Time domain Dielectric Spectroscopy Study of Human Cells. II. Normal and Malignant White Blood Cells

open access articleThe dielectric properties of human lymphocyte suspensions were studied by time domain dielectric spectroscopy (TDDS). Nine populations of malignant and normal lymphocytes were investigated. Analysis of the dielectric parameters of cell structural parts were performed in the framework of Maxwell^Wagner mixture formula and the double-shell model of cell. The specific capacitance of the cell membranes was estimated by the Hanai^Asami^Koisumi formula. It was shown that the dielectric permittivity, capacitance and conductivity values of cell membranes are higher for normal lymphocytes than for the malignant ones. The difference of the same parameters for normal B- and T-cells is also discussed

Effect of penetration enhancers on the dynamic behavior of phosphatidylcholine headgroups in liposomes

The results of a time-domain dielectric spectroscopy (TDDS) study of the effect of two skin penetration modulators on phosphatidylcholine (PC) bilayer vesicles are presented. The complex dielectric permittivity spectra of PC vesicle suspensions were described as the sum of two processes: the interfacial polarization of the bilayer and the reorientation of the zwitterionic PC headgroups in a plane approximately tangential to the bilayer surface. The influence of two additives (Azone and Transcutol) on the structure and dynamic behavior of PC headgroups of the bilayer vesicles was analyzed in terms of the interconnection of the dielectric spectra Cole-Davidson parameter, β, and the correlation factor, g, of the dielectric relaxation Kirkwood cell model. Analytically, these parameters are connected in the proposed model via the spatial distribution of headgroup dipole nonhomogeneities. In terms of the physical modulation of the polar surface phase, it appears that these additives can behave either as enhancers or as retarders. Their activity in this respect depends on the concentration of additive and temperature. © 2000 American Chemical Society

A toy model of fractal glioma development under RF electric field treatment

A toy model for glioma treatment by a radio frequency electric field is suggested. This low-intensity, intermediate-frequency alternating electric field is known as the tumor-treating-field (TTF). In the framework of this model the efficiency of this TTF is estimated, and the interplay between the TTF and the migration-proliferation dichotomy of cancer cells is considered. The model is based on a modification of a comb model for cancer cells, where the migration-proliferation dichotomy becomes naturally apparent. Considering glioma cancer as a fractal dielectric composite of cancer cells and normal tissue cells, a new effective mechanism of glioma treatment is suggested in the form of a giant enhancement of the TTF. This leads to the irreversible electroporation that may be an effective non-invasive method of treating brain cancer.Comment: Submitted for publication in European Physical Journal

Nanoelectropulse-driven membrane perturbation and small molecule permeabilization

BACKGROUND: Nanosecond, megavolt-per-meter pulsed electric fields scramble membrane phospholipids, release intracellular calcium, and induce apoptosis. Flow cytometric and fluorescence microscopy evidence has associated phospholipid rearrangement directly with nanoelectropulse exposure and supports the hypothesis that the potential that develops across the lipid bilayer during an electric pulse drives phosphatidylserine (PS) externalization. RESULTS: In this work we extend observations of cells exposed to electric pulses with 30 ns and 7 ns durations to still narrower pulse widths, and we find that even 3 ns pulses are sufficient to produce responses similar to those reported previously. We show here that in contrast to unipolar pulses, which perturb membrane phospholipid order, tracked with FM1-43 fluorescence, only at the anode side of the cell, bipolar pulses redistribute phospholipids at both the anode and cathode poles, consistent with migration of the anionic PS head group in the transmembrane field. In addition, we demonstrate that, as predicted by the membrane charging hypothesis, a train of shorter pulses requires higher fields to produce phospholipid scrambling comparable to that produced by a time-equivalent train of longer pulses (for a given applied field, 30, 4 ns pulses produce a weaker response than 4, 30 ns pulses). Finally, we show that influx of YO-PRO-1, a fluorescent dye used to detect early apoptosis and activation of the purinergic P2X(7 )receptor channels, is observed after exposure of Jurkat T lymphoblasts to sufficiently large numbers of pulses, suggesting that membrane poration occurs even with nanosecond pulses when the electric field is high enough. Propidium iodide entry, a traditional indicator of electroporation, occurs with even higher pulse counts. CONCLUSION: Megavolt-per-meter electric pulses as short as 3 ns alter the structure of the plasma membrane and permeabilize the cell to small molecules. The dose responses of cells to unipolar and bipolar pulses ranging from 3 ns to 30 ns duration support the hypothesis that a field-driven charging of the membrane dielectric causes the formation of pores on a nanosecond time scale, and that the anionic phospholipid PS migrates electrophoretically along the wall of these pores to the external face of the membrane

ТЕХНОЛОГИЯ БИОПСИИ СИГНАЛЬНОГО ЛИМФАТИЧЕСКОГО УЗЛА С ИСПОЛЬЗОВАНИЕМ ФЛУОРЕСЦЕНТНОЙ ЛИМФОГРАФИИ. ПРЕДВАРИТЕЛЬНЫЕ РЕЗУЛЬТАТЫ

С целью изучения возможности биопсии сигнального лимфатического  узла (СЛУ) методом  флуоресцентной лимфографии с применением зелёного индоцианина оперированы 65 больных раком молочной железы (РМЖ) 0-III стадий,  в том числе: 1) 8 больных РМЖ cTisN0M0; 2) 45 больных РМЖ cT1–4N0M0; 3) 12 больных РМЖ cT1–4N1–3M0 после эффективной системной терапии с неопределяемыми регионарными метастазами. Больным первой группы выполнялись биопсия СЛУ и мастэктомия с первичной реконструкцией. Дополнительная подмышечная лимфаденэктомия не производилась. Больным второй и третьей групп первым этапом операции выполнялась биопсия СЛУ, затем – органосохраняющая операция или радикальная мастэктомия с сохранением грудных мышц +/- первичная реконструкция молочной железы + подмышечная лимфаденэктомия I–II или  I–II–III уровней. СЛУ были выявлены у 60 больных – 92%, не найдены в 5 случаях. В том числе в первой  группе  СЛУ был найден у 7, у всех – без метастатического поражения.Во второй  группе  СЛУ найден  у 43 – в 96%. В 11 случаях из 43 обнаружены метастазы в СЛУ (26%). Ложноотрицательный результат 1 из 43 (2%). При РМЖ cT1–4N1–3M0 после эффективной системной терапии с исчезновением регионарных метастазов: из 12 таких больных СЛУ найден  у 10 – в 83%. В 4 случаях из 10 обнаружены метастазы в СЛУ (40%). Ложноотрицательных результатов 0 из 10. Не было зафиксировано  ни одного случая аллергических реакций или других побочных реакций при стандартном подкожном применении индоцианина. Флуоресцентный метод поиска СЛУ имеет свои технологические особенности: в большинстве случаев СЛУ не визуализируется через кожу, его нужно искать в ране, ориентируясь на ход лимфатического протока. Выполнение метода поиска от введения препарата до получения СЛУ занимает 15–30 минут. По нашей предварительной оценке, метод не уступает радионуклидному методу по частоте обнаружения СЛУ и частоте ложноотрицательных результатов

Experimental Diagnostics of the Emotional State of Individuals Using External Stimuli and a Model of Neurocognitive Brain Activity

In this paper, we study ways and methods to diagnose the emotional state of individuals using external audiovisual stimuli and heart telemetry tools. We apply a mathematical model of neurocognitive brain activity developed specifically for this study to interpret the experimental scheme and its results. This experimental technique is based on monitoring and analyzing the dynamics of heart rate variability (HRV), taking into account the particular context and events occurring around the subject of the study. In addition, we provide a brief description of the theory of information images/representations used for the paradigm and interpretation of the experiment. For this study, we viewed the human mind as a one-dimensional potential hole with finite walls of different sizes and an internal potential barrier modeling the border between consciousness and subconsciousness. We also provided the foundations of the mathematical apparatus for this particular view. This experiment allowed us to identify the characteristic markers of influencing external stimuli, which form a foundation for diagnosing the emotional state of an individual

Effect of penetration enhancers on the dynamic behavior of phosphatidylcholine headgroups in liposomes

The results of a time-domain dielectric spectroscopy (TDDS) study of the effect of two skin penetration modulators on phosphatidylcholine (PC) bilayer vesicles are presented. The complex dielectric permittivity spectra of PC vesicle suspensions were described as the sum of two processes: the interfacial polarization of the bilayer and the reorientation of the zwitterionic PC headgroups in a plane approximately tangential to the bilayer surface. The influence of two additives (Azone and Transcutol) on the structure and dynamic behavior of PC headgroups of the bilayer vesicles was analyzed in terms of the interconnection of the dielectric spectra Cole-Davidson parameter, β, and the correlation factor, g, of the dielectric relaxation Kirkwood cell model. Analytically, these parameters are connected in the proposed model via the spatial distribution of headgroup dipole nonhomogeneities. In terms of the physical modulation of the polar surface phase, it appears that these additives can behave either as enhancers or as retarders. Their activity in this respect depends on the concentration of additive and temperature. © 2000 American Chemical Society