Sensitivity of Visual System in 5-Day "Dry" Immersion With High-Frequency Electromyostimulation.

The aim of this work was to study the sensitivity of the visual system in 5-day "dry" immersion with a course of high-frequency electromyostimulation (HFEMS) and without it. "Dry" immersion (DI) is one of the most effective models of microgravity. DI reproduces three basic effects of weightlessness: physical inactivity, support withdrawal and elimination of the vertical vascular gradient. The "dry" immersion included in the use of special waterproof and highly elastic fabric on of immersion in a liquid similar in density to the tissues of the human body. The sensitivity of the visual system was assessed by measuring contrast sensitivity and magnitude of the Müller-Lyer illusion. The visual contrast sensitivity was measured in the spatial frequency range from 0.4 to 10.0 cycles/degree. The strength of visual illusion was assessed by means of motor response using "tracking." Measurements were carried out before the start of immersion, on the 1st, 3rd, 5th days of DI, and after its completion. Under conditions of "dry" immersion without HFEMS, upon the transition from gravity to microgravity conditions (BG and DI1) we observed significant differences in contrast sensitivity in the low spatial frequency range, whereas in the experiment with HFEMS-in the medium spatial frequency range. In the experiment without HFEMS, the Müller-Lyer illusion in microgravity conditions was absent, while in the experiment using HFEMS it was significantly above zero at all stages. Thus, we obtained only limited evidence in favor of the hypothesis of a possible compensating effect of HFEMS on changes in visual sensitivity upon the transition from gravity to microgravity conditions and vice versa. The study is a pilot and requires further research on the effect of HFEMS on visual sensitivity.

Comprehensive study of the drug delivery properties of poly(l-lactide)-poly(ethylene glycol) nanoparticles in rats and tumor-bearing mice.

Nanoparticles made of polylactide-poly(ethylene glycol) block-copolymer (PLA-PEG) are promising vehicles for drug delivery due to their biodegradability and controllable payload release. However, published data on the drug delivery properties of PLA-PEG nanoparticles are heterogeneous in terms of nanoparticle characteristics and mostly refer to low injected doses (a few mg nanoparticles per kg body weight). We have performed a comprehensive study of the biodistribution of nanoparticle formulations based on PLA-PEG nanoparticles of ~100nm size at injected doses of 30 to 140mg/kg body weight in healthy rats and nude tumor-bearing mice. Nanoparticle formulations differed by surface PEG coverage and by release kinetics of the encapsulated model active pharmaceutical ingredient (API). Increase in PEG coverage prolonged nanoparticle circulation half-life up to ~20h in rats and ~10h in mice and decreased retention in liver, spleen and lungs. Circulation half-life of the encapsulated API grew monotonously as the release rate slowed down. Plasma and tissue pharmacokinetics was dose-linear for inactive nanoparticles, but markedly dose-dependent for the model therapeutic formulation, presumably because of the toxic effects of released API. A mathematical model of API distribution calibrated on the data for inactive nanoparticles and conventional API form correctly predicted the distribution of the model therapeutic formulation at the lowest investigated dose, but for higher doses the toxic action of the released API had to be explicitly modelled. Our results provide a coherent illustration of the ability of controllable-release PLA-PEG nanoparticles to serve as an effective drug delivery platform to alter API biodistribution. They also underscore the importance of physiological effects of released drug in determining the biodistribution of therapeutic drug formulations at doses approaching tolerability limits.

Effects of Polyoxidonium on Phagocytic Cell Functions. Experimental and Clinical Estimation of Potential Inclusion of Polyoxidonium in Complex Therapy in Penetrating Eye Injury.

The purpose of present paper is the investigation of polyoxidonium effects on the functions of circulating pool of phagocytic cells and the estimation of its potential inclusion in complex therapy in penetrating eye injuries. On experimental model of eye injuring in rats there has been established that polyoxidonium attenuated some negative glucocorticoid effects on phagocytic cells. Inclusion of polyoxidonium in complex therapy optimized the course of injuring process according to parameters of the least infiltration of damage area with immunocompetent and effector cells, scar structure and other parameters. The stimulation of neutrophil, and in a less degree of eosinophil phagocytosis, was demonstrated at concentration range from 10(-11) to 10 &mgr;g/ml under conditions of 1 h drug preincubation in vitro with blood cells of healthy people. At concentrations 10(-11)-10(-8) &mgr;g/ml polyoxidonium caused a slightly stimulated effect on the parameters of monocyte phagocytosis. As a whole the results obtained show that further studies are promising for potential use of polyoxidonium in complex therapy for penetrating eye injuries.