Effectiveness of Repeated Administration of Praziquantel with Disodium Glycyrrhizinate and Two Enantiomers of Praziquantel on Opisthorchis felineus (Rivolta, 1884).

BACKGROUND: Nowadays, it is still important to develop effective anti-opisthorchiasis agents. In this work, we tested a complex of praziquantel (PZQ) with a plant origin compound-disodium glycyrrhizinate-in the ratio 1:10 PZQ:Na2GA, containing 11-fold less of the active ingredient. Our aim was to study various ways to treat trematode Opisthorchis felineus with this complex in vitro. Additionally, an in vitro comparison of the anthelmintic action was made among racemic-PZQ, (R)-PZQ, and (S)-PZQ on juvenile and adult maritae of O. felineus. METHODS: Worms extracted from the hamsters were subjected to various regimens of administration of the complex: once a day for 3 days or three times within 1 day. Moreover, mature maritae and juvenile worms of O. felineus were subjected to the comparison the anthelmintic effectiveness of racemic-PZQ, (R)-PZQ, and (S)-PZQ. RESULTS: The O. felineus maritae that received PZQ:Na2GA (1:10) thrice within 1 day were most strongly affected by the drug. Their motility substantially decreased already on the second day after the last dose, and the percentage of live worms by the end of the experimental period was the lowest. These results indicate a cumulative anthelmintic effect of this substance under the regimen "three times within 1 day." For the first time, we report that among the three substances (racemic-PZQ and two enantiomers), (R)-PZQ has the highest anthelmintic activity, toward both juvenile and sexually mature maritae of O. felineus. CONCLUSION: These findings suggest that the development of a supramolecular complex of (R)-PZQ with disodium glycyrrhizinate and administration of this complex three times within 1 day are promising approaches.

Physicochemical Properties and Anti-Opisthorchosis Effect of Mechanochemically Synthesized Solid Compositions of Praziquantel with Glycyrrhizic Acid Disodium Salt.

The mechanochemical preparation of solid compositions of praziquantel with plant saponin (glycyrrhizic acid disodium salt) is described. The study of a number of physicochemical parameters showed that dissolving solid compositions in water is accompanied by the inclusion of praziquantel molecules into micelles, which are formed in the solution of the glycyrrhizic acid disodium salt. Using the opisthorchiasis model caused by Opisthorchis felineus, we found a 4- to 11-fold increase in the anthelmintic activity of praziquantel in the composition as compared to the official praziquantel. According to the pharmacokinetic data, the use of the composition increased the bioavailability of praziquantel 3 times.

Quasisolitons in self-diffusive excitable systems, or Why asymmetric diffusivity obeys the Second Law.

Solitons, defined as nonlinear waves which can reflect from boundaries or transmit through each other, are found in conservative, fully integrable systems. Similar phenomena, dubbed quasi-solitons, have been observed also in dissipative, "excitable" systems, either at finely tuned parameters (near a bifurcation) or in systems with cross-diffusion. Here we demonstrate that quasi-solitons can be robustly observed in excitable systems with excitable kinetics and with self-diffusion only. This includes quasi-solitons of fixed shape (like KdV solitons) or envelope quasi-solitons (like NLS solitons). This can happen in systems with more than two components, and can be explained by effective cross-diffusion, which emerges via adiabatic elimination of a fast but diffusing component. We describe here a reduction procedure can be used for the search of complicated wave regimes in multi-component, stiff systems by studying simplified, soft systems.

Wave reflection in a reaction-diffusion system: breathing patterns and attenuation of the echo.

Formation and interaction of the one-dimensional excitation waves in a reaction-diffusion system with the piecewise linear reaction functions of the Tonnelier-Gerstner type are studied. We show that there exists a parameter region where the established regime of wave propagation depends on initial conditions. Wave phenomena with a complex behavior are found: (i) the reflection of waves at a growing distance (the remote reflection) upon their collision with each other or with no-flux boundaries and (ii) the periodic transformation of waves with the jumping from one regime of wave propagation to another (the periodic trigger wave).

Classification of wave regimes in excitable systems with linear cross diffusion.

We consider principal properties of various wave regimes in two selected excitable systems with linear cross diffusion in one spatial dimension observed at different parameter values. This includes fixed-shape propagating waves, envelope waves, multienvelope waves, and intermediate regimes appearing as waves propagating at a fixed shape most of the time but undergoing restructuring from time to time. Depending on parameters, most of these regimes can be with and without the "quasisoliton" property of reflection of boundaries and penetration through each other. We also present some examples of the behavior of envelope quasisolitons in two spatial dimensions.

Envelope quasisolitons in dissipative systems with cross-diffusion.

We consider two-component nonlinear dissipative spatially extended systems of reaction-cross-diffusion type. Previously, such systems were shown to support "quasisoliton" pulses, which have a fixed stable structure but can reflect from boundaries and penetrate each other. Herein we demonstrate a different type of quasisolitons, with a phenomenology resembling that of the envelope solitons in the nonlinear Schrödinger equation: spatiotemporal oscillations with a smooth envelope, with the velocity of the oscillations different from the velocity of the envelope.

Speed of traveling fronts in a sigmoidal reaction-diffusion system.

We study a sigmoidal version of the FitzHugh-Nagumo reaction-diffusion system based on an analytic description using piecewise linear approximations of the reaction kinetics. We completely describe the dynamics of wave fronts and discuss the properties of the speed equation. The speed diagrams show front bifurcations between branches with one, three, or five fronts that differ significantly from the classical FitzHugh-Nagumo model. We examine how the number of fronts and their speed vary with the model parameters. We also investigate numerically the stability of the front solutions in a case when five fronts exist.

[Negative refractoriness in excitable systems with cross-diffusion].

The results of numerical experiments with mathematical models of excitable systems with cross-diffusion are presented. It was shown that the refractoriness in such systems may be negative. The effects of negative refractoriness on the propagation and interaction of waves are demonstrated.

[Dynamics of bacterial population waves in relation to the function of chemotaxis response].

The time of formation and rate of bacterial population waves as a function of substrate concentration has been investigated. It was shown both theoretically and in experiment that the time of wave formation increases with substrate concentration. At the same time, the rate of wave propagation decreases at relatively high substrate concentrations. A comparative analysis of the dynamics of bacterial population waves in different chemotaxis responses was carried out in in silico experiments with the Keller-Segel model.

Spontaneous traveling waves in oscillatory systems with cross diffusion.

We identify a type of pattern formation in spatially distributed active systems. We simulate one-dimensional two-component systems with predator-prey local interaction and pursuit-evasion taxis between the components. In a sufficiently large domain, spatially uniform oscillations in such systems are unstable with respect to small perturbations. This instability, through a transient regime appearing as spontaneous focal sources, leads to establishment of periodic traveling waves. The traveling wave regime is established even if boundary conditions do not favor such solutions. The stable wavelength is within a range bounded both from above and from below, and this range does not coincide with instability bands of the spatially uniform oscillations.

[Transient currents and Ca2+ gradient relaxation in characean algae cells: theory and experiment].

Transient Ca2+ and Ca2+-dependent Cl- currents of plasmatic membranes of voltage-clamped Chara corallina freshwater alga cells were studied. Our earlier described method was used for rapid (approximately 10 ms) injection of Ca2+ ions into the cell during the deactivation period of calcium channels following their activation by a positive voltage pulse (injection by "tail" Ca2+ current). This procedure allowed one to determine the amplitude of the Ca2+ component, as well as the amplitude and kinetics of the submembrane Ca2+ concentration-dependent Cl- component for the transient current. Calculations based on the cell model allowing for Ca2+ diffusion, the Ca2+-buffering properties of the cytoplasm, and the nonlinear dependency of iCl on [Ca2+]cyt, as well as the presence of chloroplasts agreed well with the experimentally observed behavior of the transient current. The slow stage of the [Ca2+]cyt relaxation to the resting level (approximately 10(-7) M), related to the functioning of Ca2+-ATPases, was shown to take approximately 10(2) s. We assume this stage to determine the duration of the refractory period after the generation of action potential.

[Soliton-like and non-soliton regimes of interaction of taxis waves (illustrated with an example of bacterial population waves)].

It has been shown in our previous studies that, during collision, bacterial population waves can penetrate each other or stop. In the present study, the mechanism of the two regimes of interaction is considered in detail. Based on the experimental and theoretical research, it has been shown that this interaction is a vivid example to confirm one of the characteristic properties of waves in cross-diffusion systems.

Pursuit-evasion predator-prey waves in two spatial dimensions.

We consider a spatially distributed population dynamics model with excitable predator-prey kinetics, where species propagate in space due to their taxis with respect to each other's gradient in addition to, or instead of, their diffusive spread. Earlier, we have described new phenomena in this model in one spatial dimension, not found in analogous systems without taxis: reflecting and self-splitting waves. Here we identify new phenomena in two spatial dimensions: unusual patterns of meander of spirals, partial reflection of waves, swelling wave tips, attachment of free wave ends to wave backs, and as a result, a novel mechanism of self-supporting complicated spatiotemporal activity, unknown in reaction-diffusion population models.

Half-soliton interaction of population taxis waves in predator-prey systems with pursuit and evasion.

In this paper, we use numerical simulations to demonstrate a half-soliton interaction of waves in a mathematical model of a "prey-predator" system with taxis when of two colliding waves, one annihilates and the other continues to propagate. We show that this effect depends on the "ages" or, equivalently, "widths" of the colliding waves. In two spatial dimensions we demonstrate that the type of interaction, i.e., annihilation, quasisoliton, or half-soliton, depends not only on curvature and width of the colliding waves, but also on the angle of the collision. When conditions of collision are varying in such a way that only a part of a wave survives the collision, then "taxitons," compact pieces of solitary waves, may form, which can exist for a significant time.

Quasisoliton interaction of pursuit-evasion waves in a predator-prey system.

We consider a system of partial differential equations describing two spatially distributed populations in a "predator-prey" interaction with each other. The spatial evolution is governed by three processes: positive taxis of predators up the gradient of prey (pursuit), negative taxis of prey down the gradient of predators (evasion), and diffusion resulting from random motion of both species. We demonstrate a new type of propagating wave in this system. The mechanism of propagation of these waves essentially depends on the taxis and is entirely different from waves in a reaction-diffusion system. Unlike typical reaction-diffusion waves, which annihilate on collision, these "taxis" waves can often penetrate through each other and reflect from impermeable boundaries.

[Adaptive mutagenesis accelerates microorganism evolution only while competing for resources: mathematic modeling]. / Adaptivnyi mutagenez uskoriaet évoliutsiiu mikroorganizmov tol'ko pri konkurentsii za resursy: matematicheskoe modelirovanie.

Mathematical simulation of adaptive mutagenesis was carried out. The results obtained indicate that adaptive mutagenesis can play an essential role in the survival of microbial populations. We show that the competition for natural resources is a necessary factor of adaptive mutagenesis.