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SCENAR: again on its effectiveness Ya. Grinberg B. Kulizhky The effectiveness of SCENAR-therapy in terms of physical influencing factors was already considered in some works [1-6]. These articles identified the reason for stimulating pulse dynamics, showed that stimulation energy of SCENAR is concentrated mainly on the thin layer of epidermis, and analyzed potential influence of the intercellular fluid. One of the main physical factors in SCENAR-therapy is skin vibration (manifested as skin sounding). Our skin begins to sound under the influence of the pulse signal. The skin transforms SCENAR-signal like electrostatic loudspeaker. SCENAR-therapy can be identified as a new class of electric therapy – high-voltage pulse electric therapy. However, still we can’t find simple answers to some questions. Variety of stimulation modes (modulations). Modulation (frequency or amplitude) and pulse modifications (damping) do not determine energy concentration, dynamic properties of a signal, skin vibration (though they influence the vibration spectrum). Our experience of using simple devices (with no additional modulations) proves that they are effective. However, we recommend to use other operating modes that are proven in practice to be effective if you have no results during the treatment. Our customers often say they managed to get treatment dynamics using some specific mode (swing, informational modulation, etc.). What can explain the effectiveness of these modes that were selected emperically? Device settings. We say our devices have specific settings. It has almost no connection with physical factors that we mentioned. Then what are these settings for? Why those devices that have no specific settings provide worse therapeutic effect? Dynamic properties of a signal are used for diagnostics. Each signal is different and that helps to avoid body addiction to it. Are there other mechanisms of pulse dynamics? The objective of our research is to explain and provide scientific background for the operating modes that were intuitively selected following the treatment results of medical practitioners. Uor approach is based on the phenomenon of electroporation (by B. Kulizhky). Electroporation is a significant increase in the permeability of the cell plasma membrane caused by externally applied electrical field. Cell membranes can concentrate electric field (according to laws of electrical engineering) and that is the basic principle of electroporation. Intercellular environment can be considered as low-conductivity electrolyte. If we place such electrolyte between two parallel live flat electrodes (let’s call this space a cell), field intensity will evenly spread in the space between them. If we place bilayer membrane, difference of potentials will concentrate on the membrane. The reason for this effect is in very high resistance of the membrane (if compared with electrolyte). The membrane can be considered as non-conductivity dielectric. Pay your attention, the same is the SCENAR-electrode placed on dry skin. As we have already mentioned all the energy is concentrated on the thin corneal layer of epidermis. When between the electrodes there are cells with about 10 microns in diameter, external field will be screened by the mobile ions that make the diffused plates of electric double layers. Therefore, cell electroporation requires greater voltage. In laboratory practice pulses of electric field are applied to cell suspension with 10.000-100.000 V/cm in a pulse lasting from a few microseconds to a millisecond. That causes the sharp increase of membrane conductivity [7]. In some period of time, from several seconds to several minutes, the cell conductivity normalizes [8]. If we take tissue cells, e.g. skin, we can increase the cell membrane permeability (for medicines or nutritional agents) for a piece of tissue in the interelectrode space. Let’s take the introduction of DNA fragments into cell. DNA cells and fragments that should be introduced are added into the electroporation medium (see Figure). High-voltage pulses are transmitted through the medium and that creates holes in the plasma membrane. Time during which these holes exist and their size is enough to uptake the macromolecules, such as DNA, under the influence of osmotic forces. Electrode DNA Solution Electrode Pic. It should be noted that electroporation can transfer the macromolecules that are in diameter greater than the diameter of electric holes through membranes [9]. The transfer of the DNA molecules shows that they can make the holes larger and after electoporation the holes slowly (~ 100 sec.) relax to the initial state. Electric field gradually and slowly presses the plasmid DNA into the small hole thus making it larger. Intensity and duration of the electric field for each system of cells is selected empirically. Electroporation is also used to prepare competent cells and provides the cells of the highest competency available for today. Cell competency is the ability to “decode” induced signals correctly. Electroporation is widely used in cosmetology to introduce highmolecular substances (hyaluronic acid) into the skin. Methods for electroporation of immunoglobulin, vaccine solutions and insulin are now investigated. [10]. Specifications of electroporators and SCENAR device. Electroporators: amplitude (in different devices) - 20-3000 V; pulse duration 15 msec — 5 msec; pulse shape is exponential (more often controlled), in cosmetology the current is 5-100 Hz with neural bipolar pulse shape (due to its physiological features and favorable tolerability by patients, if compared with other pulse shapes). SCENAR: no-load amplitude up to 500 V (limited according to safety standards), in treatment mode - 100-200 V (on normal skin); pulse shape is exponentially damped sinusoid (neural bipolar pulse) with 14-340 Hz frequency; duration of the second phase first pulse (pulse of maximum amplitude in the damping signal) is about 10 msec — 150 msec; duration of the whole damping signal is up to 1000 msec. As we see, the specifications of electroporators and SCENAR devices are much similar. Let’s come to explanation of the approaches based on the results of using SENARs in practice. Various stimulation modes. When the body suffers from any pathology, it produces biologically active substances and fragments that surround the cells. The aim of these substances is to induce cells to promote body healing. SCENAR-stimulation provides additional production of bioactive substances, including those of peptide nature. Without any help they slowly penetrate into the pathological focus and need much time to fight with the pathology. SCENAR, which generates high-voltage (high-amplitude) pulse signal, is at the same tame the electroporator. High-amplitude stimulation increases biomembrane permeability, biologically active substances penetrate into cells and we observe faster activation of sanogenesis processes in the body. As we have already mentioned, intensity and duration of electric field for each system of cells is selected empirically and great variety of stimulation modes enables the user to apply this empirical mechanisms. Specific device settings. The key factor here, as before, is the empirical character of elecroporation. Literature considers [11-12] field intensity and pulse duration. Still, we can’t forget that pulse shape is also important in providing such effect. We can suppose that appropriate settings of the device increase cell competency in relation to bioactive substances produced in sanogenesis. Dynamic properties of a signal are known to be connected with the following processes: formation of the double layer capacity and simultaneous pulse stimulation. Formation of the double-layer capacity is connected with the phenomena occurring on the border of the first (metal) and second (organic and inorganic electrolyte) class conductors. In fact, when the electrode is placed on the skin we observe width-pulse modulation. As a rule the pulse is stretched, i.e. a series of stretching pulses impact the cell. And we can expect the increased effect of electroporation. Physiological effects in “soft” reverse electroporation and electropermeability (increase of permeability) occur on cellular and tissue levels [13,14]. Electroporation of separate cells contributes to better metabolism in them and their activation [15] with the increase in production and acceleration in proliferation. Electroporation and, as a result, permeability of the tissue improves functionality of microvasculature [16], increases the perfusion of tissue fluid and consequently the nutrition and oxygen supply [17]. Tissue electroporation accelerates the movement of formed elements and macrophages in the intercellular space [18], and that results in faster and localized immune reaction [19]. That provides great increase in the level of antioxidative enzymes, decrease of the inflammatory process, and inhibition of oxidative stress. Same physiological effects (or their consequencies) are observed in SCENAR-therapy. [3,20-22 ]. Skin vibration. We didn’t consider the effect of vibration on electroporation before. When we read about electroporation we find no data on any scientific research of the vibration effect. At the same time practical use of electroporation in cosmetology shows the impact of electric pulses and vibration: electric pulses enable the substances to penetrate inside, while vibration stimulate certain receptors (Merkel’s cells). It should be also noted that while preparing competent cells using chemical procedure, shaking is necessary. Therefore, we can expect that skin vibration in SCENAR-therapy enhances the effect of electroporation. Findings 1. SCENAR-therapy as high-voltage pulse electric therapy has the properties of electropirators. 2. Electropiration explains many physiological effects of SCENAR-therapy. 3. Mechanisms and principles of electroporation provide the background for some solutions and decisions made when developing SCENAR devices empirically. References 1. Гринберг. Я.З. Об одном эффекте СКЭНАР–воздействия. Известия ТРТУ. Тематический выпуск. Материалы научно – технической конференции Медицинские информационные системы – МИС -2004». – Таганрог: изд-во ТРТУ, 2004, «№ 6(41), - С.100-105. 2. Гринберг Я.З. СКЭНАР–терапия и СКЭНАР–экспертиза. Некоторые аспекты. Журнал «Рефлексология», №3 (7), 2005, с. 5-10. 3. Гринберг Я.З. СКЭНАР: построение, физические механизмы, основы эффективности. Журнал «Нелекарственная медицина», №3(4), 2006, с. 37-42. 4. Гринберг Я.З Ещё раз об особенностях СКЭНАР – воздействия. Известия ТРТУ. Тематический выпуск. Материалы научно – технической конференции Медицинские информационные системы – МИС -2006». – Таганрог: изд-во ТРТУ, 2006, «№ 11(46), - С.144-147. 5. Гринберг Я.З. СКЭНАР: новые результаты, новые гипотезы. Известия ЮФУ. Тематический выпуск. «Медицинские информационные системы». – Таганрог: изд-во ТТИ ЮФУ, 2008, № 5(82), - С.127- 130. 6. Гринберг Я.З. СКЭНАР: новые результаты, новые возможности. 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Electroporation: a general phenomenon for manipulating cells and tissues. J Cell Biochem. 1993 Apr;51(4):426–435. 14. Антонов В.Ф., Аносов А.А., Норик В.П., Смирнова Е.Ю., Немченко О.Ю. Мягкая порация мембран и адресная дставка лекарства. II Евразийский конгресс по медицинской физике и инженерии. «Медицинская физика -2005» Москва 21-24 июня 2005 г. 15. Pavselj N, Préat V, Miklavcic D. A numerical model of skin electropermeabilization based on in vivo experiments. PMID: 17849185. 16. Kalluri H, Banga AK. Transdermal delivery of proteins. AAPS PharmSciTech. 2011 Mar;12(1):431-41. Epub 2011 Mar 3. PMID: 21369712. 17. Turjanski P, Olaiz N, Maglietti F, Michinski S, Suárez C, Molina FV, Marshall G. The role of pH fronts in reversible electroporation. PLoS One. 2011 Apr 29;6(4):e17303. PMID: 21559079. 18. Малинин B.C.. Шаров B.C., Осипов А.Н.. Вилков С.А., Путинский А.В. 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