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Y Chizmadzhev

Publications and source records attributed to Y Chizmadzhev.

3 recordsLinked to original sources

Theory of electrical creation of aqueous pathways across skin transport barriers.

Experimental studies have shown that application of electrical pulses to human skin that result in U(skin)>30 V for durations of about 1 ms or longer causes a large decrease in electrical resistance within microseconds, followed in seconds by an increase in molecular transport of water-soluble molecules. Local transport regions (LTRs), within which molecular transport is concentrated, mostly form away from the skin's appendages and rete pegs. Theoretical attempts to explain this behavior involve electrically created aqueous pathways ("pores"). For short (about 1 ms) "high voltage" (HV) pulses leading to about U(skin)>50 V, it was hypothesized that such pulses cause electroporation of the multilamellar lipid bilayer membranes of the skin's stratum corneum (SC). Much of the present experimental evidence supports the more specific hypothesis that such pulses create "straight through aqueous pathways", mostly within LTRs, that perforate the SC lipid bilayers and pass through the interiors of hydrated corneocytes. Theoretical estimates of the localized heating within LTRs predict relatively small temperature rises. The theory of LTR formation is incomplete, with both stochastic and deterministic models under consideration. Moderate voltage (MV) pulses leading to about 5<U(skin)<50 V, are consistent with appendageal activation and electroporation. The largest molecular fluxes occur for HV pulses, for which theory predicts large numbers of straight-through aqueous pathways. Both appendageal and stratum corneum electroporation are different from iontophoresis, which occurs at U(skin)<5 V.

Journal Article↗

Theory of skin electroporation: implications of straight-through aqueous pathway segments that connect adjacent corneocytes.

Previous in vitro experiments have shown that transdermal high-voltage pulses (Uskin approximately 100 V; duration approximately 1 ms) create local transport regions (LTR) away from appendages in human skin. Quantitative interpretation of the associated ionic and molecular transport led to the view that a large number of aqueous pathways were created, and these connect the corneocytes within an LTR. Here we use the "brick wall" model of the stratum corneum, modified so that morphology important to understanding electrical behavior is emphasized. In this model a minimum-size LTR is regarded as an idealized stack of corneocytes in which the 5-6 multilamellar lipid bilayer membranes between adjacent corneocytes are electroporated. As in artificial planar bilayer and cell membrane electroporation, a distribution of pathway sizes is expected during pulsing, and during recovery after pulsing individual pathway segments are expected to shrink and close randomly, with a time constant tau(seg) that depends on temperature and on lipid composition. Numerical simulations based on stochastic closure of individual segments were used to predict the electrical conductance G(LTR)(t) of a minimum-size LTR after pulsing stops. These theoretical results show that simple exponential decay, G(LTR)(t) = G(LTR)(0)exp(-t/tau(seg)), occurs with minimal fluctuations if the number of pathways is large (np > 10(2)), but for much smaller values the conduction decreases erratically. A "stochastic bottleneck" leading to complete closure is reached only at about np < 3. Thus, for the same number of electrically created pathways, the stratum corneum will remain "open" longer if the pathways are located within an LTR than if the same number of pathways are distributed sparsely over the skin. These predictions are relevant to postpulse transport, including the trapping of linear macromolecules that can hold pathway segments open for prolonged intervals.

Electroporation↗

Electromagnetic fields and cells.

There is strong public interest in the possibility of health effects associated with exposure to extremely low frequency (elf) electromagnetic (EM) fields. Epidemiological studies suggest a probable, but controversial, link between exposure to elf EM fields and increased incidence of some cancers in both children and adults. There are hundreds of scientific studies that have tested the effects of elf EM fields on cells and whole animals. A growing number of reports show that exposure to elf EM fields can produce a large array of effects on cells. Of interest is an increase in specific transcripts in cultured cells exposed to EM fields. The interaction mechanism with cells, however, remains elusive. Evidence is presented for a model based on cell surface interactions with EM fields.

Animals↗