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BCR (biological cell regulation) with microcurrent Principle - Indications - Therapies Dr.med.univ. Vlastimil Voracek Orthop disches Therapiezentrum /OTZ - Memmingen – PowerPoint PPT presentation

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Title: BCR


1
BCR
(biological cell regulation) with microcurrent
Principle - Indications - Therapies
Dr.med.univ. Vlastimil Voracek Orthopädisches
Therapiezentrum /OTZ - Memmingen
2
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.
3
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.
4
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.
5
Why the physician is looked up by a patient ?
Function
Limited range of motion (functio laesa) Pain
(dolor) Swelling (tumor) Temperture (calor)
Redness (rubor)
Metabolism Immunology
6
Psyche, vegetative nervous system
function neuromotorics
metabolism immunology
morphology
7
Where is the causal beginning of the biological
cell therapy (BCR) by microcurrent?
Metabolism
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.
8
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-oxidati
ve phosphorylation).
9
The main energy carrier of humans
ATP Adenosin-5triphosphat
Humans produce between 70 - 800 KG ATP a day
10
chemiosmotic theory of Peter MitchellOxidative
Phosphorylisation
F1/0 ATP-Synthase P-Phosphattransporter T-Adeninn
ukleotid-Translokase Komplex I-IV der Atmungskette
ATP-Synthasen in the inner mitochondrial membran
11
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.
Na/KATPase Transmembranpotentials -50 bis 70
mV
12
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.
Activ transportprocess in the cell and through
the biomembranes
13
Proton pumps are transmembranproteins, which
transport positively charged hydrogen ions
(protons) over a cell membranes, against
electro-chemical gradients.
H - concentration (protons) which is defined as
pH volume. Proton gradient pH gradient
concentration gradient ?H
14
The most important process within an organism.
Storage of chemical energy in the form of ATP
Measure for the energy of a thermodynamic system
?H Enthalpy ( Joule, J ) H U p V
H heat content, p pressure, Uinternal
energy, V Volumen, pVVolumenarbeit
15
Gipps-Energy (G) J/mol Free Enthalpie
G U pV - T S G H - T S
T variable temperature,S Entropy, p pressure,
U inner energy, V volumen
16
Energy balance of the system
?G 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. ?G
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.
17
What is a common goal in all illnesses?
Limited range of motion (functio laesa) Pain
(dolor) Swelling (tumor) Temperture (calor)
Redness (rubor)
shift of the redox potentials Modification of
the intracellular metabolism with deviation from
the tissue-specific enthalpy or from the
energetic equilibrium
18
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.
19
Endergones disease picture blocking of the
breathing chain
?G positiv pH EF binded H high energy
level
Exergones disease picture decoupling of the
breathing chain
?G negativ pH EF free H low energy
level
20
Blockers of the breath chain enderogone Reaktion
der ATP-Synthase Oligomycin des
Adeninnukleotidaustauscher Atractylosid
Retenone Insektizid Amytal Thiopental,
Barbiturat Hypnotikum Antimycin A
Antibiotikum CN Cyanide CO Kohlenmonoxid N3
Azide, AZT
21
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
22
Increase of mitochondrial defects and the lost of
ATP gradient in the aging process is the reason
of typical agingsigns
23
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24
Astumian RD University of Maine, Orono, Maine
04469-5709, USA. astumian_at_maine.edu. Phys Rev
Lett 2003 Sep 1291(11)118102    (ISSN
0031-9007)
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).
25
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
On the Efficiency and Reversibility of Active
Ligand Transport Induced by Alternating
Rectangular Electric Pulses
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).
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.
Active transport of ions across erythrocyte
membranes mediated by Na-K-ATPases could be
achieved by applying a regularly oscillating
electric field
26
Astumian RD, Derenyi I.Department of Physics,
University of Maine, Orono, Maine 04469-5709,
USA. Astumian_at_Maine.edu
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.
27
Beech JA , Bioelectromagnetics 199718(5)341-8
   (ISSN 0197-8462)
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.
28
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
Resonance electroconformational coupling (ECC)
A proposed mechanism for energy and signal
transductions by membrane proteins
 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.
29
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.
30
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_at_sports.uct.ac.za. Med Sci
Sports Exerc 2002 Apr34(4)602-7    (ISSN
0195-9131)
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 lt 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 lt
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 lt 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.
31
Electricity to heal wounds
Researchers in Aberdeen have made an exciting
breakthrough in showing that electricity has a
major impact on the healing of wounds.
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
32
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.
33
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.
34
Quantification of the migration rates of the
healing cornea epithelium from 3 7 experiment
for a period of 120 min at each condition.
35
Applikation von microcurrent between 10 600 µA
Increase of Adenosintriphosphat,( ATP ) up to
500 Aktivation of the cellmetabolism and
Proteinsynthesis up to 73.
36
Neurological problems
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.
Alzheimer Multiple Skleroses M. Parkinson Apoplex
Nerval trauma
glyceraldehyde-3-phosphate dehydrogenase (GAPDH)
triosephosphate isomerase (TPI)
37
Glyceraldehyde-3-phosphat Dehydrogenase catalyzes
an important energy gain-step in the
Kohlenhydratmetabolism, the reversible oxydative
phosphorylation of Glyceraldehyde-3-phosphate in
presence of the inorganic phosphate and
Nikotinamidadenindinucleotid (NAD).
Plasmodium falciparum GAPDH as target structure
during the medicine development
38
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