Modulation of gel formation and drug-release characteristics of lidocaine-loaded poly(vinyl alcohol)-tetraborate hydrogel systems using scavenger polyol sugars

Polyol sugars, displaying a plurality Of hydroxyl groups, were shown to modulate tetra hydroxyborate (borate) cross-linking in lidocaine hydrochloride containing poly(vinyl alcohol) scini-solid hydrogels. Without polyol, demixing of borate cross-linked PVA hydrogels into two distinct phases was noticeable upon lidocaine hydrochloride addition, preventing further use as a topical System. D-Mannitol incorporation was found to be particularly suitable in cicumventing network constriction induced by ionic and pH effects upon adding the hydrochloride salt of lidocaine. A test formulation (4% w/v lidocaine HCl, 2% W/V D-mannitol, 10% w/v PVA and 2.5%, w/v THB) was shown to constitute an effective delivery system, which was characterised by an initial burst release and a drug release mechanism dependent on temperature, changing from a diffusion-controlled system to one with the properties of a reservoir system. The novel flow properties and innocuous adhesion of PVA-tetrahydroxyborate hydrogels Support their application for drug delivery to exposed epithelial surfaces, Such as lacerated wounds. Furthermore, addition of a polyol, such as mannitol, allows incorporation of soluble salt forms of active therapeutic agents by modulation of cross-linking density. (C) 2008 Elsevier B.V. All rights reserved.

Differential modulation of a radiation-induced bystander effect in glioblastoma cells by pifithrin-alpha and wortmannin

The implication of radiation-induced bystander effect (RIBE) for both radiation protection and radiotherapy has attracted significant attention, but a key question is how to modulate the RIBE. The present study found that, when a fraction of glioblastoma cells in T98G population were individually targeted with precise helium particles through their nucleus, micronucleus (MN) were induced and its yield increased non-linearly with radiation dose. After co-culturing with irradiated cells, additional MN could be induced in the non-irradiated bystander cells and its yield was independent of irradiation dose, giving direct evidence of a RIBE. Further results showed that the RIBE could be eliminated by pifithrin-alpha (p53 inhibitor) but enhanced by wortmannin (PI3K inhibitor). Moreover, it was found that nitric oxide (NO) contributed to this RIBE, and the levels of NO of both irradiated cells and bystander cells could be extensively diminished by pifithrin-alpha but insignificantly reduced by wortmannin. Our results indicate that RIBE can be modulated by p53 and PI3K through a NO-dependent and NO-independent pathway, respectively. (C) 2009 Elsevier B.V. All rights reserved.

Differential modulation of angiogenesis by erythropoiesis-stimulating agents in a mouse model of ischaemic retinopathy

Background: Erythropoiesis stimulating agents (ESAs) are widely used to treat anaemia but concerns exist about their potential to promote pathological angiogenesis in some clinical scenarios. In the current study we have assessed the angiogenic potential of three ESAs; epoetin delta, darbepoetin alfa and epoetin beta using in vitro and in vivo models.

Methodology/Principal Findings: The epoetins induced angiogenesis in human microvascular endothelial cells at high doses, although darbepoetin alfa was pro-angiogenic at low-doses (1-20 IU/ml). ESA-induced angiogenesis was VEGF-mediated. In a mouse model of ischaemia-induced retinopathy, all ESAs induced generation of reticulocytes but only epoetin beta exacerbated pathological (pre-retinal) neovascularisation in comparison to controls (p<0.05). Only epoetin delta induced a significant revascularisation response which enhanced normality of the vasculature (p<0.05). This was associated with mobilisation of haematopoietic stem cells and their localisation to the retinal vasculature. Darbepoetin alfa also increased the number of active microglia in the ischaemic retina relative to other ESAs (p<0.05). Darbepoetin alfa induced retinal TNF alpha and VEGF mRNA expression which were up to 4 fold higher than with epoetin delta (p<0.001).

Conclusions: This study has implications for treatment of patients as there are clear differences in the angiogenic potential of the different ESAs.

Oblique amplitude modulation of dust-acoustic plasma waves

Theoretical and numerical studies are presented of the nonlinear amplitude modulation of dust-acoustic (DA) waves propagating in an unmagnetized three component, weakly-coupled, fully ionized plasma consisting of electrons, positive ions and charged dust particles, considering perturbations oblique to the carrier wave propagation direction. The stability analysis, based on a nonlinear Schrodinger-type equation (NLSE), shows that the wave may become unstable; the stability criteria depend on the angle theta between the modulation and propagation directions. Explicit expressions for the instability rate and threshold have been obtained in terms of the dispersion laws of the system. The possibility and conditions for the existence of different types of localized excitations have also been discussed.

Ion-acoustic waves in a two-electron-temperatute plasma: oblique modulation and envelope excitations

Theoretical and numerical studies are carried out for the nonlinear amplitude modulation of ion-acoustic waves propagating in an unmagnetized, collisionless, three-component plasma composed of inertial positive ions moving in a background of two thermalized electron populations. Perturbations oblique to the carrier wave propagation direction have been considered. The stability analysis, based on a nonlinear Schrodinger-type equation, shows that the wave may become unstable; the stability criteria depend on the angle theta between the modulation and propagation directions. Different types of localized excitations (envelope solitary waves) are shown to exist in qualitative agreement with satellite observations in the magnetosphere.

Electron-acoustic plasma waves: Oblique modulation and envelope solitons

Theoretical and numerical studies are presented of the amplitude modulation of electron-acoustic waves (EAWs) propagating in space plasmas whose constituents are inertial cold electrons, Boltzmann distributed hot electrons, and stationary ions. Perturbations oblique to the carrier EAW propagation direction have been considered. The stability analysis, based on a nonlinear Schrodinger equation, reveals that the EAW may become unstable; the stability criteria depend on the angle theta between the modulation and propagation directions. Different types of localized EA excitations are shown to exist.

Nonlinear modulation of transverse dust lattice waves in complex plasma crystals

The occurrence of the modulational instability in transverse dust lattice waves propagating in a one-dimensional dusty plasma crystal is investigated. The amplitude modulation mechanism, which is related to the intrinsic nonlinearity of the sheath electric field, is shown to destabilize the carrier wave under certain conditions, possibly leading to the formation of localized envelope excitations. Explicit expressions for the instability growth rate and threshold are presented and discussed. (C) 2004 American Institute of Physics.

Modulational instability of dust acoustic waves in dusty plasmas: Modulation obliqueness, background ion nonthermality, and dust charging effects

The oblique modulational instability of dust acoustic (DA) waves in an unmagnetized warm dusty plasma with nonthermal ions, taking into account dust grain charge variation (charging), is investigated. A nonlinear Schrodinger-type equation governing the slow modulation of the wave amplitude is derived. The effects of dust temperature, dust charge variation, ion deviation from Maxwellian equilibrium (nonthermality) and constituent species' concentration on the modulational instability of DA waves are examined. It is found that these parameters modify significantly the oblique modulational instability domain in the k-theta plane. Explicit expressions for the instability rate and threshold have been obtained in terms of the dispersion laws of the system. The possibility and conditions for the existence of different types of localized excitations are also discussed. The findings of this investigation may be useful in understanding the stable electrostatic wave packet acceleration mechanisms close to the Moon, and also enhances our knowledge on the occurrence of instability associated to pickup ions around unmagnetized bodies, such as comets, Mars, and Venus.

Oblique modulation of electrostatic modes and envelope excitations in pair-ion and electron-positron plasmas

The nonlinear amplitude modulation of electrostatic waves propagating in a collisionless two-component plasma consisting of negative and positive species of equal mass and absolute charge is investigated. Pair-ion (e.g., fullerene) and electron-positron (e-p) plasmas (neglecting recombination) are covered by this description. Amplitude perturbation oblique to the direction of propagation of the wave has been considered. Two distinct linear electrostatic modes exist, namely an acoustic lower mode and Langmuir-type optic-type upper one. The behavior of each of these modes is examined from the modulational stability point of view. The stability criteria are investigated, depending on the electrostatic carrier wave number, the angle theta between the modulation and propagation directions, and the positron-to-electron temperature ratio sigma. The analysis shows that modulated electrostatic wavepackets associated to the lower (acoustic) mode are unstable, for small values of carrier wave number k (i.e., for large wavelength lambda) and for finite (small) values of the angle theta (yet stable for higher theta), while those related to the upper (optic-like) mode are stable for large values of the angle theta only, in the same limit, yet nearly for all values of sigma. These results are of relevance in astrophysical contexts (e.g., in pulsar environments), where e-p plasmas are encountered, or in pair fullerene-ion plasmas, in laboratory. (c) 2006 American Institute of Physics.

Dust-acoustic wave modulation in the presence of superthermal ions

A study is presented of the nonlinear self-modulation of low-frequency electrostatic (dust acoustic) waves propagating in a dusty plasma, in the presence of a superthermal ion (and Maxwellian electron) background. A kappa-type superthermal distribution is assumed for the ion component, accounting for an arbitrary deviation from Maxwellian equilibrium, parametrized via a real parameter kappa. The ordinary Maxwellian-background case is recovered for kappa ->infinity. By employing a multiple scales technique, a nonlinear Schrodinger-type equation (NLSE) is derived for the electric potential wave amplitude. Both dispersion and nonlinearity coefficients of the NLSE are explicit functions of the carrier wavenumber and of relevant physical parameters (background species density and temperature, as well as nonthermality, via kappa). The influence of plasma background superthermality on the growth rate of the modulational instability is discussed. The superthermal feature appears to control the occurrence of modulational instability, since the instability window is strongly modified. Localized wavepackets in the form of either bright-or dark-type envelope solitons, modeling envelope pulses or electric potential holes (voids), respectively, may occur. A parametric investigation indicates that the structural characteristics of these envelope excitations (width, amplitude) are affected by superthermality, as well as by relevant plasma parameters (dust concentration, ion temperature).

Nonlinear modulation of ion-acoustic waves in two-electron-temperature plasmas

The amplitude modulation of ion-acoustic waves IS investigated in a plasma consisting of adiabatic warm ions, and two different populations of thermal electrons at different temperatures. The fluid equations are reduced to nonlinear Schrodinger equation by employing a multi-scale perturbation technique. A linear stability analysis for the wave packet amplitude reveals that long wavelengths are always stable, while modulational instability sets in for shorter wavelengths. It is shown that increasing the value of the hot-to-cold electron temperature ratio (mu), for a given value of the hot-to-cold electron density ratio (nu): favors instability. The role of the ion temperature is also discussed. In the limiting case nu = 0 (or nu -> infinity). which correspond(s) to an ordinary (single) electron-ion plasma, the results of previous works are recovered.