings.

  11. Sesamin ameliorates arterial dysfunction in spontaneously hypertensive rats via downregulation of NADPH oxidase subunits and upregulation of eNOS expression

    Institute of Scientific and Technical Information of China (English)

    Jun-xiu ZHANG; Jie-ren YANG; Guo-xiang CHEN; Li-juan TANG; Wen-xing LI; Hui YANG; Xiang KONG

    2013-01-01

    Aim:Sesamin is one of the major lignans in sesame seeds with antihyperlipidemic,antioxidative and antihypertensive activities.The aim of this study was to examine the effects of sesamin on arterial function in spontaneously hypertensive rats (SHRs).Methods:SHRs were orally administered sesamin (40,80 and 160 mg·kg-1·d-1) for 16 weeks.After the rats were killed,thoracic aortas were dissected out.The vasorelaxation responses of aortic rings to ACh and nitroprusside were measured.The expression of eNOS and NADPH oxidase subunits p4Tphox and p22phox in aortas were detected using Western blotting and immunohistochemistry.Aortic nitrotyrosine was measured with ELISA.The total antioxidant capacity (T-AOC) and MDA levels in aortas were also determined.Results:The aortic rings of SHRs showed significantly smaller ACh-induced and nitroprusside-induced relaxation than those of control rats.Treatment of SHRs with sesamin increased both the endothelium-dependent and endothelium-independent relaxation of aortic rings in a dose-dependent manner.In aortas of SHRs,the level of T-AOC and the expression of nitrotyrosine,p22phox and p47phox proteins were markedly increased,while the level of MDA and the expression of eNOS protein were significantly decreased.Treatment of SHRs with sesamin dose-dependently reversed these biochemical and molecular abnormalities in aortas.Conclusion:Long-term treatment with sesamin improves arterial function in SHR through the upregulation of eNOS expression and downregulation of p22phox and p47phox expression.

  12. mRNA expression and localization of bNOS, eNOS and iNOS in human cervix at preterm and term labour

    Directory of Open Access Journals (Sweden)

    Byström Birgitta

    2005-08-01

    Full Text Available Abstract Background Preterm birth is the primary cause of the neonatal mortality and morbidity. There will be no preterm birth without a cervical softening. Nitric oxide (NO is shown to be a mediator of term cervical ripening. The aim of this study was to investigate mRNA expression of the three isomers of NO synthases (NOS and to identify them by immunohistochemistry in the human cervix at preterm birth compared to term. Methods The three isomers of NOS- inducible (iNOS, endothelial (eNOS and neuronal (bNOS – were investigated in the human cervix. The expression of mRNA was determined using Real-Time Multiplex RT-PCR. The localisation of synthases in the cervical tissue was analysed using immunohistochemistry. Cervical biopsies were obtained from 4 groups of women without clinical signs of infection: preterm (PTL, term labour (TL, preterm not in labour (PTnotL and term not in labour (TnotL patients. One-Way ANOVA, Kruskal-Wallis, Student t-test or Mann-Whitney test were applied as appropriate to determine statistically significant differences among the groups. Results Patients in preterm labour had significantly (p Conclusion The mRNA levels were higher in the preterm labour group compared to the women at term labour. The significant increase of the eNOS mRNA expression, from the unripe to the favourable cervical state during labour, may indicate a role of eNOS and supports the role of NO in the cervical ripening process. All the three synthases were identified by immunohistochemistry in all the groups of study.

  13. [Carotid and brachial intima-media thickness of the allelic variants G894T and T-789C of eNOS in systemic sclerosis patients].

    Science.gov (United States)

    Martínez-Godínez, Ángeles; Miliar-García, Ángel; Bautista-Jiménez, María Itandehui; Jandete-Rivera, Fernando; Vera-Lastra, Olga Lidia; Jara, Luis J; Bizueto-Rosas, Héctor; del Pilar Cruz-Domínguez, María

    2015-01-01

    Introducción: el objetivo de este estudio es evaluar comparativamente el grosor íntima-media (IMT) carotídeo y braquial con ultrasonido Doppler, la presión arterial pulmonar ecocardiográfica y la variación alélica de los genes G894T y T-789C de la eNOS en pacientes con esclerodermia. Métodos: estudio transversal en pacientes con esclerodermia. Criterios de inclusión: edad 18-70 años, diagnosticado con esclerodermia, previo consentimiento informado. Se evaluó IMT, índice de resistencia (IR) e índice de pulsatilidad (IP) mediante Doppler carotídeo y braquial, perfil de lípidos, proteína C reactiva, polimorfismo G894T y T-789C de óxido nítrico sin tasa endotelial (eNOS). Analizamos con estadística descriptiva, prueba t de Student o chi cuadrada para asociación de variables y Spearman para correlacionar las variables cuantitativas. Resultados: encontramos IMT anormalmente alto en arterias carotídeas y braquiales. Observamos baja correlación entre ambas braquiales, buena correlación entre carótidas y ninguna correlación entre carótidas y braquiales. El IMT braquial izquierdo > 0.65 corresponde con presión arteria pulmonar > 30 mmHg ecocardiográfica. El polimorfismo del gen G894T se asoció con mayor IMT en carótida derecha.Conclusión: El polimorfismo G894T de eNOS se asocia a mayor IMT en carótida derecha. El IMT carotídeo concuerda con su IMT contralateral. El IMT braquial izquierdo mayor a 0.65 sugiere la posibilidad de hipertensión arterial pulmonar.

  14. Induction of Haemeoxygenase-1 Directly Improves Endothelial Function in Isolated Aortas from Obese Rats through the Ampk-Pi3k/Akt-Enos Pathway

    Directory of Open Access Journals (Sweden)

    Fang Han

    2015-07-01

    Full Text Available Background: Induction of haemeoxygenase-1 (HO-1 increases adiponectin secretion by remodeling adipose tissue in obesity. The objective of our study is to explore whether HO-1 induction directly improves endothelial function independent of adiponectin changes in obese rats. Methods: Rats were divided into control and obesity groups. Aortic endothelial function was determined by measuring endothelium-dependent vasodilatation (EDV. Vascular segments of the obese rats were incubated in an organ bath in the presence or absence of cobalt protoporphyrin (CoPP or CoPP plus stannous protoporphyrin. Nitric oxide (NO production, superoxide anion production and NF-κB p65 expression in the aorta were determined. The expression of AMP-activated kinase (AMPK, Akt and endothelial nitric oxide synthase (eNOS in endothelial cells was determined by western blotting. The aortic rings from the obese rats were then incubated with CoPP in the presence of specific inhibitors of AMPK, phosphatidylinositol 3-kinase (PI3K or eNOS. Results: Acetylcholine-induced EDV was significantly attenuated in the obese rats, compared with the NC group (p p in vitro in the presence of inhibitors of AMPK, PI3K or eNOS. HO-1 induction with CoPP significantly increased the activation of the AMPK-PI3K/Akt-eNOS pathway and NO production in parallel with reduced superoxide anion production and NF-κB p65 expression in obese rats. Conclusions: HO-1 induction with CoPP directly improved endothelial function in obese rats independent of adiponectin changes. The mechanism of this protective effect is related to increasing NO production by activation of the AMPK-PI3K/Akt-eNOS signaling pathway.

  15. Common variants of eNOS and XRCC1 genes may predict acute skin toxicity in breast cancer patients receiving radiotherapy after breast conserving surgery.

    Science.gov (United States)

    Terrazzino, Salvatore; La Mattina, Pierdaniele; Masini, Laura; Caltavuturo, Tina; Gambaro, Giuseppina; Canonico, Pier Luigi; Genazzani, Armando A; Krengli, Marco

    2012-05-01

    To evaluate the impact of functional polymorphisms in genes related to DNA repair mechanisms (XRCC1, TP53, MSH2, MSH3, XPD), oxidative stress response (GSTP1, GSTA1, eNOS, SOD2) and fibroblast proliferation (TGFβ1) on the risk of acute skin toxicity in breast cancer patients receiving radiotherapy. Skin toxicity was scored according to the Radiation Therapy Oncology Group criteria in 286 breast cancer patients who received radiotherapy after breast conserving surgery. Genotyping was conducted by PCR-RFLP analysis and real-time PCR allelic discrimination assay on genomic DNA extracted from peripheral blood. In the multivariate analysis, nominally significant associations, before multiple testing corrections, were found between XRCC1 T-77C (T carriers vs. CC, OR: 2.240, 95% CI: 1.015-4.941, P=0.046), eNOS G894T polymorphisms (TT vs. G carriers, OR: 2.473, 95% CI: 1.220-5.012, P=0.012), breast diameter (OR: 1.138, 95% CI: 1.001-1.293, P=0.048), boost dose-fractionation (3 Gy vs. no boost, OR: 4.902, 95% CI: 1.458-16.483, P=0.010) and ≥ grade 2 acute radiation skin toxicity in breast cancer patients. As our exploratory study suggests that XRCC1 T-77C and eNOS G874T may confer an increased risk of acute skin reactions to radiotherapy in breast cancer patients, further confirmatory studies are warranted to determine the clinical significance. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  16. Human umbilical cord expresses several vasoactive peptides involved in the local regulation of vascular tone: protein and gene expression of Orphanin, Oxytocin, ANP, eNOS and iNOS

    Directory of Open Access Journals (Sweden)

    Aldo Gerbino

    2011-07-01

    Full Text Available Full-term human umbilical cord contains three blood vessels: two arteries coiled around a vein and surrounded by Wharton’s jelly, a mucous tissue with few mesenchymal stromal cells and abundant extracellular matrix. Umbilical vessels lack innervations, thus endothelial cells must play a role in the control of blood flow. The aim of this study was to investigate in human umbilical cord the expression of five peptides that could be involved in the regulation of vascular tone: Orphanin FQ, Oxytocin, Atrial Natriuretic Peptide (ANP, endothelial Nitric Oxide Synthase (eNOS and inducible Nitric Oxide Synthase (iNOS. The expression of these molecules in full-term human umbilical cord was investigated through immunohistochemistry and RT-PCR. Immunoreactivity for Orphanin FQ was detected in Wharton’s jelly, vessel musculature and endothelium; Oxytocin, ANP and eNOS were expressed by the umbilical epithelium, Wharton’s jelly and endothelium, whereas iNOS only by endothelial cells. RT-PCR analysis showed transcriptional expression of Oxytocin, ANP and eNOS mRNAs. The presence of Orphanin, Oxytocin, ANP, eNOS and iNOS proteins was identified in the human umbilical cord. mRNA expression for Oxytocin, ANP and eNOS suggest that these molecules are synthesized by umbilical cord cells themselves. The expression of these vasoactive molecules could be part of a general mechanism locally regulating vascular tone. (Folia Histochemica et Cytobiologica 2011; Vol. 49, No. 2, pp. 211–218

  17. Impairment of the Ability of HDL From Patients With Metabolic Syndrome but Without Diabetes Mellitus to Activate eNOS: Correction by S1P Enrichment.

    Science.gov (United States)

    Denimal, Damien; Monier, Serge; Brindisi, Marie-Claude; Petit, Jean-Michel; Bouillet, Benjamin; Nguyen, Amandine; Demizieux, Laurent; Simoneau, Isabelle; Pais de Barros, Jean-Paul; Vergès, Bruno; Duvillard, Laurence

    2017-05-01

    High-density lipoprotein (HDL) from nondiabetic patients with metabolic syndrome (MetS) displays abnormalities in their lipidome, such as triglyceride enrichment and sphingosine-1-phosphate depletion. We hypothesized that these abnormalities could impair the ability of HDL to stimulate endothelial nitric oxide synthase (eNOS). Compared with HDL from control subjects, HDL from normoglycemic patients with MetS was 39% richer in triglycerides (Pdiabetes mellitus and that sphingosine-1-phosphate depletion of HDL is the main factor responsible for this defect. This has important consequences on the impairment of HDL functionality and antiatherogenic properties in these patients. © 2017 American Heart Association, Inc.

  18. Association of G894T eNOS, 4G/5G PAI and T1131C APOA5 polymorphisms with susceptibility to myocardial infarction in Morocco.

    Science.gov (United States)

    Hassani Idrissi, Hind; Hmimech, Wiam; Diakite, Brehima; Korchi, Farah; Baghdadi, Dalila; Habbal, Rachida; Nadifi, Sellama

    2016-09-01

    Myocardial infarction (MI) is a common multifactorial disease. Numerous studies have found that genetic plays an essential role in MI occurrence. The main objective of our case-control study is to explore the association of G894T eNOS (rs1799983), 4G/5G PAI (rs1799889) and T1131C APOA5 (rs662799) polymorphisms with MI susceptibility in the Moroccan population. 118 MI patients were recruited vs 184 healthy controls. DNA samples were genotyped by PCR-RFLP method using MboI, BslI and MseI restriction enzymes respectively for the G894T eNOS, 4G/5G PAI and T1131C APOA5 polymorphisms. Our results show that the G894T eNOS was significantly associated with increased risk of MI under the three genetic transmission models (dominant: OR = 1.64, 95% CI = 1.05-2.58, P = 0.003; recessive: OR = 2.15, 95% CI = 0.74-6.16, P = 0.03; additive: OR = 1.54, 95% CI = 1.06-2.23, P = 0.001). The T1131C APOA5 polymorphism was associated to MI risk in recessive and additive models (OR = 1.53, 95% CI = 0.72-3.2, P = 0.04 and OR = 1.78, 95% CI = 1.26-2.51, P = 0.03 respectively). For the 4G/5G PAI variant, even the cases and controls groups were not in Hardy-Weinberg Equilibrium (HWE), the dominant and additive models show a statistically significant association with MI risk (OR = 7.96, 95%CI = 3.83-16.36, P = 0.01 and OR = 1.96, 95% CI = 1.4-2.72, P = 0.03 respectively). Our results suggest that G894T eNOS and T1131C APOA5 polymorphisms may be considered as genetic markers of MI among the Moroccan population. Further studies including larger sample sizes and exploring more genetic associations are needed to confirm our results and to better understand the susceptibility to MI.

  19. Novel Formulations for Antimicrobial Peptides

    Directory of Open Access Journals (Sweden)

    Ana Maria Carmona-Ribeiro

    2014-10-01

    Full Text Available Peptides in general hold much promise as a major ingredient in novel supramolecular assemblies. They may become essential in vaccine design, antimicrobial chemotherapy, cancer immunotherapy, food preservation, organs transplants, design of novel materials for dentistry, formulations against diabetes and other important strategical applications. This review discusses how novel formulations may improve the therapeutic index of antimicrobial peptides by protecting their activity and improving their bioavailability. The diversity of novel formulations using lipids, liposomes, nanoparticles, polymers, micelles, etc., within the limits of nanotechnology may also provide novel applications going beyond antimicrobial chemotherapy.

  20. Formulation of Complex Action Theory

    OpenAIRE

    Nagao, Keiichi; Nielsen, Holger Bech

    2011-01-01

    We formulate a complex action theory which includes operators of coordinate and momentum $\\hat{q}$ and $\\hat{p}$ being replaced with non-hermitian operators $\\hat{q}_{new}$ and $\\hat{p}_{new}$, and their eigenstates ${}_m

  1. Formulation optimization of arecoline patches.

    Science.gov (United States)

    Wu, Pao-Chu; Tsai, Pi-Ju; Lin, Shin-Chen; Huang, Yaw-Bin

    2014-01-01

    The response surface methodology (RSM) including polynomial equations has been used to design an optimal patch formulation with appropriate adhesion and flux. The patch formulations were composed of different polymers, including Eudragit RS 100 (ERS), Eudragit RL 100 (ERL) and polyvinylpyrrolidone K30 (PVP), plasticizers (PEG 400), and drug. In addition, using terpenes as enhancers could increase the flux of the drug. Menthol showed the highest enhancement effect on the flux of arecoline.

  2. Formulation Optimization of Arecoline Patches

    Directory of Open Access Journals (Sweden)

    Pao-Chu Wu

    2014-01-01

    Full Text Available The response surface methodology (RSM including polynomial equations has been used to design an optimal patch formulation with appropriate adhesion and flux. The patch formulations were composed of different polymers, including Eudragit RS 100 (ERS, Eudragit RL 100 (ERL and polyvinylpyrrolidone K30 (PVP, plasticizers (PEG 400, and drug. In addition, using terpenes as enhancers could increase the flux of the drug. Menthol showed the highest enhancement effect on the flux of arecoline.

  3. Niosomal Formulation Of Orlistat: Formulation And In-Vitro Evaluation

    Directory of Open Access Journals (Sweden)

    SAMYUKTHA RANI. B

    2011-06-01

    Full Text Available The purpose of the research was to prepare Orlistat niosomes from proniosome to improve its poor and variable oral bioavailability. The non-ionic surfactant vesicles are prepared by the reverse phase evaporation technique (slurry method. The slurry of - Cyclodextrin and Span 60 was dried to form a free flowing powder in rotary flash evaporator which could be rehydrated by addition of buffer (0.5% NaCl with 3% SLS at pH 6.0. The lipid mixture consisted of cholesterol, Span 60 and - Cyclodextrin carrier in molar ratios of (0.1:0.9:1 to 0.9:0.1:1 respectively. The niosomal formulations were evaluated for particle size, entrapment efficiency, in-vitro drug release, release kinetics, Interactions and compatibility (FT-IR, surface morphology (SEM, stability studies, conductivity and sedimentation rate, pH density, viscosity. The formulation OT9 which showed higher entrapment efficiency of 44.09% and invitro releases of 94.59% at the end of 12hrs was found to be best among all the 9 formulations. Release was best fitted with Hixson kinetics and it shows that the drug release may follow diffusion mechanism. FT-IR data revealed that, compatible and there were no interactions between the drug and excipients added in the formulation. SEM images of niosomes with various magnifications revealed the mean size of the niosomes were 100 nm with smooth surface. Niosome formulation has showed appropriate stability for 90 days by storing the formulation at room temperature. Thus the niosomal formulations could be a promising delivery system for Orlistat with improved oral bioavailability, stability and for sustained drug release.

  4. Bioavailability of cefuroxime axetil formulations.

    Science.gov (United States)

    Donn, K H; James, N C; Powell, J R

    1994-06-01

    Cefuroxime axetil tablets have proved effective for the treatment of a variety of community-acquired infections. A suspension formulation has been developed for use in children. Two studies have been conducted to determine if the cefuroxime axetil formulations are bioequivalent. In the initial randomized, two-period crossover study, 24 healthy men received 250-mg doses of suspension and tablet formulations of cefuroxime axetil every 12 h after eating for seven doses. Each treatment period was separated by 4 days. Comparisons of serum and urine pharmacokinetic parameters indicated that the suspension and tablet formulations of cefuroxime axetil are not bioequivalent. Following the initial bioequivalency study, 0.1 % sodium lauryl sulfate (SLS) was added to the suspension to assure the homogeneity of the granules during the manufacturing process. In the subsequent randomized, three-period crossover study, 24 healthy men received single 250-mg doses of three cefuroxime axetil formulations: suspension without SLS, suspension with SLS, and tablet. Again each treatment period was separated by 4 days. Pharmacokinetic analyses demonstrated that while the suspension with SLS and suspension without SLS are bioequivalent, bioequivalence between the suspension with SLS and the tablet was not observed. Thus, the addition of the SLS surfactant to the suspension did not alter the bioavailability of the formulation.

  5. Vasoinhibins prevent retinal vasopermeability associated with diabetic retinopathy in rats via protein phosphatase 2A-dependent eNOS inactivation.

    Science.gov (United States)

    García, Celina; Aranda, Jorge; Arnold, Edith; Thébault, Stéphanie; Macotela, Yazmín; López-Casillas, Fernando; Mendoza, Valentín; Quiroz-Mercado, Hugo; Hernández-Montiel, Hebert Luis; Lin, Sue-Hwa; de la Escalera, Gonzalo Martínez; Clapp, Carmen

    2008-06-01

    Increased retinal vasopermeability contributes to diabetic retinopathy, the leading cause of blindness in working-age adults. Despite clinical progress, effective therapy remains a major need. Vasoinhibins, a family of peptides derived from the protein hormone prolactin (and inclusive of the 16-kDa fragment of prolactin), antagonize the proangiogenic effects of VEGF, a primary mediator of retinal vasopermeability. Here, we demonstrate what we believe to be a novel function of vasoinhibins as inhibitors of the increased retinal vasopermeability associated with diabetic retinopathy. Vasoinhibins inhibited VEGF-induced vasopermeability in bovine aortic and rat retinal capillary endothelial cells in vitro. In vivo, vasoinhibins blocked retinal vasopermeability in diabetic rats and in response to intravitreous injection of VEGF or of vitreous from patients with diabetic retinopathy. Inhibition by vasoinhibins was similar to that achieved following immunodepletion of VEGF from human diabetic retinopathy vitreous or blockage of NO synthesis, suggesting that vasoinhibins inhibit VEGF-induced NOS activation. We further showed that vasoinhibins activate protein phosphatase 2A (PP2A), leading to eNOS dephosphorylation at Ser1179 and, thereby, eNOS inactivation. Moreover, intravitreous injection of okadaic acid, a PP2A inhibitor, blocked the vasoinhibin effect on endothelial cell permeability and retinal vasopermeability. These results suggest that vasoinhibins have the potential to be developed as new therapeutic agents to control the excessive retinal vasopermeability observed in diabetic retinopathy and other vasoproliferative retinopathies.

  6. Vasoinhibins prevent retinal vasopermeability associated with diabetic retinopathy in rats via protein phosphatase 2A–dependent eNOS inactivation

    Science.gov (United States)

    García, Celina; Aranda, Jorge; Arnold, Edith; Thébault, Stéphanie; Macotela, Yazmín; López-Casillas, Fernando; Mendoza, Valentín; Quiroz-Mercado, Hugo; Hernández-Montiel, Hebert Luis; Lin, Sue-Hwa; de la Escalera, Gonzalo Martínez; Clapp, Carmen

    2008-01-01

    Increased retinal vasopermeability contributes to diabetic retinopathy, the leading cause of blindness in working-age adults. Despite clinical progress, effective therapy remains a major need. Vasoinhibins, a family of peptides derived from the protein hormone prolactin (and inclusive of the 16-kDa fragment of prolactin), antagonize the proangiogenic effects of VEGF, a primary mediator of retinal vasopermeability. Here, we demonstrate what we believe to be a novel function of vasoinhibins as inhibitors of the increased retinal vasopermeability associated with diabetic retinopathy. Vasoinhibins inhibited VEGF-induced vasopermeability in bovine aortic and rat retinal capillary endothelial cells in vitro. In vivo, vasoinhibins blocked retinal vasopermeability in diabetic rats and in response to intravitreous injection of VEGF or of vitreous from patients with diabetic retinopathy. Inhibition by vasoinhibins was similar to that achieved following immunodepletion of VEGF from human diabetic retinopathy vitreous or blockage of NO synthesis, suggesting that vasoinhibins inhibit VEGF-induced NOS activation. We further showed that vasoinhibins activate protein phosphatase 2A (PP2A), leading to eNOS dephosphorylation at Ser1179 and, thereby, eNOS inactivation. Moreover, intravitreous injection of okadaic acid, a PP2A inhibitor, blocked the vasoinhibin effect on endothelial cell permeability and retinal vasopermeability. These results suggest that vasoinhibins have the potential to be developed as new therapeutic agents to control the excessive retinal vasopermeability observed in diabetic retinopathy and other vasoproliferative retinopathies. PMID:18497878

  7. Computational and anti-tumor studies of 7a-Aza-B-homostigmast-5-eno [7a, 7-d] tetrazole-3β-yl chloride

    Science.gov (United States)

    Alam, Mahboob; Alam, Mohammad Jane; Nami, Shahab A. A.; Lee, Dong-Ung; Azam, Mohammad; Ahmad, Shabbir

    2016-03-01

    The present paper reports the detailed computational study including molecular docking of a biologically active steroidal tetrazole, 7a-Aza-B-homostigmast-5-eno [7a,7-d] tetrazole-3β-yl chloride. The molecular structure, IR and NMR (13C and 1H) spectra of the tetrazole were interpreted by comparing the experimental results with the theoretical, B3LYP/6-311G(d,p) calculations. The vibrational bands appearing in the FTIR are assigned with great accuracy using animated modes. Molecular properties like HOMO-LUMO analysis, chemical reactivity descriptors, MEP mapping, dipole moment and natural atomic charges have been presented at the same level of theory. The theoretical results are found in good correlation with the experimental data. Moreover, the Hirshfeld analysis was carried out to ascertain the secondary interactions and associated 2D fingerprint plots. The in vitro anti-tumor activity of 7a-Aza-B-homostigmast-5-eno [7a,7-d] tetrazole-3β-yl chloride has also been carried out against five human tumor cell lines. Doxorubicin is used as a standard drug for the in vitro anti-tumor screening.

  8. eNOS S-nitrosylates β-actin on Cys374 and regulates PKC-θ at the immune synapse by impairing actin binding to profilin-1

    Science.gov (United States)

    García-Ortiz, Almudena; Martín-Cofreces, Noa B.; Ibiza, Sales; Ortega, Ángel; Izquierdo-Álvarez, Alicia; Trullo, Antonio; Victor, Víctor M.; Calvo, Enrique; Sot, Begoña; Martínez-Ruiz, Antonio; Vázquez, Jesús; Sánchez-Madrid, Francisco

    2017-01-01

    The actin cytoskeleton coordinates the organization of signaling microclusters at the immune synapse (IS); however, the mechanisms involved remain poorly understood. We show here that nitric oxide (NO) generated by endothelial nitric oxide synthase (eNOS) controls the coalescence of protein kinase C-θ (PKC-θ) at the central supramolecular activation cluster (c-SMAC) of the IS. eNOS translocated with the Golgi to the IS and partially colocalized with F-actin around the c-SMAC. This resulted in reduced actin polymerization and centripetal retrograde flow of β-actin and PKC-θ from the lamellipodium-like distal (d)-SMAC, promoting PKC-θ activation. Furthermore, eNOS-derived NO S-nitrosylated β-actin on Cys374 and impaired actin binding to profilin-1 (PFN1), as confirmed with the transnitrosylating agent S-nitroso-L-cysteine (Cys-NO). The importance of NO and the formation of PFN1-actin complexes on the regulation of PKC-θ was corroborated by overexpression of PFN1- and actin-binding defective mutants of β-actin (C374S) and PFN1 (H119E), respectively, which reduced the coalescence of PKC-θ at the c-SMAC. These findings unveil a novel NO-dependent mechanism by which the actin cytoskeleton controls the organization and activation of signaling microclusters at the IS. PMID:28394935

  9. Effects of chronic treatment with the eNOS stimulator Impaza on penis length and sexual behaviors in rats with a high baseline of sexual activity.

    Science.gov (United States)

    Chu, X; Zhavbert, E S; Dugina, J L; Kheyfets, I A; Sergeeva, S A; Epstein, O I; Agmo, A

    2014-01-01

    Endothelial nitric oxide synthase (eNOS) has an important role in erection, and it also affects aspects of sexual behavior. In this experiment, we determined whether a compound enhancing the activity of eNOS, Impaza, could stimulate any aspect of sexual behavior and increase penis length in rats with a high baseline of sexual activity. For comparison, the PDE5 inhibitor sildenafil was included. Male rats were orally treated with Impaza or sildenafil for 28 days. Impaza (3 ml kg(-1)) was given daily while sildenafil (3 mg kg(-1)) was given twice weekly. Tests for sexual incentive motivation and copulatory behavior were performed just before drug treatment and at days 7, 14 and 28 of treatment. In addition, the length of the protruding penis at mount, intromission and ejaculation was measured. Impaza but not sildenafil increased penis length at mount after 14 and 28 days of treatment. The compounds failed to modify sexual incentive motivation or copulatory behavior. It is suggested that Impaza enhanced intracavernous pressure, as such a pressure increase is the most likely explanation for enhanced penis length at mount. This effect, together with an absence of motivational actions, suggests that Impaza may be the most valuable treatment for erectile dysfunction.

  10. Vascular endothelial dysfunction in β-thalassemia occurs despite increased eNOS expression and preserved vascular smooth muscle cell reactivity to NO.

    Directory of Open Access Journals (Sweden)

    Ekatherina Stoyanova

    Full Text Available AIMS: The hereditary β-thalassemia major condition requires regular lifelong blood transfusions. Transfusion-related iron overloading has been associated with the onset of cardiovascular complications, including cardiac dysfunction and vascular anomalies. By using an untransfused murine model of β-thalassemia major, we tested the hypothesis that vascular endothelial dysfunction, alterations of arterial structure and of its mechanical properties would occur despite the absence of treatments. METHODS AND RESULTS: Vascular function and structure were evaluated ex vivo. Compared to the controls, endothelium-dependent vasodilation with acetylcholine was blunted in mesenteric resistance arteries of β-thalassemic mice while the endothelium-independent vasodilator (sodium nitroprusside produced comparable vessel dilation, indicating endothelial cell impairment with preserved smooth muscle cell reactivity to nitric oxide (NO. While these findings suggest a decrease in NO bioavailability, Western blotting showed heightened expression of aortic endothelial NO synthase (eNOS in β-thalassemia. Vascular remodeling of the common carotid arteries revealed increased medial elastin content. Under isobaric conditions, the carotid arteries of β-thalassemic mice exhibited decreased wall stress and softening due to structural changes of the vessel wall. CONCLUSIONS: A complex vasculopathy was identified in untransfused β-thalassemic mice characterized by altered carotid artery structure and endothelial dysfunction of resistance arterioles, likely attributable to reduced NO bioavailability despite enhanced vascular eNOS expression.

  11. Relationship of the MTHFD1 (rs2236225, eNOS (rs1799983, CBS (rs2850144 and ACE (rs4343 gene polymorphisms in a population of Iranian pediatric patients with congenital heart defects

    Directory of Open Access Journals (Sweden)

    Mehri Khatami

    2017-09-01

    Full Text Available Congenital heart defects are structural cardiovascular malformations that arise from abnormal formation of the heart or major blood vessels during the fetal period. To investigate the association of 4 single nucleotide polymorphisms (SNPs in the MTHFD1, eNOS, CBS and ACE genes, we evaluated their relationship with CHD in Iranian patients. In this case–control study, a total of 102 children with CHD and 98 control children were enrolled. Four SNPs including MTHFD1 G1958A, eNOS G894T, CBS C-4673G and ACE A2350G were genotyped by PCR-SSCP, Multiplex ARMS PCR and PCR-RFLP methods and confirmed by direct sequencing. We genotyped 102 patients and 98 controls for four polymorphisms by statistically analysis. There were three SNPs including MTHFD1 G1958A, eNOS G894T and ACE A2350G which might increase the risk of CHD, but CBS C-4673G was not significantly different between patients and controls. (P = 0.017, P = 0.048, P = 0.025 and P = 0.081 respectively. The allele frequencies of three SNPs for MTHFD1 G1958A, eNOS G894T and ACE A2350G in CHD are higher than that in control. Our results show that there is a significant relationship between MTHFD1 G1958A, eNOS G894T and ACE A2350G polymorphisms with CHD. Therefore, The AA and GA genotypes of MTHFD1 G1958A, TT and GT genotypes of eNOS G894T and the AA and GA genotypes of ACE A2350G are susceptible factors for CHD and may increase the risk of CHD.

  12. Relationship of the MTHFD1 (rs2236225), eNOS (rs1799983), CBS (rs2850144) and ACE (rs4343) gene polymorphisms in a population of Iranian pediatric patients with congenital heart defects.

    Science.gov (United States)

    Khatami, Mehri; Ratki, Farzaneh Morteza; Tajfar, Saba; Akrami, Fatemeh

    2017-09-01

    Congenital heart defects are structural cardiovascular malformations that arise from abnormal formation of the heart or major blood vessels during the fetal period. To investigate the association of 4 single nucleotide polymorphisms (SNPs) in the MTHFD1, eNOS, CBS and ACE genes, we evaluated their relationship with CHD in Iranian patients. In this case-control study, a total of 102 children with CHD and 98 control children were enrolled. Four SNPs including MTHFD1 G1958A, eNOS G894T, CBS C-4673G and ACE A2350G were genotyped by PCR-SSCP, Multiplex ARMS PCR and PCR-RFLP methods and confirmed by direct sequencing. We genotyped 102 patients and 98 controls for four polymorphisms by statistically analysis. There were three SNPs including MTHFD1 G1958A, eNOS G894T and ACE A2350G which might increase the risk of CHD, but CBS C-4673G was not significantly different between patients and controls. (P = 0.017, P = 0.048, P = 0.025 and P = 0.081 respectively). The allele frequencies of three SNPs for MTHFD1 G1958A, eNOS G894T and ACE A2350G in CHD are higher than that in control. Our results show that there is a significant relationship between MTHFD1 G1958A, eNOS G894T and ACE A2350G polymorphisms with CHD. Therefore, The AA and GA genotypes of MTHFD1 G1958A, TT and GT genotypes of eNOS G894T and the AA and GA genotypes of ACE A2350G are susceptible factors for CHD and may increase the risk of CHD. Copyright © 2017. Published by Elsevier Taiwan.

  13. Social Groupwork. A Model for Goal Formulation.

    Science.gov (United States)

    Tompkins, Rosamond P.; Gallo, Frank T.

    1978-01-01

    A conceptual model for goal formulation in social groupwork, discussion of existing models and their limitations, and an attempt to formulate an encompassing groupwork model that facilitates goal formulation. (Author/PD)

  14. Four formulations of noncommutative quantum mechanics

    CERN Document Server

    Gouba, Laure

    2016-01-01

    Four formulations of noncommutative quantum mechanics are reviewed. These are the canonical, path-integral, Weyl-Wigner and systematic formulations. The four formulations are charaterized by a deformed Heisenberg algebra but differ in mathematical and conceptual overview.

  15. Tactile friction of topical formulations.

    Science.gov (United States)

    Skedung, L; Buraczewska-Norin, I; Dawood, N; Rutland, M W; Ringstad, L

    2016-02-01

    The tactile perception is essential for all types of topical formulations (cosmetic, pharmaceutical, medical device) and the possibility to predict the sensorial response by using instrumental methods instead of sensory testing would save time and cost at an early stage product development. Here, we report on an instrumental evaluation method using tactile friction measurements to estimate perceptual attributes of topical formulations. Friction was measured between an index finger and an artificial skin substrate after application of formulations using a force sensor. Both model formulations of liquid crystalline phase structures with significantly different tactile properties, as well as commercial pharmaceutical moisturizing creams being more tactile-similar, were investigated. Friction coefficients were calculated as the ratio of the friction force to the applied load. The structures of the model formulations and phase transitions as a result of water evaporation were identified using optical microscopy. The friction device could distinguish friction coefficients between the phase structures, as well as the commercial creams after spreading and absorption into the substrate. In addition, phase transitions resulting in alterations in the feel of the formulations could be detected. A correlation was established between skin hydration and friction coefficient, where hydrated skin gave rise to higher friction. Also a link between skin smoothening and finger friction was established for the commercial moisturizing creams, although further investigations are needed to analyse this and correlations with other sensorial attributes in more detail. The present investigation shows that tactile friction measurements have potential as an alternative or complement in the evaluation of perception of topical formulations. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. Formulations of Amlodipine: A Review

    Directory of Open Access Journals (Sweden)

    Muhammad Ali Sheraz

    2016-01-01

    Full Text Available Amlodipine (AD is a calcium channel blocker that is mainly used in the treatment of hypertension and angina. However, latest findings have revealed that its efficacy is not only limited to the treatment of cardiovascular diseases as it has shown to possess antioxidant activity and plays an important role in apoptosis. Therefore, it is also employed in the treatment of cerebrovascular stroke, neurodegenerative diseases, leukemia, breast cancer, and so forth either alone or in combination with other drugs. AD is a photosensitive drug and requires protection from light. A number of workers have tried to formulate various conventional and nonconventional dosage forms of AD. This review highlights all the formulations that have been developed to achieve maximum stability with the desired therapeutic action for the delivery of AD such as fast dissolving tablets, floating tablets, layered tablets, single-pill combinations, capsules, oral and transdermal films, suspensions, emulsions, mucoadhesive microspheres, gels, transdermal patches, and liposomal formulations.

  17. Covariant Formulations of Superstring Theories.

    Science.gov (United States)

    Mikovic, Aleksandar Radomir

    1990-01-01

    Chapter 1 contains a brief introduction to the subject of string theory, and tries to motivate the study of superstrings and covariant formulations. Chapter 2 describes the Green-Schwarz formulation of the superstrings. The Hamiltonian and BRST structure of the theory is analysed in the case of the superparticle. Implications for the superstring case are discussed. Chapter 3 describes the Siegel's formulation of the superstring, which contains only the first class constraints. It is shown that the physical spectrum coincides with that of the Green-Schwarz formulation. In chapter 4 we analyse the BRST structure of the Siegel's formulation. We show that the BRST charge has the wrong cohomology, and propose a modification, called first ilk, which gives the right cohomology. We also propose another superparticle model, called second ilk, which has infinitely many coordinates and constraints. We construct the complete BRST charge for it, and show that it gives the correct cohomology. In chapter 5 we analyse the properties of the covariant vertex operators and the corresponding S-matrix elements by using the Siegel's formulation. We conclude that the knowledge of the ghosts is necessary, even at the tree level, in order to obtain the correct S-matrix. In chapter 6 we attempt to calculate the superstring loops, in a covariant gauge. We calculate the vacuum-to -vacuum amplitude, which is also the cosmological constant. We show that it vanishes to all loop orders, under the assumption that the free covariant gauge-fixed action exists. In chapter 7 we present our conclusions, and briefly discuss the random lattice approach to the string theory, as a possible way of resolving the problem of the covariant quantization and the nonperturbative definition of the superstrings.

  18. L-Arginine ameliorates cardiac left ventricular oxidative stress by upregulating eNOS and Nrf2 target genes in alloxan-induced hyperglycemic rats

    Energy Technology Data Exchange (ETDEWEB)

    Ramprasath, Tharmarajan; Hamenth Kumar, Palani; Syed Mohamed Puhari, Shanavas; Senthil Murugan, Ponniah; Vasudevan, Varadaraj [Molecular Cardiology Unit, Department of Biochemistry, Center for Excellence in Genomic Sciences, School of Biological Sciences, Madurai Kamaraj University, Madurai 625 021, Tamilnadu (India); Selvam, Govindan Sadasivam, E-mail: drselvamgsbiochem@rediffmail.com [Molecular Cardiology Unit, Department of Biochemistry, Center for Excellence in Genomic Sciences, School of Biological Sciences, Madurai Kamaraj University, Madurai 625 021, Tamilnadu (India)

    2012-11-23

    Highlights: Black-Right-Pointing-Pointer L-Arginine treatment reduced the metabolic disturbances in diabetic animals. Black-Right-Pointing-Pointer Antioxidant marker proteins were found high in myocardium by L-arginine treatment. Black-Right-Pointing-Pointer Elevated antioxidant status, mediates the reduced TBA-reactivity in left ventricle. Black-Right-Pointing-Pointer L-Arginine treatment enhanced the Nrf2 and eNOS signaling in left ventricle. Black-Right-Pointing-Pointer Improved cell survival signaling by arginine, offers a novel tactic for targeting. -- Abstract: Hyperglycemia is independently related with excessive morbidity and mortality in cardiovascular disorders. L-Arginine-nitric oxide (NO) pathway and the involvement of NO in modulating nuclear factor-E2-related factor-2 (Nrf2) signaling were well established. In the present study we investigated, whether L-arginine supplementation would improve the myocardial antioxidant defense under hyperglycemia through activation of Nrf2 signaling. Diabetes was induced by alloxan monohydrate (90 mg kg{sup -1} body weight) in rats. Both non-diabetic and diabetic group of rats were divided into three subgroups and they were administered either with L-arginine (2.25%) or L-NAME (0.01%) in drinking water for 12 days. Results showed that L-arginine treatment reduced the metabolic disturbances in diabetic rats. Antioxidant enzymes and glutathione levels were found to be increased in heart left ventricles, thereby reduction of lipid peroxidation by L-arginine treatment. Heart histopathological analysis further validates the reversal of typical diabetic characteristics consisting of alterations in myofibers and myofibrillary degeneration. qRT-PCR studies revealed that L-arginine treatment upregulated the transcription of Akt and downregulated NF-{kappa}B. Notably, transcription of eNOS and Nrf2 target genes was also upregulated, which were accompanied by enhanced expression of Nrf2 in left ventricular tissue from diabetic

  19. Formulating Policy for Summer Schools.

    Science.gov (United States)

    Marriot, Helen

    1991-01-01

    Explores issues relating to the formulation of policy for summer programs for language learning, describing one university's experience with student demand, student motivation and progress, course timing and structure, academic staffing, administrative organization, student and staff evaluation, and funding. (three references) (CB)

  20. Hyperbolic Formulation of General Relativity

    CERN Document Server

    Abrahams, A M; Choquet-Bruhat, Y; York, J W; Abrahams, Andrew; Anderson, Arlen; Choquet-Bruhat, Yvonne; York, James W.

    1998-01-01

    Two geometrical well-posed hyperbolic formulations of general relativity are described. One admits any time-slicing which preserves a generalized harmonic condition. The other admits arbitrary time-slicings. Both systems have only the physical characteristic speeds of zero and the speed of light.

  1. eNOS se correlaciona com a biogênese mitocondrial em corações com cardiopatia congênita e cianose

    Directory of Open Access Journals (Sweden)

    Juan Xiao

    2012-09-01

    Full Text Available FUNDAMENTO: O programa de biogênese mitocondrial no coração parece apresentar remodelação adaptativa após estresse biomecânico e oxidativo. Os mecanismos adaptativos que protegem o metabolismo do miocárdio durante a hipóxia são coordenados, em parte, pelo óxido nítrico (NO. OBJETIVO: Observar a biogênese mitocondrial e expressão do óxido nítrico sintase (NOS em corações de cardiopatia congênita com cianose; discutir a resposta mitocondrial à hipóxia crônica do miocárdio. MÉTODOS: Foram investigados 20 pacientes com defeitos cardíacos cianóticos (n = 10 ou acianóticos (n = 10. Foram estudadas amostras do miocárdio na via de saída ventricular direita, tomadas durante a operação. A análise morfométrica de mitocôndrias foi realizada por microscopia eletrônica de transmissão. A relação mtDNA/nDNA foi determinada com PCR em tempo real. Os níveis de transcrição da subunidade I da citocromo c oxidase (COXI, coativador-1α do receptor γ ativado por proliferador de peroxissoma (PGC-1α, o fator respiratório nuclear 1 (NRF1, e fator de transcrição mitocondrial A (Tfam foram detectados por reação em cadeia da polimerase via transcriptase reversa (RT-PCR ativado por fluorescência em tempo real. Os níveis proteicos de COXI e nNOS, iNOS e eNOS foram medidos por técnica de Western Blot. RESULTADOS: A densidade volumétrica mitocondrial (Vv e a densidade numérica (Nv foram significativamente elevadas em pacientes com cianose, em comparação com a cardiopatia congênita acianótica. MtDNA elevada e suprarregulação dos níveis de COXI, PGC-1 α, NRF1 e Tfam mRNA foram observadas em pacientes cianóticos. Os níveis de proteína de COXI e eNOS foram significativamente maiores no miocárdio de pacientes cianóticos que nos de acianóticos. Os níveis de transcrição do PGC-1α se correlacionam com os níveis de eNOS. CONCLUSÃO: A biogênese mitocondrial é ativada no miocárdio da via de saída ventricular na

  2. Bezafibrate enhances proliferation and differentiation of osteoblastic MC3T3-E1 cells via AMPK and eNOS activation

    Institute of Scientific and Technical Information of China (English)

    Xing ZHONG; Ling-ling XIU; Guo-hong WEI; Yuan-yuan LIU; Lei SU; Xiao-pei CAO; Yan-bing LI; Hai-peng XIAO

    2011-01-01

    Aim: To investigate the effects of bezafibrate on the proliferation and differentiation of osteoblastic MC3T3-E1 cells, and to determine the signaling pathway underlying the effects.Methods: MC3T3-E1 cells, a mouse osteoblastic cell line, were used. Cell viability and proliferation were examined using MTT assay and colorimetric BrdU incorporation assay, respectively. NO production was evaluated using the Griess reagent. The mRNA expression of ALP, collagen I, osteocalcin, BMP-2, and Runx-2 was measured using real-time PCR. Western blot analysis was used to detect the expression of AMPK and eNOS proteins.Results: Bezafibrate increased the viability and proliferation of MC3T3-E1 cells in a dose- and time-dependent manner. Bezafibrate (100 μmol/L) significantly enhanced osteoblastic mineralization and expression of the differentiation markers ALP, collagen I and osteocalcin. Bezaflbrate (100 μmol/L) increased phosphorylation of AMPK and eNOS, which led to an increase of NO production by 4.08-fold, and upregulating BMP-2 and Runx-2 mRNA expression. These effects could be blocked by AMPK inhibitor compound C (5 μmol/L), or the PPARβ inhibitor GSK0660 (0.5 μmol/L), but not by the PPARa inhibitor MK886 (10 μmol/L). Furthermore, GSK0660, compound C, or N-nitro-L-arginine methyl ester hydrochloride (L-NAME, 1 mmol/L) could reverse the stimulatory effects of bezafibrate (100 pmol/L) on osteoblast proliferation and differentiation, whereas MK886 only inhibited bezafibrate-induced osteoblast prolifera-tion.Conclusion: Bezafibrate stimulates proliferation and differentiation of MC3T3-E1 cells, mainly via a PPARβ-dependent mechanism. The drug might be beneficial for osteoporosis by promoting bone formation.

  3. Application of genetic algorithms to service restoration in distribution system. Fuka yuzu mondai eno identeki algorithm no tekiyo

    Energy Technology Data Exchange (ETDEWEB)

    Fukuyama, Y.; Ueki, Y. (Fuji Electric Co. R and D Ltd., Tokyo (Japan))

    1994-04-10

    This paper describes genetic algorithms to decision on power supply feeders for each load in service restoration in a distribution system. Service restoration is a power supply distribution operation that calls for a system switching operation for retransmission when a non-service restoration section has occurred due to feeder failures. The operation determines the on-off condition of switches and decides the power supply feeders. The power supply feeder decision formulates as an objective function that minimization of the total sum of the load amount in load nodes that may cause a power failure under such conditions as radiation-formed loads, power supply capacity restriction, and transport pass restriction, and averaging of the reserve supply power. The genetic algorithm that derives the optimal solution thereof has the advantage that it does not use the gradient of the evaluation function and increase the calculation speed by means of parallel processing. The formulation by means of the genetic algorithm uses a string expression method, which reduces the string length and decaying strings. The method derives solutions by evaluating the set strings and repeating such processes as the crossing (partial replacement of service restoration conditions), the modified operator (modifies the strings to meet the restrictions) and sudden change (change in power supply direction in one load). 19 refs., 12 figs.

  4. Electromyographic activity of shoulder muscles during exercises performed with oscillatory and non-oscillatory poles Atividade eletromiográfica dos músculos do ombro durante exercícios executados com hastes oscilatória e não oscilatória

    Directory of Open Access Journals (Sweden)

    Camilla Z. Hallal

    2011-04-01

    Full Text Available BACKGROUND: Pain and dysfunction of the shoulder complex are commonly found physiotherapy practice. These musculoskeletal abnormalities are related to instability and inadequate kinematic function, that depend on the integrity of the muscle tissues. Thus, to enhance the results of exercise therapies, and prevent and attenuate pain and dynfunction, the use of oscillatory pole has been implemented in clinical practice. OBJECTIVES: The purpose of this study was to analyze the electromyographic (EMG activity of shoulder stabilizing muscles during exercises performed with an oscillatory and a non-oscillatory pole. METHODS: Twelve female volunteers, aged 20.4 years±1.9, participated in this study. EMG data were collected from upper trapezius (UT, lower trapezius (LT and middle deltoid (MD during three different exercises with an oscillatory and a non-oscillatory pole. The EMG signals were analyzed in the time domain through the calculation of Root Mean Square (RMS. The RMS values were normalized by the peak value obtained over all trials for each muscle. Statistical analysis was performed with repeated measures ANOVA and post-hoc of Bonferroni tests. RESULTS: The EMG activity of UT, LT and MD muscles were significantly higher with the oscillatory pole than the non-oscillatory pole (all pCONTEXTUALIZAÇÃO: A dor e a disfunção no complexo articular do ombro é comumente encontrada na prática fisioterapêutica. Essas anormalidades musculoesqueléticas estão relacionadas à instabilidade e inadequado funcionamento cinemático, que dependem da integridade dos tecidos musculares. Assim, no sentido de prevenir e reabilitar esses sintomas, o uso da haste oscilatória vem sendo implantado para melhorar os resultados de técnicas cinesioterapêuticas. OBJETIVOS: Analisar a atividade eletromiográfica (EMG dos músculos que estabilizam a articulação do ombro durante a realização de exercícios com haste oscilatória e haste não-oscilatória. M

  5. An exact approach for aggregated formulations

    DEFF Research Database (Denmark)

    Gamst, Mette; Spoorendonk, Simon

    cause an infeasible solution. In this paper, we consider (mixed) integer program formulations and propose a method for ensuring an optimal solution to the original (disaggregated) problem using an aggregated formulation. The method is based on Benders’ decomposition on a combination of the disaggregated...... mathematical formulation and the aggregated formulation. The method allows usage of relaxed aggregated formulations and enables branching on both aggregated and disaggregated variables. Also, the method guarantees an LP bound at least as good as those for the disaggregated and aggregated formulations...

  6. Perfume formulation: words and chats.

    Science.gov (United States)

    Ellena, Céline

    2008-06-01

    What does it mean to create fragrances with materials from chemistry and/or from nature? How are they used to display their characteristic differences, their own personality? Is it easier to create with synthetic raw materials or with essential oils? This review explains why a perfume formulation corresponds in fact to a conversation, an interplay between synthetic and natural perfumery materials. A synthetic raw material carries a single information, and usually is very linear. Its smell is uniform, clear, and faithful. Natural raw materials, on the contrary, provide a strong, complex and generous image. While a synthetic material can be seen as a single word, a natural one such as rose oil could be compared to chatting: cold, warm, sticky, heavy, transparent, pepper, green, metallic, smooth, watery, fruity... full of information. Yet, if a very small amount of the natural material is used, nothing happens, the fragrance will not change. However, if a large amount is used, the rose oil will swallow up everything else. The fragrance will smell of nothing else except rose! To formulate a perfume is not to create a culinary recipe, with only dosing the ingredients in well-balanced amounts. To formulate rather means to flexibly knit materials together with a lively stitch, meeting or repelling each other, building a pleasant form, which is neither fixed, nor solid, nor rigid. A fragrance has an overall structure, which ranges from a clear sound, made up of stable, unique, and linear items, to a background chat, comfortable and reassuring. But that does, of course, not mean that there is only one way of creating a fragrance!

  7. Polymorphic variations in manganese superoxide dismutase (MnSOD) and endothelial nitric oxide synthase (eNOS) genes contribute to the development of type 2 diabetes mellitus in the Chinese Han population.

    Science.gov (United States)

    Li, J Y; Tao, F; Wu, X X; Tan, Y Z; He, L; Lu, H

    2015-10-21

    Impaired antioxidant defense increases the oxidative stress and contributes to the development of type 2 diabetes mellitus (T2DM). MnSOD and eNOS are important antioxidant enzymes. This aim of this study was to verify the association of MnSOD and eNOS tagSNPs with T2DM in a Chinese Han population. Four tagSNPs of MnSOD and eight tagSNPs of eNOS were detected using TaqMan technology in 1272 healthy controls and 1234 T2DM patients. All study participants were unrelated members of the Han ethnic group in China. In this study, the frequency of the rs4880 MnSOD single nucleotide polymorphisms (SNP) genotype differed significantly between T2DM patients and controls [allele: P = 0.03, genotype: P = 0.04, odd's ratio (OR) = 1.26; 95% confidence interval (CI) = 1.07-1.49]. The A-T haplotype and G-T haplotype remained significant in T2DM after Bonferroni correction (P = 1.58 x 10(-6) and 8.00 x 10(-4), respectively) with a global p-value of 7.25 x 10(-8). The rs1799983 and rs891512 SNPs of eNOS differed significantly between T2DM patients and controls [rs1799983: corrected allele: P = 2.10 x 10(-3), corrected genotype: P = 6.30 x 10(-3), OR = 1.43 (95%CI = 1.18-1.73); rs891512, corrected allele: P = 3.50 x 10(-3), corrected genotype: P = 9.10 x 10(-3), OR = 1.70 (95%CI = 1.26-2.30)]. Following Bonferroni correction, none of the haplotypes of eNOS were significant in T2DM. These results indicate that common variants in MnSOD and eNOS increased the risk of T2DM in the Chinese Han population.

  8. Effect of L-Arginine on eNOS in Banked Red Blood Cells%精氨酸对库存红细胞eNOS的影响作用研究

    Institute of Scientific and Technical Information of China (English)

    曹慧; 王海平; 卓海龙; 冯双利; 刘佳; 王全立

    2012-01-01

    Objective To observe the effects of L-arginine (L-Arg) on the phosphorylation, activity and NO synthasis of endothelial nitric oxide synthase ( eNOS) in banked red blood cells. Methods The amount of L-Arg (3, 000μmol/L) was added to the blood preservation solution ( CPDA-1 ) and stored at 4℃ for testing after every 8' day. Western blot ( WB) was used to determine the level of phosphorylation of eNOS in RBCs. Fluorescence assay was used to detect the activity of eNOS. The NO content synthased was measured by spectrophotometric assay. Results Adding of L-Arg can increase the level of phosphorylation in Ser1177 and Ser113 loci of eNOS, reducing the level of phosphorylation of Thr495 sites; enhancing the activity of eNOS. Therefor, the content of NO was increased. Conclusion Adding of L-Arg in the preservation solution can increase the activity of eNOS and NO content in banked red blood cells.%目的 观察L-精氨酸(L-Arg)对库存红细胞上内皮型一氧化氮合酶(endothelial nitricoxide synthase,eNOS)的磷酸化、活性和NO合成的影响.方法 在红细胞保养液中添加3 000 μmmol/L的L-精氨酸,每8天收集标本1次,Western印迹检测eNOS的磷酸化,荧光法检测其活性,分光光度法检测NO含量.结果 L-精氨酸可提高eNOS的Sert1 177和Ser113位点的磷酸化水平,降低Thr495位点的磷酸化水平,提高eNOS的活性,增加NO的含量.结论 保存液中添加L-Arg可以提高eNOS的活性,维持库存红细胞中NO的含量.

  9. A Geometric Formulation of Supersymmetry

    CERN Document Server

    Freedman, Daniel Z; Van Proeyen, Antoine

    2016-01-01

    The scalar fields of supersymmetric models are coordinates of a geometric space. We propose a formulation of supersymmetry that is covariant with respect to reparametrizations of this target space. Employing chiral multiplets as an example, we introduce modified supersymmetry variations and redefined auxiliary fields that transform covariantly under reparametrizations. The resulting action and transformation laws are manifestly covariant and highlight the geometric structure of the supersymmetric theory. The covariant methods are developed first for general theories (not necessarily supersymmetric) whose scalar fields are coordinates of a Riemannian target space.

  10. BRST formulation of 4-monopoles

    CERN Document Server

    Gianvittorio, R; Restuccia, A

    1996-01-01

    A supersymmetric gauge invariant action is constructed over any 4-dimensional Riemannian manifold describing Witten's theory of 4-monopoles. The topological supersymmetric algebra closes off-shell. The multiplets include the auxiliary fields and the Wess-Zumino fields in an unusual way, arising naturally from BRST gauge fixing. A new canonical approach over Riemann manifolds is followed, using a Morse function as an euclidean time and taking into account the BRST boundary conditions that come from the BFV formulation. This allows a construction of the effective action starting from gauge principles.

  11. Formulation of soy oil products

    Directory of Open Access Journals (Sweden)

    Woerfel, John B.

    1995-12-01

    Full Text Available The paper comments different formulations of soy oil products such as salad and cooking oils, margarine, shortenings, commercial shortenings, frying shortenings, and fluid shortenings. Hydrogenation and its influence on final products is also included.

    El trabajo presenta diferentes formulaciones a base de aceite de soja tales como aceites para ensalada y cocinado, margarina, grasas sólidas (shortenings, grasas sólidas comerciales, grasas sólidas para frituras y grasas fluidas. Hace también referencia al proceso de hidrogenación y a sus efectos en los productos finales.

  12. Necessity of rethinking oral pediatric formulations

    DEFF Research Database (Denmark)

    Bar-Shalom, Daniel

    2014-01-01

    This commentary reviews the difficulties in formulating oral products for children. The significance of the fragmentation of the pediatric population in terms of development and ability to ingest different dosage formulations is examined. It is postulated that a flexible formulation, acceptable...

  13. Formulation, Preparation, and Characterization of Polyurethane Foams

    Science.gov (United States)

    Pinto, Moises L.

    2010-01-01

    Preparation of laboratory-scale polyurethane foams is described with formulations that are easy to implement in experiments for undergraduate students. Particular attention is given to formulation aspects that are based on the main chemical reactions occurring in polyurethane production. This allows students to develop alternative formulations to…

  14. Formulation, Preparation, and Characterization of Polyurethane Foams

    Science.gov (United States)

    Pinto, Moises L.

    2010-01-01

    Preparation of laboratory-scale polyurethane foams is described with formulations that are easy to implement in experiments for undergraduate students. Particular attention is given to formulation aspects that are based on the main chemical reactions occurring in polyurethane production. This allows students to develop alternative formulations to…

  15. Obesity, inflammation, and exercise training: relative contribution of iNOS and eNOS in the modulation of vascular function in the mouse aorta

    Directory of Open Access Journals (Sweden)

    Josiane Fernandes da Silva

    2016-09-01

    Full Text Available Background - The understanding of obsesity-related vascular dysfunction remains controversial mainly because of the diseases associated with vascular injury. Exercise training is known to prevent vascular dysfunction. Using an obesity model without comorbidities, we aimed at investigating the underlying mechanism of vascular dysfunction and how exercise interferes with this process.Methods - High-sugar diet was used to induce obesity in mice. Exercise training was performed 5 days/week. Body weight, energy intake, and adipose tissues were assessed; blood metabolic and hormonal parameters were determined; and serum TNFα was measured. Blood pressure and heart rate were assessed by plethysmography. Changes in aortic isometric tension were recorded on myograph. Western blot was used to analyze protein expression. Nitric oxide (NO was evaluated using fluorescence microscopy. Antisense oligodeoxynucleotides were used for inducible nitric oxide synthase isoform (iNOS knockdown.Results - Body weight, fat mass, total cholesterol, low-density lipoprotein cholesterol fraction, insulin, and leptin were higher in the sedentary obese group (SD than in the sedentary control animals (SS. Exercise training prevented these changes. No difference in glucose tolerance, insulin sensitivity, blood pressure, and heart rate was found. Decreased vascular relaxation and reduced endothelial nitric oxide synthase (eNOS functioning in the SD group were prevented by exercise. Contractile response to phenylephrine was decreased in the aortas of the wild SD mice, compared with that of the SS group; however, no alteration was noted in the SD iNOS-/- animals. The decreased contractility was endothelium-dependent, and was reverted by iNOS inhibition or iNOS silencing. The aortas from the SD group showed increased basal NO production, serum TNFα, TNF receptor-1, and phospho-IκB. Exercise training attenuated iNOS-dependent reduction in contractile response in high-sugar diet

  16. Obesity, Inflammation, and Exercise Training: Relative Contribution of iNOS and eNOS in the Modulation of Vascular Function in the Mouse Aorta

    Science.gov (United States)

    Silva, Josiane F.; Correa, Izabella C.; Diniz, Thiago F.; Lima, Paulo M.; Santos, Roger L.; Cortes, Steyner F.; Coimbra, Cândido C.; Lemos, Virginia S.

    2016-01-01

    Background: The understanding of obsesity-related vascular dysfunction remains controversial mainly because of the diseases associated with vascular injury. Exercise training is known to prevent vascular dysfunction. Using an obesity model without comorbidities, we aimed at investigating the underlying mechanism of vascular dysfunction and how exercise interferes with this process. Methods: High-sugar diet was used to induce obesity in mice. Exercise training was performed 5 days/week. Body weight, energy intake, and adipose tissues were assessed; blood metabolic and hormonal parameters were determined; and serum TNFα was measured. Blood pressure and heart rate were assessed by plethysmography. Changes in aortic isometric tension were recorded on myograph. Western blot was used to analyze protein expression. Nitric oxide (NO) was evaluated using fluorescence microscopy. Antisense oligodeoxynucleotides were used for inducible nitric oxide synthase isoform (iNOS) knockdown. Results: Body weight, fat mass, total cholesterol, low-density lipoprotein cholesterol fraction, insulin, and leptin were higher in the sedentary obese group (SD) than in the sedentary control animals (SS). Exercise training prevented these changes. No difference in glucose tolerance, insulin sensitivity, blood pressure, and heart rate was found. Decreased vascular relaxation and reduced endothelial nitric oxide synthase (eNOS) functioning in the SD group were prevented by exercise. Contractile response to phenylephrine was decreased in the aortas of the wild SD mice, compared with that of the SS group; however, no alteration was noted in the SD iNOS−/− animals. The decreased contractility was endothelium-dependent, and was reverted by iNOS inhibition or iNOS silencing. The aortas from the SD group showed increased basal NO production, serum TNFα, TNF receptor-1, and phospho-IκB. Exercise training attenuated iNOS-dependent reduction in contractile response in high-sugar diet–fed animals

  17. Remote ischemic perconditioning prevents liver transplantation-induced ischemia/reperfusion injury in rats: Role of ROS/RNS and eNOS

    Science.gov (United States)

    He, Ning; Jia, Jun-Jun; Li, Jian-Hui; Zhou, Yan-Fei; Lin, Bing-Yi; Peng, Yi-Fan; Chen, Jun-Jie; Chen, Tian-Chi; Tong, Rong-Liang; Jiang, Li; Xie, Hai-Yang; Zhou, Lin; Zheng, Shu-Sen

    2017-01-01

    AIM To investigate the underlying mechanisms of the protective role of remote ischemic perconditioning (RIPerC) in rat liver transplantation. METHODS Sprague-Dawley rats were subjected to sham, orthotopic liver transplantation (OLT), ischemic postconditioning (IPostC) or RIPerC. After 3 h reperfusion, blood samples were taken for measurement of alanine aminotransferase, aspartate aminotransferase, creatinine (Cr) and creatinine kinase-myocardial band (CK-MB). The liver lobes were harvested for the following measurements: reactive oxygen species (ROS), H2O2, mitochondrial membrane potential (ΔΨm) and total nitric oxide (NO). These measurements were determined using an ROS/H2O2, JC1 and Total NOx Assay Kit, respectively. Endothelial NO synthase (eNOS) was analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and western blotting, and peroxynitrite was semi-quantified by western blotting of 3-nitrotyrosine. RESULTS Compared with the OLT group, the grafts subjected to RIPerC showed significantly improved liver and remote organ functions (P < 0.05). ROS (P < 0.001) including H2O2 (P < 0.05) were largely elevated in the OLT group as compared with the sham group, and RIPerC (P < 0.05) reversed this trend. The collapse of ΔΨm induced by OLT ischemia/reperfusion (I/R) injury was significantly attenuated in the RIPerC group (P < 0.001). A marked increase of NO content and phosphoserine eNOS, both in protein and mRNA levels, was observed in liver graft of the RIPerC group as compared with the OLT group (P < 0.05). I/R-induced 3-nitrotyrosine content was significantly reduced in the RIPerC group as compared with the OLT group (P < 0.05). There were no significant differences between the RIPerC and IPostC groups for all the results except Cr. The Cr level was lower in the RIPerC group than in the IPostC group (P < 0.01). CONCLUSION Liver graft protection by RIPerC is similar to or better than that of IPostC, and involves inhibition of oxidative stress and up

  18. Formulation Patents and Dermatology and Obviousness

    Directory of Open Access Journals (Sweden)

    Josephine Liu

    2011-11-01

    Full Text Available Most patents covering dermatologic products contain patent claims directed to the pharmaceutical formulation of the product. Such patents, known as formulation patents, are vulnerable to attacks based on the legal argument that the formulations covered are obvious over formulations already known prior to the filing of the patent application. Because obviousness is an important concept in patent law, recent court cases concerning obviousness and formulation patents were examined and discussed below. Courts have ruled that patent claims are obvious when features of the claimed formulation are found in the prior art, even if the features or characteristics of the formulation are not explicitly disclosed in the prior art. However, patentees have successfully overcome obviousness challenges where there were unexpected results or properties and/or the prior art taught away from the claimed invention.

  19. Docosahexaenoic acid inhibits vascular endothelial growth factor (VEGF)-induced cell migration via the GPR120/PP2A/ERK1/2/eNOS signaling pathway in human umbilical vein endothelial cells.

    Science.gov (United States)

    Chao, Che-Yi; Lii, Chong-Kuei; Ye, Siou-Yu; Li, Chien-Chun; Lu, Chia-Yang; Lin, Ai-Hsuan; Liu, Kai-Li; Chen, Haw-Wen

    2014-05-07

    Cell migration plays an important role in angiogenesis and wound repair. Vascular endothelial growth factor (VEGF) is an endothelial cell-specific mitogen that is essential for endothelial cell survival, proliferation, and migration. Docosahexaenoic acid (DHA), an n-3 polyunsaturated fatty acid, shows both anti-inflammatory and antioxidant activities in vitro and in vivo. This study investigated the molecular mechanism by which DHA down-regulates VEGF-induced cell migration. HUVECs were used as the study model, and the MTT assay, Western blot, wound-healing assay, and phosphatase activity assay were used to explore the effects of DHA on cell migration. GPR120 is the putative receptor for DHA action. The results showed that DHA, PD98059 (an ERK1/2 inhibitor), and GW9508 (a GPR120 agonist) inhibited VEGF-induced cell migration. In contrast, pretreatment with okadaic acid (OA, a PP2A inhibitor) and S-nitroso-N-acetyl-DL-penicillamine (an NO donor) reversed the inhibition of cell migration by DHA. VEGF-induced cell migration was accompanied by phosphorylation of ERK1/2 and eNOS. Treatment of HUVECs with DHA increased PP2A enzyme activity and decreased VEGF-induced phosphorylation of ERK1/2 and eNOS. However, pretreatment with OA significantly decreased DHA-induced PP2A enzyme activity and reversed the DHA inhibition of VEGF-induced ERK1/2 and eNOS phosphorylation. These results suggest that stimulation of PP2A activity and inhibition of the VEGF-induced ERK1/2/eNOS signaling pathway may be involved in the DHA suppression of VEGF-induced cell migration. Thus, the effect of DHA on angiogenesis and wound repair is at least partly by virtue of its attenuation of cell migration.

  20. Interactions of MinK and e-NOS gene polymorphisms appear to be inconsistent predictors of atrial fibrillation propensity, but long alleles of ESR1 promoter TA repeat may be a promising marker.

    Science.gov (United States)

    Smalcelj, Anton; Sertić, Jadranka; Golubić, Karlo; Jurcić, Ljiljana; Banfić, Ljiljana; Brida, Margarita

    2009-09-01

    Interactions of MinK and e-NOS Gene Polymorphisms Appear to Be Inconsistent Predictors of Atrial Fibrillation Propensity, but Long Alleles of ESR1 Promoter TA Repeat May Be a Promising Marker. We analyzed minK, e-NOS and ESR1 gene polymorphisms in 40 patients with atrial fibrillation (AF) without major structural heart disease compared to 35 healthy controls. A missense polymorphism in the minK gene with A/G substitution at nucleotide 112 causing serine (S) to glycine (G) change, 786 T/C polymorphism in the 5' flanking region of e-NOS gene and TA polymorphism in the regulatory region of estrogen receptor ESR1 gene with long (> or = 19 TA repeats) and short alleles were examined. Only a slight increase in minK G allele frequency, but with marked excess in AG/TT combination of minK and e-NOS polymorphisms was found in the AF group. The interpretation remains tentative due to small groups precluding statistical significance of differences, possible lab flaws and inconsistencies with earlier data. However, ESR1 long allele homozygotes were strikingly more frequent in the AF than in control group, reaching statistical significance surprisingly in males (p < 0.02). Functional activity of estrogen receptors may be more critical in males than in females with abundance of circulating estrogen. Contrasting the intricate complexity of genetic polymorphisms influencing cardiac rhythm with our modest research, we would limit the conclusion to the plea for further research of ESR1 role in AF.

  1. Hamiltonian formulation of teleparallel gravity

    Science.gov (United States)

    Ferraro, Rafael; Guzmán, María José

    2016-11-01

    The Hamiltonian formulation of the teleparallel equivalent of general relativity is developed from an ordinary second-order Lagrangian, which is written as a quadratic form of the coefficients of anholonomy of the orthonormal frames (vielbeins). We analyze the structure of eigenvalues of the multi-index matrix entering the (linear) relation between canonical velocities and momenta to obtain the set of primary constraints. The canonical Hamiltonian is then built with the Moore-Penrose pseudoinverse of that matrix. The set of constraints, including the subsequent secondary constraints, completes a first-class algebra. This means that all of them generate gauge transformations. The gauge freedoms are basically the diffeomorphisms and the (local) Lorentz transformations of the vielbein. In particular, the Arnowitt, Deser, and Misner algebra of general relativity is recovered as a subalgebra.

  2. On Hamiltonian formulation of cosmologies

    Indian Academy of Sciences (India)

    K D Krori; S Dutta

    2000-03-01

    Novello et al [1,2] have shown that it is possible to find a pair of canonically conjugate variables (written in terms of gauge-invariant variables) so as to obtain a Hamiltonian that describes the dynamics of a cosmological system. This opens up the way to the usual technique of quantization. Elbaz et al [4] have applied this method to the Hamiltonian formulation of FRW cosmological equations. This note presents a generalization of this approach to a variety of cosmologies. A general Schrödinger wave equation has been derived and exact solutions have been worked out for the stiff matter era for some cosmological models. It is argued that these solutions appear to hint at their possible relevance in the early phase of cosmological evolution.

  3. Hamiltonian formulation of teleparallel gravity

    CERN Document Server

    Ferraro, Rafael

    2016-01-01

    The Hamiltonian formulation of the teleparallel equivalent of general relativity (TEGR) is developed from an ordinary second-order Lagrangian, which is written as a quadratic form of the coefficients of anholonomy of the orthonormal frames (vielbeins). We analyze the structure of eigenvalues of the multi-index matrix entering the (linear) relation between canonical velocities and momenta to obtain the set of primary constraints. The canonical Hamiltonian is then built with the Moore-Penrose pseudo-inverse of that matrix. The set of constraints, including the subsequent secondary constraints, completes a first class algebra. This means that all of them generate gauge transformations. The gauge freedoms are basically the diffeomorphisms, and the (local) Lorentz transformations of the vielbein. In particular, the ADM algebra of general relativity is recovered as a sub-algebra.

  4. Liposomal formulations of cytotoxic drugs.

    Science.gov (United States)

    Janknegt, R

    1996-07-01

    Liposomes are microscopic particles of lipid bilayer membrane that enclose aqueous internal compartments. These drug-delivery systems offer a very interesting opportunity for delivering cytotoxic drugs with equal or improved clinical efficacy and reduced toxicity. The most important clinical application of liposomes until now has been the inclusion of amphotericin B. At the same dose level, liposomal amphotericin B is as effective or slightly less effective than the conventional formulation, but much higher dosages, up to 5-7 mg kg-1day-1, can be given with acceptable toxicity. There are three preparations of cytotoxic drugs in an advanced stage of commercial development. Two of these (Doxil and TLD D99) contain doxorubicin and the other (DaunoXome) contains daunorubicin. The cardiac toxicity of the three preparations under clinical evaluation appears to be low in comparison with conventional doxorubicin or daunorubicin. No direct comparisons between the new formulations are available, so it is not yet possible to make any statements concerning their relative efficacy and toxicity. DaunoXome is the only drug that is approved in any country, and is also the best documented. It is too early to make recommendations concerning the place of these drugs in therapy. The marked increase in concentrations at the site of the tumour has yet to lead to increased therapeutic efficacy. These findings need further investigation. The efficacy of liposomal preparations in Kaposi's sarcoma appears to be similar to that of standard therapy and the clinical tolerance is good. Perhaps combination therapy with other cytotoxic agents could result in improved clinical efficacy. Their cost will probably be high in comparison with standard therapies.

  5. Implicações farmacogenéticas de polimorfismos da eNOS para drogas de ação cardiovascular

    Directory of Open Access Journals (Sweden)

    Pâmela Souza Silva

    2011-02-01

    Full Text Available A farmacogenética é um dos campos mais promissores da medicina. A conclusão do Projeto Genoma permitiu que esse campo começasse a descobrir fatores complexos modulando a resposta às drogas, e novas tecnologias estão a poucos passos de permitir uma grande expansão da área. As doenças cardiovasculares estão atualmente entre as maiores causas de internações hospitalares e morte, e têm sido alvo de grande parte dos estudos genéticos de doenças complexas. Paralelamente à identificação de marcadores de suscetibilidade à doença, é necessária a investigação de como perfis genéticos diferentes podem alterar respostas aos fármacos atualmente empregados. O sistema biológico que controla a produção endotelial do óxido nítrico tem sido um dos grandes alvos nas respostas farmacológicas aos fármacos usados na terapia de doenças cardiovasculares. Esta revisão tem como objetivo abordar os conhecimentos correntes da interação entre as variações genéticas da eNOS e as respostas farmacológicas aos fármacos empregados no sistema cardiovascular.

  6. Ellagic Acid Prevents L-NAME-Induced Hypertension via Restoration of eNOS and p47phox Expression in Rats

    Directory of Open Access Journals (Sweden)

    Thewarid Berkban

    2015-06-01

    Full Text Available The effect of ellagic acid on oxidative stress and hypertension induced by Nω-Nitro-l-arginine methyl ester hydrochloride (L-NAME was investigated. Male Sprague-Dawley rats were administrated with L-NAME (40 mg/kg/day for five weeks. L-NAME induced high systolic blood pressure (SBP and increased heart rate (HR, hindlimb vascular resistance (HVR and oxidative stress. Concurrent treatment with ellagic acid (7.5 or 15 mg/kg prevented these alterations. Co-treatment with ellagic acid was associated with up-regulation of endothelial nitric oxide synthase (eNOS protein production and alleviation of oxidative stress as indicated by decreased superoxide production in the vascular tissue, reduced plasma malondialdehyde levels, reduced NADPH oxidase subunit p47phox expression and increased plasma nitrate/nitrite levels. Our results indicate that ellagic acid attenuates hypertension by reducing NADPH oxidase subunit p47phox expression, which prevents oxidative stress and restores NO bioavailability.

  7. Synergistic Antihypertensive Effect of Carthamus tinctorius L. Extract and Captopril in l-NAME-Induced Hypertensive Rats via Restoration of eNOS and AT1R Expression

    Directory of Open Access Journals (Sweden)

    Putcharawipa Maneesai

    2016-02-01

    Full Text Available This study examined the effect of Carthamus tinctorius (CT extract plus captopril treatment on blood pressure, vascular function, nitric oxide (NO bioavailability, oxidative stress and renin-angiotensin system (RAS in Nω-Nitro-l-arginine methyl ester (l-NAME-induced hypertension. Rats were treated with l-NAME (40 mg/kg/day for five weeks and given CT extract (75 or 150 or 300 or 500 mg/kg/day: captopril (5 mg/kg/day or CT extract (300 mg/kg/day plus captopril (5 mg/kg/day for two consecutive weeks. CT extract reduced blood pressure dose-dependently, and the most effective dose was 300 mg/kg/day. l-NAME-induced hypertensive rats showed abnormalities including high blood pressure, high vascular resistance, impairment of acetylcholine-induced vasorelaxation in isolated aortic rings and mesenteric vascular beds, increased vascular superoxide production and plasma malondialdehyde levels, downregulation of eNOS, low level of plasma nitric oxide metabolites, upregulation of angiotensin II type 1 receptor and increased plasma angiotensin II. These abnormalities were alleviated by treatment with either CT extract or captopril. Combination treatment of CT extract and captopril normalized all the abnormalities found in hypertensive rats except endothelial dysfunction. These data indicate that there are synergistic antihypertensive effects of CT extract and captopril. These effects are likely mediated by their anti-oxidative properties and their inhibition of RAS.

  8. Synergistic Antihypertensive Effect of Carthamus tinctorius L. Extract and Captopril in L-NAME-Induced Hypertensive Rats via Restoration of eNOS and AT₁R Expression.

    Science.gov (United States)

    Maneesai, Putcharawipa; Prasarttong, Patoomporn; Bunbupha, Sarawoot; Kukongviriyapan, Upa; Kukongviriyapan, Veerapol; Tangsucharit, Panot; Prachaney, Parichat; Pakdeechote, Poungrat

    2016-02-29

    This study examined the effect of Carthamus tinctorius (CT) extract plus captopril treatment on blood pressure, vascular function, nitric oxide (NO) bioavailability, oxidative stress and renin-angiotensin system (RAS) in N(ω)-Nitro-l-arginine methyl ester (l-NAME)-induced hypertension. Rats were treated with l-NAME (40 mg/kg/day) for five weeks and given CT extract (75 or 150 or 300 or 500 mg/kg/day): captopril (5 mg/kg/day) or CT extract (300 mg/kg/day) plus captopril (5 mg/kg/day) for two consecutive weeks. CT extract reduced blood pressure dose-dependently, and the most effective dose was 300 mg/kg/day. l-NAME-induced hypertensive rats showed abnormalities including high blood pressure, high vascular resistance, impairment of acetylcholine-induced vasorelaxation in isolated aortic rings and mesenteric vascular beds, increased vascular superoxide production and plasma malondialdehyde levels, downregulation of eNOS, low level of plasma nitric oxide metabolites, upregulation of angiotensin II type 1 receptor and increased plasma angiotensin II. These abnormalities were alleviated by treatment with either CT extract or captopril. Combination treatment of CT extract and captopril normalized all the abnormalities found in hypertensive rats except endothelial dysfunction. These data indicate that there are synergistic antihypertensive effects of CT extract and captopril. These effects are likely mediated by their anti-oxidative properties and their inhibition of RAS.

  9. Synergistic Antihypertensive Effect of Carthamus tinctorius L. Extract and Captopril in l-NAME-Induced Hypertensive Rats via Restoration of eNOS and AT1R Expression

    Science.gov (United States)

    Maneesai, Putcharawipa; Prasarttong, Patoomporn; Bunbupha, Sarawoot; Kukongviriyapan, Upa; Kukongviriyapan, Veerapol; Tangsucharit, Panot; Prachaney, Parichat; Pakdeechote, Poungrat

    2016-01-01

    This study examined the effect of Carthamus tinctorius (CT) extract plus captopril treatment on blood pressure, vascular function, nitric oxide (NO) bioavailability, oxidative stress and renin-angiotensin system (RAS) in Nω-Nitro-l-arginine methyl ester (l-NAME)-induced hypertension. Rats were treated with l-NAME (40 mg/kg/day) for five weeks and given CT extract (75 or 150 or 300 or 500 mg/kg/day): captopril (5 mg/kg/day) or CT extract (300 mg/kg/day) plus captopril (5 mg/kg/day) for two consecutive weeks. CT extract reduced blood pressure dose-dependently, and the most effective dose was 300 mg/kg/day. l-NAME-induced hypertensive rats showed abnormalities including high blood pressure, high vascular resistance, impairment of acetylcholine-induced vasorelaxation in isolated aortic rings and mesenteric vascular beds, increased vascular superoxide production and plasma malondialdehyde levels, downregulation of eNOS, low level of plasma nitric oxide metabolites, upregulation of angiotensin II type 1 receptor and increased plasma angiotensin II. These abnormalities were alleviated by treatment with either CT extract or captopril. Combination treatment of CT extract and captopril normalized all the abnormalities found in hypertensive rats except endothelial dysfunction. These data indicate that there are synergistic antihypertensive effects of CT extract and captopril. These effects are likely mediated by their anti-oxidative properties and their inhibition of RAS. PMID:26938552

  10. eNOS transfection of adipose-derived stem cells yields bioactive nitric oxide production and improved results in vascular tissue engineering.

    Science.gov (United States)

    McIlhenny, Stephen; Zhang, Ping; Tulenko, Thomas; Comeau, Jason; Fernandez, Sarah; Policha, Aleksandra; Ferroni, Matthew; Faul, Elizabeth; Bagameri, Gabor; Shapiro, Irving; DiMuzio, Paul

    2015-11-01

    This study evaluates the durability of a novel tissue engineered blood vessel (TEBV) created by seeding a natural vascular tissue scaffold (decellularized human saphenous vein allograft) with autologous adipose-derived stem cells (ASC) differentiated into endothelial-like cells. Previous work with this model revealed the graft to be thrombogenic, likely due to inadequate endothelial differentiation as evidenced by minimal production of nitric oxide (NO). To evaluate the importance of NO expression by the seeded cells, we created TEBV using autologous ASC transfected with the endothelial nitric oxide synthase (eNOS) gene to produce NO. We found that transfected ASC produced NO at levels similar to endothelial cell (EC) controls in vitro which was capable of causing vasorelaxation of aortic specimens ex vivo. TEBV (n = 5) created with NO-producing ASC and implanted as interposition grafts within the aorta of rabbits remained patent for two months and demonstrated a non-thrombogenic surface compared to unseeded controls (n = 5). Despite the xenograft nature of the scaffold, the TEBV structure remained well preserved in seeded grafts. In sum, this study demonstrates that upregulation of NO expression within adult stem cells differentiated towards an endothelial-like lineage imparts a non-thrombogenic phenotype and highlights the importance of NO production by cells to be used as endothelial cell substitutes in vascular tissue engineering applications.

  11. Effects of dietary L-arginine or N-carbamylglutamate supplementation during late gestation of sows on the miR-15b/16, miR-221/222, VEGFA and eNOS expression in umbilical vein.

    Science.gov (United States)

    Liu, X D; Wu, X; Yin, Y L; Liu, Y Q; Geng, M M; Yang, H S; Blachier, Francois; Wu, G Y

    2012-06-01

    Placental vascular formation and blood flow are crucial for fetal survival, growth and development, and arginine regulates vascular development and function. This study determined the effects of dietary arginine or N-carbamylglutamate (NCG) supplementation during late gestation of sows on the microRNAs, vascular endothelial growth factor A (VEGFA) and endothelial nitric oxide synthase (eNOS) expression in umbilical vein. Twenty-seven landrace×large white sows at day (d) 90 of gestation were assigned randomly to three groups and fed the following diets: a control diet and the control diet supplemented with 1.0% L-arginine or 0.10% NCG. Umbilical vein of fetuses with body weight around 2.0 kg (oversized), 1.5 kg (normal) and 0.6 kg (intrauterine growth restriction, IUGR) were obtained immediately after farrowing for miR-15b, miR-16, miR-221, miR-222, VEGFA and eNOS real-time PCR analysis. Compared with the control diets, dietary Arg or NCG supplementation enhanced the reproductive performance of sows, significantly increased (P<0.05) plasma arginine and decreased plasma VEGF and eNOS (P<0.05). The miR-15b expression in the umbilical vein was higher (P<0.05) in the NCG-supplemented group than in the control group. There was a trend in that the miR-222 expression in the umbilical vein of the oversized fetuses was higher (0.05eNOS in both Arg-supplemented and NCG-supplemented group were lower (P<0.05) than in the control group. The expression of VEGFA was higher (P<0.05) in the NCG-supplemented group than in the Arg-supplemented and the control group. Meanwhile, the expression of VEGFA of the oversized fetuses was higher (P<0.05) than the normal and IUGR fetuses. In conclusion, this study demonstrated that dietary Arg or NCG supplementation may affect microRNAs (miR-15b, miR-222) targeting VEGFA and eNOS gene expressions in umbilical vein, so as to regulate the function and volume of the umbilical vein

  12. An exact approach for aggregated formulations

    DEFF Research Database (Denmark)

    Gamst, Mette; Spoorendonk, Simon

    optimality cannot be guaranteed by branching on the aggregated variables. In this presentation, we propose a general method for solving aggregated formulations, such that the solution is optimal to the original problem. The method is based on applying Benders’ decomposition on a combination of the original...... to mathematical formulations with a different solution space than that for the original formulation, i.e., the aggregated formulation may be a relaxation of the original problem. In a branch-and-bound context, variable aggregation can also lead to a formulation where branching is not trivial, for example when...... and aggregated formulations. Put in a branch-and-bound context, branching can be performed on the original variables to ensure optimality. We show how to apply the method on well-known optimization problems....

  13. On fictitious domain formulations for Maxwell's equations

    DEFF Research Database (Denmark)

    Dahmen, W.; Jensen, Torben Klint; Urban, K.

    2003-01-01

    We consider fictitious domain-Lagrange multiplier formulations for variational problems in the space H(curl: Omega) derived from Maxwell's equations. Boundary conditions and the divergence constraint are imposed weakly by using Lagrange multipliers. Both the time dependent and time harmonic...... formulations of the Maxwell's equations are considered. and we derive well-posed formulations for both cases. The variational problem that arises can be discretized by functions that do not satisfy an a-priori divergence constraint....

  14. Formulation and optimization of potassium iodide tablets

    OpenAIRE

    Al-Achi, Antoine; Patel, Binit

    2014-01-01

    The use of potassium iodide (KI) as a protective agent against accidental radioactive exposure is well established. In this study, we aimed to prepare a KI tablet formulation using a direct compression method. We utilized Design of Experiment (DoE)/mixture design to define the best formulation with predetermined physical qualities as to its dissolution, hardness, assay, disintegration, and angle of repose. Based on the results from the DoE, the formulation had the following components (%w/w):...

  15. Formulation of disperse systems science and technology

    CERN Document Server

    Tadros, Tharwat F

    2014-01-01

    This book presents comprehensively the science and technology behind the formulation of disperse systems like emulsions, suspensions, foams and others. Starting with a general introduction, the book covers a broad range of topics like the role of different classes of surfactants, stability of disperse systems, formulation of different dispersions, evaluation of formulations and many more. Many examples are included, too. Written by the experienced author and editor Tharwart Tadros, this book is indispensable for every scientist working in the field.

  16. CANONICAL FORMULATION OF NONHOLONOMIC CONSTRAINED SYSTEMS

    Institute of Scientific and Technical Information of China (English)

    GUO YONG-XIN; YU YING; HUANG HAI-JUN

    2001-01-01

    Based on the Ehresmann connection theory and symplectic geometry, the canonical formulation of nonholonomic constrained mechanical systems is described. Following the Lagrangian formulation of the constrained system, the Hamiltonian formulation is given by Legendre transformation. The Poisson bracket defined by an anti-symmetric tensor does not satisfy the Jacobi identity for the nonintegrability of nonholonomic constraints. The constraint manifold can admit symplectic submanifold for some cases, in which the Lie algebraic structure exists.

  17. FORMULATION OF CLINDAMYCIN NANO-EMULSION

    Directory of Open Access Journals (Sweden)

    K. Jiyauddin *, A. Fadli , J. C. Wei , A. Jawad , A. D. Samer , M. Kaleemullah, S. Budiasih, S. Rasha , M. R. Rasny , Y. K. Sung , A. H. Junainah , H. Todo and Y. Eddy

    2015-05-01

    Full Text Available Nano-emulsions consist of fine oil-in-water or water-in-oil dispersions, having droplets covering the size range of 10 - 600 nm. The aim of this study is to formulate nano-emulsion of Clindamycin by using Emulsion Phase Inversion method and olive oil as the oil phase. Pseudo ternary phase diagram was first developed by using distilled water, olive oil and mixture of surfactants (Tween®80 and Span®20 at a ratio of 1:1. Then, appearance test and microscopic examination were done for all the pre-formulation. Three potential pre-formulation were then selected and incorporated with the Clindamycin Phosphate and Methyl Paraben. The mean droplet size and stability studies were done for these three formulations. Clindamycin Nano-emulsions were not obtained using the Emulsion Phase Inversion (EPI method in this study, whereby the mean droplet sizes were in micro-range. However, out of all the three formulations which undergone extensive studies which include the heating-cooling cycle, whereby the formulation F8 and F17 were found to be physically stable. Significant differences were identified on the pH value and viscosity measurement for all the three formulations which undergone the heating-cooling cycle; except for the pH in F17. Furthermore, the formulation F8 had the smallest droplet size of 0.92 µm. Future research on this topic is needed to reduce the droplet size of the formulation.

  18. A new formulation of fenofibrate: suprabioavailable tablets.

    Science.gov (United States)

    Guichard, J P; Blouquin, P; Qing, Y

    2000-01-01

    The rationale for, and development of, a new suprabioavailable fenofibrate tablet formulation is described. The new suprabioavailable tablet formulation combines well-established micronisation technology with a new micro-coating process. The new formulation provides more predictable and reliable drug absorption. Owing to the strong relationship between the fenofibrate dissolution performance and its oral bioavailability, equivalent plasma levels of active principal are achieved at a lower dose, with less inter-subject variability and a reduced food effect. The new suprabioavailable tablet may, therefore, be a more efficient and better tolerated formulation.

  19. Necessity of rethinking oral pediatric formulations.

    Science.gov (United States)

    Bar-Shalom, Daniel

    2014-02-01

    This commentary reviews the difficulties in formulating oral products for children. The significance of the fragmentation of the pediatric population in terms of development and ability to ingest different dosage formulations is examined. It is postulated that a flexible formulation, acceptable by all patient groups, is needed, and an automated compounding concept is proposed. The finishing of the formulation is done at the dispensing pharmacy using an automated process. The individual components (pudding-like carrier, microencapsulated drug, and the dispensing robot and its software) are reviewed. The involvement of different stakeholders is considered because new regulatory, clinical, and marketing thinking is required. Copyright © 2014 Elsevier HS Journals, Inc. All rights reserved.

  20. Formulation of Complex Action Theory

    CERN Document Server

    Nagao, Keiichi

    2011-01-01

    We formulate the complex action theory from a fundamental level so that we can deal with a complex coordinate $q$ and a complex momentum $p$. We extend $| q >$ and $| p>$ to complex $q$ and $p$ by utilizing coherent states of harmonic oscillators. Introducing a philosophy to keep the analyticity in parameter variables of Feynman path integral, we define a modified set of complex conjugate, real and imaginary parts, hermitian conjugates and bras. They enable us to have both orthogonality and completeness relations for $|q >$ and $|p >$ with complex $q$ and $p$. We also pose a theorem on the relation between functions and operators to make it clear to some extent. Furthermore, extending our previous work \\cite{Nagao:2010xu} to the complex coordinate case, we study a system defined by a diagonalizable non-hermitian bounded Hamiltonian, and show that a hermitian Hamiltonian is effectively obtained after a long time development by introducing a proper inner product. If the hermitian Hamiltonian is given in a local...

  1. MOND and its bimetric formulation

    CERN Document Server

    Milgrom, Mordehai

    2013-01-01

    I first give a succinct account of the MOND paradigm--emphasizing the centrality of scale invariance in the nonrelativistic, deep-MOND limit--and describing rudiments of its phenomenology. I then present my credo, and some generalities, concerning existing MOND theories. Then I concentrate on one relativistic formulation of MOND in the form of a bimetric theory (BIMOND). I describe its various limits: the weak field, with application to gravitational waves, the nonrelativistic limit, and their further deep-MOND (low acceleration) limits, which are scale invariant. Other aspects of BIMOND that have been explored are aspects of cosmology, matter fluctuations in cosmology, and matter-twin-matter interactions. BIMOND remains largely unexplored, despite its promise in several regards: It tends to GR for a0 goes to 0 (a0 is the MOND constant); it has a simple nonrelativistic limit; it describes gravitational lensing correctly; and, it has a generic appearance of a cosmological-constant term that is of order a0^2/c^...

  2. Postmodern string theory stochastic formulation

    CERN Document Server

    Aurilia, A

    1994-01-01

    In this paper we study the dynamics of a statistical ensemble of strings, building on a recently proposed gauge theory of the string geodesic field. We show that this stochastic approach is equivalent to the Carath\\'eodory formulation of the Nambu-Goto action, supplemented by an averaging procedure over the family of classical string world-sheets which are solutions of the equation of motion. In this new framework, the string geodesic field is reinterpreted as the Gibbs current density associated with the string statistical ensemble. Next, we show that the classical field equations derived from the string gauge action, can be obtained as the semi-classical limit of the string functional wave equation. For closed strings, the wave equation itself is completely analogous to the Wheeler-DeWitt equation used in quantum cosmology. Thus, in the string case, the wave function has support on the space of all possible spatial loop configurations. Finally, we show that the string distribution induces a multi-phase, or ...

  3. Inhibition of kidney proximal tubular glucose reabsorption does not prevent against diabetic nephropathy in type 1 diabetic eNOS knockout mice.

    Directory of Open Access Journals (Sweden)

    Muralikrishna Gangadharan Komala

    Full Text Available BACKGROUND AND OBJECTIVE: Sodium glucose cotransporter 2 (SGLT2 is the main luminal glucose transporter in the kidney. SGLT2 inhibition results in glycosuria and improved glycaemic control. Drugs inhibiting this transporter have recently been approved for clinical use and have been suggested to have potential renoprotective benefits by limiting glycotoxicity in the proximal tubule. We aimed to determine the renoprotective benefits of empagliflozin, an SGLT2 inhibitor, independent of its glucose lowering effect. RESEARCH DESIGN AND METHODS: We induced diabetes using a low dose streptozotocin protocol in 7-8 week old endothelial nitric oxide (eNOS synthase knockout mice. We measured fasting blood glucose on a monthly basis, terminal urinary albumin/creatinine ratio. Renal histology was assessed for inflammatory and fibrotic changes. Renal cortical mRNA transcription of inflammatory and profibrotic cytokines, glucose transporters and protein expression of SGLT2 and GLUT1 were determined. Outcomes were compared to diabetic animals receiving the angiotensin receptor blocker telmisartan (current best practice. RESULTS: Diabetic mice had high matched blood glucose levels. Empagliflozin did not attenuate diabetes-induced albuminuria, unlike telmisartan. Empagliflozin did not improve glomerulosclerosis, tubular atrophy, tubulointerstitial inflammation or fibrosis, while telmisartan attenuated these. Empagliflozin did not modify tubular toll-like receptor-2 expression in diabetic mice. Empagliflozin did not reduce the upregulation of macrophage chemoattractant protein-1 (MCP-1, transforming growth factor β1 and fibronectin mRNA observed in the diabetic animals, while telmisartan decreased transcription of MCP-1 and fibronectin. Empagliflozin increased GLUT1 mRNA expression and telmisartan increased SGLT2 mRNA expression in comparison to untreated diabetic mice. However no significant difference was found in protein expression of GLUT1 or SGLT2 among the

  4. ROLE OF CYCLODEXTRINS IN NEW ANTIMYCOBACTERIAL FORMULATIONS

    Directory of Open Access Journals (Sweden)

    Veaceslav Boldescu

    2014-06-01

    Full Text Available This paper is dedicated to the role of cyclodextrins in new formulations for the treatment of infections with Mycobacterium tuberculosis that are in the process of design and development. Cyclodextrins play the role of solubilizing agents and promoters of the antimycobacterial substances penetration inside the mycobacterial cell. Different formulations and their advantages and disadvantages are discussed.

  5. Digluconate and Isopropyl Alcohol Biocide Formulation

    Directory of Open Access Journals (Sweden)

    Barbara Conway

    2012-10-01

    Full Text Available Effective surface disinfection is a fundamental infection control strategy within healthcare. This study assessed the antimicrobial efficacy of novel biocide formulations comprising 5% and 2% eucalyptus oil (EO combined with 2% chlorhexidine digluconate (CHG and 70% isopropyl alcohol (IPA contained within a wipe. The efficacy of this novel antimicrobial formulation to remove and eliminate methicillin-resistant Staphylococcus aureus (MRSA, Escherichia coli and Candida albicans from steel surfaces was investigated. Adpression studies of pre-contaminated wipes were also utilised to assess their potential to induce cross-contamination between hard surfaces. Furthermore, the bactericidal nature of the EO-formulation was established in addition to time-kill. The EO-containing formulations demonstrated bactericidal antimicrobial efficacy against all microorganisms and did not induce surface cross-contamination. There was no significant difference (p < 0.05 between the 5% and 2% EO formulations in their ability to remove microorganisms from steel surfaces, however both significantly (p < 0.05 removed more than the control formulations. Microbial biofilms were eliminated within 10 min (p < 0.05 when exposed to the EO formulations. Our novel EO-formulation demonstrated rapid antimicrobial efficacy for potential disinfection and elimination of microbial biofilms from hard surfaces and may therefore be a useful adjunct to current infection control strategies currently employed within healthcare facilities.

  6. Bioavailability of sustained-release theophylline formulations.

    Science.gov (United States)

    Bonora Regazzi, M; Rondanelli, R; Vidale, E; Cristiani, D

    1983-05-01

    Sustained-release formulations of theophylline as well as of other drugs are designed to effect a delayed but constant release of the active principle in the gastrointestinal tract, thus ensuring more prolonged blood level curves. This study was made to assess the bioavailability of two sustained-release microencapsulated formulations and one sustained-release Diffucaps formulation, in comparison with an equivalent dose of theophylline solution. As regards bioavailability, none of the three formulations differed significantly from the reference formulation. The blood levels at steady state were estimated on the basis of data obtained after a single-dose study. All three sustained release formulations showed good results after prolonged administration in terms of peaks and troughs. The time duration at which the theophylline plasma levels remain higher than 75% of the maximum steady-state levels, following 12-h dosing interval, was evaluated: for the sustained-release microencapsulated formulations this time duration reaches 100% of the dosing interval. A multiple-dose administration of the sustained-release formulations used in this study should guarantee almost complete time coverage, with blood levels sharply exceeding the minimum threshold level of the theophylline therapeutic range.

  7. Preformulation and Formulation of Investigational New Drugs

    Science.gov (United States)

    1999-01-01

    2000 THIS PAGE IS UNCLASSIFIED AD Award Number DAMDl7-92-C-2035 TITLE: Preformulation and Formulation of Investigational New Drugs PRINCIPAL...TITLE AND SUBTITLE 5. FUNDING NUMBERS Preformulation and Formulation of Investigational New Drugs DAMD17-92-C-2035 6. AUTHOR(S) Douglas Flanagan, Ph.D. 7

  8. A New Resistance Formulation for Carbon Nanotubes

    Directory of Open Access Journals (Sweden)

    Ji-Huan He

    2008-01-01

    Full Text Available A new resistance formulation for carbon nanotubes is suggested using fractal approach. The new formulation is also valid for other nonmetal conductors including nerve fibers, conductive polymers, and molecular wires. Our theoretical prediction agrees well with experimental observation.

  9. Constructing Extended Formulations from Reflection Relations

    CERN Document Server

    Kaibel, Volker

    2010-01-01

    There are many examples of optimization problems whose associated polyhedra can be described much nicer, and with way less inequalities, by projections of higher dimensional polyhedra than this would be possible in the original space. However, currently not many general tools to construct such extended formulations are available. In this paper, we develop a framework of polyhedral relations that generalizes inductive constructions of extended formulations via projections, and we particularly elaborate on the special case of reflection relations. The latter ones provide polynomial size extended formulations for several polytopes that can be constructed as convex hulls of the unions of (exponentially) many copies of an input polytope obtained via sequences of reflections at hyperplanes. We demonstrate the use of the framework by deriving small extended formulations for the G-permutahedra of all finite reflection groups G (generalizing both Goeman's extended formulation of the permutahedron of size O(n log n) an...

  10. Inherent formulation issues of kinase inhibitors.

    Science.gov (United States)

    Herbrink, M; Schellens, J H M; Beijnen, J H; Nuijen, B

    2016-10-10

    The small molecular Kinase Inhibitor (smKI) drug class is very promising and rapidly expanding. All of these drugs are administered orally. The clear relationship between structure and function has led to drugs with a general low intrinsic solubility. The majority of the commercial pharmaceutical formulations of the smKIs are physical mixtures that are limited by the low drug solubility of a salt form. This class of drugs is therefore characterized by an impaired and variable bioavailability rendering them costly and their therapies suboptimal. New formulations are sparingly being reported in literature and patents. The presented data suggests that continued research into formulation design can help to develop more efficient and cost-effective smKI formulation. Moreover, it may also be of help in the future design of the formulations of new smKIs.

  11. Subscale testing of prompt agent defeat formulations

    Science.gov (United States)

    Knott, A.; Stamatis, D.; Svingala, F.; Lightstone, J.; Miller, K.; Bensman, M.; Bohmke, M.

    2017-01-01

    There is a need to improve the current bioagent defeat systems with formulations that produce lower peak pressure and impulse, sustained high temperatures, and release of biocidal species for prompt defeat applications. In this work, explosive charge configurations similar to fuel-air explosives were detonated in a semi-enclosed chamber configuration. Binder type and fuel-to-oxidizer ratios were varied to observe the effects on combustion performance. Thermocouple measurements and high-speed video were used to monitor the combustion of the dispersed formulation. The down-selected formulations were then tested in a sub-scale vented agent defeat system developed to evaluate performance of formulations against aerosolized Bacillus thuringiensis (Bt) spores. Diagnostics including thermocouples and piezoelectric pressure gauges were utilized to characterize the detonation event. Biological sampling with surface coupons, liquid impingement, and filters of the post detonation environment were utilized to determine spore survivability and to rank the relative effectiveness of each formulation.

  12. Amphotericin B formulations and drug targeting.

    Science.gov (United States)

    Torrado, J J; Espada, R; Ballesteros, M P; Torrado-Santiago, S

    2008-07-01

    Amphotericin B is a low-soluble polyene antibiotic which is able to self-aggregate. The aggregation state can modify its activity and pharmacokinetical characteristics. In spite of its high toxicity it is still widely employed for the treatment of systemic fungal infections and parasitic disease and different formulations are marketed. Some of these formulations, such as liposomal formulations, can be considered as classical examples of drug targeting. The pharmacokinetics, toxicity and activity are clearly dependent on the type of amphotericin B formulation. New drug delivery systems such as liposomes, nanospheres and microspheres can result in higher concentrations of AMB in the liver and spleen, but lower concentrations in kidney and lungs, so decreasing its toxicity. Moreover, the administration of these drug delivery systems can enhance the drug accessibility to organs and tissues (e.g., bone marrow) otherwise inaccessible to the free drug. During the last few years, new AMB formulations (AmBisome, Abelcet, and Amphotec) with an improved efficacy/toxicity ratio have been marketed. This review compares the different formulations of amphotericin B in terms of pharmacokinetics, toxicity and activity and discusses the possible drug targeting effect of some of these new formulations.

  13. Isotretinoin Oil-Based Capsule Formulation Optimization

    Directory of Open Access Journals (Sweden)

    Pi-Ju Tsai

    2013-01-01

    Full Text Available The purpose of this study was to develop and optimize an isotretinoin oil-based capsule with specific dissolution pattern. A three-factor-constrained mixture design was used to prepare the systemic model formulations. The independent factors were the components of oil-based capsule including beeswax (X1, hydrogenated coconut oil (X2, and soybean oil (X3. The drug release percentages at 10, 30, 60, and 90 min were selected as responses. The effect of formulation factors including that on responses was inspected by using response surface methodology (RSM. Multiple-response optimization was performed to search for the appropriate formulation with specific release pattern. It was found that the interaction effect of these formulation factors (X1X2, X1X3, and X2X3 showed more potential influence than that of the main factors (X1, X2, and X3. An optimal predicted formulation with Y10 min, Y30 min, Y60 min, and Y90 min release values of 12.3%, 36.7%, 73.6%, and 92.7% at X1, X2, and X3 of 5.75, 15.37, and 78.88, respectively, was developed. The new formulation was prepared and performed by the dissolution test. The similarity factor f2 was 54.8, indicating that the dissolution pattern of the new optimized formulation showed equivalence to the predicted profile.

  14. Formulation of heat absorbing glasses

    Directory of Open Access Journals (Sweden)

    Álvarez-Casariego, Pedro

    1996-06-01

    Full Text Available In the thermal exchanges between buildings and environment, glazing is an element of major importance, for it largely influences the so-called Solar Heat Gain and Thermal Losses. These parameters can be modified by applying different type of coatings onto glass surface or by adding colorant compounds during glass melting. The latter is a cheaper way to control the Solar Heat Gain. The knowledge of the laws governing the interaction between colorant compounds and solar radiation, allows us to define glass formulations achieving specific aesthetic requirements and solar energy absorption. In this paper two examples of application of the modelling of glass colorants spectral absorptance are presented. First is addressed to obtaining a glass with high luminous transmittance and low solar energy transmittance, and the other one to obtaining a glass with neutral colour appearance and minimized solar energy transmittance. Calculation formulas are defined together with photometric properties so-obtained. These type of glasses are particularly suitable to be used as building and automotive glazing, for they retain the mechanical characteristics and possibilities of transformation of standard glass.

    En los intercambios de energía entre un edificio y el medio exterior, el vidrio es el elemento de mayor importancia, por su influencia en la Ganancia de Calor Solar y en las Pérdidas Térmicas. Estos parámetros pueden ser modificados mediante el depósito de capas sobre el vidrio o mediante la adición de compuestos absorbentes de la radiación solar. Esta última vía es la más económica para controlar la Ganancia de Calor Solar. El conocimiento de las leyes que gobiernan la interacción de los diversos colorantes con la radiación solar, permite definir formulaciones de vidrios con características especificas de tipo estético y de absorción energética. En este trabajo se presentan dos ejemplos de aplicación de esta modelización de las

  15. MicroRNA-27b plays a role in pulmonary arterial hypertension by modulating peroxisome proliferator-activated receptor γ dependent Hsp90-eNOS signaling and nitric oxide production

    Energy Technology Data Exchange (ETDEWEB)

    Bi, Rui; Bao, Chunrong; Jiang, Lianyong; Liu, Hao; Yang, Yang; Mei, Ju; Ding, Fangbao, E-mail: dbcar126@126.com

    2015-05-01

    Pulmonary artery endothelial dysfunction is associated with pulmonary arterial hypertension (PAH). Based on recent studies showing that microRNA (miR)-27b is aberrantly expressed in PAH, we hypothesized that miR-27b may contribute to pulmonary endothelial dysfunction and vascular remodeling in PAH. The effect of miR-27b on pulmonary endothelial dysfunction and the underlying mechanism were investigated in human pulmonary artery endothelial cells (HPAECs) in vitro and in a monocrotaline (MCT)-induced model of PAH in vivo. miR-27b expression was upregulated in MCT-induced PAH and inversely correlated with the levels of peroxisome proliferator-activated receptor (PPAR)-γ, and miR-27b inhibition attenuated MCT-induced endothelial dysfunction and remodeling and prevented PAH associated right ventricular hypertrophy and systolic pressure in rats. PPARγ was confirmed as a direct target of miR-27b in HPAECs and shown to mediate the effect of miR-27b on the disruption of endothelial nitric oxide synthase (eNOS) coupling to Hsp90 and the suppression of NO production associated with the PAH phenotype. We showed that miR-27b plays a role endothelial function and NO release and elucidated a potential mechanism by which miR-27b regulates Hsp90-eNOS and NO signaling by modulating PPARγ expression, providing potential therapeutic targets for the treatment of PAH. - Highlights: • miR-27b plays a role in endothelial function and NO release. • miR-27b inhibition ameliorates MCT-induced endothelial dysfunction and PAH. • miR-27b targets PPARγ in HPAECs. • miR-27b regulates PPARγ dependent Hsp90-eNOS and NO signaling.

  16. A covariant formulation of classical spinning particle

    CERN Document Server

    Cho, J H; Kim, J K; Jin-Ho Cho; Seungjoon Hyun; Jae-Kwan Kim

    1994-01-01

    Covariantly we reformulate the description of a spinning particle in terms of the which entails all possible constraints explicitly; all constraints can be obtained just from the Lagrangian. Furthermore, in this covariant reformulation, the Lorentz element is to be considered to evolve the momentum or spin component from an arbitrary fixed frame and not just from the particle rest frame. In distinction with the usual formulation, our system is directly comparable with the pseudo-classical formulation. We get a peculiar symmetry which resembles the supersymmetry of the pseudo-classical formulation.

  17. The Electromagnetic Duality Formulation of Geometric Phases

    Science.gov (United States)

    Zhang, Yuchao; Li, Kang

    2015-06-01

    This paper focuses on the electromagnetic(EM) duality formulation of geometric phases of Aharonov-Bohm(A-B) effect and Aharonov-Casher(A-C) effect. Through the two four-vector potential formulation of electromagnetic theory, we construct a EM duality formulation for both A-B effect and A-C effect. The He-McKellar-Wilkens(HMW) effect is included as a EM duality counterpart of the A-C effect, and also the EM duality counterpart of the A-B effect is also predicted.

  18. Geometric Formulation of Gauge Theory of Gravity

    Institute of Scientific and Technical Information of China (English)

    WUNing; ZHANGDa-Hua; RUANTu-Nan

    2003-01-01

    DitTerential geometric formulation of quantum gauge theory of gravity is studied in this paper. The quantum gauge theory of gravity is formulated completely in the framework of traditional quantum field theory. In order to study the relationship between quantum gauge theory of gravity and traditional quantum gravity which is formulated in curved space, it is important to set up the geometry picture of quantum gauge theory of gravity. The correspondence between quantum gauge theory of gravity and differential geometry is discussed and the geometry picture of quantum gauge theory of gravity is studied.

  19. Geometric Formulation of Gauge Theory of Gravity

    Institute of Scientific and Technical Information of China (English)

    WU Ning; ZHANG Da-Hua; RUAN Tu-Nan

    2003-01-01

    Differential geometric formulation of quantum gauge theory of gravity is studied in this paper. The quantumgauge theory of gravity is formulated completely in the framework of traditional quantum field theory. In order to studythe relationship between quantum gauge theory of gravity and traditional quantum gravity which is formulated in curvedspace, it is important to set up the geometry picture of quantum gauge theory of gravity. The correspondence betweenquantum gauge theory of gravity and differential geometry is discussed and the geometry picture of quantum gaugetheory of gravity is studied.

  20. A possible gauge formulation for gravity?

    CERN Document Server

    Gaitan, R

    2001-01-01

    A possible Yang-Mills like lagrangian formulation for gravity is explored. The starting point consists on two next assumptions. First, the metric is assumed as a real map from a given gauge group. Second, a gauge invariant lagrangian density is considered with the condition that it is related to the Einstein one up to a bound term. We study a stationary solution of the abelian case for the spherical symmetry, which is connected to the M\\"oller's Maxwell like formulation for gravity. Finally, it is showed the consistence of this formulation with the Newtonian limit.

  1. Formulation and stability of cytokine therapeutics.

    Science.gov (United States)

    Lipiäinen, Tiina; Peltoniemi, Marikki; Sarkhel, Sanjay; Yrjönen, Teijo; Vuorela, Heikki; Urtti, Arto; Juppo, Anne

    2015-02-01

    Cytokines are messenger proteins that regulate the proliferation and differentiation of cells and control immune responses. Interferons, interleukins, and growth factors have applications in cancer, autoimmune, and viral disease treatment. The cytokines are susceptible to chemical and physical instability. This article reviews the structure and stability issues of clinically used cytokines, as well as formulation strategies for improved stability. Some general aspects for identifying most probable stability concerns, selecting excipients, and developing stable cytokine formulations are presented. The vast group of cytokines offers possibilities for new biopharmaceuticals. The formulation approaches of the current cytokine products could facilitate development of new biopharmaceuticals.

  2. An exact approach for aggregated formulations

    DEFF Research Database (Denmark)

    Gamst, Mette; Spoorendonk, Simon; Røpke, Stefan

    optimality cannot be guaranteed by branching on aggregated variables. We present a generic exact solution method to remedy the drawbacks of aggregation. It combines the original and aggregated formulations and applies Benders' decomposition. We apply the method to the Split Delivery Vehicle Routing Problem.......Aggregating formulations is a powerful approach for problems to take on tractable forms. Aggregation may lead to loss of information, i.e. the aggregated formulation may be an approximation of the original problem. In branch-and-bound context, aggregation can also complicate branching, e.g. when...

  3. 1-Oxoeudesm-11(13)-eno-12,8a-lactone induces G2/M arrest and apoptosis of human glioblastoma cells in vitro

    Institute of Scientific and Technical Information of China (English)

    Shan-shan LIU; Yan-feng WANG; Li-sha MA; Bei-bei ZHENG; Lin LI; Wei-dong XiE; Xia LI

    2013-01-01

    Aim: To investigate the effects of 1-oxoeudesm-11(13)eno-12,8a-lactone (OEL),a novel eudesmane-type sesquiterpene isolated from Aster himalaicus,on the cell cycle and apoptosis in human glioblastoma cells in vitro.Methods: Human malignant glioblastoma cell lines U87 and A172 were used.The cytotoxicity of OEL was examined using the MTT assay.Cell apoptosis was assessed with DAPI staining and flow cytometry.DNA damage was determined by measuring the phosphorylation of H2AX using immunofluorescence staining and Western blotting.Cell cycle profiles were measured with flow cytometry.The mRNA expression of p53 and p21Waf1/Cip1 was investigated using real-time PCR.The protein expression of γ-H2AX,caspase-9,caspase-3,p53,p21Waf1/Cip1,cyclin B1,and cdc2 was analyzed with Western blotting.Results: Treatment of the malignant glioblastoma cells with OEL inhibited the cell growth in dose-and time-dependent manners (thevalues of IC50 at 48 and 72 h were 29.5 and 16.99 μmol/L,respectively,in U87 cells; 7.2 and 9.5 μmol/L,respectively,in A172 cells).OEL (10-30μmol/L) induced apoptosis and G2/M phase arrest in both U87 and A172 cells.OEL induced the phosphorylation of cdc2,a G2/M phase cyclin-dependent kinase,and decreased the expression of cyclin B1 required for progression through the G2/M phase in U87 cells.The compound remarkably increased the phosphorylation of H2AX in U87 cells.Moreover,OEL increased the mRNA and protein levels of p53 and its target gene p21waf1/cip1 in U87 cells.The compound also induced p53 phosphorylation.Pretreatment withPFT-α,a specific inhibitor of p53 transcriptional activity,could partially reverse the inhibition of OEL on the viability of U87 and A172 cells.Conclusion: OEL suppresses the growth of human glioblastoma cells in vitro via inducing DNA damage,p53-mediated cell cycle arrest and apoptosis,thus warrants further studies as a lead compound of anti-glioblastoma drug.

  4. Algebraic formulation of higher gauge theory

    Science.gov (United States)

    Zucchini, Roberto

    2017-06-01

    In this paper, we present a purely algebraic formulation of higher gauge theory and gauged sigma models based on the abstract theory of graded commutative algebras and their morphisms. The formulation incorporates naturally Becchi - Rouet -Stora - Tyutin (BRST) symmetry and is also suitable for Alexandrov - Kontsevich - Schwartz-Zaboronsky (AKSZ) type constructions. It is also shown that for a full-fledged Batalin-Vilkovisky formulation including ghost degrees of freedom, higher gauge and gauged sigma model fields must be viewed as internal smooth functions on the shifted tangent bundle of a space-time manifold valued in a shifted L∞-algebroid encoding symmetry. The relationship to other formulations where the L∞-algebroid arises from a higher Lie groupoid by Lie differentiation is highlighted.

  5. Formulating and Solving Problems in Computational Chemistry.

    Science.gov (United States)

    Norris, A. C.

    1980-01-01

    Considered are the main elements of computational chemistry problems and how these elements can be used to formulate the problems mathematically. Techniques that are useful in devising an appropriate solution are also considered. (Author/TG)

  6. Drug Nanoparticle Formulation Using Ascorbic Acid Derivatives

    Directory of Open Access Journals (Sweden)

    Kunikazu Moribe

    2011-01-01

    Full Text Available Drug nanoparticle formulation using ascorbic acid derivatives and its therapeutic uses have recently been introduced. Hydrophilic ascorbic acid derivatives such as ascorbyl glycoside have been used not only as antioxidants but also as food and pharmaceutical excipients. In addition to drug solubilization, drug nanoparticle formation was observed using ascorbyl glycoside. Hydrophobic ascorbic acid derivatives such as ascorbyl mono- and di-n-alkyl fatty acid derivatives are used either as drugs or carrier components. Ascorbyl n-alkyl fatty acid derivatives have been formulated as antioxidants or anticancer drugs for nanoparticle formulations such as micelles, microemulsions, and liposomes. ASC-P vesicles called aspasomes are submicron-sized particles that can encapsulate hydrophilic drugs. Several transdermal and injectable formulations of ascorbyl n-alkyl fatty acid derivatives were used, including ascorbyl palmitate.

  7. Formulation and characterization of caffeine biodegradable chewing ...

    African Journals Online (AJOL)

    Methods: Biodegradable plasticized poly(D,L-lactic acid) caffeine-MCGs were formulated with a fixed concentration (15 ... Caffeine serves as a key component in various beverages such as ..... reasonable shelf life, and long-lasting flavour.

  8. Paclitaxel Albumin-stabilized Nanoparticle Formulation

    Science.gov (United States)

    This page contains brief information about paclitaxel albumin-stabilized nanoparticle formulation and a collection of links to more information about the use of this drug, research results, and ongoing clinical trials.

  9. On the Mathematical Formulation of Radiance

    CERN Document Server

    Lessig, Christian; Desbrun, Mathieu

    2012-01-01

    Radiance is widely regarded as the principal quantity in light transport theory. Yet, the concept of radiance in use today has remained mostly unchanged since Lambert's work in the 18th century. His formulation of the measurement of light intensity is based on classical differentials, and is known to suffer from several theoretical and practical limitations. After tracing the historic development of radiance and its shortcomings, we provide a modern formulation of light intensity measurements that models radiance as a differential form. We demonstrate the utility of this use of exterior calculus for questions in light transport theory by rigorously deriving the cosine term and the area formulation, without the need for postulates or heuristic arguments. The formulation of radiance as a differential form introduced in this paper hence provides the first step towards a modern theory of light transport.

  10. Hepatoprotective activity studies of herbal formulations

    Directory of Open Access Journals (Sweden)

    Kamble Manisha

    2008-01-01

    Full Text Available Traditional system of medicine recommends various hepatoprotective agents and preparations to treat hepatic disorders. Polyherbal formulations F1 and F2 were developed for treatment of liver disorders by exploiting the knowledge of traditional system of medicine and evaluated for hepatoprotective activity using acute liver toxicity models of CCl 4 and Paracetamol induced liver damage in rats. The rats were monitored for morphological changes in liver, biochemical parameter Serum Glutamate Oxaloacetate Transaminase, Serum Glutamate Pyruvate Transaminase, Serum Alkaline Phosphatase, and Serum bilirubin, histopathological studies, and pentobarbitone sleeping time. Both of these formulations F1 and F2 showed significant hepatoprotective activity at dose of 400 mg/kg, which was comparable to silymarin at 6 mg/kg. Formulations F1 and F2 are effective both as prophylactic and therapeutic in experimental liver damage. Biochemical parameters showed better results for formulation F2 but morphological, pentobarbitone sleeping time and hisptopathological observation were similar for both the groups.

  11. The Boltzmann equation in the difference formulation

    Energy Technology Data Exchange (ETDEWEB)

    Szoke, Abraham [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Brooks III, Eugene D. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2015-05-06

    First we recall the assumptions that are needed for the validity of the Boltzmann equation and for the validity of the compressible Euler equations. We then present the difference formulation of these equations and make a connection with the time-honored Chapman - Enskog expansion. We discuss the hydrodynamic limit and calculate the thermal conductivity of a monatomic gas, using a simplified approximation for the collision term. Our formulation is more consistent and simpler than the traditional derivation.

  12. Clinical pharmacology of novel anticancer drug formulations

    OpenAIRE

    Stuurman, F.E.

    2013-01-01

    Studies outlined in this thesis describe the impact of drug formulations on pharmacology of anticancer drugs. It consists of four parts and starts with a review describing the mechanisms of low oral bioavailability of anti-cancer drugs and strategies for improvement of the bioavailability. The majority of new anti-cancer drugs are oral pharmaceutical formulations, consisting of new chemical entities, like molecular targeted agents and novel variants of existing drugs. The development of oral ...

  13. Chemicals-Based Formulation Design: Virtual Experimentations

    DEFF Research Database (Denmark)

    Conte, Elisa; Gani, Rafiqul

    2011-01-01

    This paper presents a systematic procedure for virtual experimentations related to the design of liquid formulated products. All the experiments that need to be performed when designing a liquid formulated product (lotion), such as ingredients selection and testing, solubility tests, property mea...... on the design of an insect repellent lotion will show that the software is an essential instrument in decision making, and that it reduces time and resources since experimental efforts can be focused on one or few product alternatives....

  14. Puruvana puruvanavana : [luuletused] / Eno Raud

    Index Scriptorium Estoniae

    Raud, Eno, 1928-1996

    2000-01-01

    Sisu: Puruvana puruvanavana ; Vetesell ; Pada ja katel ; Nääripäkapikk ; Vanapaar ; Mere peremees ; Lepamaim ; Kiilaspää kiilasjääl ; Tõugu unistus ; Naljatilk silk ; Muttide jalutuskäik ; Hiir lumes ; Kalakari salakaril ; Naljalammas ; Mesilastest ; Kure mure ; Voki laul karule ; Põrsalaul ; Kurk ja kõrvits ; Tuhk ja tina ; Õige pea ja vale pea ; Suu pea, puupea! ; Siga õuel

  15. Puruvana puruvanavana : [luuletused] / Eno Raud

    Index Scriptorium Estoniae

    Raud, Eno, 1928-1996

    2000-01-01

    Sisu: Puruvana puruvanavana ; Vetesell ; Pada ja katel ; Nääripäkapikk ; Vanapaar ; Mere peremees ; Lepamaim ; Kiilaspää kiilasjääl ; Tõugu unistus ; Naljatilk silk ; Muttide jalutuskäik ; Hiir lumes ; Kalakari salakaril ; Naljalammas ; Mesilastest ; Kure mure ; Voki laul karule ; Põrsalaul ; Kurk ja kõrvits ; Tuhk ja tina ; Õige pea ja vale pea ; Suu pea, puupea! ; Siga õuel

  16. Microbiological quality of pediatric oral liquid formulations

    Directory of Open Access Journals (Sweden)

    Maria Josep Cabañas Poy

    2016-09-01

    Full Text Available The oral administration of drugs to the pediatric population involves the extemporaneous preparation of liquid formulations. These formulations have studies on their physicochemical stability, but they often lack microbiological studies. The objective of this study is to check the microbiological quality of five oral liquid formulations prepared with different excipients, which represent five major combinations, in two conditions: kept unopened until the day of the test, and in a multi-dose vial opened daily. The formulations were prepared according to standard operating procedures. Half of each batch was packaged in vials that remained closed until the day of testing, and the other half in a single container which was opened daily. Both the vials and the containers had been previously sterilized. Microbiological tests were performed weekly during the first month of the study, and then every two weeks, until the expiration date. The microbiological quality of oral liquid formulations is determined by the Royal Spanish Pharmacopoeia. The conclusion was that none of the formulations prepared that were packaged in sterilized containers became contaminated, either in unopened vials or in multi-dose containers when they were opened daily

  17. Sterile Filtration of Highly Concentrated Protein Formulations: Impact of Protein Concentration, Formulation Composition, and Filter Material.

    Science.gov (United States)

    Allmendinger, Andrea; Mueller, Robert; Huwyler, Joerg; Mahler, Hanns-Christian; Fischer, Stefan

    2015-10-01

    Differences in filtration behavior of concentrated protein formulations were observed during aseptic drug product manufacturing of biologics dependent on formulation composition. The present study investigates filtration forces of monoclonal antibody formulations in a small-scale set-up using polyvinylidene difluoride (PVDF) or polyethersulfone (PES) filters. Different factors like formulation composition and protein concentration related to differences in viscosity, as well as different filtration rates were evaluated. The present study showed that filtration behavior was influenced by the presence or absence of a surfactant in the formulation, which defines the interaction between filter membrane and surface active formulation components. This can lead to a change in filter resistance (PES filter) independent on the buffer system used. Filtration behavior was additionally defined by rheological non-Newtonian flow behavior. The data showed that high shear rates resulting from small pore sizes and filtration pressure up to 1.0 bar led to shear-thinning behavior for highly concentrated protein formulations. Differences in non-Newtonian behavior were attributed to ionic strength related to differences in repulsive and attractive interactions. The present study showed that the interplay of formulation composition, filter material, and filtration rate can explain differences in filtration behavior/filtration flux observed for highly concentrated protein formulations thus guiding filter selection.

  18. Formulation and optimization of potassium iodide tablets.

    Science.gov (United States)

    Al-Achi, Antoine; Patel, Binit

    2015-01-01

    The use of potassium iodide (KI) as a protective agent against accidental radioactive exposure is well established. In this study, we aimed to prepare a KI tablet formulation using a direct compression method. We utilized Design of Experiment (DoE)/mixture design to define the best formulation with predetermined physical qualities as to its dissolution, hardness, assay, disintegration, and angle of repose. Based on the results from the DoE, the formulation had the following components (%w/w): Avicel 48.70%, silicon dioxide 0.27%, stearic acid (1.00%), magnesium stearate 2.45%, and dicalcium phosphate 18.69%, in addition to potassium iodide 28.89% (130 mg/tablet). This formulation was scaled-up using two tablet presses, a single-punch press and a rotary mini tablet press. The final scaled-up formulation was subjected to a variety of quality control tests, including photo-stability testing. The results indicate that potassium iodide tablets prepared by a rotary mini tablet press had good pharmaceutical characteristics and a shelf-life of 25 days when stored at room temperature protected from light.

  19. Biopolymeric Formulations for Biocatalysis and Biomedical Applications

    Directory of Open Access Journals (Sweden)

    Magdy M. M. Elnashar

    2014-01-01

    Full Text Available Three gel disks formulations prepared using chitosan (Chito or polyethylenimine (PEI followed by glutaraldehyde were prepared for biocatalysis and biomedical applications. The carriers have been used to immobilize lactase covalently and it was evaluated in terms of enzyme loading capacity and enzyme kinetics (km and Vmax. The Km of the Chito formulation was almost half that of the PEI formulations, which is favored in industries. On the other hand, the gel disks were evaluated in terms of their swelling kinetics and the gels’ morphology using SEM. The mechanism of the three gels’ swelling was also studied and it was found to be non-Fickian, where the mechanism of transport depends on both the diffusion and polymer relaxation, which are controlling the overall rate of water uptake. The Chito formulation was 2–5 folds and PEI formulations were 33–62 folds in terms of the swelling rate constant and the diffusion rate, respectively. These results were highly supported by the SEM. This study will help scientists to design the right polymer network for enzymes immobilization as well as control the surface area and the swelling power of the polymers for different applications such as drug delivery systems and tissue engineering.

  20. Self-Setting Calcium Orthophosphate Formulations

    Directory of Open Access Journals (Sweden)

    Sergey V. Dorozhkin

    2013-11-01

    Full Text Available In early 1980s, researchers discovered self-setting calcium orthophosphate cements, which are bioactive and biodegradable grafting bioceramics in the form of a powder and a liquid. After mixing, both phases form pastes, which set and harden forming either a non-stoichiometric calcium deficient hydroxyapatite or brushite. Since both of them are remarkably biocompartible, bioresorbable and osteoconductive, self-setting calcium orthophosphate formulations appear to be promising bioceramics for bone grafting. Furthermore, such formulations possess excellent molding capabilities, easy manipulation and nearly perfect adaptation to the complex shapes of bone defects, followed by gradual bioresorption and new bone formation. In addition, reinforced formulations have been introduced, which might be described as calcium orthophosphate concretes. The discovery of self-setting properties opened up a new era in the medical application of calcium orthophosphates and many commercial trademarks have been introduced as a result. Currently such formulations are widely used as synthetic bone grafts, with several advantages, such as pourability and injectability. Moreover, their low-temperature setting reactions and intrinsic porosity allow loading by drugs, biomolecules and even cells for tissue engineering purposes. In this review, an insight into the self-setting calcium orthophosphate formulations, as excellent bioceramics suitable for both dental and bone grafting applications, has been provided.

  1. Bioequivalence assessment of two formulations of ibuprofen

    KAUST Repository

    Al-Talla, Zeyad

    2011-10-19

    Background: This study assessed the relative bioavailability of two formulations of ibuprofen. The first formulation was Doloraz , produced by Al-Razi Pharmaceutical Company, Amman, Jordan. The second forumulation was Brufen , manufactured by Boots Company, Nottingham, UK. Methods and results: A prestudy validation of ibuprofen demonstrated long-term stability, freeze-thaw stability, precision, and accuracy. Twenty-four healthy volunteers were enrolled in this study. After overnight fasting, the two formulations (test and reference) of ibuprofen (100 mg ibuprofen/5 mL suspension) were administered as a single dose on two treatment days separated by a one-week washout period. After dosing, serial blood samples were drawn for a period of 14 hours. Serum harvested from the blood samples was analyzed for the presence of ibuprofen by high-pressure liquid chromatography with ultraviolet detection. Pharmacokinetic parameters were determined from serum concentrations for both formulations. The 90% confidence intervals of the ln-transformed test/reference treatment ratios for peak plasma concentration and area under the concentration-time curve (AUC) parameters were found to be within the predetermined acceptable interval of 80%-125% set by the US Food and Drug Administration. Conclusion: Analysis of variance for peak plasma concentrations and AUC parameters showed no significant difference between the two formulations and, therefore, Doloraz was considered bioequivalent to Brufen. 2011 Al-Talla et al, publisher and licensee Dove Medical Press Ltd.

  2. Gamma Ray Bursts Cook Book I: Formulation

    CERN Document Server

    Ziaeepour, Houri

    2008-01-01

    Since the suggestion of relativistic shocks as the origin of gamma-ray bursts (GRBs) in early 90's, the mathematical formulation of this process has stayed at phenomenological level. One of the reasons for the slow development of theoretical works in this domain has been the simple power-law behaviour of the afterglows hours or days after the prompt gamma-ray emission. Nowadays with the launch of the Swift satellite, gamma-ray bursts can be observed in multi-wavelength from a few tens of seconds after trigger onward. These observations have leaded to the discovery of features unexplainable by the simple formulation of the shocks and emission processes used up to now. But "devil is in details" and some of these features may be explained with a more detailed formulation of phenomena and without adhoc addition of new processes. Such a formulation is the goal of this work. We present a consistent formulation of the collision between two spherical relativistic shells. The model can be applied to both internal and ...

  3. Additive Technology for EU Ecolabel Formulations

    Institute of Scientific and Technical Information of China (English)

    Eric Nehls; Tassilo Habereder; Edward Ng

    2009-01-01

    Currently, Bio -lubricants are still regarded as niche products. Within the global lubricant market, however, the ar-ea of environmentally acceptable fluids represents one of the fast growing markets with an estimated annual growth of more than 6% per year. This growth is supported by various market drivers such as legal regulations, public subsidies and the im-plementation of national or international labeling schemes.With the implementation of the European Ecolabel for lubricants in 2005, a common standard specifying ecological and performance requirements for Bio - lubricants was defined. Applying for the EU Ecolabel requires a comprehensive assess-ment, not only of the final formulation, but also of the additives used. Additives are required to meet specifications for oxi-dation and thermal stability, as well as to impart metal protection (of both steel and yellow metals), thus improving corro-sion protection and wear performance of the formulation. Therefore, it is challenging in terms of formulation technology to develop the right formulation that meets the technical specifications as well as the stringent requirements of the EU - Ecola-bel.The paper describes how, by using ester base fluids and additives currently available in the market, lubricants can be developed to meet the technical and eco - toxicological requirements of the EU - Ecolabel, approaching the performance lev-els of lubricants formulated with traditional base fluids.

  4. FORMULATION AND EVALUATION OF AMISULPRIDE ORODISPERSIBLE TABLET

    Directory of Open Access Journals (Sweden)

    Dr. Hitesh P. Dalvadi

    2016-03-01

    Full Text Available Orodispersible dosage forms have lured the market for a certain section of the patient population which includes dysphagia, bed ridden, psychic, and geriatric patients. Moreover Orodispersible tablets shows increased bioavailability as compared to conventional dosage forms. Amisulpride is a psychotropic agent belonging to the chemical class of benzamide derivatives. At low doses, it enhances dopaminergic neurotransmission by preferentially blocking presynaptic dopamine D2/D3 auto receptors. The tablets were prepared by using direct compression method, and drug solubility is enhanced by solid dispersion. Formulation were prepared by using different superdisintegrant, combination of different superdisintegrant and effect of hydrophilic lubricant was studied and evaluated pre and post compression parameters. Tablets were evaluated for content uniformity, Disintegration time, wetting time, hardness, friability and In-vitro dissolution studies. More than 90% of drug was released from almost all the formulations within 10 min. Formulation C4 containing Sodium starch glycolate (4.5%, Crospovidone (2.5% and crosscarmellose sodium (3.5%, was having disintegration time 24 seconds, wetting time 18 seconds, hardness 3.4Kg/cm2 and in vitro drug release of 99.96% in pH 6.8. Based on this data C4 was found to be the best formulation. Further formulations were subjected to accelerated stability studies. Tablets showed no appreciable changes with respect to disintegration and dissolution profiles. Results of this study indicate among the superdisintegrants tried, combination of superdisintegrant gave the best result.

  5. Formulation and optimization of carbamazepine floating tablets

    Directory of Open Access Journals (Sweden)

    Patel D

    2007-01-01

    Full Text Available Floating tablets of carbamazepine were developed using melt granulation technique. Bees wax was used as a hydrophobic meltable material. Hydroxypropylmethylcellulose, sodium bicarbonate and ethyl cellulose were used as matrixing agent, gas-generating agent and floating enhancer, respectively. The tablets were evaluated for in vitro buoyancy and dissolution studies. A simplex lattice design was applied to investigate the combined effect of 3 formulation variables i.e. amount of hydroxypropyl methylcellulose ( X 1 , ethyl cellulose ( X 2 and sodium bicarbonate ( X 3 . The floating lag time (F lag , time required for 50% (t 50 and 80% drug dissolution (t 80 were taken as responses. Results of multiple regression analysis indicated that, low level of X 1 and X 2 , and high level of X 3 should be used to manufacture the tablet formulation with desired in vitro floating time and dissolution. Formulations developed using simplex lattice design were fitted to various kinetic models for drug release. Formulation S3 was selected as a promising formulation and was found stable at 40 o and 75% relative humidity for 3 months. Present study demonstrates the use of simplex lattice design in the development of floating tablets with minimum experimentation.

  6. Formulation and evaluation of saquinavir injection

    Directory of Open Access Journals (Sweden)

    Nahar M

    2006-01-01

    Full Text Available Acquired immunodeficiency syndrome (AIDS pandemic is one of the biggest challenges of the 21st century. With the development of antiretroviral therapy, the count of human immunodeficiency virus (HIV-infected people may decrease to a certain extent. Presently available formulations for this disease are found not to be very useful due to poor bioavailability, leading to poor efficacy, various side effects and high cost. In the present investigation, it was proposed to formulate the aqueous injection of saquinavir, which should definitely be more effective, economical, safe and with the least side effects as compared to its existing dosage forms, e.g., hard and soft gelatin capsule. The solubilization of saquinavir (antiHIV drug, practically insoluble in water, by means of physiologically active hydrotropes and cosolvents has been investigated. The results indicate that enhancement in solubility of saquinavir in the presence of hydrotrope at low concentration is due to weak ionic interaction. At higher concentrations (>0.4 M, complexation is found to be the probable mechanism for solubility enhancement by nicotinamide but nature of complex formed is not clear; whereas for ascorbic acid, self-association is the probable mechanism at these concentrations. Using these two approaches, various formulations of saquinavir were developed, and haemolysis study and dilution study of these formulations were carried out. Formulation containing nicotinamide as hydrotrope showed promising results.

  7. Relativistic MHD and excision: formulation and initial tests

    Energy Technology Data Exchange (ETDEWEB)

    Neilsen, David; Hirschmann, Eric W; Millward, R Steven [Department of Physics and Astronomy, Brigham Young University, Provo, UT 84602 (United States)

    2006-08-21

    A new algorithm for solving the general relativistic MHD equations is described in this paper. We design our scheme to incorporate black hole excision with smooth boundaries, and to simplify solving the combined Einstein and MHD equations with AMR. The fluid equations are solved using a finite difference convex ENO method. Excision is implemented using overlapping grids. Elliptic and hyperbolic divergence cleaning techniques allow for maximum flexibility in choosing coordinate systems, and we compare both methods for a standard problem. Numerical results of standard test problems are presented in two-dimensional flat space using excision, overlapping grids and elliptic and hyperbolic divergence cleaning.

  8. Relativistic MHD and black hole excision: Formulation and initial tests

    CERN Document Server

    Neilsen, D; Millward, R S; Hirschmann, Eric W; Neilsen, David

    2006-01-01

    A new algorithm for solving the general relativistic MHD equations is described in this paper. We design our scheme to incorporate black hole excision with smooth boundaries, and to simplify solving the combined Einstein and MHD equations with AMR. The fluid equations are solved using a finite difference Convex ENO method. Excision is implemented using overlapping grids. Elliptic and hyperbolic divergence cleaning techniques allow for maximum flexibility in choosing coordinate systems, and we compare both methods for a standard problem. Numerical results of standard test problems are presented in two-dimensional flat space using excision, overlapping grids, and elliptic and hyperbolic divergence cleaning.

  9. Formulations for children: problems and solutions

    Science.gov (United States)

    Batchelor, Hannah K; Marriott, John F

    2015-01-01

    Paediatric formulation design is complex as there is a need to understand the developmental physiological changes that occur during childhood and their impact on the absorption of drugs. Paediatric dose adjustments are usually based on achieving pharmacokinetic or pharmacodynamic profiles equivalent to those achieved in adult populations. However, differences in the way in which children handle adult products or the use of bespoke paediatric formulations can result in unexpected pharmacokinetic drug profiles with altered clinical efficacy. Differences in drug formulations need to be understood by healthcare professionals involved in the prescribing, administration or dispensing of drugs to children such that appropriate advice is given to ensure that therapeutic outcomes are achieved. This issue is not confined to oral medicines but is applicable for all routes of administration encountered in paediatric therapy. PMID:25855822

  10. Aeroelastic formulations for turbomachines and propellers

    Science.gov (United States)

    Crawley, E. F.

    1984-01-01

    The task of the aeroelastic analysis is to combine the formulations of the structural dynamic and unsteady aerodynamic models in a consistent manner, to solve the resulting aeroelastic model to determine the dynamic behavior (e.g., stability, forced vibration), and to interpret those results for both qualitative trends, and quantitative detail. A review of the various formulations of the aeroelastic problem and a comparison of their relative advantages will be the subject of this paper. Specifically, the topics to be addressed are: the formulation of the aeroelastic problem, including a summary of the relations necessary to transform various diverse structural and aerodynamic models to a consistent notation for oscillatory motion; an approximate transformation for arbitrary temporal behavior; and a brief review of the applicable solution techniques.

  11. Quantum Holonomy Theory, Lattice-Independent Formulation

    CERN Document Server

    Aastrup, Johannes

    2016-01-01

    Quantum holonomy theory is a candidate for a non-perturbative theory of quantum gravity coupled to fermions. The theory is based on the QHD-algebra, which essentially encodes how local degrees of freedom are moved on a three-dimensional manifold. In this paper we continue the development of the theory by providing a lattice-independent formulation. We first define a Dirac type operator over a configuration space of Ashtekar connections and use it to formulate a graded version of the QHD-algebra. Next we formulate necessary conditions for a state to exist on this algebra and use the GNS construction to build a kinematical Hilbert space. Finally we find that operators, that correspond to the Dirac and gravitational Hamiltonians in a semi-classical limit, are background independent.

  12. "Sustained release formulation of Metoclopramide Hydrochloride "

    Directory of Open Access Journals (Sweden)

    Dabbagh MA

    2000-08-01

    Full Text Available In this research, several formulations containing, an anti emetic agent (Metoclopramide hydrochloride, a hydrophilic polymer (hydroxypropylmethylcellulose and a hydrophobic polymer (ethylcellulose 10 cP were prepared by direct compression. Different factors such as: the effect of different ratios of the polymers, particle size, pressure force and differences of release in acidic and distilled water as media were investigated. After developing the ideal formulation, the effect of changing the ratio of drug in core: coating on the formulation was investigated. Coating of tablets with ethylcellulose, changed the release mechanism of drug and shifted it to near zero order release. The results showed that except when matrices were coated with ethylcellulose, drug release was proportioned to the square root of time, which might be due to the change of release pattern from matrix to reservoir system.

  13. Engaged Problem Formulation in IS Research

    DEFF Research Database (Denmark)

    Nielsen, Peter Axel; Persson, John Stouby

    2016-01-01

    problems requires a more substantial engagement with the different stakeholders, especially when their problems are ill structured and situated in complex organizational settings. On this basis, we present an engaged approach to formulating IS problems with, not for, IS practitioners. We have come......“Is this the problem?”: the question that haunts many information systems (IS) researchers when they pursue work relevant to both practice and research. Nevertheless, a deliberate answer to this question requires more than simply asking the involved IS practitioners. Deliberately formulating...... to understand engaged problem formulation as joint researching and as the defining of contemporary and complex problems by researchers and those practitioners who experience and know these problems. We used this approach in investigating IS management in Danish municipalities. In this paper, we present...

  14. Patented herbal formulations and their therapeutic applications.

    Science.gov (United States)

    Musthaba, Mohamed; Baboota, Sanjula; Athar, Tanwir M D; Thajudeen, Kamal Y; Ahmed, Sayeed; Ali, Javed

    2010-11-01

    Recently, there is a greater global interest in non synthetic, natural medicines derived from plant sources due to better tolerance and minimum adverse drug reactions as compared to synthetic medicines. Herbal products are also commonly used by the patients with certain chronic medical conditions, including breast cancer, liver disease, human immunodeficiency, asthma and rheumatological disorders. WHO estimates that about three-quarters of the world's population currently uses herbs and other forms of traditional medicines for the treatment of various diseases. The herbs are formulated in different modern dosage forms, such as Tablets, Capsules, Topical cream, Gel, Ointment and even some novel drug delivery forms, like extended release, sustained release, and microencapsules dosage forms. Patenting of herbal formulations has increased over the past few years and scientific evidence of therapeutic activity has been reported by performing various in vitro and in vivo experiments. This manuscript deals with various patented herbal formulations with their therapeutic application against various diseases.

  15. Assessing Component Effects in Formulation Systems

    Energy Technology Data Exchange (ETDEWEB)

    Snee, Ronald D.; Piepel, Gregory F.

    2012-12-17

    The purpose of Snee (2011) was to discuss and illustrate how using Six Sigma concepts and approaches can lead to a better understanding of formulation systems. Central to the recommended approach is estimating and interpreting the effects of the components in the formulation on the response variable. Knowledge of components that have no effect, small or large effects (positive or negative), and similar effects is very helpful in understanding how the formulation system works. This understanding helps one decide 1) which components having large effects should be increased or decreased, and 2) what to do about components with no effects or similar effects. Correspondence between the authors following Snee (2011), along with further review of the literature, have pointed out that the approaches discussed in Snee (2011), and the interpretation of component effects in general, need further clarification. That is the focus of this article.

  16. Engaged Problem Formulation in IS Research

    DEFF Research Database (Denmark)

    Nielsen, Peter Axel; Persson, John Stouby

    2016-01-01

    “Is this the problem?”: the question that haunts many information systems (IS) researchers when they pursue work relevant to both practice and research. Nevertheless, a deliberate answer to this question requires more than simply asking the involved IS practitioners. Deliberately formulating...... to understand engaged problem formulation as joint researching and as the defining of contemporary and complex problems by researchers and those practitioners who experience and know these problems. We used this approach in investigating IS management in Danish municipalities. In this paper, we present...... the approach to formulating problems in an engaged way. We discuss it in relation to ideas and assumptions that underpin engaged scholarship, and we discuss the implications for IS action research, design science research, and mixed approaches....

  17. Chemical-Based Formulation Design: Virtual Experimentation

    DEFF Research Database (Denmark)

    Conte, Elisa; Gani, Rafiqul

    This paper presents a software, the virtual Product-Process Design laboratory (virtual PPD-lab) and the virtual experimental scenarios for design/verification of consumer oriented liquid formulated products where the software can be used. For example, the software can be employed for the design...... system engineering community, it is possible now to replace, at least, some of the experimental steps with efficient and validated model-based approaches. For example, the search space can be significantly reduced through computer-aided screenings of the active ingredient (AI), the solvent mixture......, the additives and/or their mixtures (formulations). Therefore, the experimental resources can focus on a few candidate product formulations to find the best product. The virtual PPD-lab allows various options for experimentations related to design and/or verification of the product. For example, the selection...

  18. RAACFDb: Rheumatoid arthritis ayurvedic classical formulations database.

    Science.gov (United States)

    Mohamed Thoufic Ali, A M; Agrawal, Aakash; Sajitha Lulu, S; Mohana Priya, A; Vino, S

    2017-02-02

    In the past years, the treatment of rheumatoid arthritis (RA) has undergone remarkable changes in all therapeutic modes. The present newfangled care in clinical research is to determine and to pick a new track for better treatment options for RA. Recent ethnopharmacological investigations revealed that traditional herbal remedies are the most preferred modality of complementary and alternative medicine (CAM). However, several ayurvedic modes of treatments and formulations for RA are not much studied and documented from Indian traditional system of medicine. Therefore, this directed us to develop an integrated database, RAACFDb (acronym: Rheumatoid Arthritis Ayurvedic Classical Formulations Database) by consolidating data from the repository of Vedic Samhita - The Ayurveda to retrieve the available formulations information easily. Literature data was gathered using several search engines and from ayurvedic practitioners for loading information in the database. In order to represent the collected information about classical ayurvedic formulations, an integrated database is constructed and implemented on a MySQL and PHP back-end. The database is supported by describing all the ayurvedic classical formulations for the treatment rheumatoid arthritis. It includes composition, usage, plant parts used, active ingredients present in the composition and their structures. The prime objective is to locate ayurvedic formulations proven to be quite successful and highly effective among the patients with reduced side effects. The database (freely available at www.beta.vit.ac.in/raacfdb/index.html) hopefully enables easy access for clinical researchers and students to discover novel leads with reduced side effects. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  19. Effects of Formulation Variables and Storage Conditions on Light Protected Vitamin B12 Mixed Parenteral Formulations

    Directory of Open Access Journals (Sweden)

    Farnaz Monajjemzadeh

    2014-12-01

    Full Text Available Purpose: In this research the effect of vitamin B1 and B6 on cyanocobalamin stability in commercial light protected parenteral formulations and upon adding stabilizing agents will be investigated and best formulation composition and proper storage condition will be introduced. Methods: In this research some additives such as co solvents and tonicity adjusters, surfactants, antioxidants and chelating agents as well as buffer solutions, were used to improve the stability of the parenteral mixed formulations of B12 in the presence of other B vitamins (B1 and B6. Screening tests and accelerated stability tests were performed according to ICH guidelines Q1A (R2. Results: Shelf life evaluation revealed the best formulation and the proper storage condition. The results indicated the first kinetic models for all tested formulations and the optimum pH value was determined to be 5.8. There was no evidence of B12 loss when mixed with B1 and B6 in a medical syringe at room temperature for maximum of 8 hours. Conclusion: It is necessary to formulate vitamin B12 mixed parenteral solutions using proper phosphate buffers (pH=5.8 and to indicate “Store in refrigerator” on the mixed parenteral formulations of vitamin B12 with other B vitamins, which has not been expressed on the label of tested Brand formulations at the time of this study.

  20. From the Berkovits formulation to the Witten formulation in open superstring field theory

    Science.gov (United States)

    Iimori, Yuki; Noumi, Toshifumi; Okawa, Yuji; Torii, Shingo

    2014-03-01

    The Berkovits formulation of open superstring field theory is based on the large Hilbert space of the superconformal ghost sector. We discuss its relation to the Witten formulation based on the small Hilbert space. We introduce a one-parameter family of conditions for partial gauge fixing of the Berkovits formulation such that the cubic interaction of the theory under the partial gauge fixing reduces to that of the Witten formulation in a singular limit. The local picture-changing operator at the open-string midpoint in the Witten formulation is regularized in our approach, and the divergence in on-shell four-point amplitudes coming from collision of picture-changing operators is resolved. The quartic interaction inherited from the Berkovits formulation plays a role of adjusting different behaviors of the picture-changing operators in the s channel and in the t channel of Feynman diagrams with two cubic vertices, and correct amplitudes in the world-sheet theory are reproduced. While gauge invariance at the second order in the coupling constant is obscured in the Witten formulation by collision of picture-changing operators, it is well defined in our approach and is recovered by including the quartic interaction inherited from the Berkovits formulation.

  1. From the Berkovits formulation to the Witten formulation in open superstring field theory

    Energy Technology Data Exchange (ETDEWEB)

    Iimori, Yuki [Department of Physics, Nagoya University,Nagoya 464-8602 (Japan); Noumi, Toshifumi [Mathematical Physics Laboratory, RIKEN Nishina Center,Saitama 351-0198 (Japan); Okawa, Yuji [Institute of Physics, The University of Tokyo,Komaba, Meguro-ku, Tokyo 153-8902 (Japan); Torii, Shingo [Mathematical Physics Laboratory, RIKEN Nishina Center,Saitama 351-0198 (Japan)

    2014-03-07

    The Berkovits formulation of open superstring field theory is based on the large Hilbert space of the superconformal ghost sector. We discuss its relation to the Witten formulation based on the small Hilbert space. We introduce a one-parameter family of conditions for partial gauge fixing of the Berkovits formulation such that the cubic interaction of the theory under the partial gauge fixing reduces to that of the Witten formulation in a singular limit. The local picture-changing operator at the open-string midpoint in the Witten formulation is regularized in our approach, and the divergence in on-shell four-point amplitudes coming from collision of picture-changing operators is resolved. The quartic interaction inherited from the Berkovits formulation plays a role of adjusting different behaviors of the picture-changing operators in the s channel and in the t channel of Feynman diagrams with two cubic vertices, and correct amplitudes in the world-sheet theory are reproduced. While gauge invariance at the second order in the coupling constant is obscured in the Witten formulation by collision of picture-changing operators, it is well defined in our approach and is recovered by including the quartic interaction inherited from the Berkovits formulation.

  2. Pharmacokinetics of formulated tenoxicam transdermal delivery systems.

    Science.gov (United States)

    Kim, Taekyung; Kang, Eunyoung; Chun, Inkoo; Gwak, Hyesun

    2008-01-01

    To investigate the feasibility of developing a new tenoxicam transdermal delivery system (TDS), the pharmacokinetics of tenoxicam from various formulated TDS were evaluated and compared with values following oral administration of tenoxicam and with application of a piroxicam plaster (Trast) marketed in Korea. Based on previous in-vitro study results, a mixture of diethylene glycol monoethyl ether (DGME) and propylene glycol monolaurate (PGML) (40:60) was used as a vehicle, and caprylic acid, capric acid, lauric acid, oleic acid or linoleic acid (each at 3%) was added as an enhancer. Triethanolamine (5%) was used as a solubilizer, and Duro-Tak 87-2510 as a pressure-sensitive adhesive. Among these fatty acids used for the formulation of tenoxicam TDS, caprylic acid showed the greatest enhancing effect; the area under the plasma concentration-time profile (AUC) decreased in the order of caprylic acid>linoleic acid>or=oleic acid>lauric acid>capric acid. Compared with oral administration, maximum plasma concentration (Cmax) was significantly lower, and time to reach Cmax (Tmax) delayed with all formulated tenoxicam TDS. All formulated TDS resulted in a lower AUC than with the oral formulation, except for TDS containing caprylic acid, although the difference was statistically significant only with capric acid. The AUC for all the formulated tenoxicam TDS was significantly higher than that of the piroxicam plaster; TDS with caprylic acid increased AUC 8.53-fold compared with the piroxicam plaster. Even though the Tmax of tenoxicam TDS was not significantly different from that of the piroxicam plaster, Cmax was higher; formulations containing caprylic acid and linoleic acid increased Cmax by 7.39- and 8.76-fold, respectively. In conclusion, a formulation containing 1.5 mL DGME-PGML (40:60) with 3% caprylic acid and 5% triethanolamine mixed with 6 g Duro-Tak 87-2510 could be a good candidate for developing a new tenoxicam TDS to maintain a comparable extent of absorption

  3. A Novel Formulation of Baroclinic Rotational Equilibria

    CERN Document Server

    Yasutake, Nobutoshi

    2014-01-01

    We have developed a new formulation to obtain self-gravitating, axisymmetric configurations in permanent rotation. It is applicable not only to barotropic equations of state but also to baroclinic ones, for which angular momentum distributions are not cylindrical. The formulation is based on the Lagrangian variational principle. Some test calculations are presented, in which we have achieved an error of $O(10^{-4})$ in the Virial relation. We believe that this method could be a major break-through in stellar evolution theory, in which it is a common practice that rotation is included only approximately in one dimensional models.

  4. Application of UV Imaging in Formulation Development

    DEFF Research Database (Denmark)

    Sun, Yu; Østergaard, Jesper

    2017-01-01

    defining formulation behavior after exposure to the aqueous environments and pharmaceutical performance is critical in pharmaceutical development, manufacturing and quality control of drugs. UV imaging has been explored as a tool for qualitative and quantitative characterization of drug dissolution...... and release with the characteristic feature of providing real-time visualization of the solution phase drug transport in the vicinity of the formulation. Events occurring during drug dissolution and release, such as polymer swelling, drug precipitation/recrystallization, or solvent-mediated phase transitions...

  5. Design of formulated products: a systematic methodology

    DEFF Research Database (Denmark)

    Conte, Elisa; Gani, Rafiqul; Ng, K.M.

    2011-01-01

    -based computer-aided methodology for design and verification of a class of chemical-based products (liquid formulations) is presented. This methodology is part of an integrated three-stage approach for design/verification of liquid formulations where stage-1 generates a list of feasible product candidates and....../or verifies a specified set through a sequence of predefined activities (work-flow). Stage-2 and stage-3 (not presented here) deal with the planning and execution of experiments, for product validation. Four case studies have been developed to test the methodology. The computer-aided design (stage-1...

  6. Quaternionic formulation of the exact parity model

    Energy Technology Data Exchange (ETDEWEB)

    Brumby, S.P.; Foot, R.; Volkas, R.R.

    1996-02-28

    The exact parity model (EPM) is a simple extension of the standard model which reinstates parity invariance as an unbroken symmetry of nature. The mirror matter sector of the model can interact with ordinary matter through gauge boson mixing, Higgs boson mixing and, if neutrinos are massive, through neutrino mixing. The last effect has experimental support through the observed solar and atmospheric neutrino anomalies. In the paper it is shown that the exact parity model can be formulated in a quaternionic framework. This suggests that the idea of mirror matter and exact parity may have profound implications for the mathematical formulation of quantum theory. 13 refs.

  7. Novel self-nanoemulsifying formulation of quercetin

    DEFF Research Database (Denmark)

    Jain, Amit K; Thanki, Kaushik; Jain, Sanyog

    2014-01-01

    UNLABELLED: The present work focuses on the anticancer potential of quercetin (QT) loaded self-nanoemulsifying drug delivery system (QT-SNEDDS) composed of Capmul MCM, Tween 20 and ethanol. In vitro cell culture studies revealed potential cell cytotoxicity of developed formulation mediated by its...... to that of free QT (~20%). Finally, safety profile of developed formulation was established assessing various hepatotoxicity markers. FROM THE CLINICAL EDITOR: This basic science study focuses on the anticancer potential of a specific quercetin loaded self-nanoemulsifying drug delivery system. At higher doses...... significantly higher therapeutic anticancer efficacy (~65% tumor suppression) was noted in the same model as compared to that of free quercetin (~20%)....

  8. 3a micromagnetic solution by finite formulation

    Energy Technology Data Exchange (ETDEWEB)

    Giuffrida, C. [Politecnico di Torino, Dip. Ingegneria Elettrica, C.so Duca Abruzzi 24, I-10129 Turin (Italy); Ragusa, C. [Politecnico di Torino, Dip. Ingegneria Elettrica, C.so Duca Abruzzi 24, I-10129 Turin (Italy); Repetto, M. [Politecnico di Torino, Dip. Ingegneria Elettrica, C.so Duca Abruzzi 24, I-10129 Turin (Italy)]. E-mail: maurizio.repetto@polito.it

    2006-02-01

    In this paper, a method for the numerical solution of micromagnetic problems in 3D cases is presented. These problems require the solution of electromagnetic field coupled with Landau-Lifshitz-Gilbert equation, governing magnetization dynamics. Finite formulation of electromagnetic fields (FFEF) is used to compute the magnetostatic contribution to the effective field in terms of line integrals of magnetic vector potential, while integral boundary conditions are obtained computing magnetic scalar potential using magnetization values as source. Magnetization dynamics is evaluated by an implicit formulation. Results on benchmark configurations are shown.

  9. Determination of carbamazepine in pharmaceutical formulations

    Directory of Open Access Journals (Sweden)

    Lílian Grace da Silva Solon

    2010-09-01

    Full Text Available The aim of this study was to evaluate the quality of five different solid formulations of carbamazepine. The reference formulation was Tegretol® 200.00 mg (Novartis and the others were: generic formulation of carbamazepine 200.00 mg (National Industry, similar formulation of carbamazepine 200.00 mg (National Industry, and two formulations of carbamazepine 200.00 mg acquired from two different compounding pharmacies. The latter consisted of capsules obtained in Natal, the capital city of the Brazilian State of Rio Grande do Norte. The quality of samples was evaluated through physical and physical-chemical tests, including: weight, diameter, thickness, content, dissolution, disintegration, hardness, friability and moisture. The results of friability analysis showed that all formulations met Brazilian and United States Pharmacopeia (USP specifications. In spite of having a higher hardness compared to the reference, the generic formulation had a lower disintegration time. This could be associated to the presence of crospovidone in its formulation. Results of this study showed that all formulations had dissolutions which were in accordance with Brazilian Pharmacopoeia specifications, and quality control tests. An exception was found for the similar formulation, which had a hardness parameter that exceeded the USP standard. However, this difference was not significant given the similar formulation's satisfactory disintegration time.O objetivo desse trabalho foi avaliar a qualidade de cinco formulações de carbamazepina na dosagem de 200,00 mg: medicamento referência Tegretol® (Novartis, medicamento genérico (indústria nacional, medicamento similar (indústria nacional e cápsulas do mesmo medicamento obtidas de duas farmácias de manipulação da cidade do Natal, RN. Os ensaios realizados foram: peso médio, diâmetro, espessura, teor, dissolução, desintegração, dureza, friabilidade e umidade. Foi observado que nenhuma das amostras

  10. State-Space Formulation for Circuit Analysis

    Science.gov (United States)

    Martinez-Marin, T.

    2010-01-01

    This paper presents a new state-space approach for temporal analysis of electrical circuits. The method systematically obtains the state-space formulation of nondegenerate linear networks without using concepts of topology. It employs nodal/mesh systematic analysis to reduce the number of undesired variables. This approach helps students to…

  11. Implicit Hamiltonian formulation of bond graphs

    NARCIS (Netherlands)

    Golo, G.; Schaft, A.J. van der; Breedveld, P.C.; Maschke, B.M.

    2003-01-01

    This paper deals with mathematical formulation of bond graphs. It is proven that the power continuous part of bond graphs, the junction structure, can be associated with a Dirac structure and that equations describing a bond graph model correspond to an implicit port-controlled Hamiltonian system wi

  12. New lipid formulation of octenidine dihydrochloride.

    Science.gov (United States)

    Szostak, Kamila; Czogalla, Aleksander; Przybyło, Magdalena; Langner, Marek

    2017-01-18

    Octenidine dihydrochloride is an effective antiseptic compound which mode of action is based on destabilization plasma membrane of microorganisms. This ensures that microorganisms cannot develop the drug resistance in a straightforward way, as the entire cellular structure, rather than specific molecular target is affected. Since the octenidine is a hydrophobic compound, it requires organic solvent such as phenoxyethanol in order to be effectively administered. However, the presence of phenoxyethanol has strong irritating effect, particularly when applied on open wounds and mucous membranes. Phospholipids are known as neutral excipients free of side effects and in their aggregated form may serve as solvent for octenidine. In this article, we propose a new antiseptic formulation composed of equimolar ratio of lipids and octenidine. The resulting particles are ∼4 nm in diameter showing that their topology is different from that known for liposomes. The new formulation has proven to be equally effective as octenidine dihydrochloride formulation marketed under the name of Octenisept®. The main advantage of the new formulation is that it does not contain phenoxyethanol, which opens new possibilities for broader application spectrum of octenidine, including treatments of mucous membranes and open wounds.

  13. Clinical pharmacology of novel anticancer drug formulations

    NARCIS (Netherlands)

    Stuurman, F.E.

    2013-01-01

    Studies outlined in this thesis describe the impact of drug formulations on pharmacology of anticancer drugs. It consists of four parts and starts with a review describing the mechanisms of low oral bioavailability of anti-cancer drugs and strategies for improvement of the bioavailability. The

  14. A parcel formulation for Hamiltonian layer models

    NARCIS (Netherlands)

    Bokhove, O.; Oliver, M.

    2009-01-01

    Starting from the three-dimensional hydrostatic primitive equations, we derive Hamiltonian N-layer models with isentropic tropospheric and isentropic or isothermal stratospheric layers. Our construction employs a new parcel Hamiltonian formulation which describes the fluid as a continuum of Hamilton

  15. Structural design using equilibrium programming formulations

    Science.gov (United States)

    Scotti, Stephen J.

    1995-06-01

    Solutions to increasingly larger structural optimization problems are desired. However, computational resources are strained to meet this need. New methods will be required to solve increasingly larger problems. The present approaches to solving large-scale problems involve approximations for the constraints of structural optimization problems and/or decomposition of the problem into multiple subproblems that can be solved in parallel. An area of game theory, equilibrium programming (also known as noncooperative game theory), can be used to unify these existing approaches from a theoretical point of view (considering the existence and optimality of solutions), and be used as a framework for the development of new methods for solving large-scale optimization problems. Equilibrium programming theory is described, and existing design techniques such as fully stressed design and constraint approximations are shown to fit within its framework. Two new structural design formulations are also derived. The first new formulation is another approximation technique which is a general updating scheme for the sensitivity derivatives of design constraints. The second new formulation uses a substructure-based decomposition of the structure for analysis and sensitivity calculations. Significant computational benefits of the new formulations compared with a conventional method are demonstrated.

  16. Clinical pharmacology of novel anticancer drug formulations

    NARCIS (Netherlands)

    Stuurman, F.E.

    2013-01-01

    Studies outlined in this thesis describe the impact of drug formulations on pharmacology of anticancer drugs. It consists of four parts and starts with a review describing the mechanisms of low oral bioavailability of anti-cancer drugs and strategies for improvement of the bioavailability. The major

  17. [Optimization of formulations for dietetic pastry products].

    Science.gov (United States)

    Villarroel, M; Uquiche, E; Brito, G; Cancino, M

    2000-03-01

    Optimized formulations of dietetic pastry products such as cake and sponge cake premixes were formulated using the surface response methodology. % Emulsifier agent and baking time were the selected independent variables for cake, as well as % emulsifier agent % chlorinated flour the variables selected for sponge cake. Three different level of each variable summing up thirteen experimental formulae of each product were assessed to optimize the variables that could have some influence in the sensory characteristics of these dietetic products. The total sensory quality was determined for both dietetic products using the composite scoring test and a panel of 18 trained judges. Looking at the contour graphic and considering economic aspects the best combination of variables for cake formulation was 2% emulsifier agent and 48 minutes for baking time, With respect to sponge cake, the best combination was 6% emulsifier agent and 48% chlorinated flour. Shelf life studies showed that both dietetic formulations remained stable during storage conditions of 75 days at 30 degrees C. During this period, significant differences in sensory characteristics were not found (p < 0.05). Data of peroxide values were kept under the critical value reported for detection of organoleptic rancidity. Reported values of hedonic test showed that these dietetics pastry products had good acceptability, and open up marketing opportunities for new products with potential health benefits to consumers.

  18. Engaged Problem Formulation in IS Research

    DEFF Research Database (Denmark)

    Nielsen, Peter Axel; Persson, John Stouby

    2016-01-01

    problems requires a more substantial engagement with the different stakeholders, especially when their problems are ill structured and situated in complex organizational settings. On this basis, we present an engaged approach to formulating IS problems with, not for, IS practitioners. We have come...

  19. Preformulation and Formulation Investigational New Drugs

    Science.gov (United States)

    1990-07-01

    pyridostigmine. Formulation Strate~y Since hydroxypropylmethylcellulose (HPMC) and hydrogenated castor oil (Castorwax@)/polyvinylpyrolidone (PVP) had been used... hydroxypropylmethylcellulose (MethocelO K4M CR) for 10 minutes in a V-blender. Povidone was added to this mixture and blended for a further 10 minutes. The

  20. Innate antioxidant activity of some traditional formulations

    Directory of Open Access Journals (Sweden)

    Gunpreet Kaur

    2017-01-01

    Full Text Available Herbal medicine is the oldest form of healthcare known to humanity. Recently, much attention is being directed toward the use of antioxidants. There are some very commonly used Ayurvedic preparations that might have inbuilt antioxidant activity, and their therapeutic potential can be partially attributable to its antioxidant activity. Hence, it was proposed to find out antioxidant activity of such common formulations. Estimation of innate antioxidant activity of some commonly used traditional formulations. In this study, five formulations were evaluated for antioxidant activity in comparison to gallic acid (standard using the in vitro reducing power method and superoxide radical scavenging activity by dimethyl sulfoxide method followed by calculation of scavenging activity and inhibitory concentration 50% (IC 50 . The result shows that Ayurvedic drug extracts possess good reducing power and antioxidant activity. Laxmivilas Ras shows higher reducing power ranging from 117 ± 0.021 to 0.176 ± 0.012 as compared to other extracts. The drug extracts were also found to be an efficient scavenger of superoxide radical. The IC 50 values for Laxmivilas Ras, Agnitundi Vati, Ajmodadi Churna, Tribhuvankirti Rasa, gallic acid (standard and Sitopladi Churna, were found to be 50.07, 98.41, 105.13, 116.39, 176.80, and 200.17, respectively. From this study, it can be concluded that the above Ayurvedic formulations possess antioxidant property. However, work could be initiated on the isolation and identification of these antioxidant components.

  1. A Generalized Fluid Formulation for Turbomachinery Computations

    Science.gov (United States)

    Merkle, Charles L.; Sankaran, Venkateswaran; Dorney, Daniel J.; Sondak, Douglas L.

    2003-01-01

    A generalized formulation of the equations of motion of an arbitrary fluid are developed for the purpose of defining a common iterative algorithm for computational procedures. The method makes use of the equations of motion in conservation form with separate pseudo-time derivatives used for defining the numerical flux for a Riemann solver and the convergence algorithm. The partial differential equations are complemented by an thermodynamic and caloric equations of state of a complexity necessary for describing the fluid. Representative solutions with a new code based on this general equation formulation are provided for three turbomachinery problems. The first uses air as a working fluid while the second uses gaseous oxygen in a regime in which real gas effects are of little importance. These nearly perfect gas computations provide a basis for comparing with existing perfect gas code computations. The third case is for the flow of liquid oxygen through a turbine where real gas effects are significant. Vortex shedding predictions with the LOX formulations reduce the discrepancy between perfect gas computations and experiment by approximately an order of magnitude, thereby verifying the real gas formulation as well as providing an effective case where its capabilities are necessary.

  2. PERFORMANCE OF LOCALLY FORMULATED FEEDS FOR ...

    African Journals Online (AJOL)

    ACSS

    sector, providing almost 20% of the world's protein supply; however, the trend in fish production from capture fisheries has reached its limits due to overfishing. ... each were stocked with 320 catfish fry each, and fed with formulated feeds at 5% of ...

  3. Formulation of statistical mechanics for chaotic systems

    Indian Academy of Sciences (India)

    Vishnu M Bannur; Ramesh Babu Thayyullathil

    2009-02-01

    We formulate the statistical mechanics of chaotic system with few degrees of freedom and investigated the quartic oscillator system using microcanonical and canonical ensembles. Results of statistical mechanics are numerically verified by considering the dynamical evolution of quartic oscillator system with two degrees of freedom.

  4. Potential vorticity formulation of compressible magnetohydrodynamics.

    Science.gov (United States)

    Arter, Wayne

    2013-01-04

    Compressible ideal magnetohydrodynamics is formulated in terms of the time evolution of potential vorticity and magnetic flux per unit mass using a compact Lie bracket notation. It is demonstrated that this simplifies analytic solution in at least one very important situation relevant to magnetic fusion experiments. Potentially important implications for analytic and numerical modelling of both laboratory and astrophysical plasmas are also discussed.

  5. Preparation of Copper-loaded Microcapsule Formulations

    Directory of Open Access Journals (Sweden)

    Nenad Jalšenjak

    2011-06-01

    Full Text Available Novel copper-loaded chitosan or chitosan/alginate based microcapsules formulations have been presented. It was shown that prolonged release of copper from microcapsules accompanied with possible prolonged presence of copper on leaves is useful in crop protection.

  6. Preparation of Copper-loaded Microcapsule Formulations

    Directory of Open Access Journals (Sweden)

    Nenad Jalšenjak

    2014-02-01

    Full Text Available Novel copper-loaded chitosan or chitosan/alginate based microcapsules formulations have been presented. It was shown that prolonged release of copper from microcapsules accompanied with possible prolonged presence of copper on leaves is useful in crop protection.

  7. Engaged Problem Formulation in IS Research

    DEFF Research Database (Denmark)

    Nielsen, Peter Axel; Persson, John Stouby

    2016-01-01

    “Is this the problem?”: the question that haunts many information systems (IS) researchers when they pursue work relevant to both practice and research. Nevertheless, a deliberate answer to this question requires more than simply asking the involved IS practitioners. Deliberately formulating...

  8. Screening of mucoadhesive vaginal gel formulations

    Directory of Open Access Journals (Sweden)

    Ana Ochoa Andrade

    2014-12-01

    Full Text Available Rational design of vaginal drug delivery formulations requires special attention to vehicle properties that optimize vaginal coating and retention. The aim of the present work was to perform a screening of mucoadhesive vaginal gels formulated with carbomer or carrageenan in binary combination with a second polymer (carbomer, guar or xanthan gum. The gels were characterised using in vitroadhesion, spreadability and leakage potential studies, as well as rheological measurements (stress and frequency sweep tests and the effect of dilution with simulated vaginal fluid (SVF on spreadability. Results were analysed using analysis of variance and multiple factor analysis. The combination of polymers enhanced adhesion of both primary gelling agents, carbomer and carrageenan. From the rheological point of view all formulations presented a similar behaviour, prevalently elastic and characterised by loss tangent values well below 1. No correlation between rheological and adhesion behaviour was found. Carbomer and carrageenan gels containing the highest percentage of xanthan gum displayed good in vitro mucoadhesion and spreadability, minimal leakage potential and high resistance to dilution. The positive results obtained with carrageenan-xanthan gum-based gels can encourage the use of natural biocompatible adjuvants in the composition of vaginal products, a formulation field that is currently under the synthetic domain.

  9. An alternative formulation of classical electromagnetic duality

    CERN Document Server

    Li, K; Li, Kang; Naón, Carlos M.

    2001-01-01

    By introducing a doublet of electromagnetic four dimensional vector potentials, we set up a manifestly Lorentz covariant and SO(2) duality invariant classical field theory of electric and magnetic charges. In our formulation one does not need to introduce the concept of Dirac string.

  10. Efeitos da atorvastatina e do polimorfismo T-786C do gene eNOS sobre parâmetros do metabolismo lipídico plasmático

    Directory of Open Access Journals (Sweden)

    Vanessa Helena de Souza Zago

    2013-01-01

    Full Text Available FUNDAMENTO: A atividade do óxido nítrico sintase endotelial (eNOS pode ser modulada pelo colesterol da lipoproteína de alta densidade (HDL-C, estatinas ou polimorfismos, como o T-786C de eNOS. OBJETIVO: Este estudo teve como objetivo avaliar se o polimorfismo T-786C está associado a alterações nos efeitos da atorvastatina no perfil lipídico, nas concentrações de metabólitos de óxido nítrico (NO e da proteína C reativa de alta sensibilidade (PCR-as. MÉTODOS: Trinta voluntários do sexo masculino, assintomáticos, com idade entre 18-56 anos foram genotipados e classificados de acordo com a ausência (TT, n = 15 ou presença (CC, n = 15 do polimorfismo. Eles foram selecionados aleatoriamente para a utilização de placebo e atorvastatina (10 mg/dia por 14 dias. Após cada tratamento foram medidos lípides, lipoproteínas, frações HDL2 e HDL3, atividade da proteína de transferência de colesteril éster (CETP, metabólitos de NO e PCR-as. RESULTADOS: As comparações entre genótipos após a administração de placebo mostraram aumento da atividade da CETP polimorfismo-dependente (TT, 12 ± 7; CC, 22 ± 12, p < 0,05. As análises da interação entre os tratamentos indicaram que a atorvastatina tem efeito sobre colesterol, LDL, nitrito e razões lípides/proteínas (HDL2 e HDL3 (p < 0,001 em ambos os genótipos. É interessante notar as interações genótipo/droga sobre a CETP (p < 0,07 e a lipoproteína (a [Lp(a] (p < 0,056, levando a uma diminuição limítrofe da CETP, embora sem afetar a Lp(a. A PRC-as não mostrou alterações. CONCLUSÃO: Os resultados sugerem que o tratamento com estatinas pode ser relevante para a prevenção primária da aterosclerose em pacientes com o polimorfismo T-786C do eNOS, considerando os efeitos no metabolismo lipídico.

  11. Bioequivalence assessment of two formulations of ibuprofen

    Directory of Open Access Journals (Sweden)

    Al-Talla ZA

    2011-10-01

    Full Text Available Zeyad A Al-Talla1, Sabah H Akrawi2, Luke T Tolley3, Salim H Sioud1, Mohammed F Zaater4, Abdul-Hamid M Emwas1 1Analytical and NMR Core Laboratories, King Abdullah University of Science and Technology, Thuwal, Kingdom of Saudia Arabia; 2College of Pharmacy, Al-Ain University, Al-Ain, United Arab Emirates; 3Department of Chemistry and Biochemistry, Southern Illinois University Carbondale, Carbondale, IL, USA; 4Department of Chemistry, Jordan University of Science and Technology, Jordan University of Science and Technology, Irbid, Jordan Background: This study assessed the relative bioavailability of two formulations of ibuprofen. The first formulation was Doloraz®, produced by Al-Razi Pharmaceutical Company, Amman, Jordan. The second forumulation was Brufen®, manufactured by Boots Company, Nottingham, UK. Methods and results: A prestudy validation of ibuprofen demonstrated long-term stability, freeze-thaw stability, precision, and accuracy. Twenty-four healthy volunteers were enrolled in this study. After overnight fasting, the two formulations (test and reference of ibuprofen (100 mg ibuprofen/5 mL suspension were administered as a single dose on two treatment days separated by a one-week washout period. After dosing, serial blood samples were drawn for a period of 14 hours. Serum harvested from the blood samples was analyzed for the presence of ibuprofen by high-pressure liquid chromatography with ultraviolet detection. Pharmacokinetic parameters were determined from serum concentrations for both formulations. The 90% confidence intervals of the ln-transformed test/reference treatment ratios for peak plasma concentration and area under the concentration-time curve (AUC parameters were found to be within the predetermined acceptable interval of 80%–125% set by the US Food and Drug Administration. Conclusion: Analysis of variance for peak plasma concentrations and AUC parameters showed no significant difference between the two formulations and

  12. Reduction of Adhesion Molecule Production and Alteration of eNOS and Endothelin-1 mRNA Expression in Endothelium by Euphorbia hirta L. through Its Beneficial β-Amyrin Molecule

    Directory of Open Access Journals (Sweden)

    Mei Fen Shih

    2014-07-01

    Full Text Available The inflammatory reaction in large blood vessels involves up-regulation of vascular adhesion molecules such as endothelial cell selectin (E-selectin, soluble vascular cell adhesion molecule (sVCAM-1, and soluble intercellular adhesion molecule (sICAM-1. These vascular dysfunctions are associated with the development of atherosclerosis. β-Amyrin, an active component of Euphorbia hirta L., has potent anti-inflammatory effects. So far, its preventive effects against the expression of inflammatory mediator-induced adhesion molecules have not been investigated. Endothelial cells (SVEC4-10 cell line were treated with 50% RAW conditioned media (i.e., normal SVEC4-10 culture media contains 50% of lipopolysaccharide-activated macrophage culture media without or with β-amyrin (0.6 and 0.3 µM. The production levels of E-selectin, sICAM-1, and sVCAM-1 in the SVEC4-10 cells were measured with ELISA assay kits. Under the same treatment conditions, expression of endothelin (ET-1 and endothelial type of NO synthase (eNOS mRNA were analyzed by RT-PCR and agarose gel. With β-amyrin, the 50% RAW conditioned media-induced E-selectin, sICAM-1, and sVCAM-1 levels as well as ET-1 gene expression were all suppressed. β-Amyrin treatment also restored the 50% RAW conditioned media-suppressed eNOS mRNA expression. These data indicate that β-amyrin is potentially useful in preventing chronic inflammation-related vascular diseases.

  13. Increased vascular eNOS and cystathionine-γ-lyase protein after 6 weeks oral administration of 3, 5, 7, 3', 4'-pentamethoxyflavone to middle-aged male rats.

    Science.gov (United States)

    Yorsin, Somruedee; Kanokwiroon, Kanyanatt; Radenahmad, Nisaudah; Jansakul, Chaweewan

    2016-11-01

    Effects of treatment of middle-aged male rats with 3, 5, 7, 3', 4'-pentamethoxyflavone (PMF) on vascular and perivascular adipose tissue (PVAT) functions and blood chemistry were investigated. Rats received PMF (22 mg/kg), orally or vehicle, twice a day for 6 weeks. The PMF-treated rats had lower serum glucose, higher HDL-C levels, but no change in other parameters. Thoracic aortic and mesenteric rings of PMF treated rats produced lower maximal contraction to phenylephrine that was normalized by N(G)-nitro-L-arginine (L-NA) or endothelial removal. The aortic- and mesenteric rings of the PMF treated rats showed improved relaxation to acetylcholine, but not to glyceryl trinitrate, and had higher eNOS protein. DL-propargylglycine (PAG) caused greater increase in the baseline tension of the PMF-treated aortic ring and higher contraction to low concentrations of phenylephrine. PVAT lowered the contractile response of the L-NA pretreated aortic rings to phenylephrine for both groups, but PAG had no effect. The cystathionine-γ-lyase (CSE) protein of the thoracic rings, but not of the PVAT, shows increased expression after PMF treatment. Overall, PMF treatment of middle aged rats appeared to increase production of NO and H2S from the blood vessels by upregulating the expression of eNOS and CSE. PMF also decreased fasting serum glucose and increased HDL-C levels, with no toxicity to liver and kidney functions. Thus, PMF is a novel compound for possible use as a health product to prevent and/or to reduce the development of diabetes type II and/or cardiovascular disease.

  14. Formulation of Pine Tar Antidandruff Shampoo Assessment and Comparison With Some Commercial Formulations

    Directory of Open Access Journals (Sweden)

    M. Gharavi

    1990-07-01

    Full Text Available In this study a pine tar shampoo as a new antidandruff formulation is presented. Assessment of antidandruff preparations has been hampered by the lack of standardized schedules, and reliable methods of evaluation.Some antidandruff agents such as : Zinc pyri-thione pine tar, selenium sulphide and (sulfure were used in shampoos. Samples were coded as numbers 1,2 formulated by us and 3,4 formulated commercially. The grading scheme based on 10 point scale, and corneocyte count was carried out on 50 selected volunte¬ers. Corneocyte count and fungal study proved that pine tor shampoo is effective against pityrosporum ovale. Draize lest was used for determination of the irritancy potential of the samples. Results showed that samples numbered 1,2 were relatively innocous in comparison with the others. I urthermore,s kin sensitination test on rabbit also confirmed the results obtained by Draize test. Consumer judgments proved that all formulations were acceptable.

  15. 携带eNOS基因的小口径人工血管在犬的体内研究%Study on small diameter artificial vascular graft with eNOS gene transfected endothelial cells in canine

    Institute of Scientific and Technical Information of China (English)

    薛冠华; 张纪蔚; 张皓; 张柏根

    2008-01-01

    目的 观察转染内皮型一氧化氮合酶(eNOS)基因的内皮细胞(EC)种植小口径人工血管在实验犬体内的通畅效果.方法 采用"高压灌注两步法"将转染eNOS基因的EC种植于3 mm人工血管;并植入实验犬股动脉,分1、4、12、24周行数字减影血管造影(DSA)、扫描电镜和透射电镜观察植入后情况.结果 转染eNOS基因的EC种植3 mm人工血管,贴附率在90%以上;10 d左右延伸为一层完整连续的内膜.植入犬体内后1周,单纯人工血管组1/3(3/9)血管阻塞;术后4周,单纯人工血管组全部阻塞(9/9),未转染组近半数阻塞(5/10、4/9);术后12周,单纯人工血管组全部阻塞,未转染组几乎全部阻塞(9/9、9/10);术后24周,未转染组全部阻塞,eNOS转染组8/10通畅.电镜检查表明,eNOS转染组人工血管腔面EC排列紧密,形成一层连续完整的内膜,仅见少许红细胞、血小板及白细胞沉积.结论 转染eNOS基因的EC种植小口径人工血管效果满意,植入实验犬体内后通畅效果良好.%Objective To investigate the patency efficacy of small diameter artificial vascular graft with eNOS gene transfected endothelial cells in canine. Methods By using the two steps high pressure injection, eNOS gene transfected endothelial cells were planted on artificial vascular graft with a diameter of 3 mm. The artificial vascular grafts were transplanted into canine femoral artery, and the patency of the artery was observed through digital subtracted angiography (DSA) and electron telescope 1, 4, 12 and 24 weeks after the operation. Results The adherence rate of eNOS gene transfected endothelial cells to artificial vascular grafts was up to 90%. For 10 days, the cells extended and formed a continuous intima. One week after the operation, 3/9 grafts were obstructed in the group of simple artificial vascular grafts; 4 weeks after, all of grafts (9/9) were obstructed in the group of simple artificial vascular grafts and almost half grafts (5

  16. Dual Foliation Formulations of General Relativity

    CERN Document Server

    Hilditch, David

    2015-01-01

    A dual foliation treatment of General Relativity is presented. The basic idea of the construction is to consider two foliations of a spacetime by spacelike hypersurfaces and relate the two geometries. The treatment is expected to be useful in various situations, and in particular whenever one would like to compare objects represented in different coordinates. Potential examples include the construction of initial data and the study of trapped tubes. It is common for studies in mathematical relativity to employ a double-null gauge. In such studies local well-posedness is treated by referring back, for example, to the generalized harmonic formulation, global properties of solutions being treated in a separate formalism. As a first application of the dual foliation formulation we find that one can in fact obtain local well-posedness in the double-null coordinates directly, which should allow their use in numerical relativity with standard methods. With due care it is expected that practically any coordinates can...

  17. Linear derivative Cartan formulation of General Relativity

    CERN Document Server

    Kummer, Wolfgang

    2004-01-01

    Beside diffeomorphism invariance also manifest SO(3,1) local Lorentz invariance is implemented in a formulation of Einstein Gravity (with or without cosmological term) in terms of initially completely independent vielbein and spin connection variables and auxiliary two-form fields. In the systematic study of all possible embeddings of Einstein gravity into that formulation with auxiliary fields, the introduction of a ``bi-complex'' algebra possesses crucial technical advantages. Certain components of the new two-form fields directly provide canonical momenta for spatial components of all Cartan variables, whereas the remaining ones act as Lagrange multipliers for a large number of constraints, some of which have been proposed already in different, less radical approaches. The time-like components of the Cartan variables play that role for the Lorentz constraints and others associated to the vierbein fields. Although also some ternary ones appear, we show that relations exist between these constraints, and how...

  18. A novel formulation for mebeverine hydrochloride.

    Science.gov (United States)

    Abdel-Hamid, Sameh M; Abdel-Hady, Seham E; El-Shamy, Abdel-Hamid A; El-Dessouky, Hadir F

    2007-10-01

    The antispasmodic drug mebeverine hydrochloride was formulated into a film-forming gel to be used as a topical local anesthetic. A mixture of cellulose derivatives was used as a base. Additives were used to enhance the release as well as the residence time. Formulations were characterized in terms of drug release, mucoadhesion and rheology. Clinically, the selected formula has shown faster onset (p = 0.0156), longer duration (p = 0.0313), better film residence (p = 0.0313), and no foreign body sensation (p = 0.0313) in comparison to Solcoseryl dental paste. Histopathological examination showed no change in inflammatory cells count, concluding that this topical anesthetic is efficacious and safe orally.

  19. Spray drying formulation of amorphous solid dispersions.

    Science.gov (United States)

    Singh, Abhishek; Van den Mooter, Guy

    2016-05-01

    Spray drying is a well-established manufacturing technique which can be used to formulate amorphous solid dispersions (ASDs) which is an effective strategy to deliver poorly water soluble drugs (PWSDs). However, the inherently complex nature of the spray drying process coupled with specific characteristics of ASDs makes it an interesting area to explore. Numerous diverse factors interact in an inter-dependent manner to determine the final product properties. This review discusses the basic background of ASDs, various formulation and process variables influencing the critical quality attributes (CQAs) of the ASDs and aspects of downstream processing. Also various aspects of spray drying such as instrumentation, thermodynamics, drying kinetics, particle formation process and scale-up challenges are included. Recent advances in the spray-based drying techniques are mentioned along with some future avenues where major research thrust is needed.

  20. Consistency of canonical formulation of Horava gravity

    Energy Technology Data Exchange (ETDEWEB)

    Soo, Chopin, E-mail: cpsoo@mail.ncku.edu.tw [Department of Physics, National Cheng Kung University, Tainan, Taiwan (China)

    2011-09-22

    Both the non-projectable and projectable version of Horava gravity face serious challenges. In the non-projectable version, the constraint algebra is seemingly inconsistent. The projectable version lacks a local Hamiltonian constraint, thus allowing for an extra graviton mode which can be problematic. A new formulation (based on arXiv:1007.1563) of Horava gravity which is naturally realized as a representation of the master constraint algebra (instead of the Dirac algebra) studied by loop quantum gravity researchers is presented. This formulation yields a consistent canonical theory with first class constraints; and captures the essence of Horava gravity in retaining only spatial diffeomorphisms as the physically relevant non-trivial gauge symmetry. At the same time the local Hamiltonian constraint is equivalently enforced by the master constraint.

  1. Critical Review of Path Integral Formulation

    CERN Document Server

    Fujita, Takehisa

    2008-01-01

    The path integral formulation in quantum mechanics corresponds to the first quantization since it is just to rewrite the quantum mechanical amplitude into many dimensional integrations over discretized coordinates $x_n$. However, the path integral expression cannot be connected to the dynamics of classical mechanics, even though, superficially, there is some similarity between them. Further, the field theory path integral in terms of many dimensional integrations over fields does not correspond to the field quantization. We clarify the essential difference between Feynman's original formulation of path integral in QED and the modern version of the path integral method prevailing in lattice field theory calculations, and show that the former can make a correct second quantization while the latter cannot quantize fields at all and its physical meaning is unknown.

  2. New Variational Formulations of Hybrid Stress Elements

    Science.gov (United States)

    Pian, T. H. H.; Sumihara, K.; Kang, D.

    1984-01-01

    In the variational formulations of finite elements by the Hu-Washizu and Hellinger-Reissner principles the stress equilibrium condition is maintained by the inclusion of internal displacements which function as the Lagrange multipliers for the constraints. These versions permit the use of natural coordinates and the relaxation of the equilibrium conditions and render considerable improvements in the assumed stress hybrid elements. These include the derivation of invariant hybrid elements which possess the ideal qualities such as minimum sensitivity to geometric distortions, minimum number of independent stress parameters, rank sufficient, and ability to represent constant strain states and bending moments. Another application is the formulation of semiLoof thin shell elements which can yield excellent results for many severe test cases because the rigid body nodes, the momentless membrane strains, and the inextensional bending modes are all represented.

  3. Gauge-Invariant Formulation of Circular Dichroism.

    Science.gov (United States)

    Raimbault, Nathaniel; de Boeij, Paul L; Romaniello, Pina; Berger, J A

    2016-07-12

    Standard formulations of magnetic response properties, such as circular dichroism spectra, are plagued by gauge dependencies, which can lead to unphysical results. In this work, we present a general gauge-invariant and numerically efficient approach for the calculation of circular dichroism spectra from the current density. First we show that in this formulation the optical rotation tensor, the response function from which circular dichroism spectra can be obtained, is independent of the origin of the coordinate system. We then demonstrate that its trace is independent of the gauge origin of the vector potential. We also show how gauge invariance can be retained in practical calculations with finite basis sets. As an example, we explain how our method can be applied to time-dependent current-density-functional theory. Finally, we report gauge-invariant circular dichroism spectra obtained using the adiabatic local-density approximation. The circular dichroism spectra we thus obtain are in good agreement with experiment.

  4. Formulation and application of Russell's method

    Science.gov (United States)

    Hou, J. W.

    1985-01-01

    It is shown that the numerical technique of Russell's momentum approach can be derived by using Hamilton's principle and Vance's numerical scheme. It results in a set of first order differnce equations for solving the angular velocities. The numerical examples show that the method is reliable. The algorithm is modified next to perform the analysis of N-body systems with closed loop topology. To increase the formulation flexibility, the equations of motion are represented by using Cartesian coordinates and Lagrange multipliers. The algorithm consists of two parts, Vance's scheme and an unconstrained minimization. The Vance's scheme is used to find the angular velocities, and the unconstrained minimization is applied to provide the correct angular displacements. The proposed scheme is further extended to find the design sensitivity of an N-body system with closed loop configuration, and to carry out the design optimization as well. The numerical example of a small-scaled mechanical system is presented to verify the proposed formulation.

  5. Formulation and characterization of rifampicin microcapsules

    Directory of Open Access Journals (Sweden)

    Md.Sarfaraz

    2010-01-01

    Full Text Available Rifampicin biodegradable microcapsules were prepared by feasible emulsification-ionic gelation method for a novel controlled release product. Sodium alginate and Carbopol 974P were used as coating polymers in different ratios 1:1, 1:2, 1:3 and 1:4 to obtain elegant microcapsules. The formulations were characterized for encapsulation efficiency, drug loading, sieve analysis, scanning electron microscopy and in vitro release studies. The microcapsules were discrete, large, almost spherical and free flowing with encapsulation efficiency in the range of 75% to 89%, drug loading 75% to 86% and size 440 µm to 500 µm. Rifampicin release from these microcapsules was slow and extended over longer periods of time depending on the polymer coat. Drug release was diffusion controlled and followed first order kinetics. The formulation MC1 with a coating ratio of 1:1 (Sodium alginate: Carbopol 974P was found to be suitable for oral controlled release.

  6. Itraconazole nanosuspension for oral delivery: Formulation, characterization and in vitro comparison with marketed formulation

    Directory of Open Access Journals (Sweden)

    M Nakarani

    2010-06-01

    Full Text Available "n Background and the purpose of the study:Itraconazole is a poorly water soluble drug which results in its insufficient bioavailability. The purpose of the present study was to formulate Itraconazole in a nanosuspension to increase the aqueous solubility and to improve its formulation related parameters, dissolution and hence oral bioavailability. "nMethods:Itraconazole nanosuspension was prepared by pearl milling technique using zirconium oxide beads as a milling media, Poloxamer 407 as a stabilizer and glycerol as a wetting agent. Effects of various process parameters like, stirring time and the ratio of the beads were optimized by keeping drug:surfactant:milling media (1:3.0:50 as a constant initially and then optimized process parameters were used to optimize formulation parameters by 32 factorial designs. The optimized nanosuspension was lyophilized using mannitol (1:1 ratio as a cryoprotectant. Nanosuspension was characterized by particle size and size distribution, drug content, scanning electron microscopy, differential scanning colorimetry and X-ray diffraction techniques. "nResults:Optimized nanosuspension showed spherical shape with surface oriented surfactant molecules and a mean particle diameter of 294 nm. There was no significant change in crystalline nature after formulation and it was found to be chemically stable with high drug content. Conclusion:The in vitro dissolution profile of the optimized formulation compared to the pure drug and marketed formulation (Canditral Capsule by using 0.1N Hydrochloric acid as release medium showed higher drug release.

  7. From the Berkovits formulation to the Witten formulation in open superstring field theory

    CERN Document Server

    Iimori, Yuki; Okawa, Yuji; Torii, Shingo

    2014-01-01

    The Berkovits formulation of open superstring field theory is based on the large Hilbert space of the superconformal ghost sector. We discuss its relation to the Witten formulation based on the small Hilbert space. We introduce a one-parameter family of conditions for partial gauge fixing of the Berkovits formulation such that the cubic interaction of the theory under the partial gauge fixing reduces to that of the Witten formulation in a singular limit. The local picture-changing operator at the open-string midpoint in the Witten formulation is regularized in our approach, and the divergence in on-shell four-point amplitudes coming from collision of picture-changing operators is resolved. The quartic interaction inherited from the Berkovits formulation plays a role of adjusting different behaviors of the picture-changing operators in the $s$ channel and in the $t$ channel of Feynman diagrams with two cubic vertices, and correct amplitudes in the world-sheet theory are reproduced. While gauge invariance at th...

  8. On the Relativistic Formulation of Matter

    CERN Document Server

    Vishwakarma, Ram Gopal

    2012-01-01

    A critical analysis of the relativistic formulation of matter reveals some surprising inconsistencies and paradoxes. Corrections are discovered which lead to the long-sought-after equality of the gravitational and inertial masses, which are otherwise different in general relativity. Realizing the potentially great impact of the discovered corrections, an overview of the situation is provided resulting from the newly discovered crisis, amid the evidences defending the theory.

  9. Consistent formulation of the spacelike axial gauge

    Energy Technology Data Exchange (ETDEWEB)

    Burnel, A.; Van der Rest-Jaspers, M.

    1983-12-15

    The usual formulation of the spacelike axial gauge is afflicted with the difficulty that the metric is indefinite while no ghost is involved. We solve this difficulty by introducing a ghost whose elimination is such that the metric becomes positive for physical states. The technique consists in the replacement of the gauge condition nxA = 0 by the weaker one partial/sub 0/nxAroughly-equal0.

  10. Canonical Formulation of pp-waves

    CERN Document Server

    Balasin, Herbert

    2007-01-01

    We construct a Hamiltonian formulation for the class of plane-fronted gravitational waves with parallel rays (pp-waves). Because of the existence of a light-like Killing vector, the dynamics is effectively reduced to a 2+1 evolution with "time" chosen to be light-like. In spite of the vanishing action this allows us to geometrically identify a symplectic form as well as dynamical Hamiltonian, thus casting the system into canonical form.

  11. Ising formulations of many NP problems

    Science.gov (United States)

    Lucas, Andrew

    2014-02-01

    We provide Ising formulations for many NP-complete and NP-hard problems, including all of Karp's 21 NP-complete problems. This collects and extends mappings to the Ising model from partitioning, covering and satisfiability. In each case, the required number of spins is at most cubic in the size of the problem. This work may be useful in designing adiabatic quantum optimization algorithms.

  12. Gurson's Model: ALE Formulation and Strain Localization

    Science.gov (United States)

    da Cunda, Luiz A. B.; Creus, Guillermo J.

    2007-05-01

    This paper presents a brief review of Gurson's damage model, employed to describes the strength degradation in ductile metals submitted to large plastic deformations. The damage model is applied using finite elements and an Arbitrary Lagrangian-Eulerian formulation (ALE), to ensure a better quality to the finite elements mesh. The study of the combined application of ALE and Gurson approach to damage modeling and strain localization is the object of this paper.

  13. Domain-Independent Heuristics for Goal Formulation

    Science.gov (United States)

    2013-05-01

    on the projected consequences of achieving them. We then describe their integration in M- ARTUE , an agent that balances the satisfaction of internal...for goal formulation. For example, ARTUE (Molineaux et al. 2010a) uses manually-engineered trigger rules that add goals suggested by a rule when...its trigger conditions are met. This reactive mechanism allows the designer to instruct and control ARTUE , but prevents it from leveraging its own

  14. FORMULATION STRATEGY FOR DISSOLUTION ENHANCEMENT OF SIMVASTATIN

    OpenAIRE

    Neha Parmar et al

    2012-01-01

    The present work aim was “Formulation Strategy for Dissolution Enhancement of Simvastatin”. Simvastatin is lipid lowering drug which is known as HMG CoA reductase. The objective of this study was to increase the solubility of poorly water soluble drug, namely simvastatin, by the formation of solid dispersion and complex and also using the microwave induction technique on these formations. For solid dispersion method dispersion carrier used were poloxamer 407 and gelucire 44/14. The fusion met...

  15. Quasienergy formulation of damped response theory.

    Science.gov (United States)

    Kristensen, Kasper; Kauczor, Joanna; Kjaergaard, Thomas; Jørgensen, Poul

    2009-07-28

    We present a quasienergy-based formulation of damped response theory where a common effective lifetime parameter has been introduced for all excited states in terms of complex excitation energies. The introduction of finite excited state lifetimes leads to a set of (complex) damped response equations, which have the same form to all orders in the perturbation. An algorithm is presented for solving the damped response equations in Hartree-Fock theory and Kohn-Sham density functional theory. The use of the quasienergy formulation allows us to obtain directly the computationally simplest expressions for damped response functions by applying a set of response parameter elimination rules, which minimize the total number of damped response equations to be solved. In standard response theory broadened absorption spectra are obtained by ad hoc superimposing lineshape functions onto the absorption stick spectra, whereas an empirical lineshape function common to all excitations is an integrated part of damped response theory. By superimposing the lineshape functions inherent in damped response theory onto the stick spectra of standard response theory, we show that the absorption spectra obtained in standard and damped response theory calculations are identical. We demonstrate that damped response theory may be applied to obtain absorption spectra in all frequency ranges, also those that are not readily addressed using standard response theory. This makes damped response theory an effective tool, e.g., for determining absorption spectra for large molecules, where the density of the excited states may be very high, and where standard response theory therefore is not applicable in practice. A thorough comparison is given between our formulation of damped response theory and the formulation by Norman et al. [J. Chem. Phys. 123, 194103 (2005)].

  16. Abelian Ashtekar formulation from the ADM action

    CERN Document Server

    Contreras, Ernesto

    2013-01-01

    We study the Ashtekar formulation of linear gravity starting from the ADM first order action for the non linear theory, linearizing it, and performing a canonical transformation that coordinatizes the phase space in terms of the already linearized Ashtekar variables. The results obtained in this way are in accordance with those obtained through the standard method, in which, after introducing the Ashtekar variables for the full theory, a linearization around the flat Abelian connection and its conjugate momentum is performed.

  17. Planar multibody dynamics formulation, programming and applications

    CERN Document Server

    Nikravesh, Parviz E

    2007-01-01

    Introduction Multibody Mechanical Systems Types of Analyses Methods of Formulation Computer Programming Application Examples Unit System Remarks Preliminaries Reference Axes Scalars and Vectors Matrices Vector, Array, and Matrix Differentiation Equations and Expressions Remarks Problems Fundamentals of Kinematics A Particle Kinematics of a Rigid Body Definitions Remarks Problems Fundamentals of Dynamics Newton's Laws of Motion Dynamics of a Body Force Elements Applied Forces Reaction Force Remarks Problems Point-Coordinates: Kinematics Multipoint

  18. Phytoconstituents as photoprotective novel cosmetic formulations

    Directory of Open Access Journals (Sweden)

    S Saraf

    2010-01-01

    Full Text Available Phytoconstituents are gaining popularity as ingredients in cosmetic formulations as they can protect the skin against exogenous and endogenous harmful agents and can help remedy many skin conditions. Exposure of skin to sunlight and other atmospheric conditions causes the production of reactive oxygen species, which can react with DNA, proteins, and fatty acids, causing oxidative damage and impairment of antioxidant system. Such injuries damage regulation pathways of skin and lead to photoaging and skin cancer development. The effects of aging include wrinkles, roughness, appearance of fine lines, lack of elasticity, and de- or hyperpigmentation marks. Herbal extracts act on these areas and produce healing, softening, rejuvenating, and sunscreen effects. We have selected a few photoprotective phytoconstituents, such as curcumin, resveratrol, tea polyphenols, silymarin, quercetin and ascorbic acid, and have discussed the considerations to be undertaken for the development of herbal cosmetic formulations that could reduce the occurrence of skin cancer and delay the process of photoaging. This article is aimed at providing specific and compiled knowledge for the successful preparation of photoprotective herbal cosmetic formulations.

  19. Linear derivative Cartan formulation of general relativity

    Science.gov (United States)

    Kummer, W.; Schütz, H.

    2005-07-01

    Beside diffeomorphism invariance also manifest SO(3,1) local Lorentz invariance is implemented in a formulation of Einstein gravity (with or without cosmological term) in terms of initially completely independent vielbein and spin connection variables and auxiliary two-form fields. In the systematic study of all possible embeddings of Einstein gravity into that formulation with auxiliary fields, the introduction of a “bi-complex” algebra possesses crucial technical advantages. Certain components of the new two-form fields directly provide canonical momenta for spatial components of all Cartan variables, whereas the remaining ones act as Lagrange multipliers for a large number of constraints, some of which have been proposed already in different, less radical approaches. The time-like components of the Cartan variables play that role for the Lorentz constraints and others associated to the vierbein fields. Although also some ternary ones appear, we show that relations exist between these constraints, and how the Lagrange multipliers are to be determined to take care of second class ones. We believe that our formulation of standard Einstein gravity as a gauge theory with consistent local Poincaré algebra is superior to earlier similar attempts.

  20. Midazolam-sirupus, formulation and pharmacodynamic efficacy

    Directory of Open Access Journals (Sweden)

    K. Goracinova

    2002-04-01

    Full Text Available Due to its pharmacokinetic and pharmacodynamic properties (sedation, amnesia and relief of anxiety Midazolam has become a comm only used agent for conscious sedation of children before diagnostic or therapeutic procedure or before induction of anesthesia. Con sidering the advantage of oral administration to avoid the additional trauma of starting an IV in the child, and the fact that there is no ad equate dosage form (Midazolam - Syrupus on the drug market in our country, the aim of the presented work was to formulate syrupus using syrupus b ase/aqueous solution of viscosity enhancer - HPMC, in combination with suitable sweetener, flavor, and preservatives, and to evaluate its q uality and stability. The pharmacodynamic efficacy/sedative effect of Midazolam HCl - Syrupus formulation was evaluated in 33 pediatric patients comp aring this with the efficacy of intramuscularly administered Midazolam HCl (35 pediatric patients in accordance with the Ramsay scale for analgosedation. The formulation manifested good quality in respect to physical properties, physico-chemical parameters (pH value, relative dens ity, drug content, ingredients content antimicrobial efficacy and microbiological quality according to Ph Eur 3. In the conditions chara cteristic of the second (II climate zone, the dosage form was stable for four months. The sedative effect of orally administered Midazolam was manifested in a period necessary for surgical premedication (30 - 45 min. The majority of patients (71% entered the second phase on the Ramsa y scale, when Midazolam was administered in a dose of 0.40 mg/kg.

  1. HERBAL LIPSTICK FORMULATION: A NEW APPROACH

    Directory of Open Access Journals (Sweden)

    Meher Deepali Avinash

    2011-06-01

    Full Text Available Coloring skin particularly skin of face and lips is an ancient practice going back to prehistoric period. In present days the use of such product has increased and choice of shades of color, texture and luster have been changed and become wider. This can be observed from the fact that lipsticks are marked in hundreds of shades of colors to satisfy the demand of women. The present investigation was done to formulate herbal lipstick, since lipsticks are one of the key cosmetics to be used by the women. Attempt was also made to evaluate the formulated herbal lipstick. The word herbal is a symbol of safety in contrast to the synthetic one which has adverse effects on human health. Herbal preparations viz., herbal tablets, herbal tonics, herbal paste, herbal shampoo, herbal sindhur, herbal contraceptives and herbal lipstick has become popular among the consumer herbal medicines represent the fastest growing segment to heal the various ailments. Human being have been using herbs for different purpose like food, medicine, beatifying with advancement of science & technology use of natural things including plant has been reduced except for food, vegetarian takes plant& plant only. However there is resurgence of use of herbs both as drug and cosmetics. Due to various adverse effects of available synthetic preparation the present work was conceived by us to formulate a herbal lipstick having minimal or no side effects which will extensively used by the women of our communities with great surety and satisfaction.

  2. Formulation of benzoporphyrin derivatives in Pluronics.

    Science.gov (United States)

    Chowdhary, Rubinah K; Chansarkar, Namrata; Sharif, Isha; Hioka, Noboru; Dolphin, David

    2003-03-01

    This study investigates the potential of Pluronics for the formulation of tetrapyrrole-based photosensitizers, with a particular focus on B-ring benzoporphyrin derivatives. The B-ring derivatives have a high tendency to aggregate in aqueous solutions, and this poses a significant formulation problem. Pluronics are ABA-type triblock copolymers composed of a central hydrophobic polypropylene oxide section with two hydrophilic polyethylene oxide sections of equal length at either end. Out of a range of different commercially available block copolymers studied, it was found that the longer the hydrophobic block, the better the stabilization of tetrapyrrolic drugs in monomeric form in aqueous suspensions. Of these the best performance was observed in the micelle-forming Pluronic P123. Micelle size determination by laser light scattering confirmed that particle size in stable Pluronic formulations was around 20 nm. Pluronics such as L122 formed emulsions spontaneously without the need for emulsion stabilizers; emulsions were highly stable at ambient temperatures over several days and also highly effective as potential drug delivery agents.

  3. Linear derivative Cartan formulation of general relativity

    Energy Technology Data Exchange (ETDEWEB)

    Kummer, W.; Schuetz, H. [Institute for Theoretical Physics, Vienna University of Technology, Vienna (Austria)

    2005-07-01

    Beside diffeomorphism invariance also manifest SO(3,1) local Lorentz invariance is implemented in a formulation of Einstein gravity (with or without cosmological term) in terms of initially completely independent vielbein and spin connection variables and auxiliary two-form fields. In the systematic study of all possible embeddings of Einstein gravity into that formulation with auxiliary fields, the introduction of a ''bi-complex'' algebra possesses crucial technical advantages. Certain components of the new two-form fields directly provide canonical momenta for spatial components of all Cartan variables, whereas the remaining ones act as Lagrange multipliers for a large number of constraints, some of which have been proposed already in different, less radical approaches. The time-like components of the Cartan variables play that role for the Lorentz constraints and others associated to the vierbein fields. Although also some ternary ones appear, we show that relations exist between these constraints, and how the Lagrange multipliers are to be determined to take care of second class ones. We believe that our formulation of standard Einstein gravity as a gauge theory with consistent local Poincare algebra is superior to earlier similar attempts. (orig.)

  4. Formulation and evaluation of antihelminthic polyherbal tablets

    Directory of Open Access Journals (Sweden)

    Dinesh Puri

    2011-01-01

    Full Text Available From time immemorial, man has been depending on plants as medicine. Helminthes infections are among the most common infections in man, affecting a large proportion of the world′s population. These helminthic diseases can be treated by various herbal drugs. The purpose of the present work was to formulate antihelminthic tablets. In this work, a spray dried-powder was used, which was obtained from the extract of different part of seven plants that were used in helminthic disease. The different tablets were prepared by using different types of disintegrating agents and various excipients. All parameters related to physicochemical property, trace metal and microbial examination of the spray-dried powder showed that these were within limits and could be used for the tablet formulation. The granules of the spray-dried powder were prepared by a wet granulation technique using isopropyl alcohol. The blends were evaluated for flow properties and for compressibility, which were found to be good. The tablets were prepared using a single rotatory punching machine, in which the punch size was 11 mm×8 mm, and formulated caplet-type tablets. These tablets were evaluated for the colour, odor, thickness and diameter, with visual inspection for any defects, weight variation, hardness, friability and in vitro disintegration time.

  5. On the spectral formulation of Granger causality.

    Science.gov (United States)

    Chicharro, D

    2011-12-01

    Spectral measures of causality are used to explore the role of different rhythms in the causal connectivity between brain regions. We study several spectral measures related to Granger causality, comprising the bivariate and conditional Geweke measures, the directed transfer function, and the partial directed coherence. We derive the formulation of dependence and causality in the spectral domain from the more general formulation in the information-theory framework. We argue that the transfer entropy, the most general measure derived from the concept of Granger causality, lacks a spectral representation in terms of only the processes associated with the recorded signals. For all the spectral measures we show how they are related to mutual information rates when explicitly considering the parametric autoregressive representation of the processes. In this way we express the conditional Geweke spectral measure in terms of a multiple coherence involving innovation variables inherent to the autoregressive representation. We also link partial directed coherence with Sims' criterion of causality. Given our results, we discuss the causal interpretation of the spectral measures related to Granger causality and stress the necessity to explicitly consider their specific formulation based on modeling the signals as linear Gaussian stationary autoregressive processes.

  6. On the application of subcell resolution to conservation laws with stiff source terms

    Science.gov (United States)

    Chang, Shih-Hung

    1989-01-01

    LeVeque and Yee recently investigated a one-dimensional scalar conservation law with stiff source terms modeling the reacting flow problems and discovered that for the very stiff case most of the current finite difference methods developed for non-reacting flows would produce wrong solutions when there is a propagating discontinuity. A numerical scheme, essentially nonoscillatory/subcell resolution - characteristic direction (ENO/SRCD), is proposed for solving conservation laws with stiff source terms. This scheme is a modification of Harten's ENO scheme with subcell resolution, ENO/SR. The locations of the discontinuities and the characteristic directions are essential in the design. Strang's time-splitting method is used and time evolutions are done by advancing along the characteristics. Numerical experiment using this scheme shows excellent results on the model problem of LeVeque and Yee. Comparisons of the results of ENO, ENO/SR, and ENO/SRCD are also presented.

  7. Towards a methodology to formulate sustainable diets for livestock: accounting for environmental impact in diet formulation.

    Science.gov (United States)

    Mackenzie, S G; Leinonen, I; Ferguson, N; Kyriazakis, I

    2016-05-28

    The objective of this study was to develop a novel methodology that enables pig diets to be formulated explicitly for environmental impact objectives using a Life Cycle Assessment (LCA) approach. To achieve this, the following methodological issues had to be addressed: (1) account for environmental impacts caused by both ingredient choice and nutrient excretion, (2) formulate diets for multiple environmental impact objectives and (3) allow flexibility to identify the optimal nutritional composition for each environmental impact objective. An LCA model based on Canadian pig farms was integrated into a diet formulation tool to compare the use of different ingredients in Eastern and Western Canada. By allowing the feed energy content to vary, it was possible to identify the optimum energy density for different environmental impact objectives, while accounting for the expected effect of energy density on feed intake. A least-cost diet was compared with diets formulated to minimise the following objectives: non-renewable resource use, acidification potential, eutrophication potential, global warming potential and a combined environmental impact score (using these four categories). The resulting environmental impacts were compared using parallel Monte Carlo simulations to account for shared uncertainty. When optimising diets to minimise a single environmental impact category, reductions in the said category were observed in all cases. However, this was at the expense of increasing the impact in other categories and higher dietary costs. The methodology can identify nutritional strategies to minimise environmental impacts, such as increasing the nutritional density of the diets, compared with the least-cost formulation.

  8. Chitosan-based formulations of drugs, imaging agents and biotherapeutics

    NARCIS (Netherlands)

    Amidi, M.; Hennink, W.E.

    2010-01-01

    This preface is part of the Advanced Drug Delivery Reviews theme issue on “Chitosan-Based Formulations of Drugs, Imaging Agents and Biotherapeutics”. This special Advanced Drug Delivery Reviews issue summarizes recent progress and different applications of chitosanbased formulations.

  9. Chitosan-based formulations of drugs, imaging agents and biotherapeutics

    NARCIS (Netherlands)

    Amidi, M.; Hennink, W.E.

    This preface is part of the Advanced Drug Delivery Reviews theme issue on “Chitosan-Based Formulations of Drugs, Imaging Agents and Biotherapeutics”. This special Advanced Drug Delivery Reviews issue summarizes recent progress and different applications of chitosanbased formulations.

  10. Nano-formulations of drugs: Recent developments, impact and challenges.

    Science.gov (United States)

    Jeevanandam, Jaison; Chan, Yen San; Danquah, Michael K

    2016-01-01

    Nano-formulations of medicinal drugs have attracted the interest of many researchers for drug delivery applications. These nano-formulations enhance the properties of conventional drugs and are specific to the targeted delivery site. Dendrimers, polymeric nanoparticles, liposomes, nano-emulsions and micelles are some of the nano-formulations that are gaining prominence in pharmaceutical industry for enhanced drug formulation. Wide varieties of synthesis methods are available for the preparation of nano-formulations to deliver drugs in biological system. The choice of synthesis methods depend on the size and shape of particulate formulation, biochemical properties of drug, and the targeted site. This article discusses recent developments in nano-formulation and the progressive impact on pharmaceutical research and industries. Additionally, process challenges relating to consistent generation of nano-formulations for drug delivery are discussed.

  11. Eulerian Formulation of Spatially Constrained Elastic Rods

    Science.gov (United States)

    Huynen, Alexandre

    Slender elastic rods are ubiquitous in nature and technology. For a vast majority of applications, the rod deflection is restricted by an external constraint and a significant part of the elastic body is in contact with a stiff constraining surface. The research work presented in this doctoral dissertation formulates a computational model for the solution of elastic rods constrained inside or around frictionless tube-like surfaces. The segmentation strategy adopted to cope with this complex class of problems consists in sequencing the global problem into, comparatively simpler, elementary problems either in continuous contact with the constraint or contact-free between their extremities. Within the conventional Lagrangian formulation of elastic rods, this approach is however associated with two major drawbacks. First, the boundary conditions specifying the locations of the rod centerline at both extremities of each elementary problem lead to the establishment of isoperimetric constraints, i.e., integral constraints on the unknown length of the rod. Second, the assessment of the unilateral contact condition requires, in principle, the comparison of two curves parametrized by distinct curvilinear coordinates, viz. the rod centerline and the constraint axis. Both conspire to burden the computations associated with the method. To streamline the solution along the elementary problems and rationalize the assessment of the unilateral contact condition, the rod governing equations are reformulated within the Eulerian framework of the constraint. The methodical exploration of both types of elementary problems leads to specific formulations of the rod governing equations that stress the profound connection between the mechanics of the rod and the geometry of the constraint surface. The proposed Eulerian reformulation, which restates the rod local equilibrium in terms of the curvilinear coordinate associated with the constraint axis, describes the rod deformed configuration

  12. New Formulation for the Viscosity of Propane

    Science.gov (United States)

    Vogel, Eckhard; Herrmann, Sebastian

    2016-12-01

    A new viscosity formulation for propane, using the reference equation of state for its thermodynamic properties by Lemmon et al. [J. Chem. Eng. Data 54, 3141 (2009)] and valid in the fluid region from the triple-point temperature to 650 K and pressures up to 100 MPa, is presented. At the beginning, a zero-density contribution and one for the critical enhancement, each based on the experimental data, were independently generated in parts. The higher-density contributions are correlated as a function of the reciprocal reduced temperature τ = Tc/T and of the reduced density δ = ρ/ρc (Tc—critical temperature, ρc—critical density). The final formulation includes 17 coefficients inferred by applying a state-of-the-art linear optimization algorithm. The evaluation and choice of the primary data sets are detailed due to its importance. The viscosity at low pressures p ≤ 0.2 MPa is represented with an expanded uncertainty of 0.5% (coverage factor k = 2) for temperatures 273 ≤ T/K ≤ 625. The expanded uncertainty in the vapor phase at subcritical temperatures T ≥ 273 K as well as in the supercritical thermodynamic region T ≤ 423 K at pressures p ≤ 30 MPa is assumed to be 1.5%. In the near-critical region (1.001 < 1/τ < 1.010 and 0.8 < δ < 1.2), the expanded uncertainty increases with decreasing temperature up to 3.0%. It is further increased to 4.0% in regions of less reliable primary data sets and to 6.0% in ranges in which no primary data are available but the equation of state is valid. Tables of viscosity computed for the new formulation are given in an Appendix for the single-phase region, for the vapor-liquid phase boundary, and for the near-critical region.

  13. A geometric formulation of exceptional field theory

    CERN Document Server

    Bosque, Pascal du; Lust, Dieter; Malek, Emanuel

    2016-01-01

    We formulate the full bosonic SL(5) exceptional field theory in a coordinate-invariant manner. Thereby we interpret the 10-dimensional extended space as a manifold with $\\mathrm{SL}(5)\\times\\mathbb{R}^+$-structure. We show that the algebra of generalised diffeomorphisms closes subject to a set of closure constraints which are reminiscent of the quadratic and linear constraints of maximal seven-dimensional gauged supergravities, as well as the section condition. We construct an action for the full bosonic SL(5) exceptional field theory, even when the $\\mathrm{SL}(5)\\times\\mathbb{R}^+$-structure is not locally flat.

  14. Noncompact lattice formulation of gauge theories

    CERN Document Server

    Friedberg, R; Pang, Y; Ren, H C

    1995-01-01

    We expand the gauge field in terms of a suitably constructed complete set of Bloch wave functions, each labeled by a band designation \\,n\\, and a wave number \\,\\vec K\\, restricted to the Brillouin zone. A noncompact formulation of lattice QCD (or QED) can be derived by restricting the expansion only to the \\,0^{th}-band (\\,n = 0\\,) functions, which are simple continuum interpolations of discrete values associated with sites or links on a lattice. The exact continuum theory can be reached through the inclusion of all \\,n = 0\\, and \\,n \

  15. Quality Evaluation of Pharmaceutical Formulations Containing Hydrochlorothiazide

    Directory of Open Access Journals (Sweden)

    Marcelo Antonio de Oliveira

    2014-10-01

    Full Text Available Hydrochlorothiazide is a diuretic used to treat hypertension that belongs to class IV of the Biopharmaceutics Classification System. The drug was evaluated by quality control, thermal characterization tests, and pharmaceutical formulation compatibility studies. It was concluded that the generic drug, Lab 2, was not a pharmaceutical equivalent. The compounded drugs, Lab 5 and Lab 6, produced unsatisfactory but expected results, since there is no requirement for dissolution and dissolution profile testing for the commercialization of these products. In a compatibility study, lactose and mannitol were shown to be incompatible with HCTZ, which may explain the lack of equivalence of the generic pharmaceutical product, associated with other situations.

  16. The Canvas model in project formulation

    OpenAIRE

    Ferreira-Herrera, Diana Carolina

    2016-01-01

    Purpose: The aim of this article is to determine the relevance of the Canvas methodology in project formulation through model characterization, thus answering the question: Is the Canvas methodology a relevant model for project management in an entrepreneurial context? Description: The Canvas model seeks to manage projects as business units. It is a model intended for emphasizing the entrepreneurial potential in project management. For this, texts and articles that have provided the basis for...

  17. Gradient Elasticity Formulations for Micro/Nanoshells

    Directory of Open Access Journals (Sweden)

    Bohua Sun

    2014-01-01

    Full Text Available The focus of this paper is on illustrating how to extend the second author’s gradient theory of elasticity to shells. Three formulations are presented based on the implicit gradient elasticity constitutive relation 1 -ld2∇2σij=Cijkl(1-ls2∇2εkl and its two approximations 1+ls2∇2-ld2∇2σij=Cijklεkl and σij=Cijkl(1+ld2∇2-ls2∇2εkl.

  18. A geometric formulation of exceptional field theory

    Science.gov (United States)

    du Bosque, Pascal; Hassler, Falk; Lüst, Dieter; Malek, Emanuel

    2017-03-01

    We formulate the full bosonic SL(5) exceptional field theory in a coordinateinvariant manner. Thereby we interpret the 10-dimensional extended space as a manifold with SL(5) × ℝ +-structure. We show that the algebra of generalised diffeomorphisms closes subject to a set of closure constraints which are reminiscent of the quadratic and linear constraints of maximal seven-dimensional gauged supergravities, as well as the section condition. We construct an action for the full bosonic SL(5) exceptional field theory, even when the SL(5) × ℝ +-structure is not locally flat.

  19. TANK 50 BATCH 0 SALTSTONE FORMULATION CONFIRMATION

    Energy Technology Data Exchange (ETDEWEB)

    Langton, C.

    2006-06-05

    Savannah River National Laboratory (SRNL) personnel were requested to confirm the Tank 50 Batch 0 grout formulation per Technical Task Request, SSF-TTR-2006-0001 (task 1 of 2) [1]. Earlier Batch 0 formulation testing used a Tank 50 sample collected in September 2005 and is described elsewhere [2]. The current testing was performed using a sample of Tank 50 waste collected in May 2006. This work was performed according to the Technical Task and Quality Assurance Plan (TT/QAP), WSRC-RP-2006-00594 [3]. The salt solution collected from Tank 50 in May 2006 contained approximately 3 weight percent more solids than the sample collected in September 2005. The insoluble solids took longer to settle in the new sample which was interpreted as indicating finer particles in the current sample. The saltstone formulation developed for the September 2005 Tank 50 Batch 0 sample was confirmed for the May 2006 sample with one minor exception. Saltstone prepared with the Tank 50 sample collected in May 2006 required 1.5 times more Daratard 17 set retarding admixture than the saltstone prepared with the September In addition, a sample prepared with lower shear mixing (stirring with a spatula) had a higher plastic viscosity (57 cP) than samples made with higher shear mixing in a blender (23cP). The static gel times of the saltstone slurries made with low shear mixing were also shorter ({approx}32 minutes) than those for comparable samples made in the blender ({approx}47 minutes). The addition of the various waste streams (ETP, HEU-HCAN, and GPE-HCAN) to Tank 50 from September 2005 to May 2006 has increased the amount of set retarder, Daratard 17, required for processing saltstone slurries through the Saltstone facility. If these streams are continued to be added to Tank 50, the quantity of admixtures required to maintain the same processing conditions for the Saltstone facility will probably change and additional testing is recommended to reconfirm the Tank 50 Saltstone formulation.

  20. Formulations of a hydromechanical interface element

    Institute of Scientific and Technical Information of China (English)

    Zhong-Zhi Fu; Si-Hong Liu

    2011-01-01

    A hydromechanical interface element is proposed for the consideration of the hydraulic-mechanical coupling effect along the interface.The fully coupled governing equations and the relevant finite element formulations are derived in detail for the interface element.All the involved matrices are of the same form as those of a solid element,which makes the incorporation of the model into a finite element program straightforward.Three examples are then numerically simulated using the interface element.Reasonable results confirm the correctness of the proposed model and motivate its application in hydromechanical contact problems in the future.

  1. Quality evaluation of pharmaceutical formulations containing hydrochlorothiazide.

    Science.gov (United States)

    de Oliveira, Marcelo Antonio; Yoshida, Maria Irene; Silva, Daphne Carina Gonçalves Monteiro da

    2014-10-20

    Hydrochlorothiazide is a diuretic used to treat hypertension that belongs to class IV of the Biopharmaceutics Classification System. The drug was evaluated by quality control, thermal characterization tests, and pharmaceutical formulation compatibility studies. It was concluded that the generic drug, Lab 2, was not a pharmaceutical equivalent. The compounded drugs, Lab 5 and Lab 6, produced unsatisfactory but expected results, since there is no requirement for dissolution and dissolution profile testing for the commercialization of these products. In a compatibility study, lactose and mannitol were shown to be incompatible with HCTZ, which may explain the lack of equivalence of the generic pharmaceutical product, associated with other situations.

  2. Algebraic formulation of quantum theory, particle identity and entanglement

    Science.gov (United States)

    Govindarajan, T. R.

    2016-08-01

    Quantum theory as formulated in conventional framework using statevectors in Hilbert spaces misses the statistical nature of the underlying quantum physics. Formulation using operators 𝒞∗ algebra and density matrices appropriately captures this feature in addition leading to the correct formulation of particle identity. In this framework, Hilbert space is an emergent concept. Problems related to anomalies and quantum epistemology are discussed.

  3. Formulation and method for preparing gels comprising hydrous hafnium oxide

    Science.gov (United States)

    Collins, Jack L; Hunt, Rodney D; Montgomery, Frederick C

    2013-08-06

    Formulations useful for preparing hydrous hafnium oxide gels contain a metal salt including hafnium, an acid, an organic base, and a complexing agent. Methods for preparing gels containing hydrous hafnium oxide include heating a formulation to a temperature sufficient to induce gel formation, where the formulation contains a metal salt including hafnium, an acid, an organic base, and a complexing agent.

  4. Super-group field cosmology in Batalin-Vilkovisky formulation

    CERN Document Server

    Upadhyay, Sudhaker

    2016-01-01

    In this paper, we study the third quantized super-group field cosmology, a model in multiverse scenario, in Batalin-Vilkovisky (BV) formulation. Further, we propose the superfield/super-antifield dependent BRST symmetry transformations. Within this formulation, we establish connection between the two different solutions of the quantum master equation within the BV formulation.

  5. Super-Group Field Cosmology in Batalin-Vilkovisky Formulation

    Science.gov (United States)

    Upadhyay, Sudhaker

    2016-09-01

    In this paper we study the third quantized super-group field cosmology, a model in multiverse scenario, in Batalin-Vilkovisky (BV) formulation. Further, we propose the superfield/super-antifield dependent BRST symmetry transformations. Within this formulation we establish connection between the two different solutions of the quantum master equation within the BV formulation.

  6. The role of formulation on the pharmacokinetics of antiretroviral drugs

    NARCIS (Netherlands)

    Bastiaans, Diane E T; Cressey, Tim R; Vromans, Herman; Burger, David M

    2014-01-01

    INTRODUCTION: A multitude of antiretroviral drug formulations are now available for HIV-infected adults and children. These formulations include individual and co-formulated drugs, many of which are also supplied in generic versions. Many antiretroviral drugs have a low aqueous solubility and poor b

  7. Formulation and method for preparing gels comprising hydrous aluminum oxide

    Science.gov (United States)

    Collins, Jack L.

    2014-06-17

    Formulations useful for preparing hydrous aluminum oxide gels contain a metal salt including aluminum, an organic base, and a complexing agent. Methods for preparing gels containing hydrous aluminum oxide include heating a formulation to a temperature sufficient to induce gel formation, where the formulation contains a metal salt including aluminum, an organic base, and a complexing agent.

  8. Formulation and method for preparing gels comprising hydrous cerium oxide

    Science.gov (United States)

    Collins, Jack L; Chi, Anthony

    2013-05-07

    Formulations useful for preparing hydrous cerium oxide gels contain a metal salt including cerium, an organic base, and a complexing agent. Methods for preparing gels containing hydrous cerium oxide include heating a formulation to a temperature sufficient to induce gel formation, where the formulation contains a metal salt including cerium, an organic base, and a complexing agent.

  9. Stabilisation de la formule des traces tordue

    CERN Document Server

    Moeglin, Colette

    2016-01-01

    Ce travail en deux volumes donne la preuve de la stabilisation de la formule des trace tordue. Stabiliser la formule des traces tordue est la méthode la plus puissante connue actuellement pour comprendre l'action naturelle du groupe des points adéliques d'un groupe réductif, tordue par un automorphisme, sur les formes automorphes de carré intégrable de ce groupe. Cette compréhension se fait en réduisant le problème, suivant les idées de Langlands, à des groupes plus petits munis d'un certain nombre de données auxiliaires; c'est ce que l'on appelle les données endoscopiques. L'analogue non tordu a été résolu par J. Arthur et dans ce livre on suit la stratégie de celui-ci. Publier ce travail sous forme de livre permet de le rendre le plus complet possible. Les auteurs ont repris la théorie de l'endoscopie tordue développée par R. Kottwitz et D. Shelstad et par J.-P. Labesse. Ils donnent tous les arguments des démonstrations même si nombre d'entre eux se trouvent déjà dans les travaux d'Ar...

  10. Formulation and picture of quantum phase

    Institute of Scientific and Technical Information of China (English)

    YAO ZhiXin; ZHONG JianWei; PAN BaiLiang

    2009-01-01

    Based on the concept of classical phase, we formulate a new explanation for the quantum phase from the quantum mechanical point of view. The quantum phase is the canonically conjugate variable of an angular momentum operator, which corresponds to the angular position φ in an actual physical space with a classical reference frame, but it takes a complex exponential form e~(iφ)-cosφ+i sinφin the abstract Hilbert space of a quantum reference frame. This formulation is simply the famous Euler formula in a complex number field. In particular, when φ= π/2, the correlative quantum phase is a unitary pure imaginary number e~(iπ/2)=cos(π/2)+i sin(π/2) = i. By using a photon state-vector function that is the general solution of photon Schrodinger equation and can completely describe a photon's behavior, we discuss the relationship between the angular momentum of a photon and the phase of the photon; we also analyze the intrinsic relationship between the macroscopic light wave phase and the microscopic photon phase.

  11. A novel liposomal formulation of flavopiridol.

    Science.gov (United States)

    Yang, Xiaojuan; Zhao, Xiaobin; Phelps, Mitch A; Piao, Longzhu; Rozewski, Darlene M; Liu, Qing; Lee, L James; Marcucci, Guido; Grever, Michael R; Byrd, John C; Dalton, James T; Lee, Robert J

    2009-01-05

    Flavopiridol has shown promising activities in hematologic and solid tumor models, as well as in clinical trials in chronic lymphocytic leukemia patients. Flavopiridol has relatively low solubility and high plasma protein-binding. To address these issues and to provide an alternative strategy to achieve clinical efficacy, we encapsulated flavopiridol into a liposomal carrier and characterized its physicochemical and pharmacokinetic properties. The liposomes, comprising hydrogenated soy phosphatidylcholine (HSPC), cholesterol and poly (ethylene glycol) 2000-distearoyl phosphatidylethanolamine (PEG-DSPE), were prepared by polycarbonate membrane extrusion and then loaded with flavopiridol by a pH-gradient driven remote loading procedure. The liposomes had a mean diameter of 120.7 nm and a flavopiridol entrapment efficiency of 70.4%. Pharmacokinetic study in mice after i.v. bolus injection showed that the liposomal flavopiridol had an increased elimination phase half-life (T((1/2)beta), 339.7 min vs. 57.0 min), decreased clearance (CL, 0.012 L/min vs. 0.036 L/min), and increased area under the plasma concentration-time curve (AUC, 10.8 min micromol/L vs. 3.4 min micromol/L) compared to the free drug. This indicates a significant and potentially beneficial change in flavopiridol pharmacokinetics for the liposomal formulation. Further preclinical studies are warranted to define the toxicity and therapeutic efficacy of this novel formulation.

  12. Clinical evaluation of seven anticalculus dentifrice formulations.

    Science.gov (United States)

    Scruggs, R R; Stewart, P W; Samuels, M S; Stamm, J W

    1991-01-01

    One hundred ninety-two subjects completed a clinical trial to determine the effects of seven dentifrice formulations on calculus inhibition. The double-blind study involved a ten-day control phase and a ten-day experimental phase. For the control phase, subjects were evaluated for calculus present, received a prophylaxis and had pre-weighed mylar strips attached to the lingual surfaces of the mandibular incisors to harvest mineral deposits. Subjects were then assigned the placebo dentifrice for unsupervised twice-daily use and were required to report once a day for a supervised mouthrinse using a 1:3 dilution of the dentrifice. The experimental phase was identical except that subjects were allocated the experimental dentifices using a stratified random assignment based on age, gender and the initial presence of calculus. Simple linear regression analyses of the dry and ash log weights obtained from the strips were performed. The results showed no statistically significant differences among the test products; however, two formulations containing zinc citrate showed some calculus inhibition-potential suggesting that further research and development of such products may be warranted.

  13. Formulation and picture of quantum phase

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Based on the concept of classical phase,we formulate a new explanation for the quantum phase from the quantum mechanical point of view. The quantum phase is the canonically conjugate variable of an angular momentum operator,which corresponds to the angular position θ in an actual physical space with a classical reference frame,but it takes a complex exponential form eiθ≡cosθ +i sinθ in the abstract Hilbert space of a quantum reference frame. This formulation is simply the famous Euler formula in a complex number field. In particular,when θ = π/2,the correlative quantum phase is a unitary pure imaginary number eiπ/2 ≡cos(π/2)+i sin(π/2) ≡ i. By using a photon state-vector function that is the general solution of photon Schrdinger equation and can completely describe a photon’s behavior,we discuss the relationship between the angular momentum of a photon and the phase of the photon; we also analyze the intrinsic relationship between the macroscopic light wave phase and the microscopic photon phase.

  14. Formulation of microbial cocktails for BTEX biodegradation.

    Science.gov (United States)

    Nagarajan, Karthiga; Loh, Kai-Chee

    2015-02-01

    BTEX biodegradation by a mixed community of micro-organisms offers a promising approach in terms of cost-effectiveness and elimination of secondary pollution. Two bacterial strains, Pseudomonas putida F1 and Pseudomonas stutzeri OX1 were chosen to formulate synthetic consortia based on their ability to biodegrade the mono-aromatic compounds. Benzene and toluene supported the growth of both the strains; while ethyl benzene and o-xylene were only utilized as growth substrates by P. putida F1 and P. stutzeri OX1, respectively. In a mixed substrate system, P. putida F1 exhibited incomplete removal of o-xylene while P. stutzeri OX1 displayed cometabolic removal of ethyl benzene with dark coloration of the growth medium. The biodegradation potential of the two Pseudomonas species complemented each other and offered opportunities to explore their performance as a co-culture for enhanced BTEX biodegradation. Several microbial formulations were concocted and their BTEX biodegradation characteristics were evaluated. Mixed culture biodegradation ascertained the advantages of the co-culture over the individual Pseudomonas species. This study also emphasized the significance of inoculum density and species proportion while concocting preselected micro-organisms for enhanced BTEX biodegradation.

  15. Formulation of elastic multi-structures

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Based on the creative and groundbreaking work done by Feng and Shi, some further work has been carried out comprehensively by the first author on the formulation of elastic multi-structures. The main contribution of this paper can be summarized as follows: The work of Feng and Shi has been extended to an elastic multi-structures with nonlinear structural element: shell in both linear and nonlinear case. Three general combinations of multi-structures have been formulated, that is, Case 1: linear elements of 3-D body, 1-D bar/beam, 2-D plates and 2-D shell; Case 2: nonlinear elements of 3-D body, 1-D bar/beam, 2-D plates and 2-D shell; and Case 3: the linear-nonlinear mix problem of 3-D body (nonlinear), 1-D bar/beam (linear), 2-D plates (linear) and 2-D shell (linear). From the investigation, it has proved that the higher dimensional element will have a strong influence on the lower one with the inner linkage boundaries, and also proved that solution uniqueness of elastic multi-structures is different from a single 3-D body.

  16. Formulation of elastic multi-structures

    Institute of Scientific and Technical Information of China (English)

    SUN BoHua; YE ZhiMing

    2009-01-01

    Based on the creative and groundbreaking work done by Feng and Shi, some further work has been carried out comprehensively by the first author on the formulation of elastic multi-structures. The main contribution of this paper can be summarized as follows: The work of Feng and Shi has been extended to an elastic multi-structures with nonlinear structural element: shell in both linear and nonlinear case. Three general combinations of multi-structures have been formulated, that is, Case 1: linear elements of 3-D body, 1-D bar/beam, 2-D plates and 2-D shell; Case 2: nonlinear elements of 3-D body, 1-D bar/beam, 2-D plates and 2-D shell; and Case 3: the linear-nonlinear mix problem of 3-D body (nonlinear), 1-D bar/beam (linear), 2-D plates (linear) and 2-D shell (linear). From the investigation, it has proved that the higher dimensional element will have a strong influence on the lower one with the inner linkage boundaries, and also proved that solution uniqueness of elastic mulU-structures is different from a single 3-D body.

  17. FORMULATION STRATEGY FOR DISSOLUTION ENHANCEMENT OF SIMVASTATIN

    Directory of Open Access Journals (Sweden)

    Neha Parmar et al

    2012-10-01

    Full Text Available The present work aim was “Formulation Strategy for Dissolution Enhancement of Simvastatin”. Simvastatin is lipid lowering drug which is known as HMG CoA reductase. The objective of this study was to increase the solubility of poorly water soluble drug, namely simvastatin, by the formation of solid dispersion and complex and also using the microwave induction technique on these formations. For solid dispersion method dispersion carrier used were poloxamer 407 and gelucire 44/14. The fusion method was used to prepare the dispersions. For inclusion complexation method β-cyclodextrin derivative of cyclodextrin was used to prepare complex with drug. Kneading method was used for formulation. After completion of these two techniques these polymers were used for the microwave induced fusion method. All the ratio of drug and polymer were used to heat for different time interval. These samples were used for solubility measurement. In the solid dispersion technique, simvastatin show higher increase in solubility with gelucire 44/14 in the ratio of 1:5 as compare to poloxamer 407. In the microwave induced fusion method simvastatin show higher solubility with simvastatin with gelucire 44/14 after 10 mins time interval as compare to poloxamer 407 and β-cyclodextrin. Solubility of simvastatin increased higher with gelucire 44/14 by using microwave induced fusion method as compare to other technique. By using gelucire 44/14 with simvastatin it show 94% increase in solubility of simvastatin as compare to pure drug in water.

  18. Formulation of nimodipine nanocrystals for oral administration.

    Science.gov (United States)

    Li, Jianwen; Fu, Qiang; Liu, Xiaohong; Li, Mo; Wang, Yongjun

    2016-02-01

    The aim of this paper is to optimize nimodipine (NMD) nanocrystals (NCs) for oral administration. The effects of independent process variables (microprecipitation temperature, shearing speed, shearing time, homogenization pressure and number of cycles) on the particle size have been studied. Experiments were conducted to optimize the formulation composition. A single factor exploration was used to screen the primary stabilizers. Then, the selected polymers/surfactants were further optimized using an L9 (3(4)) orthogonal design. The optimal formulation was composed of NMD (0.7 %, w/v), F127 (0.4 %, w/v), HPMC-E5 (0.1 %, w/v), and sodium deoxycholate (0.05 %, w/v) and was rod-shaped as shown by SEM observations, and it had a particle size of 833.3 ± 20.6 nm, determined by laser diffraction. These aqueous NCs were physically stable for 15 days. To further improve the stability, the NCs were freeze-dried. The powder obtained exhibited acceptable flowability and was physically stable for at least 24 months. Additionally, the NMD NCs displayed much higher dissolution profiles than the bulk drug. The pharmacokinetic results showed that the relative bioavailability was 397 % in comparison with Nimotop(®), suggesting that NCs are an efficient strategy for improving the oral bioavailability of poorly water-soluble drugs.

  19. Immunoglobulin: production, mechanisms of action and formulations

    Directory of Open Access Journals (Sweden)

    Marcia Cristina Zago Novaretti

    2011-10-01

    Full Text Available Human immunoglobulin (Ig began to be applied in the clinical practice with the treatment of primary immunodeficiencies. Quickly, applications of Ig increased, as its anti-inflammatory and immunomodulatory functions were elucidated. Currently, Ig is the most commonly used blood product. Ig is obtained by processing plasma; methods, in particular, techniques to reduce plasma viral loads have been evolving over the years and include: pasteurization, solvent/ detergent treatment, caprylic acid treatment and nanofiltration. These methods contribute to increased safety and quality of blood products. The mechanisms of action of Ig not only involve the blockade of Fc receptors of phagocytes, but also control complement pathways, idiotype-anti-idiotype dimer formation, blockage of superantigen binding to T cells, inhibition of dendritic cells and stimulation of regulatory T cells (Tregs. There are several formulations of Ig available, each one with its own peculiar characteristics. In Brazil, there is stringent legislation regulating the quality of Ig. Only Ig products that completely fulfill the quality control criteria are released for use. These standards involve different tests from visual inspection to determination of anti-complementary activity. This paper will further review the history and current status of Ig, including its production and mechanisms of action. The formulations available in Brazil and also the criteria of quality control currently applied will be presented.

  20. Formulation and Dissolution Study of Valsartan Immediate Release Tablets

    Directory of Open Access Journals (Sweden)

    B. Brahmaiah*, K. Sasikanth, Sreekanth Nama , P.Suresh, Patan Adam Khan

    2013-06-01

    Full Text Available In the present study, design of oral immediate release tablets of Valsartan by direct compression techniquewas carried out. The main aim and objective of the work is to formulate immediate release tablets usingdifferent direct compression vehicles (DCV’S in different ratios. The main motive is to compare thedissolution profile of these formulations and conclude the best formulation which release drug at a fasterrate. To determine the best fit dissolution profile for the dosage forms. Valsartan tablets were formulated byusing microcrystalline cellulose (diluents, potato starch, acacia (binder and magnesium stearate(lubricant. The granules were compressed into tablets and were subjected to dissolution studies. Thedissolution profile of the formulation F2 was found to have better dissolution rate compared to others. TheIn-vitro dissolution studies of all the formulations were conducted and the results were obtained, it wasconcluded that formulation F2 was the best with fast release of drug compared to others.

  1. Peridynamic Formulation for Coupled Thermoelectric Phenomena

    Directory of Open Access Journals (Sweden)

    Migbar Assefa

    2017-01-01

    Full Text Available Modeling of heat and electrical current flow simultaneously in thermoelectric convertor using classical theories do not consider the influence of defects in the material. This is because traditional methods are developed based on partial differential equations (PDEs and lead to infinite fluxes at the discontinuities. The usual way of solving such PDEs is by using numerical technique, like Finite Element Method (FEM. Although FEM is robust and versatile, it is not suitable to model evolving discontinuities. To avoid such shortcomings, we propose the concept of peridynamic theory to derive the balance of energy and charge equations in the coupled thermoelectric phenomena. Therefore, this paper presents the transport of heat and charge in thermoelectric material in the framework of peridynamic (PD theory. To illustrate the reliability of the PD formulation, numerical examples are presented and results are compared with those from literature, analytical solutions, or finite element solutions.

  2. Micromorphic continua: non-redundant formulations

    Science.gov (United States)

    Romano, Giovanni; Barretta, Raffaele; Diaco, Marina

    2016-11-01

    The kinematics of generalized continua is investigated and key points concerning the definition of overall tangent strain measure are put into evidence. It is shown that classical measures adopted in the literature for micromorphic continua do not obey a constraint qualification requirement, to be fulfilled for well-posedness in optimization theory, and are therefore termed redundant. Redundancy of continua with latent microstructure and of constrained Cosserat continua is also assessed. A simplest, non-redundant, kinematic model of micromorphic continua, is proposed by dropping the microcurvature field. The equilibrium conditions and the related variational linear elastostatic problem are formulated and briefly discussed. The simplest model involves a reduced number of state variables and of elastic constitutive coefficients, when compared with other models of micromorphic continua, being still capable of enriching the Cauchy continuum model in a significant way.

  3. Boson--Fermion hybrid representation formulation, I

    Energy Technology Data Exchange (ETDEWEB)

    Wu, C.; Feng, D.H.

    1981-08-01

    A boson--fermion hybrid representation is presented. In this framework, a fermion system is described concurrently by the bosonic and the fermonic degrees of freedom. A fermion pair in this representation can be treated as a boson without violating the Pauli principle. Furthermore the ''bosonic interactions'' are shown to originate from the exchange processes of the fermions and can be calculated from the original fermion interactions. Both the formulation of the BFH representations for the even and odd nuclear systems are given. We find that the basic equation of the nuclear field theory (NFT) is just the usual Schroedinger equation in such a representation with the empirical NFT diagrammatic rules emerging naturally. This theory was numerically checked in the case of four nucleons moving in a single-j shell and the exactness of the theory was established.

  4. An Entropic Formulation of Tunneling Time

    CERN Document Server

    Demir, Durmus A

    2015-01-01

    Quantum tunneling governs numerous phenomena in biology, chemistry, physics and technology. Tunneling time, formulated in various different forms due to the absence of a time operator in quantum theory, has been measured recently in experiments based on the attoclock in ultrafast laser ionization of Helium atoms [A.~Landsman {\\it et al.}, Optica {\\bf 1}, 343 (2014)]. The experiment performs a refined measurement with which no tunneling time formula in the literature exhibits adequate congruence. Here we show that, entropic considerations lead to a real tunneling time which shows remarkable agreement with the experimental data and stays always subluminal. Indeed, with phase space volume setting the number of microstates for a single evanescing particle in a state of definite momentum consistent with energy conservation, one is naturally led to a statistical description for quantum tunneling in which thermal energy sets the tunneling time. This entropic tunneling time is rather general and might also be extende...

  5. Voltammetric assay of Guaifenesin in pharmaceutical formulation.

    Science.gov (United States)

    Tapsoba, I; Belgaied, J-E; Boujlel, K

    2005-06-01

    The electrochemical oxidation of Guaifenesin in a pharmaceutical formulation containing Guaifenesin has been carried out in Britton-Robinson buffer (BRB) (0.04 mol L-1) on platinum electrode. Guaifenesin exhibits a well-defined irreversible oxidation peak at 0.924 V/ref. The influence of pH on the oxidation of Guaifenesin was studied in BRB (pH range 2-5). A method for the analysis of Guaifenesin in BRB (0.04 mol L-1, pH 2), which allows quantification over the range 20-60 microg mL-1, was proposed and successfully applied to the determination of Guaifenesin in syrup with mean recovery and relative standard deviation of 103.3% and 1.32%, respectively.

  6. Reversible Dialysis in a Microfluidic Formulator.

    Science.gov (United States)

    Selimovic, Seila; Shim, Jung-Uk; Fraden, Seth

    2006-03-01

    In order to facilitate the screening of conditions for protein crystallization, we have been using the Microfluidic Formulator chip (Stephen Quake, PNAS Vol. 101, 40 ). This PDMS device allows us to mix up to 40 different reagents and protein solutions. We use this combinatorial approach along with a ``drop-on-demand'' method whereby we employ on-chip positive displacement pumps to form aqueous droplets containing protein and separate them by plugs of oil. Subsequently, the aqueous drops containing protein are guided by surface tension forces into storage chambers. To control the chemical potential of these sub-nanoliter protein samples, we fabricate reservoirs underneath the storage compartments. A thin PDMS membrane that is permeable to water, but not to protein or salt, separates the reservoirs from the storage chambers. Water can permeate into or out of the stored samples until the chemical potentials of the reservoir and the protein solution are equal leading to protein crystallization in some chambers.

  7. Theory of photorefractive dynamic grating formulation

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The photorefractive holographic recording and two-beam coupling are both dynamic grating formulation process. The interference light intensity of the two coherent beams induces a phase grating though photo-induced refractive index variation and the phase grating changing the intensities of the two beams through beam-coupling take place at the same time. By solving simultaneously the band transport equations and wave-coupled equations, and using the light intensity modulation as the main variable, the analytic solution is obtained, which is valid for any light intensity modulation and constant light excitation efficiency. Here all the mechanics of drift, diffusion and photovoltaic effect are considered. The result shows that the modulation of the dynamic grating varies more slowly compared with that of the linear modulation approximation.

  8. Formulating formation mechanism of natural gas hydrates.

    Science.gov (United States)

    Palodkar, Avinash V; Jana, Amiya K

    2017-07-25

    A large amount of energy, perhaps twice the total amount of all other hydrocarbon reserves combined, is trapped within gas hydrate deposits. Despite emerging as a potential energy source for the world over the next several hundred years and one of the key factors in causing future climate change, gas hydrate is poorly known in terms of its formation mechanism. To address this issue, a mathematical formulation is proposed in the form of a model to represent the physical insight into the process of hydrate growth that occurs on the surface and in the irregular nanometer-sized pores of the distributed porous particles. To evaluate the versatility of this rigorous model, the experimental data is used for methane (CH4) and carbon dioxide (CO2) hydrates grown in different porous media with a wide range of considerations.

  9. Oral pulsatile delivery: rationale and chronopharmaceutical formulations.

    Science.gov (United States)

    Maroni, Alessandra; Zema, Lucia; Del Curto, Maria Dorly; Loreti, Giulia; Gazzaniga, Andrea

    2010-10-15

    Oral pulsatile/delayed delivery systems are designed to elicit programmable lag phases preceding a prompt and quantitative, repeated or prolonged release of drugs. Accordingly, they draw increasing interest because of the inherent suitability for accomplishing chronotherapeutic goals, which have recently been highlighted in connection with a number of widespread chronic diseases with typical night or early-morning recurrence of symptoms (e.g. bronchial asthma, cardiovascular disease, rheumatoid arthritis, early-morning awakening). In addition, time-based colonic release can be attained when pulsatile delivery systems are properly adapted to overcome unpredictable gastric emptying and provide delay phases that would approximately match the small intestinal transit time. Oral pulsatile delivery is pursued by means of a variety of release platforms, namely reservoir, capsular and osmotic devices. The aim of the present review is to outline the rationale and main formulation strategies behind delayed-release dosage forms intended for the pharmacological treatment of chronopathologies.

  10. Tangent bundle formulation of a charged gas

    CERN Document Server

    Sarbach, Olivier

    2013-01-01

    We discuss the relativistic kinetic theory for a simple, collisionless, charged gas propagating on an arbitrary curved spacetime geometry. Our general relativistic treatment is formulated on the tangent bundle of the spacetime manifold and takes advantage of its rich geometric structure. In particular, we point out the existence of a natural metric on the tangent bundle and illustrate its role for the development of the relativistic kinetic theory. This metric, combined with the electromagnetic field of the spacetime, yields an appropriate symplectic form on the tangent bundle. The Liouville vector field arises as the Hamiltonian vector field of a natural Hamiltonian. The latter also defines natural energy surfaces, called mass shells, which turn out to be smooth Lorentzian submanifolds. A simple, collisionless, charged gas is described by a distribution function which is defined on the mass shell and satisfies the Liouville equation. Suitable fibre integrals of the distribution function define observable fie...

  11. FORMATE-BASED FLUIDS: FORMULATION AND APPLICATION

    Directory of Open Access Journals (Sweden)

    Nediljka Gaurina-Međimurec

    2008-12-01

    Full Text Available Formate-based fluids has been successfully used in over hunders HPHT well operations since they introduced in field practice. They have many advantages when compared with conventional HPHT drilling and completion fluids such as: minimal formation damage, maintenance of additve properties at high temperatures, reduced hydraulic flow resistance, low potential for differential sticking, naturally lubricating, very low corrosion rates, biodegradable and pose little risk to the environment etc. Formate-based fluids can be applied during deep slim hole drilling, shale drilling, reservoir drilling, salt and gas hydrate formations drilling. The laboratory research was carried out to evaluate the rheological behavior of formate-based fluids as a function of temperature. Formate-based fluids were formulated using potassium formate brine, xanthan polymer, PAC, starch and calcium carbonate. Experimental results show that potassium formate improves the thermal stability of polymers.

  12. Etodolac Containing Topical Niosomal Gel: Formulation Development and Evaluation

    Directory of Open Access Journals (Sweden)

    Gyati Shilakari Asthana

    2016-01-01

    Full Text Available The present study aimed to investigate the delivery potential of Etodolac (ETD containing topical niosomal gel. Niosomal formulations were prepared by thin film hydration method at various ratios of cholesterol and Span 60 and were evaluated with respect to particle size, shape, entrapment efficiency, and in vitro characteristics. Dicetyl phosphate (DCP was also added in the niosomal formulation. Mean particle size of niosomal formulation was found to be in the range of 2 μm to 4 μm. Niosomal formulation N2 (1 : 1 ratio of cholesterol and surfactant displayed good entrapment efficiency (96.72%. TEM analyses showed that niosomal formulation was spherical in shape. Niosomal formulation (N2 displayed high percentage of drug release after 24 h (94.91 at (1 : 1 ratio of cholesterol : surfactant. Further selected niosomal formulation was used to formulate topical gel and was characterized with respect to its various parameters such as pH, viscosity, spreadability, ex vivo study, and in vivo potential permeation. Ex vivo study showed that niosomal gel possessed better skin permeation study than the plain topical gel. Further in vivo study revealed good inhibition of inflammation in case of topical niosomal gel than plain gel and niosomal formulation. The present study suggested that topical niosomal gel formulations provide sustained and prolonged delivery of drug.

  13. Formulation and characterization of benzoyl peroxide gellified emulsions.

    Science.gov (United States)

    Thakur, Naresh Kumar; Bharti, Pratibha; Mahant, Sheefali; Rao, Rekha

    2012-01-01

    The present investigation was carried out with the objective of formulating a gellified emulsion of benzoyl peroxide, an anti-acne agent. The formulations were prepared using four different vegetable oils, viz. almond oil, jojoba oil, sesame oil, and wheat germ oil, owing to their emollient properties. The idea was to overcome the skin irritation and dryness caused by benzoyl peroxide, making the formulation more tolerable. The gellified emulsions were characterized for their homogeneity, rheology, spreadability, drug content, and stability. In vitro permeation studies were performed to check the drug permeation through rat skin. The formulations were evaluated for their antimicrobial activity, as well as their acute skin irritation potential. The results were compared with those obtained for the marketed formulation. Later, the histopathological examination of the skin treated with various formulations was carried out. Formulation F3 was found to have caused a very mild dysplastic change to the epidermis. On the other hand, the marketed formulation led to the greatest dysplastic change. Hence, it was concluded that formulation F3, containing sesame oil (6%w/w), was the optimized formulation. It exhibited the maximum drug release and anti-microbial activity, in addition to the least skin irritation potential.

  14. Stability of Bacillus thuringiensis and NPV Microencapsulated Formulation under Sunlight

    Directory of Open Access Journals (Sweden)

    Samaneh Sadat Naghavi

    2016-06-01

    Full Text Available Microencapsulation technology is used for the formulation of bio pesticides and is effective against the ultra-violet radiation of sunlight. The present research studied the stability of Bt and NPV formulations microencapsulated with gelatin and sodium alginate, individually or in combination. The formulations were evaluated in outdoor space and under sunlight on potted growing cabbage. The stability of each active ingredient tested in each formulation was studied at 0, 3, 7 and 10 days after spraying on cabbage infested with diamondback moth Plutella xylostella second instars larvae. Results showed that non-formulated and microencapsulated formulations not exposed to sunlight (time zero had similar mortality. However, after being exposed to sunlight for three days, the non-formulated Bt and NPV resulted in a significantly lower mortality (less than 40%; compared with the microencapsulated bio pesticides (more than 70% mortality. Fifty percent (50% mortality was reached in microencapsulated formulations after seven and ten days of exposure to sunlight, whereas there was no mortality in larvae exposed to unformulated treated plants after ten days. ANOVA analysis showed the highest larval mortality was achieved by the Bt+NPV gelatin microencapsulated formulation followed by gelatin coated Bt, sodium alginate coated NPV, sodium alginate coated Bt+NPV, gelatin coated NPV and sodium alginate coated Bt. The formulations showed no significant LT50 differences between microencapsulated versus unformulated Bt and NPV.

  15. Etodolac Containing Topical Niosomal Gel: Formulation Development and Evaluation

    Science.gov (United States)

    Asthana, Abhay; Singh, Davinder; Sharma, Parveen Kumar

    2016-01-01

    The present study aimed to investigate the delivery potential of Etodolac (ETD) containing topical niosomal gel. Niosomal formulations were prepared by thin film hydration method at various ratios of cholesterol and Span 60 and were evaluated with respect to particle size, shape, entrapment efficiency, and in vitro characteristics. Dicetyl phosphate (DCP) was also added in the niosomal formulation. Mean particle size of niosomal formulation was found to be in the range of 2 μm to 4 μm. Niosomal formulation N2 (1 : 1) ratio of cholesterol and surfactant displayed good entrapment efficiency (96.72%). TEM analyses showed that niosomal formulation was spherical in shape. Niosomal formulation (N2) displayed high percentage of drug release after 24 h (94.91) at (1 : 1) ratio of cholesterol : surfactant. Further selected niosomal formulation was used to formulate topical gel and was characterized with respect to its various parameters such as pH, viscosity, spreadability, ex vivo study, and in vivo potential permeation. Ex vivo study showed that niosomal gel possessed better skin permeation study than the plain topical gel. Further in vivo study revealed good inhibition of inflammation in case of topical niosomal gel than plain gel and niosomal formulation. The present study suggested that topical niosomal gel formulations provide sustained and prolonged delivery of drug. PMID:27478643

  16. Scientific validation of polyherbal hepatoprotective formulation against paracetamol induced toxicity

    Institute of Scientific and Technical Information of China (English)

    Beerendra Kumar Saroj; Dayanandan Mani; Sunil Kumar Mishra

    2012-01-01

    Objective: This polyherbal formulation has been traditionally used in the Indian system of medicine as a chief formulation for the treatment of hepatic diseases as hepatoprotective. The aim of the study was to study hepatoprotective activity which will be scientific validation of traditional knowledge claimed about this polyherbal formulation. Methods: Hepatotoxicity was induced by administration of paracetamol (300mg/kg) to the animals. The levels of liver enzymes (SGOT, SGPT, Alkaline phosphatase, Serum Bilirubin), lipid profiles (triglyceride, cholesterol, HDL, LDL), creatinine, urea levels and histopathological parameters were measured in order to evaluate hepatoprotective activity of polyherbal formulation. Results: The polyherbal formulation produced a significant hepatoprotective activity of the decoction of polyherbal formulation. The polyherbal formulation (PHF = 1) shows good hepatoprotective activity by lowering the levels of SGOT, alkaline phosphatase, bilirubin parameters (P<0.05), lipid profiles - cholesterol, triglyceride, LDL and histopathological evaluations shows that PHF = 1 and PHF = 3 formulations have significantly hepatoprotective activity (P<0.05). Conclusions: The study validates that polyherbal formulation has a good hepatoprotective activity. Further standardization processes may be performed in order to make it a beneficial hepatoprotective formulation.

  17. A multilevel prediction of physiological response to challenge: Interactions among child maltreatment, neighborhood crime, endothelial nitric oxide synthase gene (eNOS), and GABA(A) receptor subunit alpha-6 gene (GABRA6).

    Science.gov (United States)

    Lynch, Michael; Manly, Jody Todd; Cicchetti, Dante

    2015-11-01

    Physiological response to stress has been linked to a variety of healthy and pathological conditions. The current study conducted a multilevel examination of interactions among environmental toxins (i.e., neighborhood crime and child maltreatment) and specific genetic polymorphisms of the endothelial nitric oxide synthase gene (eNOS) and GABA(A) receptor subunit alpha-6 gene (GABRA6). One hundred eighty-six children were recruited at age 4. The presence or absence of child maltreatment as well as the amount of crime that occurred in their neighborhood during the previous year were determined at that time. At age 9, the children were brought to the lab, where their physiological response to a cognitive challenge (i.e., change in the amplitude of the respiratory sinus arrhythmia) was assessed and DNA samples were collected for subsequent genotyping. The results confirmed that complex Gene × Gene, Environment × Environment, and Gene × Environment interactions were associated with different patterns of respiratory sinus arrhythmia reactivity. The implications for future research and evidence-based intervention are discussed.

  18. Nonequilibrium formulation of abelian gauge theories

    Energy Technology Data Exchange (ETDEWEB)

    Zoeller, Thorsten

    2013-09-01

    This work is about a formulation of abelian gauge theories out-of-equilibrium. In contrast to thermal equilibrium, systems out-of-equilibrium are not constant in time, and the interesting questions in such systems refer to time evolution problems. After a short introduction to quantum electrodynamics (QED), the two-particle irreducible (2PI) effective action is introduced as an essential technique for the study of quantum field theories out-of-equilibrium. The equations of motion (EOMs) for the propagators of the theory are then derived from it. It follows a discussion of the physical degrees of freedom (DOFs) of the theory, in particular with respect to the photons, since in covariant formulations of gauge theories unphysical DOFs are necessarily contained. After that the EOMs for the photon propagator are examined more closely. It turns out that they are structurally complicated, and a reformulation of the equations is presented which for the untruncated theory leads to an essential structural simplification of the EOMs. After providing the initial conditions which are necessary in order to solve the EOMs, the free photon EOMs are solved with the help of the reformulated equations. It turns out that the solutions diverge in time, i.e. they are secular. This is a manifestation of the fact that gauge theories contain unphysical DOFs. It is reasoned that these secularities exist only in the free case and are therefore ''artificial''. It is however emphasized that they may not be a problem in principle, but certainly are in practice, in particular for the numerical solution of the EOMs. Further, the origin of the secularities, for which there exists an illustrative explanation, is discussed in more detail. Another characteristic feature of 2PI formulations of gauge theories is the fact that quantities calculated from approximations of the 2PI effective action, which are gauge invariant in the exact theory as well as in an approximated theory at

  19. Local normal vector field formulation for periodic scattering problems formulated in the spectral domain.

    Science.gov (United States)

    van Beurden, M C; Setija, I D

    2017-02-01

    We present two adapted formulations, one tailored to isotropic media and one for general anisotropic media, of the normal vector field framework previously introduced to improve convergence near arbitrarily shaped material interfaces in spectral simulation methods for periodic scattering geometries. The adapted formulations enable the definition and generation of the normal vector fields to be confined to a region of prolongation that includes the material interfaces but is otherwise limited. This allows for a more flexible application of geometrical transformations like rotation and translation per scattering object in the unit cell. Moreover, these geometrical transformations enable a cut-and-connect strategy to compose general geometries from elementary building blocks. The entire framework gives rise to continuously parameterized geometries.

  20. Element free Galerkin formulation of composite beam with longitudinal slip

    Energy Technology Data Exchange (ETDEWEB)

    Ahmad, Dzulkarnain; Mokhtaram, Mokhtazul Haizad [Department of Civil Engineering, Universiti Selangor, Bestari Jaya, Selangor (Malaysia); Badli, Mohd Iqbal; Yassin, Airil Y. Mohd [Faculty of Civil Engineering, Universiti Teknologi Malaysia, Skudai, Johor (Malaysia)

    2015-05-15

    Behaviour between two materials in composite beam is assumed partially interact when longitudinal slip at its interfacial surfaces is considered. Commonly analysed by the mesh-based formulation, this study used meshless formulation known as Element Free Galerkin (EFG) method in the beam partial interaction analysis, numerically. As meshless formulation implies that the problem domain is discretised only by nodes, the EFG method is based on Moving Least Square (MLS) approach for shape functions formulation with its weak form is developed using variational method. The essential boundary conditions are enforced by Langrange multipliers. The proposed EFG formulation gives comparable results, after been verified by analytical solution, thus signify its application in partial interaction problems. Based on numerical test results, the Cubic Spline and Quartic Spline weight functions yield better accuracy for the EFG formulation, compares to other proposed weight functions.

  1. Geometrical Field Formulation of Thermomechanics in Rational Mechanics

    CERN Document Server

    Jianhua, Xiao

    2010-01-01

    In modern science, the thermo mechanics motion can be traced back to quantum motion in micro viewpoint. On the other hand, the thermo mechanics is definitely related with geometrical configuration motion (phase) in macro viewpoint. On this sense, the thermomechanics should be formulated by two kinds of motion: quantum motion and configuration motion. Its principle goal ought to be bridge the gap between atomic physics and engineering practice. In this research, the configuration motion is formulated by deformation geometrical field (motion transformation tensor). The quantum motion is formulated by the wave function of quantum state. Based on these two fields, the thermo stress is formulated as the coupling of quantum motion and configuration motion. Along this line, the entropy is interpreted and formulated according to thermodynamics rules. For scalar entropy, the traditional meaning of entropy is reserved. For infinitesimal configuration variation, the formulation is degenerated to the traditional elastici...

  2. Neural networks to formulate special fats

    Directory of Open Access Journals (Sweden)

    Garcia, R. K.

    2012-09-01

    Full Text Available Neural networks are a branch of artificial intelligence based on the structure and development of biological systems, having as its main characteristic the ability to learn and generalize knowledge. They are used for solving complex problems for which traditional computing systems have a low efficiency. To date, applications have been proposed for different sectors and activities. In the area of fats and oils, the use of neural networks has focused mainly on two issues: the detection of adulteration and the development of fatty products. The formulation of fats for specific uses is the classic case of a complex problem where an expert or group of experts defines the proportions of each base, which, when mixed, provide the specifications for the desired product. Some conventional computer systems are currently available to assist the experts; however, these systems have some shortcomings. This article describes in detail a system for formulating fatty products, shortenings or special fats, from three or more components by using neural networks (MIX. All stages of development, including design, construction, training, evaluation, and operation of the network will be outlined.

    Las redes neuronales son una rama de la inteligencia artificial basadas en la estructura y funcionamiento de sistemas biológicos, teniendo como principal característica la capacidad de aprender y generalizar conocimiento. Estas son utilizadas en la resolución de problemas complejos, en los cuales los sistemas computacionales tradicionales presentan una eficiencia baja. Hasta la fecha, han sido propuestas aplicaciones para los más diversos sectores y actividades. En el área de grasas y aceites, la utilización de redes neuronales se ha concentrado principalmente en dos asuntos: la detección de adulteraciones y la formulación de productos grasos. La formulación de grasas para uso específico es el caso clásico de problema complejo donde un experto o grupo de

  3. A UNIVERSAL VARIATIONAL FORMULATION FOR TWO DIMENSIONAL FLUID MECHANICS

    Institute of Scientific and Technical Information of China (English)

    何吉欢

    2001-01-01

    A universal variational formulation for two dimensional fluid mechanics is obtained, which is subject to the so-called parameter-constrained equations (the relationship between parameters in two governing equations). By eliminating the constraints, the generalized variational principle (GVPs) can be readily derived from the formulation. The formulation can be applied to any conditions in case the governing equations can be converted into conservative forms. Some illustrative examples are given to testify the effectiveness and simplicity of the method.

  4. Lagrangian formulation of continuum with internal long-range interactions

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    Based on a new definition of nonlocal variable,this paper establishes the Lagrangian formulation for continuum with internal long-range interactions.Distinguished from the existing theories,the nonlocal term in the Lagrangian formulation automatically satisfies the zero mean condition determined by the action and reaction law.By this formulation,elastic wave in a rod with the internal long-range interactions is investigated.The dispersion of the elastic wave is predicted.

  5. FORMULATION AND EVALUATION OF HERBAL GEL OF MAGNIFERA INDICA LINN

    Directory of Open Access Journals (Sweden)

    Gaikwad D.D

    2012-11-01

    Full Text Available To formulate Magnifera indica Linn bark extract in to a gel. Ethanolic extract of dried bark of Magnifera indica Linn were subjected to priliminery phytochemical evaluation studies. Different gel formulations of ethanolic extract of Magnifera indica linn (2% w/v were prepared using polymers carbopol 934 & HPMC by varying their concentration. These formulation were evaluated for physical parameters, drug contains, Ph, viscosity, Extrudability, Spread ability, primary skin irritation, study.Keywords:

  6. Viability of lactobacillus acidophilus in various vaginal tablet formulations

    OpenAIRE

    Fazeli M.R.; Toliyat T.; Samadi N.; Hajjaran S.; Jamalifar H.

    2006-01-01

    The lactobacilli which are present in vaginal fluids play an important role in prevention of vaginosis and there are considerable interests in formulation of these friendly bacteria into suitable pharmaceutical dosage forms. Formulating these microorganisms for vaginal application is a critical issue as the products should retain viability of lactobacilli during formulation and also storage. The aim of this study was to examine the viability and release of Lactobacillus acidophilus from slow-...

  7. Summary of Remediated Nitrate Salt Surrogate Formulation and Testing

    Energy Technology Data Exchange (ETDEWEB)

    Brown, Geoffrey Wayne [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Leonard, Philip [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Hartline, Ernest Leon [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Tian, Hongzhao [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-05-05

    High Explosives Science and Technology (M-7) completed all required formulation and testing of Remediated Nitrate Salt (RNS) surrogates on April 27, 2016 as specified in PLAN-TA9-2443 Rev B, "Remediated Nitrate Salt (RNS) Surrogate Formulation and Testing Standard Procedure", released February 16, 2016. This report summarizes the results of the work and also includes additional documentation required in that test plan. All formulation and testing was carried out according to PLAN-TA9-2443 Rev B. The work was carried out in three rounds, with the full matrix of samples formulated and tested in each round. Results from the first round of formulation and testing were documented in memorandum M7-J6-6042, " Results from First Round of Remediated Nitrate Salt Surrogate Formulation and Testing." Results from the second round of formulation and testing were documented in M7-16-6053 , "Results from the Second Round of Remediated Nitrate Salt Surrogate Formulation and Testing." Initial results from the third round were documented in M7-16-6057, "Initial Results from the Third Round of Remediated Nitrate Salt Formulation and Testing."

  8. The psychiatric cultural formulation: translating medical anthropology into clinical practice.

    Science.gov (United States)

    Aggarwal, Neil Krishan

    2012-03-01

    This article reviews proposed revisions to the DSM-IV Outline for Cultural Formulation for clinical practice. The author begins by exploring the theoretical development of and assumptions involved in the Cultural Formulation. A case presentation is then used to demonstrate shortcomings in the current implementation of the Cultural Formulation based on older definitions of culture. Finally, the author recommends practical questions based on the growing anthropological literature concerning the interpersonal elements of culture and the social course of illness. A simple clear format that clinically translates social science concepts has the potential to increase use of the Cultural Formulation by all psychiatrists, not just those specializing in cultural psychiatry.

  9. Accelerating Vaccine Formulation Development Using Design of Experiment Stability Studies.

    Science.gov (United States)

    Ahl, Patrick L; Mensch, Christopher; Hu, Binghua; Pixley, Heidi; Zhang, Lan; Dieter, Lance; Russell, Ryann; Smith, William J; Przysiecki, Craig; Kosinski, Mike; Blue, Jeffrey T

    2016-10-01

    Vaccine drug product thermal stability often depends on formulation input factors and how they interact. Scientific understanding and professional experience typically allows vaccine formulators to accurately predict the thermal stability output based on formulation input factors such as pH, ionic strength, and excipients. Thermal stability predictions, however, are not enough for regulators. Stability claims must be supported by experimental data. The Quality by Design approach of Design of Experiment (DoE) is well suited to describe formulation outputs such as thermal stability in terms of formulation input factors. A DoE approach particularly at elevated temperatures that induce accelerated degradation can provide empirical understanding of how vaccine formulation input factors and interactions affect vaccine stability output performance. This is possible even when clear scientific understanding of particular formulation stability mechanisms are lacking. A DoE approach was used in an accelerated 37(°)C stability study of an aluminum adjuvant Neisseria meningitidis serogroup B vaccine. Formulation stability differences were identified after only 15 days into the study. We believe this study demonstrates the power of combining DoE methodology with accelerated stress stability studies to accelerate and improve vaccine formulation development programs particularly during the preformulation stage. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  10. High-Order Entropy Stable Formulations for Computational Fluid Dynamics

    Science.gov (United States)

    Carpenter, Mark H.; Fisher, Travis C.

    2013-01-01

    A systematic approach is presented for developing entropy stable (SS) formulations of any order for the Navier-Stokes equations. These SS formulations discretely conserve mass, momentum, energy and satisfy a mathematical entropy inequality. They are valid for smooth as well as discontinuous flows provided sufficient dissipation is added at shocks and discontinuities. Entropy stable formulations exist for all diagonal norm, summation-by-parts (SBP) operators, including all centered finite-difference operators, Legendre collocation finite-element operators, and certain finite-volume operators. Examples are presented using various entropy stable formulations that demonstrate the current state-of-the-art of these schemes.

  11. St\\"uckelberg Formulation of Holography

    CERN Document Server

    Dvali, Gia; Wintergerst, Nico

    2015-01-01

    We suggest that holography can be formulated in terms of the information capacity of the St\\"uckelberg degrees of freedom that maintain gauge invariance of the theory in the presence of an information boundary. These St\\"uckelbergs act as qubits that account for a certain fraction of quantum information. Their information capacity is measured by the ratio of the inverse St\\"uckelberg energy gap to the size of the system. Systems with the smallest gap are maximally holographic. For massless gauge systems this information measure is universally equal to the inverse coupling evaluated at the systems' length scale. In this language it becomes very transparent why the St\\"uckelberg information capacity of black holes saturates the Bekenstein bound and accounts for the entire information of the system. The physical reason is that the strength of quantum interaction is bounded from below by the gravitational coupling, which scales as area. Observing the striking similarity between the scalings of the energy gap of t...

  12. Stückelberg formulation of holography

    Science.gov (United States)

    Dvali, Gia; Gomez, Cesar; Wintergerst, Nico

    2016-10-01

    We suggest that holography can be formulated in terms of the information capacity of the Stückelberg degrees of freedom that maintain gauge invariance of the theory in the presence of an information boundary. These Stückelbergs act as qubits that account for a certain fraction of quantum information. Their information capacity is measured by the ratio of the inverse Stückelberg energy gap to the size of the system. Systems with the smallest gap are maximally holographic. For massless gauge systems this information measure is universally equal to the inverse coupling evaluated at the systems' length scale. In this language it becomes very transparent why the Stückelberg information capacity of black holes saturates the Bekenstein bound and accounts for the entire information of the system. The physical reason is that the strength of quantum interaction is bounded from below by the gravitational coupling, which scales as area. Observing the striking similarity between the scalings of the energy gap of the boundary Stückelberg modes and the Bogoliubov modes of critical many-body systems, we establish a connection between holography and quantum criticality through the correspondence between these modes.

  13. Formulation of an injectable phosphocalcium cement

    Energy Technology Data Exchange (ETDEWEB)

    Goncalves, S. [CIRIMAT Equipe de Physico-Chimie des Phosphates ENSCT INP, Toulouse (France); TEKNIMED, Vic en Bigorre (France); Brouchet, A.; Delisle, B. [CHU Rangueil, Toulouse (France). Service d' Anatomie Pathologie; Freche, M.; Lacout, J.L. [CIRIMAT Equipe de Physico-Chimie des Phosphates ENSCT INP, Toulouse (France); Rodriguez, F. [Lab. de Galenique, Chmin des Maraichers, Toulouse (France)

    2001-07-01

    In orthopedic surgery, the loss or the reinforcement of osseous substance often requires filling of the defective part. In order to make the surgical operations easier we sought to make an injectable form. This study examined the effect of silicone and polyglycol on the injectability, setting time and mechanical properties of the cement. The basic solid phase was composed of a mixture of tetracalcium phosphate (Ca{sub 4}(PO{sub 4}){sub 2}O), {alpha}-tricalcium phosphate (Ca{sub 3}(PO{sub 4}){sub 2}) and sodium glycerophosphate. The basic liquid phase was made up of lime, orthophosphoric acid and water. Silicone was previously dissolved in cyclohexane and introduced in the solid phase. Polyglycol is a water-soluble compound so it is introduced in the liquid phase. For the mechanical properties, the strong increase in the percentage of additives decreased the compressive strength. Silicone and polyglycol made it possible to improve viscosity without modifying the basic setting time. The rate of evolution was different with the two different additives. From the data it was possible to optimize the formulation of cements to give predicted properties. Testing the in vivo implantation of the cement has already started. Preliminary results show the perfect osteointegration of the new cements without reactions to the foreign body in spite of the presence of silicone. (orig.)

  14. New covariant Lagrange formulation for field theories

    CERN Document Server

    Ootsuka, T

    2012-01-01

    A novel approach for Lagrange formulation for field theories is proposed in terms of Kawaguchi geometry (areal metric space). On the extended configuration space M for classical field theory composed of spacetime and field configuration space, one can define a geometrical structure called Kawaguchi areal metric K from the field Lagrangian and (M,K) can be regarded as Kawaguchi manifold. The geometrical action functional is given by K and the dynamics of field is determined by covariant Euler-Lagrange equation derived from the variational principle of the action. The solution to the equation becomes a minimal hypersurface on (M,K) which has the same dimension as spacetime. We propose that this hypersurface is what we should regard as our real spacetime manifold, while the usual way to understand spacetime is to consider it as the parameter spacetime (base manifold) of a fibre bundle. In this way, the dynamics of field and spacetime structure is unified by Kawaguchi geometry. The theory has the property of stro...

  15. A quasilinear formulation of turbulence driven current

    Energy Technology Data Exchange (ETDEWEB)

    McDevitt, C. J.; Tang, Xian-Zhu; Guo, Zehua [Theoretical Division, Los Alamos National Laboratory, Los Alamos, New Mexico 87545 (United States)

    2014-02-15

    Non-inductive current drive mechanisms, such as the familiar neoclassical bootstrap current correspond to an essential component to the realization of steady state tokamak operation. In this work, we discuss a novel collisionless mechanism through which a mean plasma current may be driven in the presence of microturbulence. In analogy with the traditional neoclassical bootstrap current drive mechanism, in which the collisional equilibrium established between trapped and passing electrons results in the formation of a steady state plasma current, here we show that resonant scattering of electrons by drift wave microturbulence provides an additional means of determining the equilibrium between trapped and passing electrons. The resulting collisionless equilibrium is shown to result in the formation of an equilibrium current whose magnitude is a function of the thermodynamic forces. A mean field formulation is utilized to incorporate the above components into a unified framework through which both collisional as well as collisionless current drive mechanisms may be self-consistently treated. Utilizing a linearized Fokker-Planck collision operator, the plasma current in the presence of both collisions as well as turbulent stresses is computed, allowing for the relative strength of these two mechanisms to be quantified as a function of collisionality and fluctuation amplitude.

  16. Controlled Release Formulations of Auxinic Herbicides

    Science.gov (United States)

    Kowalski, Witold J.; Siłowiecki, Andrzej.; Romanowska, Iwona; Glazek, Mariola; Bajor, Justyna; Cieciwa, Katarzyna; Rychter, Piotr

    2013-04-01

    Controlled release formulations are applied extensively for the release of active ingredients such as plant protection agents and fertilizers in response to growing concern for ecological problems associated with increased use of plant protection chemicals required for intensive agricultural practices [1]. We synthesized oligomeric mixtures of (R,S)-3-hydroxy butyric acid chemically bonded with 2,4-D, Dicamba and MCPA herbicides (HBA) respectively, and determined their molecular structure and molecular weight dispersion by the size exclusion chromatography, proton magnetic resonance spectrometry and electro-spray ionization mass spectrometry. Further we carried out bioassays of herbicidal effectiveness of the HBA herbicides vs. series of dicotyledonous weeds and crop injury tests [2, 3, 4]. Field bioassays were accomplished according to the EPPO standards [5]. Groups of representative weeds (the development stages in the BCCH scale: 10 - 30) were selected as targets. Statistical variabilities were assessed by the Fisher LSD test for plants treated with the studied herbicides in form of HBA oligomers, the reference herbicides in form of dimethyl ammonium salts (DMA), and untreated plants. No statistically significant differences in the crop injuries caused by the HBA vs. the DMA reference formulation were observed. The effectiveness of the HBA herbicides was lower through the initial period (ca. 2 weeks) relative to the DMA salts, but a significant increase in the effectiveness of the HBA systems followed during the remaining fraction of each assay. After 6 weeks all observed efficiencies approached 100%. The death of weeds treated with the HBA herbicides was delayed when compared with the DMA reference herbicides. The delayed uptake observed for the HBA oligomers relative to the DMA salts was due to controlled release phenomena. In case of the DMA salts the total amount of active ingredients was available at the target site. By contrast, the amount of an active

  17. Solubilizing excipients in oral and injectable formulations.

    Science.gov (United States)

    Strickley, Robert G

    2004-02-01

    A review of commercially available oral and injectable solution formulations reveals that the solubilizing excipients include water-soluble organic solvents (polyethylene glycol 300, polyethylene glycol 400, ethanol, propylene glycol, glycerin, N-methyl-2-pyrrolidone, dimethylacetamide, and dimethylsulfoxide), non-ionic surfactants (Cremophor EL, Cremophor RH 40, Cremophor RH 60, d-alpha-tocopherol polyethylene glycol 1000 succinate, polysorbate 20, polysorbate 80, Solutol HS 15, sorbitan monooleate, poloxamer 407, Labrafil M-1944CS, Labrafil M-2125CS, Labrasol, Gellucire 44/14, Softigen 767, and mono- and di-fatty acid esters of PEG 300, 400, or 1750), water-insoluble lipids (castor oil, corn oil, cottonseed oil, olive oil, peanut oil, peppermint oil, safflower oil, sesame oil, soybean oil, hydrogenated vegetable oils, hydrogenated soybean oil, and medium-chain triglycerides of coconut oil and palm seed oil), organic liquids/semi-solids (beeswax, d-alpha-tocopherol, oleic acid, medium-chain mono- and diglycerides), various cyclodextrins (alpha-cyclodextrin, beta-cyclodextrin, hydroxypropyl-beta-cyclodextrin, and sulfobutylether-beta-cyclodextrin), and phospholipids (hydrogenated soy phosphatidylcholine, distearoylphosphatidylglycerol, L-alpha-dimyristoylphosphatidylcholine, L-alpha-dimyristoylphosphatidylglycerol). The chemical techniques to solubilize water-insoluble drugs for oral and injection administration include pH adjustment, cosolvents, complexation, microemulsions, self-emulsifying drug delivery systems, micelles, liposomes, and emulsions.

  18. Formulation study of tea tree oil patches.

    Science.gov (United States)

    Minghetti, Paola; Casiraghi, Antonella; Cilurzo, Francesco; Gambaro, Veniero; Montanari, Luisa

    2009-01-01

    The antimicrobial, antifungal and anti-inflammatory properties of tea tree oil (TTO), the essential oil of Melaleuca alternifolia are well documented. In order to optimize its therapeutic activity, TTO patches were designed. The aim of this work was the formulation of monolayer patches containing TTO. Moreover, the performance of oleic acid (OA) as a skin penetration enhancer in patches was evaluated. Terpinen-4-ol (T4OL), the main component of TTO, was the marker used to evaluate TTO skin permeability. The permeation study was performed through human epidermis by using Franz diffusion cells. Patches were prepared by using methacrylic copolymers, Eudragit E100 (EuE100) or Eudragit NE (EuNE), and a silicone resin, BioPSA7-4602 (Bio-PSA). TTO and OA contents were fixed at 10% w/w and 3% w/w, respectively. The patches were prepared by a casting method and characterised in terms of T4OL content and skin permeability. All the selected polymers were suitable as the main component of the patch matrix. Since the main critical issue in the use of TTO is related to its toxicity after absorption, the local administration of TTO can take advantage of the use of patches based on EuE100 because of the high retained amount and the low permeation of T4OL. In this matrix, OA slightly increased the T4OL retained amount, improving the efficacy and safety of TTO patches.

  19. Analytical formulation of lunar cratering asymmetries

    CERN Document Server

    Wang, Nan

    2016-01-01

    We formulate the lunar cratering distribution and verify the cratering asymmetries generated by the main-belt asteroids (MBAs) as well as the near-Earth objects (NEOs). Based on a planar model that excludes the terrestrial and lunar gravitations on the impactors and assuming the impactor encounter speed with Earth $v_{\\rm{enc}}$ is higher than the lunar orbital speed $v_{\\rm{M}}$, we rigorously integrated the lunar cratering distribution, and derived its approximation to the first order of $v_{\\rm{M}}/v_{\\rm{enc}}$. Numerical simulations of lunar bombardment by the MBAs during the late heavy bombardment were performed with an Earth-Moon distance $a_{\\rm{M}}$ = 20--60 Earth radii in five cases. The analytical model directly proves the existence of a leading/trailing asymmetry and the absence of near/far asymmetry. The approximate form of the leading/trailing asymmetry is $(1 + A_1 \\cos\\beta)$, which decreases as the apex distance $\\beta$ increases. The numerical simulations show evidence of a pole/equator asym...

  20. A thermodynamic formulation of root water uptake

    Science.gov (United States)

    Hildebrandt, Anke; Kleidon, Axel; Bechmann, Marcel

    2016-08-01

    By extracting bound water from the soil and lifting it to the canopy, root systems of vegetation perform work. Here we describe how root water uptake can be evaluated thermodynamically and demonstrate that this evaluation provides additional insights into the factors that impede root water uptake. We derive an expression that relates the energy export at the base of the root system to a sum of terms that reflect all fluxes and storage changes along the flow path in thermodynamic terms. We illustrate this thermodynamic formulation using an idealized setup of scenarios with a simple model. In these scenarios, we demonstrate why heterogeneity in soil water distribution and rooting properties affect the impediment of water flow even though the mean soil water content and rooting properties are the same across the scenarios. The effects of heterogeneity can clearly be identified in the thermodynamics of the system in terms of differences in dissipative losses and hydraulic energy, resulting in an earlier start of water limitation in the drying cycle. We conclude that this thermodynamic evaluation of root water uptake conveniently provides insights into the impediments of different processes along the entire flow path, which goes beyond resistances and also accounts for the role of heterogeneity in soil water distribution.

  1. Biosurfactants in cosmetic formulations: trends and challenges.

    Science.gov (United States)

    Vecino, X; Cruz, J M; Moldes, A B; Rodrigues, L R

    2017-01-12

    Cosmetic products play an essential role in everyone's life. People everyday use a large variety of cosmetic products such as soap, shampoo, toothpaste, deodorant, skin care, perfume, make-up, among others. The cosmetic industry encompasses several environmental, social and economic impacts that are being addressed through the search for more efficient manufacturing techniques, the reduction of waste and emissions and the promotion of personal hygiene, contributing to an improvement of public health and at the same time providing employment opportunities. The current trend among consumers is the pursuit for natural ingredients in cosmetic products, as many of these products exhibit equal, better or additional benefits in comparison with the chemical-based products. In this sense, biosurfactants are natural compounds with great potential in the formulation of cosmetic products given by their biodegradability and impact in health. Indeed, many of these biosurfactants could exhibit a "prebiotic" character. This review covers the current state-of-the-art of biosurfactant research for cosmetic purposes and further discusses the future challenges for cosmetic applications.

  2. Modern Vaccines/Adjuvants Formulation Session 6: Vaccine &Adjuvant Formulation & Production 15-17 May 2013, Lausanne, Switzerland.

    Science.gov (United States)

    Fox, Christopher B

    2013-09-01

    The Modern Vaccines/Adjuvants Formulation meeting aims to fill a critical gap in current vaccine development efforts by bringing together formulation scientists and immunologists to emphasize the importance of rational formulation design in order to optimize vaccine and adjuvant bioactivity, safety, and manufacturability. Session 6 on Vaccine and Adjuvant Formulation and Production provided three examples of this theme, with speakers emphasizing the need for extensive physicochemical characterization of adjuvant-antigen interactions, the rational formulation design of a CD8+ T cell-inducing adjuvant based on immunological principles, and the development and production of a rabies vaccine by a developing country manufacturer. Throughout the session, the practical importance of sound formulation and manufacturing design accompanied by analytical characterization was highlighted.

  3. The operator tensor formulation of quantum theory.

    Science.gov (United States)

    Hardy, Lucien

    2012-07-28

    In this paper, we provide what might be regarded as a manifestly covariant presentation of discrete quantum theory. A typical quantum experiment has a bunch of apparatuses placed so that quantum systems can pass between them. We regard each use of an apparatus, along with some given outcome on the apparatus (a certain detector click or a certain meter reading for example), as an operation. An operation (e.g. B(b(2)a(3))(a(1))) can have zero or more quantum systems inputted into it and zero or more quantum systems outputted from it. The operation B(b(2)a(3))(a(1)) has one system of type a inputted, and one system of type b and one system of type a outputted. We can wire together operations to form circuits, for example, A(a(1))B(b(2)a(3))(a(1))C(b(2)a(3)). Each repeated integer label here denotes a wire connecting an output to an input of the same type. As each operation in a circuit has an outcome associated with it, a circuit represents a set of outcomes that can happen in a run of the experiment. In the operator tensor formulation of quantum theory, each operation corresponds to an operator tensor. For example, the operation B(b(2)a(3))(a(1)) corresponds to the operator tensor B(b(2)a(3))(a(1)). Further, the probability for a general circuit is given by replacing operations with corresponding operator tensors as in Prob(A(a(1))B(b(2)a(3))(a(1))C(b(2)a(3))) = Â(a(1))B(b(2)a(3))(a(1))C(b(2)a(3)). Repeated integer labels indicate that we multiply in the associated subspace and then take the partial trace over that subspace. Operator tensors must be physical (namely, they must have positive input transpose and satisfy a certain normalization condition).

  4. An exact formulation of hyperdynamics simulations

    Science.gov (United States)

    Chen, L. Y.; Horing, N. J. M.

    2007-06-01

    We introduce a new formula for the acceleration weight factor in the hyperdynamics simulation method, the use of which correctly provides an exact simulation of the true dynamics of a system. This new form of hyperdynamics is valid and applicable where the transition state theory (TST) is applicable and also where the TST is not applicable. To illustrate this new formulation, we perform hyperdynamics simulations for four systems ranging from one degree of freedom to 591 degrees of freedom: (1) We first analyze free diffusion having one degree of freedom. This system does not have a transition state. The TST and the original form of hyperdynamics are not applicable. Using the new form of hyperdynamics, we compute mean square displacement for a range of time. The results obtained agree perfectly with the analytical formula. (2) Then we examine the classical Kramers escape rate problem. The rate computed is in perfect agreement with the Kramers formula over a broad range of temperature. (3) We also study another classical problem: Computing the rate of effusion out of a cubic box through a tiny hole. This problem does not involve an energy barrier. Thus, the original form of hyperdynamics excludes the possibility of using a nonzero bias and is inappropriate. However, with the new weight factor formula, our new form of hyperdynamics can be easily implemented and it produces the exact results. (4) To illustrate applicability to systems of many degrees of freedom, we analyze diffusion of an atom adsorbed on the (001) surface of an fcc crystal. The system is modeled by an atom on top of a slab of six atomic layers. Each layer has 49 atoms. With the bottom two layers of atoms fixed, this system has 591 degrees of freedom. With very modest computing effort, we are able to characterize its diffusion pathways in the exchange-with-the-substrate and hop-over-the-bridge mechanisms.

  5. Formulating liquid ethers for microtubular SOFCs

    Science.gov (United States)

    Kendall, Kevin; Slinn, Matthew; Preece, John

    One of the key problems of applying solid oxide fuel cells (SOFCs) in transportation is that conventional fuels like kerosene and diesel do not operate directly in SOFCs without prereforming to hydrogen and carbon monoxide which can be handled by the nickel cermet anode. SOFCs can internally reform certain hydrocarbon molecules such as methanol and methane. However, other liquid fuels usable in petrol or diesel internal combustion engines (ICEs) have not easily been reformable directly on the anode. This paper describes a search for liquid fuels which can be mixed with petrol or diesel and also injected directly into an SOFC without destroying the nickel anode. When fuel molecules such as octane are injected onto the conventional nickel/yttria stabilised zirconia (Ni/YSZ) SOFC fuel electrode, the anode rapidly becomes blocked by carbon deposition and the cell power drops to near zero in minutes. This degeneration of the anode can be inhibited by injection of air or water into the anode or by some upstream reforming just before entry to the SOFC. Some smaller molecules such as methane, methanol and methanoic acid produce a slight tendency to carbon deposition but not sufficient to prevent long term operation. In this project we have investigated a large number of molecules and now found that some liquid ethers do not significantly damage the anode when directly injected. These molecules and formulations with other components have been evaluated in this study. The theory put forward in this paper is that carbon-carbon bonds in the fuel are the main reason for anode damage. By testing a number of fuels without such bonds, particularly liquid ethers such as methyl formate and dimethoxy methane, it has been shown that SOFCs can run without substantial carbon formation. The proposal is that conventional fuels can be doped with these molecules to allow hybrid operation of an ICE/SOFC device.

  6. FORMULATION AND EVALUATION OF CARVEDILOL TRANSDERMAL PATCHES

    Directory of Open Access Journals (Sweden)

    Mandal Sonjoy

    2011-01-01

    Full Text Available The present study was carried out to develop and evaluate matrix-type transdermal formulations containing carvedilol with different ratios of hydrophilic (HPMC and hydrophobic polymeric (Eudragit RS100 combinations plasticized with glycerin and dibutyl pthalate by the solvent evaporation technique. Effect of surfactant (PEG-400 and Tween 80 and permeation enhancers (DMSO and DMF were studied. The interference of the polymers were ruled out by infrared and uv spectroscopic methods. Viscosity of the polymers was determined using Brookfield viscometer (LVDV-E. The partition coefficient study was performed using n-octanol as the organic phase and phosphate buffer pH 7.4 as an aqueous phase. The prepared patches were tested for their physicochemical characteristics such as thickness, weight, and drug content uniformity, swelling index, water vapour transmission, folding endurance, and tensile strength. In vitro release studies of carvedilol-loaded patches in phosphate buffer (pH, 7.4 exhibited drug release in the range of 80.70 to 98.56 % in 24 h. Data of in vitro release from patches were fit in to different equations and kinetic models to explain release kinetics. The models used were zero and first-order equations, Hixon-Crowell, Higuchi and Korsmeyer-Peppas models. Based on physicochemical and in vitro release studies, patches containing HPMC and Eudragit RS 100 (DMSO as permeation enhancer were chosen for in vitro skin permeation studies which were performed using a modified diffusion cell across rat abdominal skin and showed first order release mechanism. Skin studies for the transdermal patches were assessed and were found to be free of irritation. The patches were subjected to short term stability studies and were found stable. Good correlation was observed (R2 = 0.810 with in vitro release Vs in vitro skin permeation studies.

  7. Pharmacokinetics of Intranasal Scopolamine Gel Formulation (Inscop)

    Science.gov (United States)

    Boyd, Jason L.; Du, Brian; Daniels, Vernie; Simmons, Rita; Buckey, Jay; Putcha, Lakshmi

    2009-01-01

    Space Motion Sickness (SMS) is commonly experienced by astronauts and often requires treatment with medications during early flight days of space missions. Orally administered scopolamine is commonly used by astronauts to prevent SMS. Bioavailability of oral (PO) SMS medications is often low and highly variable. Intranasal (IN) administration of medications achieves higher and more reliable bioavailability than from an equivalent PO dose. Methods: To test the safety and reliability of INSCOP, two clinical studies were performed, a dose escalation study and a comparison study administering INSCOP during normal ambulation and head down tilt bedrest. Efficacy was evaluated by testing INSCOP with two, different motion sickness inducing paradigms. Results: Preliminary results indicate that INSCOP demonstrates linear pharmacokinetics and a low side effect profile. In head down tilt bedrest, relative bioavailability of INSCOP was increased for females at both doses (0.2 and 0.4 mg) and for males at the higher dose (0.4 mg) but is reduced at the lower dose (0.2 mg) compared to normal ambulation. INSCOP displays gender specific differences during ABR. One of the treatment efficacy trials conducted at Dartmouth Hitchcock Medical Center demonstrated that INSCOP is efficacious at both doses (0.2 and 0.4 mg) in suppressing motion sickness symptoms as indicated by longer chair ride times with INSCOP administration than with placebo, and efficacy increases with dose. Similar results were seen using another motion sickness simulator, the motion simulator dome, at the Naval Aerospace Medical Research Laboratory, with significantly increased time in the dome in motion-susceptible subjects when using INSCOP compared to untreated controls. Conclusion: Higher bioavailability, linear pharmacokinetics, a low incidence of side effects, and a favorable efficacy profile make INSCOP a desirable formulation for prophylactic and rescue treatment of astronauts in space and military personnel on

  8. Reliability based design optimization: Formulations and methodologies

    Science.gov (United States)

    Agarwal, Harish

    Modern products ranging from simple components to complex systems should be designed to be optimal and reliable. The challenge of modern engineering is to ensure that manufacturing costs are reduced and design cycle times are minimized while achieving requirements for performance and reliability. If the market for the product is competitive, improved quality and reliability can generate very strong competitive advantages. Simulation based design plays an important role in designing almost any kind of automotive, aerospace, and consumer products under these competitive conditions. Single discipline simulations used for analysis are being coupled together to create complex coupled simulation tools. This investigation focuses on the development of efficient and robust methodologies for reliability based design optimization in a simulation based design environment. Original contributions of this research are the development of a novel efficient and robust unilevel methodology for reliability based design optimization, the development of an innovative decoupled reliability based design optimization methodology, the application of homotopy techniques in unilevel reliability based design optimization methodology, and the development of a new framework for reliability based design optimization under epistemic uncertainty. The unilevel methodology for reliability based design optimization is shown to be mathematically equivalent to the traditional nested formulation. Numerical test problems show that the unilevel methodology can reduce computational cost by at least 50% as compared to the nested approach. The decoupled reliability based design optimization methodology is an approximate technique to obtain consistent reliable designs at lesser computational expense. Test problems show that the methodology is computationally efficient compared to the nested approach. A framework for performing reliability based design optimization under epistemic uncertainty is also developed

  9. Liposomal cisplatin: a new cisplatin formulation.

    Science.gov (United States)

    Stathopoulos, George P

    2010-09-01

    Over the last three decades, cisplatin has been one of the most effective cytotoxic agents, but its administration has been hindered by its nephrotoxicity, neurotoxicity and myelo toxicity. Recently, liposomal cisplatin, lipoplatin, has been formulated and tested thoroughly in preclinical (in vitro) and phase I, II and III trials, as documented in the literature. Experiments in animals showed that lipoplatin is less toxic than cisplatin and that it produces tumour reduction. The histological examination of treated tumours from mouse xenografts was consistent with apoptosis in the tumour cells in a mechanism similar to that of cisplatin. Lipoplatin infusion in patients and measurements of platinum levels in tumour specimens showed 10-50 times higher levels in tumours and metastases than in the adjacent normal specimens. A phase I-II study using a combination of lipoplatin and gemcitabine in pretreated patients (with disease progression or stable disease) with advanced pancreatic cancer was conducted. No nephrotoxicity was observed. With lipoplatin monotherapy the dose-limiting toxicity was determined to be 350 mg/m and the maximum tolerated dose 300 mg/m; when used in combination with paclitaxel the dose-limiting toxicity for lipoplatin was 250 mg/m and for paclitaxel 175 mg/m, and the maximum tolerated dose was 200 and 175 mg/m, respectively. In two phase II randomized studies comparing the lipoplatin combination versus the cisplatin combination, it was found that the former was statistically significantly less toxic than the latter, whereas the response rate and survival were similar. Up to now, the data on lipoplatin treatment in malignant tumours are quite impressive, because of the negligible toxicity and because it is equal if not superior to cisplatin with regard to response rate. This review aims to chronologically document publications relevant to liposomal cisplatin to date.

  10. A new formulation for feedforward neural networks.

    Science.gov (United States)

    Razavi, Saman; Tolson, Bryan A

    2011-10-01

    Feedforward neural network is one of the most commonly used function approximation techniques and has been applied to a wide variety of problems arising from various disciplines. However, neural networks are black-box models having multiple challenges/difficulties associated with training and generalization. This paper initially looks into the internal behavior of neural networks and develops a detailed interpretation of the neural network functional geometry. Based on this geometrical interpretation, a new set of variables describing neural networks is proposed as a more effective and geometrically interpretable alternative to the traditional set of network weights and biases. Then, this paper develops a new formulation for neural networks with respect to the newly defined variables; this reformulated neural network (ReNN) is equivalent to the common feedforward neural network but has a less complex error response surface. To demonstrate the learning ability of ReNN, in this paper, two training methods involving a derivative-based (a variation of backpropagation) and a derivative-free optimization algorithms are employed. Moreover, a new measure of regularization on the basis of the developed geometrical interpretation is proposed to evaluate and improve the generalization ability of neural networks. The value of the proposed geometrical interpretation, the ReNN approach, and the new regularization measure are demonstrated across multiple test problems. Results show that ReNN can be trained more effectively and efficiently compared to the common neural networks and the proposed regularization measure is an effective indicator of how a network would perform in terms of generalization.

  11. Cast Stone Formulation At Higher Sodium Concentrations

    Energy Technology Data Exchange (ETDEWEB)

    Fox, K. M.; Edwards, T. A.; Roberts, K. B.

    2013-10-02

    A low temperature waste form known as Cast Stone is being considered to provide supplemental Low Activity Waste (LAW) immobilization capacity for the Hanford site. Formulation of Cast Stone at high sodium concentrations is of interest since a significant reduction in the necessary volume of Cast Stone and subsequent disposal costs could be achieved if an acceptable waste form can be produced with a high sodium molarity salt solution combined with a high water to premix (or dry blend) ratio. The objectives of this study were to evaluate the factors involved with increasing the sodium concentration in Cast Stone, including production and performance properties and the retention and release of specific components of interest. Three factors were identified for the experimental matrix: the concentration of sodium in the simulated salt solution, the water to premix ratio, and the blast furnace slag portion of the premix. The salt solution simulants used in this study were formulated to represent the overall average waste composition. The cement, blast furnace slag, and fly ash were sourced from a supplier in the Hanford area in order to be representative. The test mixes were prepared in the laboratory and fresh properties were measured. Fresh density increased with increasing sodium molarity and with decreasing water to premix ratio, as expected given the individual densities of these components. Rheology measurements showed that all of the test mixes produced very fluid slurries. The fresh density and rheology data are of potential value in designing a future Cast Stone production facility. Standing water and density gradient testing showed that settling is not of particular concern for the high sodium compositions studied. Heat of hydration measurements may provide some insight into the reactions that occur within the test mixes, which may in turn be related to the properties and performance of the waste form. These measurements showed that increased sodium

  12. Cast Stone Formulation At Higher Sodium Concentrations

    Energy Technology Data Exchange (ETDEWEB)

    Fox, K. M.; Roberts, K. A.; Edwards, T. B.

    2014-02-28

    A low temperature waste form known as Cast Stone is being considered to provide supplemental Low Activity Waste (LAW) immobilization capacity for the Hanford site. Formulation of Cast Stone at high sodium concentrations is of interest since a significant reduction in the necessary volume of Cast Stone and subsequent disposal costs could be achieved if an acceptable waste form can be produced with a high sodium molarity salt solution combined with a high water to premix (or dry blend) ratio. The objectives of this study were to evaluate the factors involved with increasing the sodium concentration in Cast Stone, including production and performance properties and the retention and release of specific components of interest. Three factors were identified for the experimental matrix: the concentration of sodium in the simulated salt solution, the water to premix ratio, and the blast furnace slag portion of the premix. The salt solution simulants used in this study were formulated to represent the overall average waste composition. The cement, blast furnace slag, and fly ash were sourced from a supplier in the Hanford area in order to be representative. The test mixes were prepared in the laboratory and fresh properties were measured. Fresh density increased with increasing sodium molarity and with decreasing water to premix ratio, as expected given the individual densities of these components. Rheology measurements showed that all of the test mixes produced very fluid slurries. The fresh density and rheology data are of potential value in designing a future Cast Stone production facility. Standing water and density gradient testing showed that settling is not of particular concern for the high sodium compositions studied. Heat of hydration measurements may provide some insight into the reactions that occur within the test mixes, which may in turn be related to the properties and performance of the waste form. These measurements showed that increased sodium

  13. Cast Stone Formulation At Higher Sodium Concentrations

    Energy Technology Data Exchange (ETDEWEB)

    Fox, K. M.; Roberts, K. A.; Edwards, T. B.

    2013-09-17

    A low temperature waste form known as Cast Stone is being considered to provide supplemental Low Activity Waste (LAW) immobilization capacity for the Hanford site. Formulation of Cast Stone at high sodium concentrations is of interest since a significant reduction in the necessary volume of Cast Stone and subsequent disposal costs could be achieved if an acceptable waste form can be produced with a high sodium molarity salt solution combined with a high water to premix (or dry blend) ratio. The objectives of this study were to evaluate the factors involved with increasing the sodium concentration in Cast Stone, including production and performance properties and the retention and release of specific components of interest. Three factors were identified for the experimental matrix: the concentration of sodium in the simulated salt solution, the water to premix ratio, and the blast furnace slag portion of the premix. The salt solution simulants used in this study were formulated to represent the overall average waste composition. The cement, blast furnace slag, and fly ash were sourced from a supplier in the Hanford area in order to be representative. The test mixes were prepared in the laboratory and fresh properties were measured. Fresh density increased with increasing sodium molarity and with decreasing water to premix ratio, as expected given the individual densities of these components. Rheology measurements showed that all of the test mixes produced very fluid slurries. The fresh density and rheology data are of potential value in designing a future Cast Stone production facility. Standing water and density gradient testing showed that settling is not of particular concern for the high sodium compositions studied. Heat of hydration measurements may provide some insight into the reactions that occur within the test mixes, which may in turn be related to the properties and performance of the waste form. These measurements showed that increased sodium

  14. In vitro study on sustained release capsule formulation of acetazolamide.

    Science.gov (United States)

    Pandey, V P; Kannan, K; Manavalan, R; Desai, N

    2003-10-01

    In the present study formulation of sustained release capsule of acetazolamide 250 mg was tried using nonpareil seeds. Nonpareil seeds were coated with drug, polyvinylpyrrolidone, glyceryl monostearate, microcrystalline wax, and glyceryl distearate either individually or in combination to achieve sustained release capsule 250 mg. In successful formulation 20% drug coated pellets and 80% wax coated pellets were taken. Wax coated pellets for successful formulation contained coating of microcrystalline wax and glyceryl distearate on drug coated pellets of the same concentration of 1.6% w/w. Successful formulated sustained release capsule 250 mg of acetazolamide was compared in in vitro study with theoretical sustained release formulation suggested by wagner and one marketed sustained release capsule 250 mg. Formulated capsule showed result superior to or on par with marketed capsule. For successful formulation pellets were filled in '1' size hard gelatin capsule and stability study was carried out in hot air over at room temperature and 45 degrees C for 5 weeks. The formulation was found stable in respect of drug content and release rate.

  15. Dermal pharmacokinetics of microemulsion formulations determined by in vivo microdialysis

    DEFF Research Database (Denmark)

    Kreilgaard, Mads

    2001-01-01

    To investigate the potential of improving dermal drug delivery of hydrophilic and lipophilic substances by formulation in microemulsion vehicles and to establish a reliable pharmacokinetic model to analyze cutaneous microdialysis data.......To investigate the potential of improving dermal drug delivery of hydrophilic and lipophilic substances by formulation in microemulsion vehicles and to establish a reliable pharmacokinetic model to analyze cutaneous microdialysis data....

  16. Enabling Strategy Formulation by ICT: A Viable Systems Approach

    NARCIS (Netherlands)

    Vriens, D.J.; Achterbergh, J.M.I.M.

    2004-01-01

    In this chapter the role of ICT for competitive intelligence is approached from the perspective of strategy formulation. The authors hold the view that competitive intelligence can be seen as knowledge necessary for the process of strategy formulation. To determine the role of ICT, it is proposed to

  17. Formulation of Higher Education Institutional Strategy Using Operational Research Approaches

    Science.gov (United States)

    Labib, Ashraf; Read, Martin; Gladstone-Millar, Charlotte; Tonge, Richard; Smith, David

    2014-01-01

    In this paper a framework is proposed for the formulation of a higher education institutional (HEI) strategy. This work provides a practical example, through a case study, to demonstrate how the proposed framework can be applied to the issue of formulation of HEI strategy. The proposed hybrid model is based on two operational research…

  18. Kepler Problem in Lagrangian Formulation Discussed from Topological Viewpoint

    Institute of Scientific and Technical Information of China (English)

    XU Gong-Ou; XU Ming-Jie

    2005-01-01

    @@ The Kepler problem in Lagrangian formulation is discussed from the topological viewpoint. Essential points are analysed. Along the same line of thoughts, it is possible to study the Kepler problem in Hamiltonian formulation as well as in quantum mechanics from the topological viewpoint for showing quantum-classical correspondence.

  19. Formulation and stability of topical water in oil emulsion containing ...

    African Journals Online (AJOL)

    Purpose: To formulate the water in oil (W/O) emulsion of corn silk (CS) extract and to evaluate its ... physical stability of the formulation was evaluated by monitoring these parameters over a period .... level of significance adopted was p < 0.05.

  20. Robertson-Schrödinger formulation of Ozawa's uncertainty principle

    Science.gov (United States)

    Bastos, Catarina; Bernardini, Alex E.; Bertolami, Orfeu; Costa Dias, Nuno; Nuno Prata, João

    2015-07-01

    A more general measurement disturbance uncertainty principle is presented in a Robertson-Schrödinger formulation. It is shown that it is stronger and having nicer properties than Ozawa's uncertainty relations. In particular it is invariant under symplectic transformations. One shows also that there are states of the probe (measuring device) that saturate the matrix formulation of measurement disturbance uncertainty principle.

  1. Robertson-Schr\\"odinger formulation of Ozawa's Uncertainty Principle

    CERN Document Server

    Bastos, Catarina; Bertolami, O; Dias, N C; Prata, J N

    2014-01-01

    A more general measurement disturbance uncertainty principle is presented in a Robertson-Schr\\"odinger formulation. It is shown that it is stronger and having nicer properties than Ozawa's uncertainty relations. In particular is invariant under symplectic transformations. One shows also that there are states of the probe (measuring device) that saturate the matrix formulation of measurement disturbance uncertainty principle.

  2. Enabling Strategy Formulation by ICT: A Viable Systems Approach

    NARCIS (Netherlands)

    Vriens, D.J.; Achterbergh, J.M.I.M.

    2004-01-01

    In this chapter the role of ICT for competitive intelligence is approached from the perspective of strategy formulation. The authors hold the view that competitive intelligence can be seen as knowledge necessary for the process of strategy formulation. To determine the role of ICT, it is proposed to

  3. Mixed finite element formulation applied to shape optimization

    Science.gov (United States)

    Rodrigues, Helder; Taylor, John E.; Kikuchi, Noboru

    1988-01-01

    The development presented introduces a general form of mixed formulation for the optimal shape design problem. The associated optimality conditions are easily obtained without resorting to highly elaborate mathematical developments. Also, the physical significance of the adjoint problem is clearly defined with this formulation.

  4. Influence of Seed Coating Formulations on Maize Production

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Effects of four coating formulations on maize production were studied. The results showec that all coating formulations had some effects on improving maize seedlings, strengthening the resistance againt diseases and pests and increasing the yields in dtifferent degrees, especially Paxil which increased the com yield by 12.0%, significantly higher than the control.

  5. Formulation of Higher Education Institutional Strategy Using Operational Research Approaches

    Science.gov (United States)

    Labib, Ashraf; Read, Martin; Gladstone-Millar, Charlotte; Tonge, Richard; Smith, David

    2014-01-01

    In this paper a framework is proposed for the formulation of a higher education institutional (HEI) strategy. This work provides a practical example, through a case study, to demonstrate how the proposed framework can be applied to the issue of formulation of HEI strategy. The proposed hybrid model is based on two operational research…

  6. Formulation of indomethacin emulsion using biopolymer of Prunus avium.

    Science.gov (United States)

    Verma, Shivangi; Dabral, Prashant; Rana, Vinod; Upadhaya, Kumud; Bhardwaj

    2012-03-01

    The aim of the investigation was to formulate Indomethacin Emulsion using Bio-polymer as Emulsifier. Different batches of emulsions were prepared by varying concentration of biopolymer prunus avium. Based evaluation of the prepared polymers, a conclusion can be drawn that in the Prunus avium bio-material can serve as a promising film forming agent for formulating various drug.

  7. Formulation of indomethacin emulsion using biopolymer of Prunus avium

    Directory of Open Access Journals (Sweden)

    Shivangi Verma

    2012-01-01

    Full Text Available The aim of the investigation was to formulate Indomethacin Emulsion using Bio-polymer as Emulsifier. Different batches of emulsions were prepared by varying concentration of biopolymer prunus avium. Based evaluation of the prepared polymers, a conclusion can be drawn that in the Prunus avium bio-material can serve as a promising film forming agent for formulating various drug.

  8. Formulation and Evaluation of Aceclofenac Loaded Cubosomal Topical Gel

    Directory of Open Access Journals (Sweden)

    K. Bhargavi

    2015-11-01

    Full Text Available The aim of present work was to formulate and evaluate sustained release formulation of Aceclofenac a Non -steroidal anti-inflammatory drug (NSAID, as cubosomal topical gel to reduce gastro intestinal effects and to improve the bioavailability of the drug. Different formulations of Aceclofenac cubosomes were prepared by Top down approach using GMO as lipid phase vehicle, Poloxamer 407 as stabilizer and distilled water as aqueous phase by varying the concentrations of GMO and Poloxamer 407. Resultant formulations were characterized for particle size, zeta potential, surface morphology, encapsulation efficiency and in-vitro drug release. Optimized formulation (F10 showed drug release of 83.25% in 8hours. Aceclofenac cubosomal gel was prepared by using optimized cubosomal formulation (F10, Carbopol 940,Carbopol 934, HPMC K4M and HPMC 15M.Gels were evaluated for pH, viscosity, drug content and in-vitro drug diffusion studies. Among all the preparations, formulation G2 was found to show entrapment efficiency of 96.85 and in vitro drug release of 78.5%. Ex-vivo permeation of optimized gel formulation (D2 was evaluated across rat epidermis.

  9. Computer-Assisted Instruction; How to Solve Drug Formulation Problems.

    Science.gov (United States)

    Mezei, Janos; And Others

    1990-01-01

    Computer simulation of drug formulation problems involves a database of pharmacological properties, chemical stability, and compatibility data on 20 active ingredients, physiological factors and requirements for parenteral solutions, and additives. The user gathers data from the database, formulates a stable and effective solution, and the drug is…

  10. Effect of formulation pH on transdermal penetration of antiemetics formulated in poloxamer lecithin organogel.

    Science.gov (United States)

    Woodall, Rachel; Arnold, John J; McKay, Doug; Asbill, C Scott

    2013-01-01

    The purpose of this study was to assess the impact of altering formulation pH on the transdermal penetration of several commonly used antiemetic, weakly basic drugs incorporated into poloxamer lecithin organogel vehicle. Poloxamer lecithin organogel formulations containing promethazine hydrochloride (25 mg/mL), metoclopramide hydrochloride (10 mg/mL), and ondansetron hydrochloride (8 mg/mL) were examined for both drug release and transdermal penetration across porcine skin in modified Franz diffusion cells for a period of 24 hours. For the transdermal studies, each antiemetic drug was formulated at a pH above and below their acid dissociation constant (pKa) in an attempt to assure that the drug would be primarily in their respective ionized or non-ionized states. In addition, drug content in skin was assessed at the end of the 24-hour experiment. Drug content analysis was determined via high-performance liquid chromatography. As a percent of total drug release from the poloxamer lecithin organogel vehicle, promethazine hydrochloride demonstrated the most transdermal drug penetration after 24 hours (30.2% +/- 20.2%), followed by ondansetron hydrochloride (2.7% +/- 1.1%) and metoclopramide hydrochloride (1.8% +/- 1.6%). Subsequently, the pH of the Pluronic F-127 gel was adjusted in order to ensure that each antiemetic drug would be primarily in its unionized state. The transdermal permeation of each antiemetic drug primarily in its unionized state increased over that observed with the drug primarily in its ionized state after 24 hours (promethazine: 1.6-fold increase; metoclopramide: 1.3-fold increase; ondansetron: 1.8-fold increase). A similar trend was noted in the amount of each drug found in the skin after 24 hours (promethazine: 1.2-fold increase; metoclopramide: 2.4-fold increase; ondansetron: 3.0-fold increase). These results suggest that proper optimization of drug ionization state may be a useful strategy for compounding pharmacists to increase the efficacy

  11. Matter coupling in partially constrained vielbein formulation of massive gravity

    Energy Technology Data Exchange (ETDEWEB)

    Felice, Antonio De [Yukawa Institute for Theoretical Physics, Kyoto University, Kyoto 606-8502 (Japan); Gümrükçüoğlu, A. Emir [School of Mathematical Sciences, University of Nottingham, University Park, Nottingham, NG7 2RD (United Kingdom); Heisenberg, Lavinia [Institute for Theoretical Studies, ETH Zurich,Clausiusstrasse 47, 8092 Zurich (Switzerland); Mukohyama, Shinji [Yukawa Institute for Theoretical Physics, Kyoto University, Kyoto 606-8502 (Japan); Kavli Institute for the Physics and Mathematics of the Universe,Todai Institutes for Advanced Study, University of Tokyo (WPI),5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8583 (Japan)

    2016-01-04

    We consider a linear effective vielbein matter coupling without introducing the Boulware-Deser ghost in ghost-free massive gravity. This is achieved in the partially constrained vielbein formulation. We first introduce the formalism and prove the absence of ghost at all scales. As next we investigate the cosmological application of this coupling in this new formulation. We show that even if the background evolution accords with the metric formulation, the perturbations display important different features in the partially constrained vielbein formulation. We study the cosmological perturbations of the two branches of solutions separately. The tensor perturbations coincide with those in the metric formulation. Concerning the vector and scalar perturbations, the requirement of absence of ghost and gradient instabilities yields slightly different allowed parameter space.

  12. Matter coupling in partially constrained vielbein formulation of massive gravity

    CERN Document Server

    De Felice, Antonio; Heisenberg, Lavinia; Mukohyama, Shinji

    2015-01-01

    We consider a consistent linear effective vielbein matter coupling without introducing the Boulware-Deser ghost in ghost-free massive gravity. This is achieved in the partially constrained vielbein formulation. We first introduce the formalism and prove the absence of ghost at all scales. As next we investigate the cosmological application of this coupling in this new formulation. We show that even if the background evolution accords with the metric formulation, the perturbations display important different features in the partially constrained vielbein formulation. We study the cosmological perturbations of the two branches of solutions separately. The tensor perturbations coincide with those in the metric formulation. Concerning the vector and scalar perturbations, the requirement of absence of ghost and gradient instabilities yields slightly different allowed parameter space.

  13. Matter coupling in partially constrained vielbein formulation of massive gravity

    Science.gov (United States)

    De Felice, Antonio; Gümrükçüoğlu, A. Emir; Heisenberg, Lavinia; Mukohyama, Shinji

    2016-01-01

    We consider a linear effective vielbein matter coupling without introducing the Boulware-Deser ghost in ghost-free massive gravity. This is achieved in the partially constrained vielbein formulation. We first introduce the formalism and prove the absence of ghost at all scales. As next we investigate the cosmological application of this coupling in this new formulation. We show that even if the background evolution accords with the metric formulation, the perturbations display important different features in the partially constrained vielbein formulation. We study the cosmological perturbations of the two branches of solutions separately. The tensor perturbations coincide with those in the metric formulation. Concerning the vector and scalar perturbations, the requirement of absence of ghost and gradient instabilities yields slightly different allowed parameter space.

  14. On the Correct Formulation of the First Law of Thermodynamics

    Science.gov (United States)

    Kalanov, Temur Z.

    2006-04-01

    The critical analysis of the generally accepted formulation of the first law of thermodynamics is proposed. The purpose of the analysis is to prove that the standard formulation contains a mathematical error and to offer the correct formulation. The correct formulation is based on the concepts of function and differential of function. Really, if internal energy Uof a system is a function of two independent variables Q=Q(t) (describing of the thermal form of energy) and R=R(t) (describing non-thermal form of energy), then the correct formulation of the first law of thermodynamics is: dU(Q,R)dt=( UQ )RdQdt+( UR )QdRdt, where t and -( UR )Q / ( UR )Q ( UQ ) . - ( UQ )R are time and measure of mutual transformation of forms of energy, correspondingly. General conclusion: standard thermodynamics is incorrect.

  15. Engaged Problem Formulation of IT Management in Danish Municipalities

    DEFF Research Database (Denmark)

    2012-01-01

    Municipalities’ effectiveness in managing information technology (IT) is increasingly important in adhering to their responsibilities for providing services to citizens. While the municipalities’ difficulty in managing IT has been well documented, it is more elusive what specific problems are most...... relevant in contemporary municipal IT management practice. On this basis, we present an engaged scholarship approach to formulate IT management problems together with municipalities - not for municipalities. We have come to understand such engaged problem formulation as joint researching and defining...... of a contemporary and complex problem by researchers and those who experience and know the problem. We present the formulated IT management problems and discuss the engaged problem formulation process in relation to engaged scholarship. Furthermore, we discuss how engaged problem formulation may contribute...

  16. Evaluation method for the drying performance of enzyme containing formulations

    DEFF Research Database (Denmark)

    Sloth, Jakob; Bach, P.; Jensen, Anker Degn;

    2008-01-01

    A method is presented for fast and cheap evaluation of the performance of enzyme containing formulations in terms of preserving the highest enzyme activity during spray drying. The method is based on modeling the kinetics of the thermal inactivation reaction which occurs during the drying process....... Relevant kinetic parameters are determined from differential scanning calorimeter (DSC) experiments and the model is used to simulate the severity of the inactivation reaction for temperatures and moisture levels relevant for spray drying. After conducting experiments and subsequent simulations...... for a number of different formulations it may be deduced which formulation performs best. This is illustrated by a formulation design study where 4 different enzyme containing formulations are evaluated. The method is validated by comparison to pilot scale spray dryer experiments....

  17. FORMULATION AND EVALUATION OF FAST DISSOLVING TABLETS OF ACETAMINOPHEN

    Directory of Open Access Journals (Sweden)

    Abhay Kumar Mourya et al.

    2012-02-01

    Full Text Available The present research work has been carried out for an optimized formulation of co-processed directly compressible vehicles in the preparation of the Acetaminophen mouth fast dissolving tablets (MFDTs. Acetaminophen was chosen due to its poor compression properties. Di-calcium Phosphate(DCP was incorporated in the neutralized aqueous starch dispersion to prepare co-processed excipient. Co-processed direct compressible DCP and Starch used as co-processed excipient were taken in good formulation ratio such as (25:75 and Cross Povidone used as superdisintegrant. The effects of other superdisintegrants were studied in the best formulation F5. Formulation F5 was found to be optimum compressibility characteristics hardness 3.62±0.40 to 4.68±0.31 kg/cm2 with fast disintegration (10 sec compare to other formulations.

  18. Improved properties of lipstick formulation with engkabang fats

    Directory of Open Access Journals (Sweden)

    Mat Husin Norazlin

    2015-01-01

    Full Text Available Engkabang fats are known as an excellent cocoa butter equivalent. It is selected to be aimed as potential softening ingredient in waxy base of lipstick formulation that promotes moisturising protection for the lips. The formulation was prepared by mixing homogenously the base and colour intermediate at 70-80°C, moulded in casing, followed by cooling at-20°C.The optimum ratio of lipstick formulation containing engkabang fats and other waxes was (10:20 in percentage. The other ingredients used were oils (60% and colour agent (10%. The physico-chemical properties of formulations were determined including texture analysis, pH, melting point, colour intensity, stability and moisture content. From the results, engkabang fats exhibited a good softening and moisturising properties. Engkabang fats lipstick formulations showed better application on the lips compared lipstick without engkabang fats.

  19. Slow Growth Formulation for DNS of Temporally Evolving Boundary Layers

    Science.gov (United States)

    Topalian, Victor; Sahni, Onkar; Oliver, Todd; Moser, Robert

    2011-11-01

    A formulation for DNS of temporally evolving boundary layers is developed and demonstrated. The formulation relies on a multiscale approach to account separately for the slow time evolution of statistical averages, and the fast time evolution of turbulent fluctuations. The source terms that arise from the multiscale analysis are modeled assuming a self-similar evolution of the averages. The performance of the formulation is evaluated using DNS of spatially evolving compressible boundary layers. This formulation was developed to provide data for the calibration of turbulence model parameters and enable the quantification of uncertainty due to the models. The extension of this formulation to homogenize spatially evolving boundary layers will also be discussed. This work is supported by the Department of Energy [National Nuclear Security Administration] under Award Number [DE-FC52-08NA28615]. Current Affiliation: Rensselaer Polytechnic Institute.

  20. A formulation to encapsulate nootkatone for tick control.

    Science.gov (United States)

    Behle, Robert W; Flor-Weiler, Lina B; Bharadwaj, Anuja; Stafford, Kirby C

    2011-11-01

    Nootkatone is a component of grapefruit oil that is toxic to the disease-vectoring tick, Ixodes scapularis Say, but unfortunately causes phytotoxicity to treated plants and has a short residual activity due to volatility. We prepared a lignin-encapsulated nootkatone formulation to compare with a previously used emulsifiable formulation for volatility, plant phytotoxicity, and toxicity to unfed nymphs of I. scapularis. Volatility of nootkatone was measured directly by trapping nootkatone vapor in a closed system and indirectly by measuring nootkatone residue on treated filter paper after exposure to simulated sunlight (Xenon). After 24 h in the closed system, traps collected only 15% of the nootkatone applied as the encapsulated formulation compared with 40% applied as the emulsifiable formulation. After a 1-h light exposure, the encapsulated formulation retained 92% of the nootkatone concentration compared with only 26% retained by the emulsifiable formulation. For plant phytotoxicity, cabbage, Brassica oleracea L., leaves treated with the encapsulated formulation expressed less necrosis, retaining greater leaf weight compared with leaves treated with the emusifiable formulation. The nootkatone in the emulsifiable formulation was absorbed by cabbage and oat, Avena sativa L., plants (41 and 60% recovered 2 h after application, respectively), as opposed to 100% recovery from the plants treated with encapsulated nootkatone. Using a treated vial technique, encapsulated nootkatone was significantly more toxic to I. scapularis nymphs (LC50 = 20 ng/cm2) compared with toxicity of the emulsifiable formulation (LC50 = 35 ng/cm2). Thus, the encapsulation of nootkatone improved toxicity for tick control, reduced nootkatone volatility, and reduced plant phytotoxicity.

  1. Pharmacological evaluation of a polyherbal formulation for its antispasmodic activity

    Directory of Open Access Journals (Sweden)

    Navdeep Saini

    2015-01-01

    Full Text Available Object: The present study was aimed to evaluate pharmacologically to a polyherbal formulation containing volatile extracts of various umbelliferae plants. Materials and Methods: The umbelliferae family was found most effective against spasm by extensive literature review and study of various rational formulations. Plants material was procured from the local market of Rajasthan. Volatile extracts were isolated from powdered plant materials through Clevenger′s method. The volatile extracts of following plants Trachyspermum ammi, Cuminum cyminum, Anethum graveolens and Foeniculum vulgare were used to make polyherbal formulation. Results: Antispasmodic effect of newly prepared polyherbal formulation demonstrated on guinea pig ileum in vitro; 50% inhibitory concentration (IC 50 was 172.5 ± 1.4 μl/ml. A very effective value identified, when compared to antispasmodic drugs, e.g. Atropine (IC 50 was 166.7 ± 1.2 μl/ml. Oral administration of polyherbal formulation dose-dependently reduced intestinal transit in mice when compared to atropine at 0.1 mg/kg i.p. and formulation at (300 mg/kg protected mice against diarrhea induced by castor oil significantly when compared to control and standard loperamide at a dose of 5 mg/kg orally. Conclusion: Polyherbal formulation inhibits acetylcholine and calcium chloride induced contraction of guinea pig ileum dose-dependently. The current research validates antispasmodic effect of newly developed polyherbal formulation. It also concluded that polyherbal formulation inhibits the contraction produced by various spasmogens like acetylcholine and calcium chloride. This suggests that the activity of developed formulation is nonspecific to any spasmogen.

  2. STRATEGY FORMULATION FOR DEVELOPING BATIK TULIS

    Directory of Open Access Journals (Sweden)

    Indah Eko Suryani

    2015-01-01

    Full Text Available The objective of this study was to formulate a development strategy in order to maintain the existence of Batik Tulis Rolla Junior. The study used a case study approach with Rumah Batik Tulis Rolla Junior as the research object. The data were analyzed by a value chain approach to determine the internal and external conditions influencing the existence of the Batik Tulis Rolla Junior. Furthermore, this study also used the analysis of Internal Factor Evaluation (IFE, External Factor Evaluation (EFE, Internal-External (IE Matrix, SWOT, dan Quantitative Strategic Planning Matrix (QSPM to create the development strategy. The results show that the strategies that can be recommended to Rolla Junior include 1 increasing the capital by Kredit Usaha Rakyat (KUR program, 2 conductiong expansions to other regencies, 3 creating a website/blog  to promote and perform business transactions, 4 increasing the frequency in joining exhibitions or EXPO both in regional and national levels, 5 conducting researches to solve the problem of coloring which requires sun rays, 6 conducting cooperations with raw material suppliers (backward integration, and 7 finding alternative suppliers of raw materials especially from the areas closer to Jember district.Keywords: development strategy, batik tulis Rolla Junior, SWOT, QSPMABSTRAKPenelitian ini bertujuan merumuskan strategi pengembangan sehingga dapat menjaga eksistensi Batik Tulis Rolla Junior. Penelitian menggunakan pendekatan studi kasus dengan Rolla Junior sebagai objek penelitiannya. Data dianalisis dengan pendekatan rantai nilai untuk mengetahui kondisi internal dan eksternal yang berpengaruh terhadap Batik Tulis kemudian menggunakan analisis Internal Factor Evaluation (IFE, External Factor Evaluation (EFE, Internal-External (IE Matrix, SWOT, dan Quantitative Strategic Planning Matrix (QSPM untuk menyusun strategi pengembangan Batik Tulis Rolla Junior. Hasil penelitian menunjukkan bahwa strategi-straegi prioritas

  3. Unconstrained Hamiltonian formulation of low energy QCD

    Directory of Open Access Journals (Sweden)

    Pavel Hans-Peter

    2014-04-01

    Full Text Available Using a generalized polar decomposition of the gauge fields into gaugerotation and gauge-invariant parts, which Abelianises the Non-Abelian Gauss-law constraints to be implemented, a Hamiltonian formulation of QCD in terms of gauge invariant dynamical variables can be achieved. The exact implementation of the Gauss laws reduces the colored spin-1 gluons and spin-1/2 quarks to unconstrained colorless spin-0, spin-1, spin-2 and spin-3 glueball fields and colorless Rarita-Schwinger fields respectively. The obtained physical Hamiltonian naturally admits a systematic strongcoupling expansion in powers of λ = g−2/3, equivalent to an expansion in the number of spatial derivatives. The leading-order term corresponds to non-interacting hybridglueballs, whose low-lying spectrum can be calculated with high accuracy by solving the Schrödinger-equation of the Dirac-Yang-Mills quantum mechanics of spatially constant fields (at the moment only for the 2-color case. The discrete glueball excitation spectrum shows a universal string-like behaviour with practically all excitation energy going in to the increase of the strengths of merely two fields, the “constant Abelian fields” corresponding to the zero-energy valleys of the chromomagnetic potential. Inclusion of the fermionic degrees of freedom significantly lowers the spectrum and allows for the study of the sigma meson. Higher-order terms in λ lead to interactions between the hybridglueballs and can be taken into account systematically using perturbation theory in λ, allowing for the study of IR-renormalisation and Lorentz invarianz. The existence of the generalized polar decomposition used, the position of the zeros of the corresponding Jacobian (Gribov horizons, and the ranges of the physical variables can be investigated by solving a system of algebraic equations. Its exact solution for the case of one spatial dimension and first numerical solutions for two and three spatial dimensions indicate

  4. CRYSTALLINE CERAMIC WASTE FORMS: REFERENCE FORMULATION REPORT

    Energy Technology Data Exchange (ETDEWEB)

    Brinkman, K.; Fox, K.; Marra, J.

    2012-05-15

    The research conducted in this work package is aimed at taking advantage of the long term thermodynamic stability of crystalline ceramics to create more durable waste forms (as compared to high level waste glass) in order to reduce the reliance on engineered and natural barrier systems. Durable ceramic waste forms that incorporate a wide range of radionuclides have the potential to broaden the available disposal options and to lower the storage and disposal costs associated with advanced fuel cycles. Assemblages of several titanate phases have been successfully demonstrated to incorporate radioactive waste elements, and the multiphase nature of these materials allows them to accommodate variation in the waste composition. Recent work has shown that they can be successfully produced from a melting and crystallization process. The objective of this report is to explain the design of ceramic host systems culminating in a reference ceramic formulation for use in subsequent studies on process optimization and melt property data assessment in support of FY13 melter demonstration testing. The waste stream used as the basis for the development and testing is a combination of the projected Cs/Sr separated stream, the Trivalent Actinide - Lanthanide Separation by Phosphorous reagent Extraction from Aqueous Komplexes (TALSPEAK) waste stream consisting of lanthanide fission products, the transition metal fission product waste stream resulting from the transuranic extraction (TRUEX) process, and a high molybdenum concentration with relatively low noble metal concentrations. In addition to the combined CS/LN/TM High Mo waste stream, variants without Mo and without Mo and Zr were also evaluated. Based on the results of fabricating and characterizing several simulated ceramic waste forms, two reference ceramic waste form compositions are recommended in this report. The first composition targets the CS/LN/TM combined waste stream with and without Mo. The second composition targets

  5. Toxicity of a dichlorvos containing insecticide formulation and an atrazine containing herbicide formulation in chicken embryos after individual administration.

    Science.gov (United States)

    Szabó, R; Keseru, M; Fejes, S; Budai, P; Juhász, E; Pongrácz, A

    2004-01-01

    A 50% dichlorvos containing insecticide formulation (Unifosz 50 EC) and a 50% atrazine containing herbicide formulation (Hungazin PK 50 WP) were studied in chicken embryos after administration as single compounds. Applied concentrations of dichlorvos were 0.1% (corresponding to the plant protection practice), 0.05%, 0.02%, 0.01%. Applied concentrations of atrazine were 0.66% (corresponding to the plant protection practice), 0.33%, 0.132%, 0.066%. The test materials were injected directly into the air-chamber of eggs on day 0 of the hatching period and evaulation was carried out on day 19 of incubation. The chicken embryos were examined for the following: rate of embryo mortality, body mass, type of developmental anomalies. After the single administrations of dichlorvos containing insecticide formulation and atrazine containing herbicide formulation on day 0 of incubation, the average body weight of chicken embryos significantly did not decrease as compared to the control. After the individual administrations of pesticides the incidence of developmental anomalies was sporadic. The embryonic mortality markedly increased at the highest concentrations of pesticides. The rate of embrio mortality were 61% (dichlorvos insecticide containing formulation) and 52% (atrazine containing herbicide formulation). In summary, the 50% dichlorvos containing insecide formulation (Unifosz 50 EC) and the 50% atrazine containing herbicide formulation (Hungazin PK 50 WP) were toxic to the developing chicken embryos at the highest concentration in our study. The toxic effect was expressed in the high rate of embrio mortality.

  6. Glyphosate and its formulations – Toxicity, occupational and environmental exposure

    Directory of Open Access Journals (Sweden)

    Marta Kwiatkowska

    2013-10-01

    Full Text Available Glyphosate (N-(phosphonomethylglycine is an active ingredient of the most widely used herbicide formulations in protecting agricultural and horticultural crops. Numerous results (mostly published in the years 2010-2013 concerning the action of glyphosate and its formulations in the recent decade were analyzed. Initial reports about alleged biodegradability of glyphosate in the environment turned out to be wrong. It has been shown that glyphosate remains in the soil and can reach people by spreading along with groundwater. Recent publications have shown that glyphosate is detected at low concentrations in the human blood. Publications cited in this article, which indicate a possible induction of neoplastic changes by glyphosate formulation, have raised great concern and controversy in the scientific world. Presenting adverse effects of glyphosate and its formulations we focused on the role of glyphosate formulations in hormonal disorders by impeding the expression of steroidogenic acute regulatory protein and the inhibition of aromatase activity. The impact of glyphosate on oxygen reactive species formation, changes in redox system and the effect on necrosis and apoptosis in various types of cells was shown. We also revealed that glyphosate as a phosphonate herbicide does not inhibit directly the activity of acetylcholinesterase. Based on numerous studies it was noted that commercial formulations of glyphosate exhibit higher toxicity than that of the active substance itself. The discussed problems clearly show the need to evaluate the toxicity of glyphosate and its formulations and related potential threat to humans. Med Pr 2013;64(5:717–729

  7. FORMULATION AND DISSOLUTION STUDY OF DILTIAZEM HYDROCHLORIDE IMMEDIATE RELEASE TABLETS

    Directory of Open Access Journals (Sweden)

    BRAHMAIAH BONTHAGARALA

    2014-08-01

    Full Text Available Objective: The main aim and objective of the work is to formulate immediate release tablets using different direct compression vehicles (DCV’S in different ratios. Methods: In the present study, design of oral immediate release tablets of Diltiazem hydrochloride by direct compression technique was carried out. Results: The main motive is to compare the dissolution profile of these formulations and conclude the best formulation which release drug at a faster rate . To determine the best fit dissolution profile for the dosage forms. Diltiazem hydrochloride tablets were formulated by using microcrystalline cellulose (diluent, potato starch, acacia (binder and magnesium stearate (lubricant. The granules were compressed into tablets and were subjected to dissolution studies. The dissolution profile of the formulation F2 was found to have better dissolution rate compared to others. Conclusion: The Invitro dissolution studies of all the formulations were conducted and the results were obtained, it was concluded that formulation F2 was the best with fast release of drug compared to others.

  8. Formulation and Evaluation of Darifenacin Hydrobromide Extended Release Matrix Tablets

    Directory of Open Access Journals (Sweden)

    Syed Meraj Sultana

    2016-08-01

    Full Text Available Darifenacin hydrobromide is a highly selective muscarinic (M3 receptor blocker that has been widely used for the treatment of overactive bladder syndrome. The bioavailability of darifenacin hydrobromide is 15–19% due to extensive first pass metabolism. Hence oral administration of darifenacin hydrobromide as extended tablets is a possible solution to overcome this problem. So the aim of the study was to formulate and evaluate Darifenacin hydrobromide extended release matrix tablets using extended release polymers like HPMC K4M, HPMC K15M and HPMC K100M, Metalose 60 SH-50 and Xanthum gum in different concentrations. Formulated tablets were characterized for different parameters like hardness, thickness, weight variation, friability, % Cumulative drug release etc. Nine formulations (F1 – F9 were formulated using direct compression technique. From the results obtained, it was concluded that the optimized formulation containing HPMC K15 M and K100M (1:2 showed better release up to 24hrs.The dissolution profiles and kinetic studies indicate that the release of Darifenacin Hydrobromide can be effectively controlled by the use of hydrophilic matrix systems. Different kinetic models were applied to the optimized formulation and observed that formulation (F9 followed first order kinetic model and Non-Fickian diffusion (or Anomalous transport as mechanism of drug release.

  9. Methodology of oral formulation selection in the pharmaceutical industry.

    Science.gov (United States)

    Kuentz, Martin; Holm, René; Elder, David P

    2016-05-25

    Pharmaceutical formulations have to fulfil various requirements with respect to their intended use, either in the development phase or as a commercial product. New drug candidates with their specific properties confront the formulation scientist with industrial challenges for which a strategy is needed to cope with limited resources, stretched timelines as well as regulatory requirements. This paper aims at reviewing different methodologies to select a suitable formulation approach for oral delivery. Exclusively small-molecular drugs are considered and the review is written from an industrial perspective. Specific cases are discussed starting with an emphasis on poorly soluble compounds, then the topics of chemically labile drugs, low-dose compounds, and modified release are reviewed. Due to the broad scope of this work, a primary focus is on explaining basic concepts as well as recent trends. Different strategies are discussed to approach industrial formulation selection, which includes a structured product development. Examples for such structured development aim to provide guidance to formulators and finally, the recent topic of a manufacturing classification system is presented. It can be concluded that the field of oral formulation selection is particularly complex due to both multiple challenges as well as opportunities so that industrial scientists have to employ tailored approaches to design formulations successfully.

  10. Formulation and evaluation of antipsoriatic gel using natural excipients

    Institute of Scientific and Technical Information of China (English)

    Raghupatruni Jhansi Laxmi; R Karthikeyan; P Srinivasa Babu; RVV Narendra Babu

    2013-01-01

    Objective:To develop topical gel formulations ofPsoralen using natural excipients to minimize the side effects of synthetic drugs.Methods:ThePsoralen gel formulations were prepared using different natural gums and polymers.The physicochemical compatibility betweenPsoralen and other excipients was confirmed by usingFourier transform infrared spectroscopy.All prepared gel formulations were evaluated for drug content uniformity, viscosity, pH, and stability.The release of psoralen from all formulations using dialysis membrane into a phosphate buffer pH6.8 at 37°C was studied.Drug release from the formulations fitted best to theHiguchi model.From the drug release data the best formulation was optimized and the biological studies on albino mice were performed.Results:Psoralen gel containing egg albumin and xanthan gum shows better incorporation of the drug.The drug activity was found to be43.3%.Anti-psoriatic drug enhances the orthokeratotic cell differentiation in the epidermal scales.Conclusion:In vitro anti-psoriatic activity ofF3 showed the significant orthokeratosis in the mouse tail test when compared to control thus indicating that the formulation is effective in treating psoriasis.

  11. Significance of Strain in Formulation in Theory of Solid Mechanics

    Science.gov (United States)

    Patnaik, Surya N.; Coroneos, Rula M.; Hopkins, Dale A.

    2003-01-01

    The basic theory of solid mechanics was deemed complete circa 1860 when St. Venant provided the strain formulation or the field compatibility condition. The strain formulation was incomplete. The missing portion has been formulated and identified as the boundary compatibility condition (BCC). The BCC, derived through a variational formulation, has been verified through integral theorem and solution of problems. The BCC, unlike the field counterpart, do not trivialize when expressed in displacements. Navier s method and the stiffness formulation have to account for the extra conditions especially at the inter-element boundaries in a finite element model. Completion of the strain formulation has led to the revival of the direct force calculation methods: the Integrated Force Method (IFM) and its dual (IFMD) for finite element analysis, and the completed Beltrami-Michell formulation (CBMF) in elasticity. The benefits from the new methods in elasticity, in finite element analysis, and in design optimization are discussed. Existing solutions and computer codes may have to be adjusted for the compliance of the new conditions. Complacency because the discipline is over a century old and computer codes have been developed for half a century can lead to stagnation of the discipline.

  12. FORMULATION AND EVALUATION OF ORODISPERSIBLE TABLETS OF TASTE MASKED NIZATIDINE

    Directory of Open Access Journals (Sweden)

    Radhika Parasuram Rajan

    2012-10-01

    Full Text Available The purpose of the research was to mask the intensely bitter taste of Nizatidine and to formulate Orodispersible tablet (ODT and get rapid onset of action, to increase bioavailability and to increase patient compliance. Orodispersible tablets are an innovative technology, which disperse rapidly, usually in a matter of seconds, without the need for water, providing optimal convenience to the patient. The taste masking was done by complexing Nizatidine with methacrylate copolymer, Eudragit E100 in different ratios by mass extrusion method. The drug polymer complex was optimized by determining the drug content and in vitro drug release in simulated salivary fluid (SSF of pH 6.8. Complex which did not release the drug in SSF was considered as the optimized batch and used for formulation of ODTs. The effects of various superdisintegrants such as Sodium Starch Glycolate, Croscarmellose sodium, Crosspovidone used in formulation of ODTs were studied. The formulation blend was evaluated for bulk density, tapped density, compressibility index, angle of repose etc. The ODTs were prepared by direct compression technique and evaluated for hardness, friability, wetting time, in vitro dispersion time, in vitro drug release etc. Among all formulation, F3 containing 5% w/w concentration of crosspovidone was considered to be the best formulation, with disintegration time of 34 seconds and in vitro drug release of 99.5% in 15 minutes in simulated gastric fluid (SGF. Thus, results conclusively demonstrated successful masking of taste and rapid disintegration of the formulated tablets.

  13. Formulation and Characterization of Waste Glasses with Varying Processing Temperature

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Dong-Sang; Schweiger, M. J.; Rodriguez, Carmen P.; Lepry, William C.; Lang, Jesse B.; Crum, Jarrod V.; Vienna, John D.; Johnson, Fabienne; Marra, James C.; Peeler, David K.

    2011-10-17

    This report documents the preliminary results of glass formulation and characterization accomplished within the finished scope of the EM-31 technology development tasks for WP-4 and WP-5, including WP-4.1.2: Glass Formulation for Next Generation Melter, WP-5.1.2.3: Systematic Glass Studies, and WP-5.1.2.4: Glass Formulation for Specific Wastes. This report also presents the suggested studies for eventual restart of these tasks. The initial glass formulation efforts for the cold crucible induction melter (CCIM), operating at {approx}1200 C, with selected HLW (AZ-101) and LAW (AN-105) successfully developed glasses with significant increase of waste loading compared to that is likely to be achieved based on expected reference WTP formulations. Three glasses formulated for AZ-101HLW and one glass for AN-105 LAW were selected for the initial CCIM demonstration melter tests. Melter tests were not performed within the finished scope of the WP-4.1.2 task. Glass formulations for CCIM were expanded to cover additional HLWs that have high potential to successfully demonstrate the unique advantages of the CCIM technologies based on projected composition of Hanford wastes. However, only the preliminary scoping tests were completed with selected wastes within the finished scope. Advanced glass formulations for the reference WTP melter, operating at {approx}1200 C, were initiated with selected specific wastes to determine the estimated maximum waste loading. The incomplete results from these initial formulation efforts are summarized. For systematic glass studies, a test matrix of 32 high-aluminum glasses was completed based on a new method developed in this study.

  14. TODGA Process Development: an Improved Solvent Formulation

    Energy Technology Data Exchange (ETDEWEB)

    Geist, Andreas [Forschungszentrum Karlsruhe, Institut fuer Nukleare Entsorgung, 76021 Karlsruhe (Germany); Modolo, Giuseppe [Forschungszentrum Juelich, Institute for Energy Research, Safety Research and Reactor Technology, 52425 Juelich (Germany)

    2009-06-15

    Introduction: TODGA (N,N,N',N'-tetra-n-octyl diglycolamide) is studied in the European ACSEPT project as a promising extractant for actinide separations. A mixture of TODGA and TBP in TPH (a kerosene) [1] was successfully used for spiked and hot continuous counter-current tests for the separation of actinides(III) and lanthanides(III) from PUREX raffinate [2, 3]. Furthermore this solvent composition is used for GANEX (group actinide extraction) process development, i.e., co-extraction of Np, Pu, Am, Cm, and Ln from PUREX raffinate with selective stripping of the actinides [4, 5]. We address two of this solvent's drawbacks by replacing TBP (which acts as phase modifier to prevent third phase formation) with 1-octanol: (1) The presence of a non-CHON compound (TBP); (2) The pronounced co-extraction of nitric acid (e.g., 0.2 M TODGA + 0.5 M TBP in TPH extracts approx. 0.6 M HNO{sub 3} from 4 M HNO{sub 3}). Results: When contacting 0.2 M TODGA in TPH with 0.1 M Nd(NO{sub 3}){sub 3} in 5 M HNO{sub 3}, as little as 3 % vol. 1-octanol suppresses the formation of a third phase. Thus, the following solvent composition is used for further studies: 0.2 M TODGA + 5 % vol. 1-octanol in TPH. Due to the absence of TBP, the amount of HNO{sub 3} extraction is reduced to approx. 50 % as compared to the solvent consisting of 0.2 M TODGA + 0.5 M TBP in TPH. Am(III) and Eu(III) distribution ratios are similar to those with the TODGA + TBP solvent [1]. Loading the solvent by extracting from solutions of up to 0.2 M Nd(NO{sub 3}){sub 3} in 3 M or 4 M HNO{sub 3} confirms a 1:3 stoichiometry of the extracted complex. Further investigations are under way. Conclusion: The improved solvent formulation reduces the HNO{sub 3} co-extraction which may be advantageous especially for GANEX process development. Furthermore, the solvent complies with the CHON principle. 1) G. Modolo, H. Asp, C. Schreinemachers, H. Vijgen, Development of a TODGA based process for partitioning of

  15. Reality conditions for Ashtekar gravity from Lorentz-covariant formulation

    Energy Technology Data Exchange (ETDEWEB)

    Alexandrov, Sergei [Institute for Theoretical Physics and Spinoza Institute, Utrecht University, Postbus 80.195, 3508 TD Utrecht (Netherlands)

    2006-03-21

    We study the limit of the Lorentz-covariant canonical formulation where the Immirzi parameter approaches {beta} = i. We show that, formulated in terms of a shifted spacetime connection, which also plays a crucial role in the covariant quantization, the limit is smooth and reproduces the canonical structure of the self-dual Ashtekar gravity. The reality conditions of Ashtekar gravity can be incorporated by means of the Dirac brackets derived from the covariant formulation and defined on an extended phase space which involves, besides the self-dual variables, also their anti-self-dual counterparts.

  16. A General Formulation for the Stiffness Matrix of Parallel Mechanisms

    CERN Document Server

    Quennouelle, Cyril

    2012-01-01

    Starting from the definition of a stiffness matrix, the authors present a new formulation of the Cartesian stiffness matrix of parallel mechanisms. The proposed formulation is more general than any other stiffness matrix found in the literature since it can take into account the stiffness of the passive joints, it can consider additional compliances in the joints or in the links and it remains valid for large displacements. Then, the validity, the conservative property, the positive definiteness and the relation with other formulations of stiffness matrices are discussed theoretically. Finally, a numerical example is given in order to illustrate the correctness of this matrix.

  17. Quantum energy inequalities and local covariance II: categorical formulation

    Science.gov (United States)

    Fewster, Christopher J.

    2007-11-01

    We formulate quantum energy inequalities (QEIs) in the framework of locally covariant quantum field theory developed by Brunetti, Fredenhagen and Verch, which is based on notions taken from category theory. This leads to a new viewpoint on the QEIs, and also to the identification of a new structural property of locally covariant quantum field theory, which we call local physical equivalence. Covariant formulations of the numerical range and spectrum of locally covariant fields are given and investigated, and a new algebra of fields is identified, in which fields are treated independently of their realisation on particular spacetimes and manifestly covariant versions of the functional calculus may be formulated.

  18. Beverages formulated with whey protein and added lutein

    Directory of Open Access Journals (Sweden)

    Juliana de Cássia Gomes Rocha

    Full Text Available ABSTRACT: This study aimed to develop and characterize beverages formulated with whey protein and added lutein. Beverages formulated with 0.5 (F1, 2.0 (F2, 4.0 (F3 and 6.0% w/v (F4 whey protein were physicochemically and microbiologically characterized, and sensory evaluated. The physicochemical analyses indicated that the protein content significantly changed (P0.05 with increased protein content. The F2 formulation showed the highest sensory acceptance. Beverages offer a promising alternative to whey use and enhance the value of the product by the addition of lutein.

  19. STANDARDIZATION OF AN AYURVEDIC FORMULATION: TRIKATU CHURNA USING BIOANALYTICAL TOOLS

    Directory of Open Access Journals (Sweden)

    Shailajan Sunita

    2011-06-01

    Full Text Available Trikatu Churna (TC is an ancient traditional Ayurvedic preparation prescribed for a wide range of disorders. Though TC is an age old formulation, there are very few references on its quality control and standardization. In this work, an attempt has been made to standardize TC by qualitatively evaluating the preliminary phytochemicals. Piperine content of TC was determined using HPTLC. Evaluation of safety potential of TC samples and stability evaluation by comparative study of the in house TC formulation with marketed TC formulations with respect to their piperine content is a value addition to the current work.

  20. Simultaneously Exploiting Two Formulations: an Exact Benders Decomposition Approach

    DEFF Research Database (Denmark)

    Lusby, Richard Martin; Gamst, Mette; Spoorendonk, Simon

    consistency between the decision variables of the respective formulations. We demonstrate the applicability of the proposed methodology to situations in which one of the formulations models a relaxation of the problem and to cases where one formulation is the Dantzig-Wolfe reformulation of the other....... Furthermore, it proves the correctness of the procedure and considers how to include interesting extensions such as cutting planes and advanced branching strategies. Finally, we test and compare the performance of the proposed approach on publicly available instances of the Bin Packing problem. Compared...

  1. Design and formulation of nano-sized spray dried efavirenz. Part I: Influence of formulation parameters

    CSIR Research Space (South Africa)

    Katata, L

    2012-10-01

    Full Text Available .770 E Solvent EA 2 2.414 F [W1] 2 % 2 0.651 G [PEG] 0.5 % 1 0.717 6 Table 6 Analysis of variance for particle size of PCL-EFV nanoparticles Symbol Factors DOF Sums of squares Variance F-Ratio Pure sum Percent (%) A W1 1 4.361 4... experimental parameters and levels for preparation of PCL-EFV nanoparticles Symbol Formulation parameters Levels 1 1 2 A W1 PVA PBS B Sugar Lactose Trehalose C [W2-PVA] 1 % 2 % D [Sugar] 3 % 5 % E Solvent DCM EA F [W1] 1 % 2 % G [PEG] 0.5 % 1...

  2. On multiple M2-brane model(s and its N=8 Superspace Formulation(s

    Directory of Open Access Journals (Sweden)

    I. A. Bandos

    2010-01-01

    Full Text Available We give a brief review of Bagger-Lambert-Gustavsson (BLG model, with emphasis on its version invariant under the volume preserving diffeomorphisms (SDiff3 symmetry. We describe the on-shell superfield formulation of this SDiff3 BLG model in standard N = 8, d = 3 superspace, as well as its superfield action in the pure spinor N = 8 superspace. We also briefly address the Aharony-Bergman-Jafferis-Maldacena (ABJM/ABJ model invariant under SU(Mk × SU(N−k gauge symmetry, and discuss the possible form of their N = 6 and, for the case of Chern-Simons level k = 1, 2, N = 8 superfield equations.

  3. New Integer Programming Formulations of the Generalized Travelling Salesman Problem

    Directory of Open Access Journals (Sweden)

    P. C. Pop

    2007-01-01

    Full Text Available The Generalized Travelling Salesman Problem, denoted by GTSP, is a variant of the classical travelling salesman problem (TSP, in which the nodes of an undirected graph are partitioned into node sets (clusters and the salesman has to visit exactly one node from every cluster. In this paper we described six distinct formulations of the GTSP as an integer programming. Apart from the standard formulations all the new formulations that we describe are 'compact' in the sense that the number of constraints and variables is a polynomial function of the number of nodes in the problem. In order to provide compact formulations for the GTSP we used two approaches using auxiliary flow variables beyond the natural binary edge and node variables and the second one by distinguishing between global and local variables. Comparisons of the polytopes corresponding to their linear relaxations are established.

  4. A Chebyshev-collation approach for a continuous formulation of ...

    African Journals Online (AJOL)

    A Chebyshev-collation approach for a continuous formulation of hybrid methods for initial value problems in ordinary differential ... Journal of the Nigerian Association of Mathematical Physics ... Open Access DOWNLOAD FULL TEXT ...

  5. Patient centric formulations for paediatrics and geriatrics: Similarities and differences.

    Science.gov (United States)

    Hanning, Sara M; Lopez, Felipe L; Wong, Ian C K; Ernest, Terry B; Tuleu, Catherine; Orlu Gul, Mine

    2016-10-30

    Paediatrics and geriatrics both represent highly heterogenous populations and require special consideration when developing appropriate dosage forms. This paper discusses similarities, differences and considerations with respect to the development of appropriate medicine formulations for paediatrics and geriatrics. Arguably the most significant compliance challenge in older people is polypharmacy, whereas for children the largest barrier is taste. Pharmaceutical technology has progressed rapidly and technologies including FDCs, multi-particulates and orodispersible dosage forms provide unprecedented opportunities to develop novel and appropriate formulations for both old and new drugs. However, it is important for the formulation scientists to work closely with patients, carers and clinicians to develop such formulations for both the paediatric and geriatric population. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Design, formulation and evaluation of nicotine chewing gum

    Directory of Open Access Journals (Sweden)

    Abolfazl Aslani

    2012-01-01

    Conclusion: Taste enhancement of nicotine gums was achieved where formulations comprised aspartame as the sweetener and cherry and eucalyptus as the flavoring agents. Nicotine gums of pleasant taste may, therefore, be used as NRT to assist smokers quit smoking.

  7. Hypersensitivity Reactions from Excipients in Systemic Glucocorticoid Formulations

    DEFF Research Database (Denmark)

    Calogiuri, Gianfranco; Garvey, Lene H; Romita, Paolo

    2016-01-01

    Glucocorticoids are the most widely used drugs for the treatment of hypersensitivity, however these drugs themselves and the excipients contained in commercial corticosteroid formulations are able to induce severe immediate-type hypersensitivity reactions. Reactions involving excipients have been...

  8. Development of amino resin for emulsion paint formulation: reactive ...

    African Journals Online (AJOL)

    Development of amino resin for emulsion paint formulation: reactive blending of methylol urea with soybean oil. ... advantages of this new system are low formaldehyde emission and water reduction characteristics. The polymer blend may ...

  9. Enhanced formulations for neutralization of chemical, biological and industrial toxants

    Science.gov (United States)

    Tucker, Mark D [Albuqueque, NM

    2008-06-24

    An enhanced formulation and method of making that neutralizes the adverse health effects of both chemical and biological compounds, especially chemical warfare (CW) and biological warfare (BW) agents, and toxic industrial chemicals. The enhanced formulation according to the present invention is non-toxic and non-corrosive and can be delivered by a variety of means and in different phases. The formulation provides solubilizing compounds that serve to effectively render the chemical and biological compounds, particularly CW and BW compounds, susceptible to attack, and at least one reactive compound that serves to attack (and detoxify or kill) the compound. The formulation includes at least one solubilizing agent, a reactive compound, a bleaching activator and water.

  10. Influence of Formulation on Mobility of Clomazone in Soil.

    Science.gov (United States)

    Włodarczyk, Małgorzata; Siwek, Hanna

    2016-10-01

    The mobility of clomazone [2-(2-chlorobenzylo)-4,4-dimetylo-1,2-oxazolidin-3-one] in a loamy sand soil and a sand soil was studied in a soil column under laboratory conditions. Commercial clomazone formulation (Command 480 EC) and clomazone immobilized in an alginate matrix were used for a leaching experiment. For both formulations, the same dose of 2.0 mg of the active substance was applied. After an application of a herbicide, the columns were irrigated with: 100, 40 and 3.7 mm of water. After 1 h, when an addition of water was completed, the soils were sampled in the 5 cm segments and were used for the analysis of the residues. The use of an alginate formulation reduced the vertical mobility of clomazone into a soil layer in comparison with the formulation EC.

  11. 43 original article prolonged use of cough formulations and the ...

    African Journals Online (AJOL)

    Dr Oboro VO

    AFRICAN JOURNAL OF CLINICAL AND EXPERIMENTAL MICROBIOLOGY JANUARY 2010 ... such formulations by patients was therefore considered a health risk on the normal bacterial flora. ... respective chemical ingredients in Table 1.

  12. Improvability of assembly systems I: Problem formulation and performance evaluation

    Directory of Open Access Journals (Sweden)

    S.-Y. Chiang

    2000-01-01

    Full Text Available This work develops improvability theory for assembly systems. It consists of two parts. Part I includes the problem formulation and the analysis technique. Part II presents the so-called improvability indicators and a case study.

  13. LP formulation of asymmetric zero-sum stochastic games

    KAUST Repository

    Li, Lichun

    2014-12-15

    This paper provides an efficient linear programming (LP) formulation of asymmetric two player zero-sum stochastic games with finite horizon. In these stochastic games, only one player is informed of the state at each stage, and the transition law is only controlled by the informed player. Compared with the LP formulation of extensive stochastic games whose size grows polynomially with respect to the size of the state and the size of the uninformed player\\'s actions, our proposed LP formulation has its size to be linear with respect to the size of the state and the size of the uninformed player, and hence greatly reduces the computational complexity. A travelling inspector problem is used to demonstrate the efficiency of the proposed LP formulation.

  14. Formulation of a New Generation of Liposomes from Bacterial and ...

    African Journals Online (AJOL)

    Formulation of a New Generation of Liposomes from. Bacterial and ... Their morphological characteristics were assessed by atomic force microscopy. (AFM). Results: At ..... Moghimipour E, Kargar M, Ramezani Z, Handali S. The potent in vitro ...

  15. A Nanodroplet Processor for Advanced Microencapsulated Drug Formulations Project

    Data.gov (United States)

    National Aeronautics and Space Administration — During this Phase II program we propose to build on the key aspects of the nanodroplet encapsulation technology to demonstrate optimized formulation and...

  16. Nanoemulsion formulation of Abatacept for lupus nephritis therapy

    African Journals Online (AJOL)

    Department of Urology, Linyi People's Hospital, Linyi, Shandong Province 276003, ... treated with the nanoemulsion formulation of abatacept showed a marked reduction in immune ..... and CTLA4-Ig resistant memory CD8 T cell activation.

  17. Comparative study of performance of shoe polishes formulated from ...

    African Journals Online (AJOL)

    GARZALI

    carbon black pigment. Polyethylene polish like the one formulated using carbon black pigment was ... paraffin wax with pigment, solvent (white spirit), turpentine oil and .... Christie R.M (1993) “Surface Coating Reviews in. Pigment Structures ...

  18. Formulation Optimization and In-vitro Evaluation of Oral Floating ...

    African Journals Online (AJOL)

    forming agents for formulating controlled release floating tablets of captopril. FTIR and DSC spectra showed ..... correspond to the stretching vibrations of C–H bond and carboxyl .... barrier which produces upward motion and as a result tablets ...

  19. Formulation of Extended-Release Metformin Hydrochloride Matrix ...

    African Journals Online (AJOL)

    Erah

    carrier, polymer and preparation method on metformin release from the formulations in vitro as well as ... Results: The physicochemical characteristics of all the granules and tablets were generally satisfactory. Optimization ..... Some physical.

  20. Formulation development and evaluation of fast dissolving film of telmisartan

    Directory of Open Access Journals (Sweden)

    Vaishali Y Londhe

    2012-01-01

    Full Text Available Hypertension is a major cause of concern not just in the elderly but also in the youngsters. An effort was made to formulate a fast dissolving film containing telmisartan which is used in the treatment of hypertension with a view to improve the onset of action, therapeutic efficacy, patient compliance and convenience. The major challenge in formulation of oral films of telmisatran is that it shows very less solubility in the pH range of 3-9. Various film forming agents and polyhydric alcohols were evaluated for optimizing composition of fast dissolving films. Fast dissolving films using hydroxypropyl methylcellulose, polyvinyl alcohol, glycerol, sorbitol, menthol and an alkalizer were formulated using solvent casting method. Optimized formulations were evaluated for their weight, thickness, folding endurance, appearance, tensile strength, disintegration time and dissolution profile.