here - RAD 2012

Download Report

Transcript here - RAD 2012

The First International Conference on Radiation and Dosimetry in Various Fields of Research
Niš, Serbia, April 25 - 27th, 2012

Odessa National Medical University
The First International Conference on Radiation and Dosimetry in Various Fields of Research
Niš, Serbia, April 25 - 27th, 2012
Field nature of Life
Valeriy Zaporozhan and Andriy Ponomarenko
Odessa National Medical University, Ukraine
Realization of the correct hierarchy of life-keeping and life-regulatory structures
and forces is very important for scientific progress. Evolution of our
conceptualization in the field has been intimately coupled with the progress in our
general scientific knowledge and accessible methodology
Conditional gradation of our understanding of the main life-keeping and liferegulating entity:
1) Spiritual:
Temple of spirit by White Citrus, from Digital Art Gallery Online
2) Morphological:
Picture from Wikipedia
3) Biochemical: knowledge about different chemicals and their biological
effects accumulated. Chemical and Biochemical aspects of Life and disease
treatment attracted most scientific interest. Pharmacists elaborated remedies for
treatment of various diseases;
Doctor and Pharmacist from: Brunschwig, Hieronymus
4) Genomic:
Author: Madprime
Accumulated data suggests that the genome is mostly an instrument than
independent player, and that the melody it produces depends significantly on
the “musician” who plays music (“musician” means: posttranslational
modifications, DNA methylation, histone acetilation and other epigenetic
effects influencing gene expression).
5) Proteomic: Understanding that the final protein structure and protein
assembly is the thing which really matters and determines biological effects,
brought to life the Proteom Era.
Examples for subcellular localisation of different proteins
Is there a need to develop any other
conceptual model of Life organization ?
If yes, what the next concept will be?
We believe it’ll be worthy to consider the
Electromagnetic Fields produced by cells and
biomolecules (the “Electromagnetic Life Matrix”) and
corresponding interactions in living objects as the most
basic level of Life organization and regulation.
Fundamental interactions
Interaction
Mediators
Relative Strength Range(m)
Strong
gluons
1038
10-15
Electromagnetic
photons
1036
infinite
Weak
W and Z
bosons
1025
10-18
Gravitation
gravitons (not
1
infinite
yet discovered)
Table from Wikipedia, the free encyclopedia
Can we find any life-specific interactions on this table ?
…enzime-substrate interactions ? …hormone-receptor interactions ?
…promoter-target gene interactions ?....
The only known force that implements all specific biological
interactions is the Electromagnetic Force.
An example of protein interaction scheme
(from Kurt W. Kohn, Molecular Biology of the Cell Vol. 10, 2703–2734, August 1999)
There is a famous statement: “Final manifestation of
each emotion is a muscle contraction”
We would say that “Final manifestation of each
emotion is ion redistribution in specific neurons and a
chain of electromagnetic interactions which elicit
muscle contraction”
Electromagnetic force in Immunity
Evidences of the regulatory function of electric charges
in immune recognition and immune response:
 The most immunogenic are regions of a protein that have
negative electrostatic potential [Geysen et al.].
 Purposeful change of surface electric charge of antigens
cause alteration of their immunogenic properties
[Muckerheide et al.].
 A straightforward correlation has been shown between the
net electrical charge on a variety of natural and synthetic
antigens and the type of antibody they elicited [Sela et al.].
DIFFERENCES IN ELECTROPHORETIC MOBILITY
BETWEEN DIFFERENT CELL TYPES:
 between T and B cells;
 between mature T-cells and
– thymocytes
--lymphocytes isolated from bone marrow;
 between normal and malignant cells;
 between “young” erythrocytes and “old” ones.
Glycocalix
 Glycocalyx is formed from free fragments of plasmalemma’s
glycoproteins interconnected whith anionic-cationic movable bridges.
 Glycocalyx is an “executive apparatus, which mediates interaction of a
cell with intercellular medium and neighbouring cells”.
 Glycocalyx is needed for perception, recognition, transmission, and
modulation of incoming and outgoing cell signals in the form of
substance, energy, and information.
 Many functions of glycocalyx are mediated via electric charge of its
components and by changes of this charge.
Electric charge of antibodies and possible
significance of this parameter

The index of Circulation and index of Epidemic danger for different influenza
strains in Odessa population at studied period according to average
concentration of positively and negatively charged specific antibodies in human
sera.
 Dynamics of the Index of epidemic danger for different influenza strains
in Odessa region (Ukraine).
Correlation between Electrokinetic potential of virions and
biological features of virus strains
Model of Influenza virus surface glycoprotein – HA (model of Wilson et al.).
Arrow indicates localization of the receptor-binding pocket
An intimate feature of life is rhythmicity.
Life on the Earth since its very beginning experienced continuous
influences of Electromagnetic Radiation in form of Sun light and
Geomagnetic field. It is natural that bio-cycles became correlated
with these natural EM-signals:
• Day-night cycles cause circadian biorhythms;
• Annual rhythms are also well known;
• Bio-rhythms of much more longer period exists, some of them
correlate with cycles of Solar activity.
An intimate feature of life is rhythmicity.
The cause and pacemaker of rhythmicity in numerous life processes
are Electromagnetic signals:
Circadian rhythm (picture from the Wikipedia)
Biological clock (file from the Wikimedia Commons)
Periodicities in solar and geomagnetic activity (from Pulkkinen, T.
"Space Weather: Terrestrial Perspective", Living Rev. Solar Phys. 2007).
Correlation between level of solar activity and influenza pandemics
in 20-th century (Tapping et al.)
Correlation of Solar and Geomagnetic activity with Human
morbidity and mortality

Stoupel E. Atherothrombosis: environmental links. J Basic Clin Physiol Pharmacol.
2008; 19 (1):37-47.

Stoupel E, Petrauskiene J, Abramson E, Kalediene R, Sulkes J. Distribution of monthly
deaths, solar (SA) and geomagnetic (GMA) activity: their interrelationship in the last
decade of the second millennium: the Lithuanian study 1990-1999. Biomed
Pharmacother. 2002; 56 Suppl 2:301s-308s.

Mikulecky M, Moravcikova C, Czanner S. Lunisolar tidal waves, geomagnetic activity and
epilepsy in the light of multivariate coherence. Braz J Med Biol Res. 1996 Aug; 29
(8):1069-72.

Neronov VV, Malkhazova SM, Ponirovskii EN, Charyev BCh. [The multiyear changes in
the epidemic activity of the foci of zoonotic cutaneous leishmaniasis at the Murgab
oasis. I. An analysis of the relations of morbidity to heliogeophysical factors]. Med
Parazitol (Mosk). 1996 Jul-Sep; (3):3-7.

Cornélissen G, Halberg F, Kovac M, Mikulecky M, Otsuka K, Bakken E. Geographic and
extraterrestrial aspects of morbidity and/or mortality patterns from myocardial infarction
and stroke. Biomed Pharmacother. 2005 Oct; 59 Suppl 1:S68-75.
What is the reason of the correlation
between
solar cycles and human health ?
 Schematic picture of “Sun wind” consisting of plasma fluxes
erupted from the Sun’s surface and their interaction with Earth’s
magnetic field.
 Magnetic fields can interact with magnetic dipoles of
electron spins, whose carriers are paramagnetic
molecules, metal ions and ion-radicals
 “Electrons and nuclei, which possess magnetic moment,
are the “magnetic antennae” in any biosystem, including
human beings. They are able to receive and radiate
electromagnetic energy selectively depending of the field’s
frequency (ν) and gyromagnetic ratio (γ)” (Fursa EY)
Proposed mechanisms of the biological effects of
extremely weak magnetic fields:
 (1) “Plasma membrane hypothesis”: cell membrane is a
primary biological receiver of magnetic signals, it responds
by changes of its potential, and distribution and activity of
integral membrane proteins and ion channels (e.g., Ca2+
channels).
 (2) Free radical mechanisms: magnetic fields can
increase the lifetime of free radicals. This results in an
increase in free radical concentration in cell compartments,
and biological changes, including activation of signaling
cascades (reviewed by M.Simko).
 (3) The ion resonance model, which implicates the
combined action of the ELF MF and a weak static magnetic
field (for example - geomagnetic field).
Radical Pair mechanism of Magnetoreception
by Schulten and coauthors, 1978

The radical pair is generated by an electron transfer from a donor molecule D to an
acceptor molecule A. An external magnetic field affects interconversion between
singlet and triplet states of the radical pair. (Reproduced from [Schulten et al., 2000] )
Cryptochromes: Ancient Regulatory Proteins Sensitive to
Electromagnetic Radiation and Magnetic Fields
 Cryptochrome is a signaling protein found in bacteria and a
wide variety of plants and animals.
 Cryptochromes are ubiquitously expressed in the organs
and tissues, and have a predominantly nuclear localization.
 Among known functions of CRY are the regulation of
growth and development (in plants) and entrainment of
circadian clocks.
Localization of CRY in nuclei of cells
(from Chaves I. еt al., 2006).
 Scheme of the magnetic field effect on the radical pairs between
FADH and tryptophan in cryptochrome active site. (From Solov'yov IA
et al., 2007, reproduced by the kind permission of the authors and the publisher)
Genome-regulatory effects of CRY
 Co-operation of CRY with the major circadian clock regulatortranscription factor CLOCK/BMAL1, transcriptional corepressors
and PER proteins. (From Chaves et al., 2006)
Scheme representing possible mechanisms of CRY bio-regulating activity. (a)
CLOCK/BMAL1-heterodimer function as transcriptional activator. (b) interaction
between CRY1 and CLOCK/BMAL1 causes CLOCK/BMAL1 to adopt a transcriptional
repression function. (c) modification of CRY activity by weak external magnetic field
and subsequent restoration of CLOCK/BMAL1 transcriptional activation function
Probable mechanisms of the magnetic field influence on gene expression and virus-host
interactions:
MAGNETIC FIELD
Cryptochromes
membrane
potential
CLOCK/BMAL1 + CBP
Ion
resonance
effects
ion channels
function
Circadian
genes
expressio
n
Circadian control of
stress and other “noncircadian” responses
by active transcriptional
repression mechanism
Ca2+ signaling
Ca2+-Operated
Transcriptional Networks
Expression and function of
proteins of NF-kB signaling
pathway
Immunity
regulation
Regulation flu
RNA synthesis
Regulation of virus-host interactions and other biological processes
 To summarize, CRY are unique bio-compounds, which
combines sensory and bioregulatory functions. They act as
mediators between living beings and their physical
environment, providing a mechanism for both the reception
of electromagnetic signals and the triggering (or entraining)
of biological responses.
It appears that biological effects of the
Electromagnetic field can be compared with
human speech: loudness has small effect, but
meaning is very important: several words can
ignite a conflict or, alternatively, to stop a war.
Signaling pathways probably affected by the
geomagnetic storms
 NF-κB is a protein complex that acts as a transcription factor. It is
widely expressed and regulates the expression of genes involved in
immune responses, inflammation, proliferation, apoptosis and other
cellular activities. It plays a key role in immune reactions, including
response to infection.
 Genes encoding proteins of Rel/NF-κB/IκB pathway are exposed to
transcriptional regulation by the CRY/CLOCK/BMAL1 complex…
 CRY/CLOCK/BMAL1 transcription complex also regulates the
transcriptional activity of the glucocorticoid receptor.
Signaling pathways probably affected by the
geomagnetic storms
 Several viruses, including HIV, have binding sites for NF-κB that
control the expression of viral genes, which in turn contribute to viral
replication and/or pathogenicity. In the case of HIV-1, activation of NFκB may, at least in part, be involved in activation of the virus from a
latent, inactive state [Hiscott, 2001]. This indicates the theoretical
possibility of magnetic field effects on the processes of HIV activation
and replication.
 NF-κB is chronically overexpressed in inflammatory diseases (arthritis,
sepsis, asthma, among others). There is evidence for a critical role of
NF-κB in carcinogenesis, and NF-κB is a key mediator of
chemotherapy resistance, as well as having a major role in tumor
development, particularly in its early phases [Pikarsky, 2006].
 “Electric fields are present in all developing and
regenerating animal tissues, yet their existence and
potential impact on tissue repair and development are
largely ignored. This is primarily due to ignorance of the
phenomenon by most researchers, some technically poor
early studies of the effects of applied fields on cells, and
widespread misunderstanding of the fundamental concepts
that underlie bioelectricity”. (McCaig et al., 2005).
Consequences of the magnetic field influence on gene expression and
virus-host interactions:
 Dynamics of our knowledge in the field confirms ideas of
Alexander Chizhevsky about the electromagnetic nature of
communications between spatially distant components of
the single whole (integrated) system comprising our
Biosphere and the Sun.
Has God separated heavens from the earth…
by geomagnetic field ?
Use of biophysical approaches and electronics
for disease diagnostics, prophylaxis and treatment
Spiritual
Morphological
Biochemical
Genomic
Electromagnetic Matrix
Proteomic
Conclusions:

1. Biological reactions in living beings, including responses to stress and
infection, are probably sensitive to the functional activity of Cryptochromes,
which in turn may be regulated by weak magnetic field, like geomagnetic field,
thanks to the radical pair mechanism of magnetoreception;

2. Presented data suggest the potential use of magnetic fields for temporary
modification of the gene expression pattern in different cell types, without the
aid of gene transfer technologies;

3. Dynamics of the biological processes could be evaluated, predicted or
changed by way of study of corresponding EM-interactions and their biological
effects;

4. Elaboration of new efficient treatment methods can be achieved by utilizing
EMF. Examples: a) Stimulation of Cell differentiation and regeneration by
Magnetic field; b) Transcranial Magnetic Stimulation (TMS) for treatment of
various neurological and psychiatric disorders; c) New Cancer treatment
methods based on cancer cell membrane permeabilization using High
frequency EMF.
 Thank you for your attention !
Millimeter-range electromagnetic waves
therapy (UHF therapy)
apparatus «EHF-ND»
 Main technical parameters





Weight, full set, kg
Consumed energy
EHF-radiation in wave length ( sweep width 100 mHz)
Power flux density of one emitter, mW/cm2
Exposure period, min
1.2
200V/50Hz- 12 W
7.1; 5.6; 4.9
4-12
1-99
Conclusions:




The correlation between EKP of virions and biological features of
influenza viruses has been shown. These results can be used for
prognosis of biological features of recently isolated and
experimentally obtained influenza viruses, that necessary both: for
perfection of epidemiological surveillance and creation of efficient
vaccines;
Correlation between average contents of definite subtypes of specific
influenza antibodies and serum inhibitors of agglutination correlates
with level of epidemiological danger of given flu strain for studied
human population;
Use of biophysical methods of treatment in clinics increases efficacy
of conventional treatment and decreases percentage of
complications.
Further exploration of direct and indirect mechanisms for
participation of electromagnetic interactions in various biological
activities is feasible and may yield many interesting results both: of
theoretical and clinical significance.