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3/15/07 THE EFFECTS OF NANO CURRENT ON CELLULAR LIFE By Xanya Sofra-Weiss, Ph.D Microcurrent (1 microamp= 1 over a millionth of an ampere) and nano current (1 nano ampere = one over a billionth of an ampere) are known to influence biological processes at the cellular level by virtue of their similarity to physiologic actions, such as depolarization of cell membranes (Hodgkin, Huxley, 1952). Microcurrent has been reported to:

- speed up wound healing by increasing cell proliferation (Goldman, Pollack, 1966).

- Stimulate cells to proliferate but inhibit proliferation after a certain threshold (Ross, 1990; Blumenthal et al, 1997).

- Increase cell proliferation, DNA and protein content (Yin et al, 2005) - Act as an antioxidant in chronic ulcers healing in human subjects (Bok

et al, 2005) After a detailed analysis of the literature, certain articles were selected to enrich our understanding of micro electricity in order to form hypotheses for future research. Although micro electrical procedures have yet to be recognized as mainstream medical treatments, recent studies based on electronic advances reliably replicate results pointing towards the cability of micro electricity to resonate the wisdom of our inherent capacity for self regeneration and healing. Micro Current Effect on Cell Proliferation, DNA and Protein Content Yi-lo Lin et al (2005) used tissue cultures of tendon fibroblasts or tenocytes (the principal cellular components of tendon tissue) taken from 20 horses. Cells from these cultures were used for microcurrent stimulation (METS) experiments. The METS devise delivered a constant current, which means that the device automatically changed voltage as necessary to deliver the same current when peripheral resistance changed. The waveform consisted of a brief monophasic square pulse, duration 0.8 milliseconds. The pulse frequency was 150 Hz. Electrical current consisted of 0, 0.05, 0.1, 0.5, and 1.5ma or miliamps (1 milliamp = one over a thousand of an ampere). Application of microcurrent was via electrodes attached to paper strips soaked in the PBS solution that were placed in the culture wells. These investigators found that application of microcurrent had a stimulatory effect on cell proliferation which was significantly increased with repeated microcurrent applications (figure 1). Same results were observed for DNA content, except that application of current only once did not have a significant content compared with the control sample. However, repeated

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microcurrent application significantly increased DNA content (Figure 2).

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Figure 1 Effect of METS on proliferation of tenocytes in culture

Figure 2 Effect of METS on DNA content of tenocytes in culture

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Protein content significantly increased after one application of 0.5 and 1ma, and after two applications of 0.1, 0,5, and 1ma. However, application of microcurrent three times, significantly decreased protein content. Apoptosis rate did not alter after the first application. However after the third microcurrent application apoptosis rate significantly increased with increasing current intensity, so that the highest rate of apoptosis occurred at 1.5ma. The results of this study provides some evidence for the positive effects of microcurrent on cell proliferation, DNA and protein content, however, it raises questions as to the specifications and specific ranges of microcurrent necessary to produce optimum cell proliferation, DNA and protein content, while minimizing apoptosis (cell death). Cheng et al (1982) who studied the effects of miliamp and microcurrent on ATP generation protein synthesis and membrane transport showed that although low microcurrent stimulated physiologic activity of damaged cells and increased ATP up to 500%, ATP progressively decreased at miliamp ranges and dived down to 0 around 1.5ma. Therefore, the cell apoptosis observed in Yi-lo Lin et all study (2005) cited above, that appeared to be maximum with repeated applications of 1.5 ma, may well be the result of miliamp ranges depleting ATP. Additionally, the frequency of 150 Hz used in Yi-lo Lin study (2005) appears to contradict a number of experimental studies that report tissue healing within 1-4Hz band (Hefferman 1996). Santos et al (2004) showed epithelial regeneration, increased number of fibroblasts, collagen production and epidermis thickening at ultra low frequencies 0.5Hz. Lee at al (2005) used ultra low microcurrent ranging from 3 milliamps to 400 nano amperes at low frequencies that prevented the electrons from traveling in short bursts to heal chronic lesions in human subjects (see below under nano current as an antioxidant). In light of the above evidence, more research is necessary in testing cell proliferation, DNA and protein content and rate of apoptosis by using:

1. Ultra low microcurrent ranging from 500 microamps down to 100 nano amperes.

2. Ultra low frequencies, from 4.0 0.1 Hz that can prevent the electrons from traveling in short bursts.

3. Constant current. Constant current is usually the result of using a constant current generator that adjusts the voltage when resistant changes. According to Ohms Law, Current is equal to Voltage over Resistance (I=V/R). In order to maintain I constant, the voltage needs to increase or decrease as resistance increases or decreases. For example if I=1 then V=R. If I=2 then 2V=R or V=1/2R and so on.

There is an additional fourth component that may be a pertinent electrical specification component: the microcurrent waveform. Neher (Nobel Prize in Physiology and Medicine, 1991) observed square electrical signals emitted by the cell membrane. According to Mel C Siff (2000) microcurrent appears to operate more on the basis of resonant attunement of the stimulus to cellular

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and subcellular processes and its effects depend on how efficiently the stimulation parameters match the electrical characteristic of the different cells. This resonant attunement may be impossible when the device merely produces a simple square waveform which is a sine waveform with a flat top that contains many higher frequencies, called harmonics. Harmonics can cause buzzing or other noise problems with some equipment. A clean complex square waveform that is composed out of several frequencies that stabilize it in the face of both electronic and biological resistances is necessary to produce the high definition signal that will tune into and resonate the cells biological processes. Nano current as an antioxidant Subatomic particle physics and the electron theory of electrical current comprise an explanation of how electrical nano currents (in the billionths of an ampere) can function as an antioxidant. An atom is made up of protons, neutrons and electrons. When molecules with weak bonds split, they can leave atoms with unpaired electrons, i.e. free radicals. Free radicals attack stable molecules to steal their electrons. When the attacked molecule loses an electron, it becomes a free radical itself, starting a chain reaction. Oxygen is attracted to a magnet, because oxygen has two unpaired electrons in its lowest energy state (Millikan, 1925). The existence of unpaired valence electrons in a stable molecule confers high chemical reactivity. Highly reactive molecules can oxidize molecules that were previously stable (oxidation refers to a loss of electrons) and turn them into free radicals. The food we eat is oxidized to produce high-energy electrons that are converted to stored energy. This energy is stored in high-energy phosphate bonds in the form of ATP (Adenosyne tri phosphate is a molecule of the structural unit of nucleotide chains forming nucleic acids as RNA and DNA). In the absence of oxygen, one molecule of glucose will yield four molecules of ATP. In the presence of oxygen we get 24 to 28 molecules of ATP from one molecule of glucose going through the Krebs cycle plus the four molecules from glycolysis. This entire oxidation process takes place in the mitochondria, making the system susceptible to the formation and effects of free radicals. A certain amount of oxidative function is necessary for proper health. For example, oxidative processes are used by the immune system to kill microorganisms. Overall, however, accumulated free radicals are one of the major contributing factors to aging and disease. Accumulated free radicals can even induce local injury to patients with poor immune systems, by reacting with lipids, proteins and nucleic acids, leading to cellular membrane damage. Antioxidants (eg. Vitamin C) are chemicals that have the ability to donate

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electrons without becoming free radicals themselves. Nano amperes act as a powerful antioxidant by infusing a steady stream of electrons to the free radicals, ending the electron stealing chain reaction caused by free radicals. This was recently hypothesized in a study by Bok Y. Lee, MD, FACS, Alfred J. Koonin, M.B., Ch, B., Ph.D., FRCS, Keith Wendell, Ph.D., and John Hillard, RN, who used ultra low microcurrent (from 3 miliamp to 400 nano amperes) combined with low frequencies and an adjustable voltage to attain constant current, to treat 25 chronic skin ulcers present for an average of 18.5 months and not responding to standard conservative treatment in a hospital setting. Most lesions were in stages III and IV. Patients age varied from 20 to 85 years old. The lesions had the following chronic etiologies:

- AIDS - Arterial Insufficiency - Cerebro-Vascular Accident - Chronic Obstructive Pulmonary Disease - Chronic Renal Failure - Congestive Cardiac Failure - Spinal Cord Injury - Traumatic Brain Injury - Venous Stasis

Bok et al (2005) reported that 100% of the lesions treated with nano current showed response to the treatment. 100% healed in a maximum time of 7 weeks. Average time of healing was 48 hours of treatment over 16 days. Surgical debridement was unnecessary as the necrotic tissue appeared to disappear spontaneously. It has also shown that the lower the frequency the more permanent the effects of nano current. None of the healed lesions showed any sign of recurrence after a period ranging from six to eighteen months. (see results on figure 1) Many studies have shown that the rate of wound healing of an individual is directly proportional to their age. From this study it can be seen that treating chronic skin ulcers with ultra-low microcurrent (nano amperes) eliminates the age factor by equalizing the healing rate at all ages. The only limiting factor in healing time with this method seems to be the duration of the lesion. Overall Lee et als study (2005) indicates that a steady flow of electrons in a relatively low concentration appears to act exactly as one would expect from any antioxidant. The fact that the electrons are focused on a small region of the body may explain why healing changes appeared so rapidly. Lee et al (2005) concluded that the actual regeneration of the tissue coupled with the absence of the age factor in healing and the concomitant improvement noticed in the patients general condition all point to a highly potent antioxidant effect on the local tissues as well as generally.

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Figure 3 -- Example of chronic lesion healing within an average of 16 days

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What are the Microcurrent and Nano Current Effects on Cell Mitosis The Cell Cycle consists of several phases. In the first phase, (G1) the cell grows and becomes larger. After cytokinesis (the process where one cell splits off its daughter cell) the cells are quite small and low on ATP. They acquire ATP and increase in size during the G1 phase. After acquiring sufficient size and ATP, the cells enter the next phase (S) where they undergo DNA synthesis and a copy or each chromosome is formed. Since the formation of new DNA is an energy draining process, the cell undergoes a second growth and energy acquisition stage, the G2 phase. The energy acquired during G2 is used in cell division or mitosis. For all organisms it is essential that the different phases of the cell cycle are precisely coordinated. The phases must follow in the correct order, and one phase must be completed before the next phase can begin. Errors in this coordination may lead to chromosomes being lost, rearranged or distributed unequally between the two daughter cells. This type of chromosome alteration is often seen in cancer cells (Hartwell, Hunt and Nurse Nobel lecture 2001). Cheng (1982) reported a significant increase of ATP, up to 500%, following microcurrent stimulation. However, Chengs study did not explore:

- the effects of increased ATP on cellular proliferation, - the effects of increased ATP on the proper coordination of cell division.

The phase of the cell cycle may be important to the effects of microcurrent as cell cycle seems to influence the receptivity of the cell to extracellular signals. Generally, cells in the G0 / G1 stage undergo division when they receive signals that instruct them to enter the active phases of the cell cycle (Morgan et al, 2002). Deregulation of the cell cycle components has been shown to induce mitotic catastrophe and also may be involved in triggering programmed cell death of apoptosis (King et al, 2004). In conclusion, more research is necessary to test the hypothesis that microcurrent may have an effect on the coordination of cell division by virtue of increasing ATP. A even more interesting research study may be examining the effects of nano current resonance with biological signals instructing cells in the G0 / G1 stage to undergo division, by testing different complex waveforms (built with several frequencies) that vary in shape or composition. Can Nano Current have an effect on how Proteins Create Life? Cell biology research has revealed that although the cell nucleus reflects the cells reproductive system while the membrane represents its brain (Pray 2004, Silverman 2004, Lipton, 2005). Following enucleation (removing the nucleus to the cell) many cells can survive for up to two or more months,

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demonstrating intelligence in their actively ingesting and metabolizing nutrients while performing all necessary physiological functions such as respiration, excretion, motility, etc. Enucleated cells die, not because they have lost their brain but because they have lost their reproductive capability. When you destroy the membrane, however, the cell dies, just as one would if ones brain was removed. Even if the membrane is left intact and you use digestive enzymes to destroy its receptor or effector proteins (Integral Membrane Proteins IMPs), the cell intelligent behavior ceases, and the cell becomes comatose. These findings have let scientists to the conclusion that the Integral Membrane Proteins (IMPs) are the fundamental units of cellular intelligence that control behaviors such as respiration, nourishment and waste (Lipton, 2005). IMPs are divided into receptor proteins that provide an awareness of environmental signals and effector (action) proteins. The receptor (awareness) - effector (action) proteins or IMPs act as a switch, translating environmental signals into cellular behavior. Studying how IMPs work has now become a field of its own called signal transduction. Signal transduction scientists focus on classifying hundreds of environmental signals and the activation of the cells behavior proteins. There are different kinds of effector proteins due to the variety of functions necessary for the smooth functioning of the cell. For example transport proteins include channel proteins that drive molecules and information from one side of the membrane barrier to the other. When the electrical charge of channel proteins is altered, the protein changes shape, allowing an open channel running through the proteins core that allows nutrients to go through the cell. In their inactive state, channel proteins are shaped like a tightly wound sphere, closed to the world outside the cell. A specific channel type sodium-potassium protein is called ATPase. This turns the cell into a constantly recharging biological battery. Another variety of effector proteins, the cytroskeletal proteins, regulates the shape and motility of the cells. A third variety called enzymes, breaks down or synthesizes molecules. When activated, all types of effector proteins provide signals that activate genes. IMPs and their byproducts provide signals that control the binding of the chromosomes regulatory proteins that form a sleeve around the DNA, thus controlling the reading of the genes. It takes about 100,000 different proteins to run our bodies. Each protein is a linear string of linked amino acid molecules, joined like a string of beads. The amino acids are linked by virtue of their electromagnetic positive and negative charges (like charges repel each other and opposite charges attract each other). The forces generated by the amino acids positive and negative charges bend and fold the flexible string of amino acids into what turns to be the most crucial elements of cellular life. The distribution of electromagnetic charge within a protein can be selectively altered by electromagnetic fields. Receptor (awareness) proteins antennas can read micro electrical signals. When these signals resonate with the receptors antennas, it will change the receptor proteins charge, causing it to change shape (Tsong 1989).

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Analogues resonance processes may apply to effector (action) proteins. The mere fact that the life of the entire cellular system is based on electromagnetic charges, preludes another hypothesis yet to be tested by research. The hypothesis primarily revolves around the conformations (final shapes) of proteins and how nano current may be involved in the shape-shifting movements of proteins that propel cellular life. More specifically nano current may affect: (1) the proteins conformation changes that may generate movement to fulfill

the cells physiological functions (eg. respiration or digestion); (2) the proteins cooperation in specific physiological functions known as

pathways, including the energy-generating Krebs cycle; (3) the proteins proper folding, necessary for optimal functioning.

Improperly folded proteins are marked for destruction by the cell, their backbone amino acids are disassembled and recycled in the synthesis of new proteins.

Considering the importance of resonance between nano signal and a proteins antennas, a key aspect in testing the above hypotheses will be the specifications of the nano electricity used. As mentioned above the device used must be capable of the following specifications:

1. Ultra low frequencies 2. Range of microcurrent from 500 micro amps (research reports an

increase of ATP up to 500%) to 100 nano amperes 3. Constant current 4. A variety of complex waveforms that consist of a number of

frequencies to ensure waveform accuracy and stability (eg. complex sine, square or rectangular waveforms.)

An example of such a device is the Perfector, a machine primarily used in the field of cosmetics for non-invasive face lifts, scar healing and to reduce pigmentations, melasma, acne and rosacea. For more information on the Perfector go to www.arasysperfector.com and click on the science section.

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