BCRBCR(biological cell regulation)

withmicrocurrent

Principle - Indications - Therapies

Dr.med.univ. Vlastimil Voracek

Orthopädisches Therapiezentrum /OTZ - Memmingen

The materialistic assertion of the subject, and

therefore also the assertion that humans are a

machine (La Mettries),

could be finally overcome by the discovery of the

electron. Since over 3000 years until today humans

are defined only

by its anatomical structure.

The interpretation and the understanding for

illnesses and therapies are determined by

modification of the subject, because they come the

understanding over the own existence as anatomical

structure next.

The release from the pure mechanical

interpretation

of illnesses however last until today because

the prevailing chemical and anatomical

diagnostics leads to a quantification and a

structuralisation of the disease pictures.

A complex processing of functional mechanism on

neuromotor and energetic level, which could be

appropriate a reason for the illnesses as a

cause or consequence, take place hardly.

Symptoms are misjudged as disease

causes and the true cause is not cured.

This leads to a chronification and a

dependency on symptomatic handling

concepts which perhaps suppresses pain

or

compensates chemical deficit.

They enable a healing rarely.

Why the physician is looked up by a patient ?

Limited range of motion (functio laesa)

Pain (dolor)

Swelling (tumor)

Temperture (calor)

Redness (rubor)

FunctionFunction

MetabolismMetabolism

ImmunologyImmunology

morphologymorphology

Psyche, Psyche,

vegetative vegetative

nervous systemnervous system

functionfunction

neuromotoricsneuromotorics

metabolismmetabolism

immunologyimmunology

Where is the causal beginning of the biological cell therapy (BCR) by

microcurrent?

In addition we need acknowledged causal effects models which however are proven by diagnostic models and in reverse. There are completely

clear models, those causality is fast visible, however others are not completely unique.

MetabolismMetabolism

All cells of the body needs energy

Living cells are subjected to the laws of the energy conversion and after the laws of

thermodynamics:

Cells cannot create new energy or destroy it.

Living cells win and change energy gradually in many individual chemical steps from the

supplied food and oxygen (glucose reduction, CIT advice cycle, breathe-chain-oxidative

phosphorylation).

Humans produce between

70 - 800 KG ATP a day

ATP – Adenosin-5´triphosphat

The main energy carrier of humans

chemiosmotic theory of Peter Mitchell

Oxidative Phosphorylisation : F1/0 –ATP-Synthase

P-Phosphattransporter

T-Adeninnukleotid-Translokase

Komplex I-IV der Atmungskette

ATP-Synthasen in the inner

mitochondrial membran

Na+/K+ATPaseNa+/K+ATPase TransmembranpotentialsTransmembranpotentials

-50 bis –70 mV -50 bis –70 mV

An ion motive ATPase is a membrane protein that pumps ions across the membrane at the expense of the chemical energy of adenosine triphosphate (ATP)

hydrolysis.

The most important ionpumps in the nature are the ATPase. We find them in every living cell from the bacteria up to the human beiing. The proton pumping ATPase are the main actors in metabolism : they build up a proton gradiant between the different compartments of the cell and cell membrane, and this again is the drive for the most important process within an organism.

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Activ transportprocess in the cell and through the

biomembranes

H+ - concentration (protons) which is defined as pH volume. Proton gradient = pH gradient = concentration gradient ΔH

Proton pumps are transmembranproteins, which transport positively charged

hydrogen ions (protons) over a cell membranes, against

electro-chemical gradients.

Storage of chemical energy in the form of ATP

ΔH = Enthalpy ( Joule, J )

H = U + p V

Measure for the energy of a thermodynamic system

H = heat content, p= pressure, U=internal energy, V= Volumen, pV=Volumenarbeit

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The most important process within an organism.

Gipps-Energy (G) J/mol

Free Enthalpie G = U + pV - T S G = H - T S

0. G < 0: exergone reaktion, which runs dependent on the conce ntration gradient;

0. G = 0: balanc ed status, no reaktion;

0. G > 0: endergone reaktion, which needs external energy to run;

T= variable temperature,S= Entropy, p= pressure, U= inner energy, V= volumen

ΔG negative: Product energetically lower than the initial state, alltogether energy is delivered.If the released energy is not converted, the

sample warms up, the reaction is exothermic or exergon.

Warmth is delivered.

ΔG positively: Product energetically higher than the the initial state, energy is taken up from the ambient heat, the environment becomes colder.Processes, with which warmth is taken up, are

endothermic or endergon.

Energy balance of the system

shift of the redox potentials

= Modification of the intracellular metabolism with deviation from the tissue-specific enthalpy or from the energetic equilibrium

Limited range of motion (functio laesa)

Pain (dolor)

Swelling (tumor)

Temperture (calor)

Redness (rubor)

What is a common goal in all illnesses?

The causal problem of the living cells is :

Osmotic crisis =

potential disease picture

It is a result of the influx or its prevention of ions and water by the semipermeable plasma membrane inside the

cells.The solvation of this problem can be

achieved only by active moving of ions, thus by ion pumps.

Endergones disease picture =

blocking of the breathing chain

Exergones disease picture =

decoupling of the breathing chain

ΔG positiv = pH EF = binded H+ = high energy level

ΔG negativ = pH EF = free H+ = low energy level

Retenone: Insektizid

Amytal: Thiopental,

Barbiturat: Hypnotikum

Antimycin A: Antibiotikum

CN: Cyanide

CO: Kohlenmonoxid

N3: Azide, AZT

Blockers of the breath chainenderogone Reaktion

der ATP-Synthase :Oligomycin

des Adeninnukleotidaustauscher:Atractylosid

decoupling of the breath chain : exergone Reaktion

„shortcut“ in H+-gradient; faillure of the membran potential without ATP-synthese under Wärmebildung.

NSADs : Indometacin, Piroxicam,

Diclofenac, Cox 1- 2 Blocker

DNP (Dinitrophenol) : zur

Gewichtsreduzierung

Thermogenin: physiological

decouplingprotein

Chemotherapeutics:Die angelieferte Energie wird lediglich in Wärme umgewandelt. Dadurch kommt es zu einer stark erhöhten Körpertemperatur ("Dieting by Cooking Yourself"). Es wird kein ATP mehr gebildet(oder nur noch sehr viel weniger). Die Zellen werden dadurch quasi "ausgehungert" und der Körper versucht, dies zu kompensieren. Dazu werden alle anderen Reserven genutzt, die als Energielieferanten dienen können. Die Leber gibt dann mehr Glukose frei und der Körper baut Fett ab als alternative Quelle für ATP. Das ist dann auch der Effekt, der zu der dramatischen Gewichtsabnahme führt. Besonders problematisch ist hierbei, dass diese Prozesse der Energiegewinnung anaerob, also ohne Beteiligung von Sauerstoff stattfinden. Das Endprodukt der anaeroben Prozesse ist Milchsäure, die zu einer Übersäuerung des Blutes führen kann

Increase of mitochondrial defects and the lost of ATP gradient in the aging

process is the reason of typical agingsigns

Adiabatic pumping mechanism for ion motive ATPases

(energetisch abgeschlossenes System)

An ion motive ATPase is a membrane protein that pumps

ions across the membrane at the expense of the chemical

energy of adenosine triphosphate (ATP) hydrolysis. Here

we describe how an external electric field, by inducing

transitions between several protein configurations, can

also power this pump. The underlying mechanism may be

very similar to that of a recently constructed

adiabatic electron pump [Science 283, 1905 (1999)].

Astumian RD University of Maine, Orono, Maine 04469-5709, USA. astumian@maine.edu. Phys Rev Lett 2003 Sep 12;91(11):118102    (ISSN: 0031-9007)

Biophysical Journal Volume 66 June 1994 2151-2158 2151

Yi-der Chen* and Tian Yow Tsong**Laboratory of Chemical Physics, National Institute of Diabetes, Digestive & Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892 USA, and Department of Biochemistry, Hong Kong University of Science & Technology, Clear Water Bay, Kowloon, Hong Kong

The energy of an oscillating electric field can be absorbed by the charged transporters and used to pump uncharged ligands across the membrane against a concentration gradient. This phenomenon has been termed the "electro-conformational coupling" (ECC) (Tsong and Astumian, 1986).

Active transport of ions across erythrocyte membranes mediated by Na-K-ATPases could be achieved by applying a regularly oscillating electric field

Here,we show that analytical solutions for the dynamics of the model are also obtainable when the membrane potential is not oscillating randomly, but regularly with rectangular pulses of uniform lifetimes.

On the Efficiency and Reversibility of Active Ligand Transport Induced by Alternating Rectangular Electric Pulses

Towards a chemically driven molecular electron pump.

Charge can be pumped through a tiny gated portal from a reservoir at low electrochemical potential to one at the same or higher electrochemical potential by cyclically modulating the portal and gate energies. A theoretically and experimentally well established mechanism is thouless adiabatic pumping, achieved by a precisely timed out-of-phase modulation of at least two parameters of the system. Here we show that stochastic modulation between two configurations of gate and portal energies can drive efficient pumping by a different, nonadiabatic, mechanism that may provide a basis for chemically driven electron pumping through a molecular wire.

Astumian RD, Derenyi I.Department of Physics, University of Maine, Orono, Maine 04469-5709, USA. Astumian@Maine.edu

Bioelectric potential gradients may initiate cell cycling:

ELF and zeta potential gradients may mimic this effect.

When a number of experimental studies in bioelectromagnetics were reviewed, those in which weak, exogenous extremely low frequency (ELF) fields were applied in fixed juxtaposition to their target tissues, were found to initiate mitogenesis or mitogenesis-related signals more successfully than when the target tissue moved freely during the irradiation. It is suggested that ELF fields in fixed juxtaposition to their target tissue and implanted foreign bodies or endogenous tissues with a significant zeta potential, mimic bioelectric fields generated at wounds. When the potential is high enough, they assist healing by moving cells into the wound and stimulating quiescent cells at the wound margin to cycle. Electrophoresis (Electrotaxis) may help the initial migration of cells into the wound to form a clot, and migration of fibroblasts and epithelial cells from the wound margin. When exposed for a long time in a fixed juxtaposition to a potential gradient too weak to show in situ microelectrophoresis along the cell membrane surface, surface particles may coalesce to form microclusters, where like-charged surface particles are in close proximity, and growth factor receptor oligomerization and other cycle-initiating reactions are facilitated.

Beech JA ,

Bioelectromagnetics 1997;18(5):341-8    (ISSN: 0197-8462)

Tian Yow Tsong1, 3   , Dao-Sheng Liu1, Francoise Chauvin1 and R. Dean Astumian2 Department of Biological Chemistry, Johns Hopkins University School of Medicine, 21205 Baltimore, Maryland, USA, Department of Biochemistry, University of Minnesota College of Biological Sciences, 55108 St Paul, Minnesota, Laboratory of Biochemistry, National Heart, Lung and Blood Institute, NIH, 20892 Bethesda, Maryland, USA

 Recent experiments show that membrane ATPases are capable of absorbing free energy from an applied oscillating electric field and converting it to chemical bond energy of ATP or chemical potential energy of concentration gradients. Presumably these enzymes would also respond to endogenous transmembrane electric fields of similar intensity and waveform. A mechanism is proposed in which energy coupling is achieved via Coulombic interaction of an electric field and the conformational equilibria of an ATPase. Analysis indicates that only an oscillating or fluctuating electric field can be used by an enzyme to drive a chemical reaction away from equilibrium.In vivo, the stationary transmembrane potential of a cell must be modulated to become locally oscillatory if it is to derive energy and signal transduction processes.

Resonance electroconformational coupling (ECC): A proposed mechanism for energy and signal transductions by membrane proteins

CHENG, N., H. VAN HOOF, E. BOCKS, M. J. HOOGMARTENS et al.: The effects of electric currents on ATP generation, protein synthesis and membran transport in rat skin. Orthopaedics a. Related 171 Research

(1982) 264-272.

In a study, which has important consequences for the microcurrent therapy, observed Cheng et al (1982) the effects of electric currents of different intensity with three crucial variables during the healing process: Adenosine triphosphate (ATP) production, protein synthesis and transmembran transport. With 500 µA ATP production in the rat skin rose around approximately 500 %. The authors meant that it concerns itself thereby around a "noteworthy increase" which occurs with increased stimulation? With the use from 1.000 to 5.000 µA (l -5mA) ATP production took starting from and when using more than 5.000 µA lowered it under the normal control values. A similar picture arose in the case of the amino acid transfer and the protein synthesis. The amino acid transfer rose with the use from 100 to 500 µA to a value, which about 30 - over the control values was appropriate for 40 %. With the increase of the current supply the picture turned. More if than 1,000 µA was used, the concentration of A-Aminoisobutteracid was reduced by 20 - 73 % and the protein synthesis was restrained around more than 50% .

Electro-membrane microcurrent therapy reduces signs and symptoms of muscle damage.

Delayed onset muscle soreness (DOMS) occurs after unaccustomed physical activity or competitive sport, resulting in stiff, painful muscles with impaired function. Electro-membrane microcurrent therapy has been used to treat postoperative pain

and soft tissue injury. RESULTS: Subjects in both groups experienced severe pain and swelling of the elbow flexors after the eccentric exercise. After 24 h, the elbow joint angle of the placebo group had increased significantly more than those in the MENS group (13.7 +/- 8.9 degrees vs 7.5 +/- 5.5 degrees; placebo vs MENS, P < 0.05), possibly as a consequence of the elbow flexor muscles shortening. For the first 48 h after exercise, maximum voluntary contraction of the elbow flexor muscles was

significantly impaired in the placebo group by up to 25% (P < 0.05), whereas muscle function was unchanged in the MENS group. Peak plasma creatine kinase activity was also lower in the MENS group (peak = 777 +/- 1438 U.L-1) versus the placebo group (peak = 1918 +/- 2067 U.L-1; (P < 0.05). The membranes were well tolerated by the subjects in both groups without any adverse effects.

CONCLUSION: These data show that treatment of muscle damage with MENS-therapy reduces the severity of the symptoms. The mechanisms of action are unknown but are likely related to maintenance of intracellular Ca2+ homeostasis after muscle damaging exercise.

Lambert MI; Marcus P; Burgess T; Noakes TD MRC/UCT Research Unit for Exercise Science and Sports Medicine, P.O. Box 115, Newlands, South Africa. mlambert@sports.uct.ac.za.

Med Sci Sports Exerc 2002 Apr;34(4):602-7    (ISSN: 0195-9131)

Professor Zhao, university of Aberdeen, Professor Colin McCaig, Head of the School of Medical Sciences, Professor John Forrester, Head of Ophthalmology and Dr Bing Song International collaborators from America (Univ. of California, Boston medical School)Japan and Austria, including Professor Josef Penninger, current director of the Institute of Molecular Biotechnology of Austrian

Academy of Science

Researchers in Aberdeen have made an exciting breakthrough in showing that electricity has a major impact on the

healing of wounds.

Electricity to heal wounds

Electrical signals direct cell migration in wound healing and activate selected signalling pathways. a,Wounding induces lateral electric fields directed towards the wound centre (red arrow), by collapsing the local transepithelial potential difference (V). Black arrows represent sizes and directions of currents. b, Directly measured currents increase over time in rat corneal and human skin wounds. c, d, An electric field (EF) directs migration of corneal epithelial cells in a monolayer model of wound healing (150mVmm21; c) and activates Akt (Ser 473), Src (Tyr 416), ERK and p38 in primary cultures of mouse keratinocyte and mouse peritoneal neutrophils in serum-free medium (200mVmm21; d). Disrupting p110g ttenuates activation of these signalling pathways. Phosphorylated JAK1 and JAK1 are shown as controls. e, Phosphorylated Src kinase polarizes in the direction of cell migration in electrotactic mouse keratinocytes (150mVmm21). Scale bar, 20mm.

PI(3)Kg is reqired for electrotactic cell movement in wound healing of stratified epithelium in ex vivo cornea cultures. Stratified corneal epithelium migrate in situ to heal a wound (towards the left). This wound healing response is significantly enhanced by an electric fields with the cathode at the wound. Impaired electric field mediate wound healing in corneas isolated from p 110g –/– mice. Electric field applied with polarity opposite to the default healing direction direct the woundedge to migrate away from the wound. This responce is impaired when p110g is disrupted.

Quantification of the migration rates of the healing cornea epithelium from 3 – 7 experiment for a period of 120 min at each condition.

Increase of Adenosintriphosphat,( ATP )

up to 500%

Aktivation of the cellmetabolism and

Proteinsynthesis up to 73%.

Applikation von microcurrent between

10 – 600 µA

Neurological problemsAlzheimer

Multiple Skleroses

M. Parkinson

Apoplex

Nerval trauma

Newest research results (2006) point out that b-cell-antibodies, which bind to the enzymes GAPDH and TPI and thereby deactivate this enzymes, are at least jointly responsible for the damage of the axons .A reduced GAPDH availability in the Mitochondria of the axons ensures that in fact smaller quantities of the cell ATP are produced. This lack of suplly can potentially lead to the fall of the axons. It is beyond that well-known, that a lack of TPI can lead to neurodegenerative illnesses.

triosephosphate isomerase (TPI)

glyceraldehyde-3-phosphate dehydrogenase (GAPDH)

Plasmodium falciparum GAPDH as target structure during the medicine development

Glyceraldehyde-3-phosphat Dehydrogenase catalyzes an important energygain-step in the Kohlenhydratmetabolism, the reversibleoxydative phosphorylation of Glyceraldehyde-3-phosphate in presence ofthe inorganic phosphate and Nikotinamidadenindinucleotid (NAD).

Recent evidence indicates that polymorphic variation within GAPDH genes is associated with an elevated risk of developing Alzheimer's disease (AD).