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Section 4. Physicochemical Biology
Pirnazarova Flora Nazarovna, PhD Degree in Physical Chemistry E-mail: flora-nazar@mail.ru
Atabekova Klara Yusupovna , PhD Degree in Immunology
Kuznetsov Vladimir Nikolaevich, Professor, PhD Degree in Medicine, E-mail: kuznetsov.med@mail.ru Center "Gulbeor", IWPF "Woman of East", Tashkent, Uzbekistan
E-mail: gulbeor@mail.ru
DETERMINATION OF QUANTITATIVE CRITERIA OF RELIABILITY IN THE EARLY DIAGNOSIS OF PRE-PATHOLOGICAL STATE
Abstract. The authors propose an innovative approach to the issues of early diagnostics of pathological states based on determining quantitative parameters of reliability - criteria of stability and reactivity, which manifest themselves in the interaction of the patient's erythrocyte membrane systems with a chaotropic agent - dosed exposure to ultrasound.
Keywords: organizational resource, reliability potential, variability, stability, reactivity, quantitative kinetic parameters, ultrasonic effect, express-analyzers.
In the modern world there is ongoing analysis of Obviously, the degree oforder of the socio-economic complex systems and their properties. The concept of system, a kind of its organizational potential, will be "reliability" was previously applied to technical sys- zero in the absence of either of the two components. tems. Now the reliability of biosystems characterizes the organizational potential, combining the criteria of structural stability and functional reactivity [1; 2].
M. Khazin and M. Elizarov [3; 4] introduced the concept of organizational resource as a composition of system asymmetry and coherence. The condition for organizational balance is a certain equilibrium between the active and passive components of the order, allowing their mutual overflow [3]. Moreover, one component without the other cannot give a full effect. Passive consistency is an uncomplaining herd, dead matter, and unorganized activity - the Brownian movement - continuous losses from endless strife.
Figure 1. Scheme of interdependencies between reliability potential, stability and reactivity
Let the organizational resource is a constant. Then the relationship between the variables (asymmetry and coherence) becomes hyperbolic, which can be easily visualized using a visual graphic model in the form of a distribution field, where systemic asymmetry(A) is taken as the horizontal axis and system coherence (C) is taken as the ordinate [3-4].
R = C x A at R = const; where R - organizational resource
But the criteria of asymmetry and coherence are difficult to measure and apply into practice. It is better with the category of reliability [2].
If we consider the category of reliability, the relationship between its variables - stability and reactivity - also has a hyperbolic character (Fig. 1): RELIABILITY = Stability x Reactivity at the permanency of the reliability resource RP = S x R at RP = const where RP - reliability potential
The third chapter of the review [2] "Stability and reactivity - the structural and functional criteria of the biological reliability of a plant" emphasizes: "The physicochemical mechanisms ofbiological reliability of higher plants consist in the development of two opposite criteria: on the one hand, the structural stability of molecular organization of cell membranes, on the other hand, high reactivity and sensitivity of membrane structures to phytopathogens as chao-tropic agents. In conclusion, the authors came to the conclusion: "Physical and chemical studies of the dynamic plant-parasite host system allowed us to declare a postulate on the presence of dynamic equilibrium of two asymmetric functions in the membrane and cell, to offer a two-compartmental model of membrane processes and possible mechanisms of reactivity of membrane structures".
Transformed from the review [2], the scheme of inter-relation of the categories of biological reliability and variability with the criteria of stability and reactivity [5] gives a broader understanding of the characteristics of living systems (Fig. 2). From this scheme, the occurrence of the reactivity phenomenon for living systems only is quite obvious. For
the inanimate (lifeless) - stable (rocks, hard rocks, crystals, etc.), the area in the coordinates STABILITY - PASSIVITY is given. For unstable inanimate (lifeless) systems (volcanoes, thunderstorms, lightning, tornadoes, typhoons, nuclear processes, etc.), the range in the coordinates INSTABILITY - PASSIVITY is given.
Figure 2. Scheme of interrelation of categories of biological reliability and variability with criteria of stability and reactivity
For living systems, the optimal ratio of sustain-ability and reactivity criteria (in the interthresholds value space) determines the range of high reliability of the biological properties of the system of higher plants - the area in the coordinates STABILITY-REACTIVITY. The optimal ratio of criteria for reactivity and lability (instability) can determine the range of optimal variability that ensures the viability and adaptive evolution of lower plants and microorganisms - in the area with coordinates LABILITY- REACTIVITY [5].
As Mikhail Leonidovich writes: "... the time has come for important revelations that relate to the most mysterious and inexplicable aspect of the world perception - a way of knowing reality" [4].
The article proposes not a vulgar understanding of the principle of unity of opposites [4], but a clear idea of the balance of two different orthogonal functions of living systems: structural stability and functional reactivity; then the composition of their indicators determines the potential reliability of a system, biological or social. Moreover, among the variation in the indicators, a "window of opportunity" [3] is revealed over the range of sustainability criteria (AS) and reactivity criteria (AR), which are characteristic of a reliable system (Fig. 3). Exceeding the resistance index above the threshold leads to ossification, system necrosis, and excess of the reactivity index above the optimal range leads to chaos and death of the system.
' s
\ PR= S x R
\ at PR = const
T to
<1
——R
■»--AR—►
reactivity
Figure 3. "Opportunities win-dow" for a system with high reliability potential (R) and optimal ranges of stability AS and reactivity AR
Therefore, not only the "anti-entropic principle" [6] is important, but also the balance, even harmony between the entropy and anti-entropy functions, since the main goal of our existence is not reduced simply to a decrease in entropy at any accessible (personal, social, global) level, but in reducing the reasonable balance of these 2 oppositely directed processes. The process of creativity itself is an entropy process, because violates the established order, but its result flows in the case of successful work in the anti-entropic, informational potential. Famous hooligan poets, burning in the "furnace of entropic processes", carved out a fire of inspiration in the throes of the creation of their masterworks - Yesenin, Mayakovsky, Khlebnikov, Blok [5].
Reactivity as a function of the entropy compartment, and sustainability as a structural characteristic of the anti-entropy compartment are equally important components of the reliability potential of a biosystem.
"PRACTICE - CRITERIA OF TRUTH". Sustainability and reactivity indicators are measurable and reproducible in practice. Here are some examples:
Example 1. Kinetic study of the immune response in a skin-allergic inflammation reaction of delayed-type to the application of DNCB, a nonspecific chaotropic agent, where resistance and reactivity indicators are clearly distinguished [7].
Example 2. Method for determining the reliability of PLANT LIFE SUPPORT [8].
Kinetic analysis of the fungus Verticillium Dahl-iae Kl. after-effects for different varieties of cotton showed the ability to predict the reliability of immunity by the speed of the response reaction, which corresponds to the criterion of reactivity, and the degree of its deceleration, which corresponds to the criterion of stability [5]. Analysis of the plant response to non-specific effects allowed developing a method for determining the reliability of plant life support [8]. The use of a conductometric method for recording the release of ions will allow automating the process.
Example 3. Kinetic analysis of the ultrasound resistance of red blood cells in the diagnosis of pre-pathological states of the organism.
Method 1. Express diagnosis of pre-patholo-gical states.
It is well known that pathology is accompanied by increased stiffness, adhesion and deformation of red blood cells, as shown by microscopy and the study of the rate of erythrocyte outflow through a series of membrane filters. These methods are used in laboratories of scientific research institutes and are not available for automation. We have proposed a method of differentiation of erythrocytes by ultrasound resistance.
Analysis of the ultrasound resistance of a patient's erythrocyte sample is carried out by measuring the optical density at a wavelength of \ = 670 nm with registration of the erythrocyte decay kinetics in the
process ofphased enhancement of ultrasound exposure. The kinetics of red blood cells decay has a gradual character depending on the time and power of ultrasound exposure and the following picture (Fig. 4): (fractions of erythrocytes: sensitive - S; resistant - R; super rigid - SR) H1 : H2: H3 = [S] : :[R] : [SR];
in the norm: [S]: [R]: [SR] = [40 ± 10%]: [50 ± ± 10%]: [10 ± 4%]. The hemoglobin content in the sample is determined by the sum of the broken red blood cells: D0 = H1 + H2 + H3
Figure 4. Kinetics of decay of blood erythro-cytes under 3-step-graded ultrasound exposure
Deviations in the direction of increasing the sensitive fraction (S) indicates the presence of allergic and somatic diseases; deviations in the direction of increasing super-resistant (SR) erythrocytes indicates the development ofpre-pathological processes and a high degree of immunodeficiency. A particularly pronounced excess of the share of SR-erythro-cytes was observed in patients with stage III and IV of cancer. The threshold of pathological resistance of erythrocytes is the excess of the share of SR-eryth-rocytes by 20 ± 2%, above which pathology obtains the character of irreversibility (Fig. 4).
Then the characteristic of the entropic compartment of reactivity is the content of the sensitive red blood cell fraction [S], and the characteristic of the
anti-entropic stability compartment is the content of the super rigid erythrocytes fraction [SR].
Method 2. Express diagnostics of quantitative parameters of the reliability of the life support of erythrocytes' membrane system.
The method allows to record the dynamics of the erythrocytes decay in standard, kinetic conditions of an experimentally developed medium by measuring the optical density at a wavelength of \ = 670 nm during exposure to ultrasound in a certain mode and power of exposure (Fig. 5). From the obtained erythrocyte decay curve, it's possible to calculate mathematically 6 quantitative parameters: reactivity criteria - pool (A) with reactivity constant k1, stability criteria - pool (B) with constant k2, relaxation time of compartments (t) and erythrocyte reliability potential (viability) (¥"). The reproducibility of the results is provided by the optimal medium (pH, t, osmosis, mixing) and the kinetic area of measurement, in which the calculated parameters haven't depended on rate of mixing of erythrocytes in the sample.
Figure 5. Erythrocyte decay kinetics under standard ultrasound expo-sure conditions for determining quantitative reliability parameters
Optimal ratios of the parameters correspond to a high degree of life support reliability, deviations of the parameter values in any direction - increase or decrease - indicate reversible or pathological shifts in the state of reactivity and stability compartments
of the subcellular structures of human erythrocytes. Considering the undoubted progress of IT technologies in processing and calculating the kinetic parameters of Big Data with statistical accuracy of deviations at least 3 times the experience of measuring a patient's blood sample, one can hope that the primary changes in the functional parameters of the cell membrane systems will be fixed much earlier than the degeneration of the genetic apparatus and the appearance of 1 pathologically perverted cell at least.
Experiments have shown that even a year after surgery (resection of the mammary gland), the content of CP-erythrocytes was recorded slightly higher than normal, after then it was encouraged the patient to continue treatment aimed at harmonizing the parameters and functions of the organism. Thus, the express analysis using the simplified method 1 can be used to monitor the effectiveness of medical procedures and treatment strategies even without the participation of a physician, using an automatic analyzer.
Both methods are available to fully automate the process with the issuance of calculated data without the participation of the "human" factor. Express analyzers of the reliability parameters of the vital supply of human erythrocytes (and animals can also be given in veterinary clinics) require the collection of a minimal amount of capillary blood of 20 ^l and 5 min of time for analyzing, processing and issuing kinetic data of express analysis. Automatic express analyzers of the reliability of life support and sowing qualities of seeds (based on registration of electrical conductivity (conductometry) - can significantly increase the efficiency and productivity of the seed and breeding stations in agriculture.
We are confident that the horizons of research and measurements of entropy and anti-entropy parameters and functions in the future are boundless. Progress in science will provide a breakthrough in agriculture, the economy, and most importantly -in health care, when express analyzers of capillary blood come to every clinic to predict and prevent any pathological abnormalities in advance.
Nobel laureate Luc Montagnier, the discoverer of human immunodeficiency virus, while in Moscow, said that very soon people will come to doctors not to treat diseases, but to prevent old age [9].
Luc Montagnier directly links aging with a decrease in immunity: "If we want to prevent the development of diseases, we need to remove the imbalance between oxidative molecules and antioxidants. For this, vitamins C, E, enzymes, microelements can be used. Unfortunately, when oxidative stress is strong, the amino acids-antioxidants that our body produces is not enough, and in old age their production decreases even more".
Montagnier believes that in the future, any person will be able to regularly undergo special tests, in time to learn about susceptibility to certain diseases. Knowing the weak link of the body, doctors will be able to prevent possible diseases, protecting them from reaching the irreversibility phase [9].
According to Sukhonos S. I. [10], any country that wants to break out of the ring of third-row, not to be a raw materials appendage or "gas station", should develop the creation of an innovative product, and any serious innovation should be turned into a good of global demand.
A full-fledged innovation industry was created in the USSR: from theoretical studies in the USSR Academy of Sciences to the inculcation of new products into production. This industry has worked successfully and has provided our priority in many areas, including nuclear energy, space and weapons. If in the future we create a similar Soviet innovation system, but for inquiries from the world market, this may lead the country to a breakthrough [10].
The innovation process has several stages, each of which must be crowned with full completeness: 1) the birth of an idea; 2) testing the idea with the help of an experiment; 3) creating an experimental model, a prototype of the future product of mass production; 4) creating experienced industrial production, in which all the nuances of the production of a new product are worked out;
5) the creation of serial production; 6) leading of a new product to the world market; 7) warranty and post-warranty services (for equipment). The
more complex the product, the longer and more expensive this chain, but its stages are the same for any innovation. The point can be put only after a new idea, embodied on the most modern technological lines, occupies its rightful niche in the world commodity segment.
A lot of ideas are born, but there's no practical implementation of a world scale, because there is no experience of creating an innovative sector of the economy, working primarily for export [10].
World practice shows that innovative developments make a profit of up to 1000%. In addition, the country can offer invaluable capital - the Creator Man, who is able to create new information.
This fact is the key to the future success of innovation. "... there is hope that it will be in this sector that a new sum of technologies will be created, which will increase the efficiency of the entire life activity of people on the planet by orders of magnitude, which will save it from the threat ofa new world war
and from the global resource crisis in general. And how can one assess the economic efficiency of the salvation of mankind? " - the author asks [10].
The intention of the authors of the article is to attract a "system customer", possibly from China or USA, since these countries have the financial power to trigger the innovation process in the Republic of Uzbekistan, the "pearl" of the Silk Road, whose young people are able to maintain the ancient traditions and cultural values of the East and at the same time be open to innovation.
The authors are very thankful to Mrs. Nurmukham-edova Maksuda Ramziddinovna, a Head of Small enterprise "Nafis" for financial and technical support in realizing the experimental analyzers according to the contract with Electronics Institute of the Academy of Sciences of Uz SSR
The authors express their sincere gratitude for the invaluable moral and informational support to the head of the Lada club at the Russian Cultural Center of the Republic of Uzbekistan Mrs. Sokolova Valentina Vik-torovna.
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