The development of laser medicine makes high demands on the experimental substantiation of the use of lasers in the clinic. At present, there are a large number of works devoted to studying the effect of low-intensity laser radiation on biological objects. However, there is still no consensus on the most favorable physical characteristics of laser radiation for living tissues, such as wavelength, pulse repetition rate, and exposure time. As a result, the question of the optimal radiation dose has not been resolved. The problem is exacerbated by the fact that different tissues and organs have different sensitivity to laser radiation, due to the fact that their various biochemical components - enzymes, hormones, vitamins, pigments - have purely individual radiation absorption characteristics. Thus, the information available in the literature on the effect of low-energy radiation on living tissues and organs, including the thyroid gland, is contradictory, and the mechanism of action has not yet been disclosed.
The purpose of this study is to study the morphological changes in the follicular apparatus of the thyroid gland under the influence of infrared laser radiation.
To solve the tasks, white outbred male rats weighing 150-200 grams were irradiated daily with a MILA-1 infrared laser for five days, the time of each exposure was 5 minutes. The laser wavelength is 0.89 µm. The irradiation dose for one procedure was 59 J/cm2 of the irradiated surface, for the entire course - 295 J/cm2. Euthanasia of animals was carried out by an overdose of Nembutal anesthesia. The material was taken on the first (group 1), tenth (group 2) and thirtieth (group 3) days after the end of the treatment course. Morphometry of histological sections of the thyroid gland, stained with hematoxylin and eosin, was performed using the Ista-Video Test image analyzer. The cross-sectional area of the follicle, the area and optical density of the colloid, the cross-sectional area of thyrocytes were determined, and their number was counted in the cross section of the follicle. The significance of the observed changes was determined by Student's t-test, the relationship of signs was established using correlation analysis.
The thyroid gland of rats of the comparison group has a typical morphological structure. In control animals, a clear follicular organization of this organ is noted. A colloid of a homogeneous consistency completely fills most of the oval follicles. Thyrocytes have a cubic shape. The connective tissue layers between the lobules are moderately developed. The lumens of blood vessels of all groups, with rare exceptions, contain blood cells.
Thyroid follicles in rats of the first experimental group look smaller, more often rounded. Thyrocytes retain a cubic shape. At the same time, there is a tendency to increase the size of the lobules and reduce the connective tissue layers between them. Venous plethora is clearly expressed against the background of the absence of blood cells in the arterial bed and hemocapillaries. In animals of the second group, similar changes are observed, only some flattening of thyrocytes and an increase in the amount of connective tissue are noted. In rats of the third group, a decrease in the amount of connective tissue is again noted. Changes in the follicular epithelium and blood vessels persist at all times.
An analysis of the results of morphometry made it possible to establish that the area of the follicles remained unchanged in rats of groups 1 and 2, while in animals of the third group there was a significant decrease in this indicator. The area of the colloid in animals of all experimental groups does not change significantly, and the area of thyrocytes sharply increases by the first day, after which the value of this indicator decreases. So on the 10th day, the thyrocyte area reaches the control level, and on the 30th day it becomes significantly lower. The number of thyrocytes in the follicle does not change. The optical density of the colloid increases by the tenth day, after which, on the 30th day, it significantly decreases, but does not reach the level of the comparison group. Correlation analysis revealed positive correlations between follicle area and colloid area and number of thyrocytes and negative relationship with thyrocyte area in rats of the comparison group. The area of the colloid is also positively associated with the number of thyrocytes, negatively with their area and the optical density of the colloid. The area of thyrocytes is negatively related to their number. Based on the data obtained, it can be concluded that in intact rats the area of the follicle increases due to an increase in the number of thyrocytes, or due to the accumulation of colloid. With an increase in the functional activity of the organ, which is manifested in an increase in the area of secretory cells, the area of the follicles decreases due to an increase in their total number. In this case, enhanced reabsorption of the colloid occurs, resulting in a decrease in its area and optical density.
In animals of experimental groups 1 and 2, the number of correlations remains unchanged, but in some cases their sign changes. So in rats of the 1st group, the change in the area of the follicle occurs due to changes in all its components: the area of the colloid, the area and number of thyrocytes. This may indicate a certain increase in the function of the thyroid gland during its irradiation with a laser, which resulted in an increase in the area of thyrocytes. In animals of the 2nd group, negative relationships appear between the area of the follicle, the area of the colloid, the area of the thyrocyte and the number of thyrocytes in the follicle. This significantly increases the optical density of the colloid, therefore, there is a decrease in the function of the organ.
On the thirtieth day after the end of exposure, correlations appear between all the studied features. At the same time, the previously existing connections do not differ in sign from the control ones. Again, negative correlations were formed between the area of the follicle, the number of thyrocytes and the optical density of the colloid and a positive relationship between the optical density of the colloid and the area of thyrocytes. Since these changes occur against the background of a decrease in the area of follicles and the area of thyrocytes with a simultaneous increase in the optical density of the colloid, it can be assumed that after the withdrawal of the stimulating effect, the thyroid gland experiences functional stress, leading to a decrease in the function of this organ.
Based on the currently widespread hypothesis about the possible mechanism of laser action on biological objects, it can be assumed that changes in the energy activity of cell membranes, the activity of the nuclear apparatus of cells, redox processes, and basic enzyme systems have occurred in the cells of the thyroid gland. During the period of exposure, the organ probably adapted to life under the conditions of energy input from the outside, which caused some enhancement of the function, which manifested itself in an increase in the area of follicular cells in group 1 rats. After a sharp cancellation of the energy source from the outside, a decrease in secretory activity is observed. The changes observed on the 3rd day after exposure may indicate the presence of adaptive processes in the organ to a lower energy level. Based on the data obtained, the following conclusions can be drawn:
During the exposure to infrared laser radiation, structural changes are formed in the follicular apparatus of the thyroid gland, which indicate a certain increase in its function.
After the cancellation of the experimental exposure, morphological changes correspond to the hypofunctional state of the thyroid gland.
3. The laser radiation used in the work had a negative effect on the thyroid gland, since the stimulating effect was of a short-term nature, and the recovery period took a rather long period of time.
follicular thyroid radiation
Literature
- 1. Amirov N. B. The use of laser exposure for the treatment of internal diseases. // Kazan Medical Journal. 2001. T 31, No. 5, p. 369-372.
- 2. A. V. Mostovnikov, G. R. Mostovnikova, V. Yu. Plavskii, L. G. Plavskaya, and R. Morozova. P., Tretyakov SA On the mechanism of the therapeutic action of low-intensity laser radiation and a constant magnetic field. // Low-intensity lasers in medicine (mechanism of action, clinical application): Proceedings of the All-Union Symposium, in two parts. Obninsk, NIIMR AMS USSR, 1991, p. 67 - 70.
Moskvin Sergey Vladimirovich - Doctor of Biological Sciences, Candidate technical sciences, Leading Researcher, Federal State Budgetary Institution “State Scientific Center for Laser Medicine named after N.N. OK. Skobelkin FMBA of Russia”, Moscow, author of more than 550 scientific publications, including more than 50 monographs, and 35 copyright certificates and patents; email mail: [email protected] website: www.lazmik.ru
A more detailed description of the primary mechanism of the biological, or, as it is now customary to say, biomodulating action (BD) of LILI, as well as the proof of the model we proposed, can be found in the first two volumes of the series of books "Effective Laser Therapy" [Moskvin S.V., 2014, 2016], which are best downloaded for free on the website http://lazmik.ru.
In this chapter, as well as in some other sections of the book, material is also presented on the secondary processes that occur during the absorption of laser light by living cells and biological tissues, the knowledge of which is extremely important for the clinical application and understanding of the LT methodology as applied to the problem of pain and trophic disorders.
We have chosen to study the mechanisms of the DB LILI systems approach to data analysis, for which some part is conventionally distinguished from the whole organism, united by the type of anatomical structure or type of functioning, but each part is considered exclusively in terms of interaction as a single system. The key point of this approach is the determination of the backbone factor [Anokhin PK, 1973]. The scientific literature was analyzed, primarily related to the study of the mechanisms of the BD, the practice of using LILI in clinical medicine, as well as modern ideas about the biochemistry and physiology of both a living cell and at the level of organizing the regulation of human homeostasis in general. Based on the data obtained, some fundamentally important conclusions were made, which were confirmed in the course of numerous experimental and clinical studies [Moskvin S.V., 2008, 2008(1), 2014].
It is shown that as a result of the absorption of LILI energy, it is transformed into biological reactions at all levels of the organization of a living organism, the regulation of which, in turn, is realized in many ways - this is the reason for the extraordinary versatility of the effects that appear as a result of such an impact. In this case, we are dealing only with the external triggering of the processes of self-regulation and self-recovery of disturbed homeostasis. Therefore, there is nothing surprising in the universality of laser therapy: it is only the result of the elimination of pathological fixation of the body outside the boundaries of normal physiological regulation. Photobiological processes can be schematically represented as the following sequence: after the absorption of photons by acceptors, the absorption spectrum of which coincides with the wavelength of the incident light, biochemical or physiological reactions are triggered that are characteristic (specific) for these absorbing elements. But for laser-induced bioeffects, everything looks as if there are no specific acceptors and responses of biological systems (cells, organs, organisms), the interaction is absolutely non-specific. This is confirmed by the relative non-specificity of the "wavelength - effect" dependence, the response of a living organism to one degree or another takes place in the entire studied spectral range, from the ultraviolet (325 nm) to the far infrared region (10,600 nm) [Moskvin S. IN 2014; Moskvin S.V., 2017].
The absence of a specific spectrum of action can only be explained by the thermodynamic nature of the interaction of LILI with a living cell, when the temperature gradient that occurs at the absorbing centers triggers the launch of various physiological regulation systems. As the primary link, as we assume, are intracellular calcium depots, capable of releasing Ca2+ under the influence of many external factors. There are enough arguments to confirm this theory, however, due to the limitation of the size of the book, we will give only one: all known effects of laser-induced biomodulation are secondary and Ca2+-dependent [Moskvin S.V., 2003, 2008, 2008(1)]!
Turning to energy regularities, even more surprising than spectral ones, let us repeat some basic concepts and foundations, the axioms of laser therapy. The most famous of them is the presence of an optimum dependence "energy density (ED) - effect", which is sometimes called "biphasic", i.e. the desired result is achieved only with the optimal ED of exposure. A decrease or increase in this value in a very narrow range leads to a decrease in the effect, its complete disappearance, or even an inverse response.
This is the fundamental difference between DB LILI and photobiological phenomena, where the dependence on EF has a linearly increasing character over a wide range. For example, the more sunlight, the more intense photosynthesis and increase in plant mass. Does the biphasic nature of the biological action of LILI contradict the laws of photobiology? Not at all! This is only a special case of the manifestation of the physiological law of the dependence of the response on the strength of the current stimulus. In the “optimum” phase, after reaching the threshold level, as the stimulus strength increases, an increase in the response of cells and tissues and a gradual achievement of the reaction maximum are observed. A further increase in the strength of the stimulus leads to inhibition of the reactions of cells and the body, inhibition of reactions or a state of parabiosis develops in the tissues [Nasonov D.N., 1962].
For effective exposure to LILR, it is necessary to provide both optimal power and power density (PM), i.e., it is important to distribute light energy over the area of cells in vitro and the area and/or volume of biological tissues in animal experiments and in the clinic.
The exposure (exposure time) to one zone is extremely important, which should not exceed 300 s (5 min), except for some variants of the method of intravenous laser illumination of blood (up to 20 min).
By multiplying the exposure by the PM, you get the power density per unit time, or EF. This is a derivative value that does not play any role, but is often and erroneously used in the special literature under the name "dose", which is absolutely unacceptable.
For pulsed lasers (pulse power is most often in the range of 10-100 W, the duration of the light pulse is 100-150 ns), with an increase in the pulse repetition rate, the average power increases proportionally, i.e., the EF of exposure.
Interestingly, the EF for pulsed lasers (0.1 J/cm2) is ten times less than for continuous LILI (1-20 J/cm2) for similar experimental models [Zharov V.P. et al., 1987; Nussbaum E.L. et al., 2002; Karu T. et al., 1994], which indicates a greater efficiency of the pulse mode. There is no analogue of such regularity in photobiology.
I would like to mention one more interesting fact- non-linear dependence of DL LILI on exposure time, which is easily explained by the periodicity of waves of increased Ca2+ concentration propagating in the cytosol after activation of intracellular calcium depots by laser light. Moreover, for completely different types of cells, these periods are completely identical and are strictly 100 and 300 s (Table 1). There are hundreds of times more clinical studies confirming the effectiveness of LT techniques using such an exposure. We also draw attention to the fact that the effect is observed in a very wide range of wavelengths, therefore, intracellular calcium depots localized in different parts of the cell have a different structure.
Table 1
Optimal exposure 100 or 300 s for maximum in vitro effect
| cell type | Result | LILI wavelength, nm | Link |
| E. coli, S. aureus | Proliferation | 467 | Podshibyakin D.V., 2010 |
| hippocampus | epileptiform activity | 488 | Walker J.B. et al., 2005 |
| fibroblasts | Proliferation | 633 | Rigau J. et al., 1996 |
| fibroblasts | Increasing the concentration of Ca2+ | 633 | Lubart R. et al., 1997(1); 2005 |
| Keratinocytes | Increase in IL-1α and IL-8 mRNA production and expression | 633 | Yu H.S. et al., 1996 |
| macrophages | Proliferation | 633 | Hemvani N. et al., 1998 |
| Fibroblasts, E. coli | Proliferation | 660 | Ribeiro M.S. et al., 2010 |
| Human neutrophils | Increased Ca2+ concentration in the cytosol | 812 | Løvschall H. et al., 1994 |
| Human buccal epithelial cells | Proliferation | 812 | Løvschall H., Arenholt-Bindslev D., 1994 |
| E. coli | Proliferation | 890 | Zharov V.P. et al., 1987 |
| Myoblasts C2C12 | Proliferation, viability | 660, 780 | Ferreira M.P.P. et al., 2009 |
| HeLa | Mitotic activity | 633, 658, 785 | Yang H.Q. et al., 2012 |
| E. coli | Proliferation | 633, 1064, 1286 | Karu T. et al., 1994 |
To illustrate and demonstrate that the activation of mitochondria is a secondary process, only a consequence of an increase in the concentration of Ca2+ in the cytosol, we present the corresponding graphs from only one study (Fig. 1) .
Rice. 1. Change in Ca2+ concentration (1) in the cytosol and redox potential of mitochondria ΔΨm (2) under the action of laser radiation (wavelength 647 nm, 0.1 mW/cm2, exposure 15 s) on human foreskin fibroblasts (Alexandratou E. et al., 2002)
The most important fact is the increase in Ca2+ concentration solely due to intracellular depots (where calcium ions are re-injected after the end of the physiological cycle after 5-6 minutes), and not as a result of the intake of ions from the outside, as many believe. Firstly, there is no correlation between the level of ATP in cells and the transport of Ca2+ into the cell from the outside, the activation of mitochondria is carried out only by increasing the concentration of Ca2+ from intracellular depots. Secondly, the removal of calcium ions from the serum does not delay the increase in the Ca2+ concentration in the anaphase of the cell cycle, i.e., the activation of cell proliferation under the action of LILI is in no way associated with extracellular calcium, membranes, specifically dependent pumps, etc. These processes are only important when exposed to cells that are in the whole body, and are secondary.
The regularities demonstrated above can be easily explained if the mechanisms of the LILR database are arranged in the following sequence: as a result of illumination of the LILR, a thermodynamic disturbance occurs inside the cell (“temperature gradient”), as a result of which the intracellular depot is activated, and they release calcium ions (Ca2+) with a short-term (up to 300 c) an increase in their concentration with the subsequent development of a cascade of responses at all levels, from cells to the body as a whole: activation of mitochondria, metabolic processes and proliferation, normalization of the immune and vascular systems, inclusion in the ANS and CNS process, analgesic effect, etc. ( Fig. 2) [Moskvin S.V., 2003, 2008, 2014, 2016].
Rice. 2. Sequence of development biological effects after exposure to LILI (mechanisms of biological and therapeutic action)
This approach makes it possible to explain the non-linear nature of the dependences "EP-effect" and "exposure-effect" by the peculiarities of the work of intracellular calcium depots, and the absence of an action spectrum - by the nonspecificity of their inclusion. We repeat that what was said above refers to “laser-” and not “photo-” (biomodulation), i.e. only for monochromatic light and in the absence of a specific effect (for example, bactericidal action).
The most important thing in knowing and correctly understanding the mechanisms of DL LILI is the ability to develop and optimize laser therapy techniques, understand the principles and conditions for the effective application of the method.
The dependence of the effect on the modulation frequency, monochromaticity, polarization, etc. forces us to consider these patterns also not entirely from the standpoint of classical photobiology. Here, in our opinion, to characterize the supporters of the “acceptor”, static approach to the study of the mechanisms of the DB LILI, it is appropriate to quote the words of the American writer G. Garrison: “They sorted out the facts. Whereas they analyzed the most complex closed system with such elements as positive and negative Feedback, or variable switching. Yes, and the whole system is in a dynamic state due to continuous homeostatic correction. No wonder they didn't get anything." So photobiologists with a similar approach to research did not understand anything about the mechanisms of the LILI database.
So how do biological processes induced by laser light develop? Is it possible to trace the entire chain, from the absorption of photons to the patient's recovery, to fully and reliably explain the existing scientific facts and on their basis to develop the most effective methods of treatment? In our opinion, there is every reason for an affirmative answer to these questions, of course, within the framework of limited general knowledge in the field of biology and physiology.
The mechanisms of the biological (therapeutic) action of low-intensity laser light on any living organism must be considered only from the standpoint of the general nature of both the acting light energy and the organization of living matter. On fig. Figure 2 shows the main sequence of reactions, starting from the primary act of absorbing a photon and ending with the reaction of various body systems. This scheme can only be supplemented with details of the pathogenesis of a particular disease.
Where does it all begin? Based on the fact that low-intensity laser light causes the corresponding effects in vitro in a single cell, it can be assumed that the initial starting point when exposed to biological tissues is the absorption of LILI by intracellular components. Let's try to figure out which ones.
The facts presented above and obtained by T. Karu et al. (1994), the data convincingly prove that such regularities can only be the result of thermodynamic processes that occur when laser light is absorbed by any, i.e., any, intracellular components. Theoretical estimates show that under the action of LILR, local "heating" of acceptors by tens of degrees is possible. Although the process lasts a very short period of time - less than 10-12 s, this is quite enough for very significant thermodynamic changes both in the group of chromophores directly and in the surrounding areas, which leads to significant changes in the properties of molecules and is the starting point of the reaction induced by laser radiation. We emphasize once again that any intracellular component that absorbs at a given wavelength, including water, which has a continuous absorption spectrum, can act as an acceptor, i.e. local temperature gradient, and we are dealing with a thermodynamic rather than a photobiological effect (in the classical sense of the term), as previously thought. This is a fundamentally important point.
At the same time, it must be understood that the “temperature gradient” does not mean a change in temperature in the generally accepted, “everyday” sense, we are talking about a thermodynamic process and terminology from the corresponding section of physics - thermodynamics, which characterizes the change in the state of the vibrational levels of macromolecules and describes exclusively energy processes [Moskvin S.V., 2014, 2016]. This "temperature" cannot be measured with a thermometer.
However, it is precisely the “lack of direct experimental evidence of a local intracellular temperature rise” that is the main argument in criticizing our theory [Ulashchik V.S., 2016]. The remark of V.S. Ulaschik (2016) regarding the fact that the result of this process cannot be only the release of calcium ions, should be recognized as fair. Indeed, there is, albeit a very limited, list of identified patterns that are difficult to explain only by Ca2+-dependent processes, this remains to be studied.
Nevertheless, the conclusions from our theory have already made it possible to qualitatively improve the efficiency of laser therapy methods, their stability and reproducibility, which is already quite enough for its recognition (although it does not reject the need for further development). And it is absolutely impossible to agree with the opinion of a highly respected specialist [Ulashchik V.S., 2016], that “theories” have the right to exist only if there are some “experimental data”, which are often very doubtful and misinterpreted, the conclusions from which are detrimental to clinical practice. For example, the consequence of all such hypotheses is the impossibility of using LILI with a wavelength in the range of 890-904 nm for laser therapy. And what would you order tens of thousands of specialists to do when they have been successfully using just such laser light for more than 30 years, consider it the most effective and get excellent treatment results? Abandon reality in favor of the ambitions of units?
There are no reasonable arguments against the thermodynamic nature of the LILI interaction at the cellular level, otherwise it is simply impossible to explain the incredibly wide and almost continuous spectrum of action (from 235 to 10 600 nm), so we will continue to adhere to our concept regarding the primary process.
With minor local thermodynamic perturbations that are insufficient to transfer the molecule to a new conformational state, however, the geometry and configuration of the molecules can change relatively strongly. The structure of the molecule is, as it were, "leaded", which is facilitated by the possibility of rotations around the single bonds of the main chain, not very strict requirements for the linearity of hydrogen bonds, etc. This property of macromolecules decisively affects their functioning. For efficient energy conversion, it is sufficient to excite such degrees of freedom of the system that slowly exchange energy with thermal degrees of freedom [Goodwin B., 1966].
Presumably, the ability to direct conformational changes, i.e. to their movement under the influence of local gradients, is a distinctive feature of protein macromolecules, and the required relaxation changes may well be caused by laser light of “low” or “therapeutic” intensity (power, energy) [Moskvin S.V., 2003(2)].
The functioning of most intracellular components is closely related not only to the nature of their conformations, but most importantly, to their conformational mobility, which depends on the presence of water. Due to hydrophobic interactions, water exists not only in the form of a bulk phase of a free solvent (cytosol), but also in the form of bound water (cytogel), the state of which depends on the nature and localization of the protein groups with which it interacts. The lifetime of weakly bound water molecules in such a hydration shell is short (t ~ 10-12 ÷ 10-11 s), but near the center it is much longer (t ~ 10-6 s). In general, several layers of water can be held stably near the surface of the protein. Small changes in the quantity and state of a relatively small fraction of water molecules that form the hydration layer of a macromolecule lead to sharp changes in the thermodynamic and relaxation parameters of the entire solution as a whole [Rubin A.B., 1987].
Explanation of the mechanisms of DB LILI from the thermodynamic point of view makes it possible to understand why the effect is achieved when exposed to laser light, and its most important property is its monochromaticity. If the width of the spectral line is significant (20-30 nm or more), i.e., commensurate with the absorption band of the macromolecule, then such light initiates the oscillation of all energy levels and only a slight, by hundredths of degrees, “heating” of the entire molecule will occur. Whereas light with a minimum spectral line width characteristic of LILR (less than 3 nm) will cause a temperature gradient of tens of degrees, so necessary for a full-fledged effect. In this case, all the light energy of the laser will be released (relatively speaking) in a small local area of the macromolecule, causing thermodynamic changes, an increase in the number of vibrational levels with a higher energy, sufficient to trigger a further physiological response. Drawing a conditional analogy, the process can be represented as follows: when a magnifying glass concentrates sunlight on a point, paper can be set on fire, while when scattered light illuminates its entire area, only a slight heating of the surface occurs.
The consequence of the photoinduced “behavior” of macromolecules is the release of calcium ions from the calcium depot into the cytosol and the propagation of waves of increased Ca2+ concentration through and between cells. And this is the main, key point of the primary stage in the development of the laser-induced process. Together with the act of absorption of a photon, the appearance and propagation of waves of increased concentration of calcium ions can be defined precisely as primary mechanism DB NILI.
The possible participation of calcium ions in laser-induced effects was first suggested by N.F. Gamaleya (1972). Later it was confirmed that the intracellular concentration of calcium ions in the cytosol under the influence of LILI increases many times [Smolyaninova N.K. et al., 1990; Tolstykh P.I. et al., 2002; Alexandratou E. et al., 2002]. However, in all studies, these changes were noted only in combination with other processes, they were not distinguished in any special way, and only we for the first time suggested that an increase in the Ca2+ concentration in the cytosol is precisely the main mechanism that subsequently triggers secondary laser-induced processes, and it has also been observed that all the physiological changes that occur as a result of this at the most diverse levels, calcium dependent [Moskvin S.V., 2003].
Why do we pay attention to calcium ions? There are several reasons for this.
- Calcium is in the greatest degree in a specifically and non-specifically bound state both in cells (99.9%) and in the blood (70%) [Murry R. et al., 2009], i.e., in principle, there is the possibility of a significant increase in concentration free calcium ions, and this process is provided by more than a dozen mechanisms. Moreover, in all living cells there are specialized intracellular depots (sarco- or endoplasmic reticulum) for storing only calcium in a bound state. The intracellular concentration of other ions and ionic complexes is regulated exclusively by transmembrane ion currents.
- The extraordinary versatility of the Ca2 + regulation mechanisms of many physiological processes, in particular: neuromuscular excitation, blood coagulation, secretion processes, maintaining the integrity and deformability of membranes, transmembrane transport, numerous enzymatic reactions, the release of hormones and neurotransmitters, the intracellular action of a number of hormones, etc. [Grenner D. , 1993(1)].
- The intracellular concentration of Ca2+ is extremely low - 0.1-10 μm/l, therefore, the release of even a small absolute amount of these ions from the bound state leads to a significant relative increase in the concentration of Ca2+ in the cytosol [Smolyaninova N.K. et al., 1990; Alexandratou E. et al., 2002].
- More and more is known about the role of calcium in maintaining homeostasis every day. For example, a Ca2+-induced change in mitochondrial membrane potential and an increase in intracellular pH lead to an increase in ATP production and ultimately stimulate proliferation [Karu TY, 2000; Schaffer M. et al., 1997]. Stimulation with visible light leads to an increase in the level of intracellular cAMP almost simultaneously with a change in the concentration of intracellular Ca2+ in the first minutes after exposure, thus contributing to the regulation carried out by calcium pumps.
- It is important to note that the organization of the cell itself ensures its homeostasis, in most cases, precisely through the influence of calcium ions on energy processes. In this case, the general cellular oscillatory circuit acts as a specific coordinating mechanism: Ca2+ of the cytosol - calmodulin (CaM) - a system of cyclic nucleotides [Meerson FZ, 1984]. Another mechanism is also involved through Ca2+-binding proteins: calbindin, calretinin, parvalbumin and effectors such as troponin C, CaM, synaptotagmin, S100 proteins and annexins, which are responsible for the activation of Ca2+-sensitive processes in cells.
- The presence of various oscillatory contours of changes in the concentrations of active intracellular substances is closely related to the dynamics of the release and regulation of the content of calcium ions. The fact is that a local increase in Ca2+ concentration does not end with a uniform diffuse distribution of ions in the cytosol or the activation of mechanisms for pumping excess into intracellular depots, but is accompanied by the propagation of waves of increased Ca2+ concentration inside the cell, causing numerous calcium-dependent processes. Calcium ions released by one cluster of specialized tubules diffuse to neighboring ones and activate them. This hopping mechanism allows the initial local signal to trigger global waves and fluctuations in Ca2+ concentrations.
- Sometimes the Ca2+ waves are very limited in space, for example, in amacrine cells of the retina, in which local signals from the dendrites are used to calculate the direction of movement. In addition to such intracellular waves, information can be propagated from cell to cell via intercellular waves, as has been described for endocrine cells, vertebrate gastrula, and intact perfused liver. In some cases, intercellular waves can move from one cell type to another, as happens in endothelial cells and smooth muscle cells. The fact of such propagation of Ca2+ waves is very important, for example, for explaining the mechanism of generalization of laser action during the healing of a significant wound (for example, a burn) under local action of LILI.
So, what happens after the waves of increased Ca2+ concentration began to propagate under the influence of LILI in the cytosol of the cell and between groups of cells at the tissue level? To answer this question, it is necessary to consider what changes LILI causes at the level of the organism. Laser therapy has become widespread in almost all areas of medicine due to the fact that LILI initiates a wide variety of biochemical and physiological responses, which are a set of adaptive and compensatory reactions resulting from the implementation of primary effects in tissues, organs and the whole living organism and aimed at its recovery:
- activation of cell metabolism and increase in their functional activity;
- stimulation of reparative processes;
- anti-inflammatory action;
- activation of blood microcirculation and an increase in the level of trophic provision of tissues;
- anesthesia;
- immunomodulatory action;
- reflexogenic effect on the functional activity of various organs and systems.
Two important points should be noted here. Firstly, in almost each of the listed points, the unidirectional influence of LILI (stimulation, activation, etc.) is a priori set. As will be shown below, this is not entirely true, and laser light can cause exactly the opposite effects, which is well known from clinical practice. Secondly, all these processes are Ca2+-dependent! This is really something no one has paid attention to before. Let us now consider exactly how the presented physiological changes occur, giving as an example only a small part of the known ways of their regulation.
Activation of cell metabolism and an increase in their functional activity occur primarily due to a calcium-dependent increase in the redox potential of mitochondria, their functional activity and ATP synthesis [Karu T.Y., 2000; Philippine L. et al., 2003; Schaffer M. et al., 1997].
Stimulation of reparative processes depends on Ca2+ at various levels. In addition to activating the work of mitochondria, with an increase in the concentration of calcium ions, protein kinases are activated, which take part in the formation of mRNA. Calcium ions are also allosteric inhibitors of membrane-bound thioredoxin reductase, an enzyme that controls the complex process of synthesis of purine deoxyribonucleotides during active DNA synthesis and cell division [Rodwell V., 1993]. In addition, the main fibroblast growth factor (bFGF) is actively involved in the physiology of the wound process, the synthesis of which and activity depend on the Ca2+ concentration.
The anti-inflammatory effect of LILI and its effect on microcirculation are due, in particular, to Ca2+-dependent release of inflammatory mediators, such as cytokines, as well as Ca2+-dependent release of vasodilator nitric oxide (NO), a precursor of endothelial vascular wall relaxation factor (EDRF), by endothelial cells.
Since exocytosis is calcium-dependent, in particular, the release of neurotransmitters from synaptic vesicles, the process of neurohumoral regulation is completely controlled by Ca2+ concentration, therefore, it is also subject to the influence of LILI. In addition, it is known that Ca2+ is an intracellular mediator of the action of a number of hormones, primarily mediators of the CNS and ANS [Grenner D., 1993], which also suggests the involvement of laser-induced effects in neurohumoral regulation.
The interaction of the neuroendocrine and immune systems has not been studied enough, but it has been established that cytokines, in particular IL-1 and IL-6, act in both directions, playing the role of modulators of the interaction of these two systems [Royt A. et al., 2000]. LILI can affect immunity both indirectly through neuroendocrine regulation and directly through immunocompetent cells (which has been proven in in vitro experiments). Among the early starting points of blast transformation of lymphocytes is a short-term increase in the intracellular concentration of calcium ions, which activates protein kinase, which is involved in the formation of mRNA in T-lymphocytes, which, in turn, is the key moment of laser stimulation of T-lymphocytes [Manteifel V.M., Karu T.J., 1999]. The impact of LILI on fibroblast cells in vitro also leads to increased generation of intracellular endogenous γ-interferon.
In addition to the physiological reactions described above, to understand the picture as a whole, it is also necessary to know how laser light can affect the mechanisms of neurohumoral regulation. LILI is considered as a non-specific factor, the action of which is not directed against the pathogen or symptoms of the disease, but to increase the body's resistance (vitality). It is a bioregulator of both cellular biochemical activity and the physiological functions of the body as a whole - neuroendocrine, endocrine, vascular and immune systems.
Data scientific research allow us to say with full confidence that laser light is not the main therapeutic agent at the level of the organism as a whole, but, as it were, eliminates obstacles, an imbalance in the central nervous system (CNS), which interferes with the sanogenetic function of the brain. This is carried out by a possible change under the action of laser light in the physiology of tissues both in the direction of strengthening and in the direction of suppressing their metabolism, depending mainly on the initial state of the body and the energy density of LILI, which leads to the attenuation of pathological processes, the normalization of physiological reactions and restoration of regulatory functions nervous system. Laser therapy, when used correctly, allows you to restore the disturbed systemic balance [Moskvin S.V., 2003(2); Skupchenko V.V., 1991].
Consideration of the CNS and the autonomic nervous system (ANS) as independent structures has ceased to suit many researchers in recent years. There are more and more facts confirming their closest interaction and mutual influence. Based on the analysis of numerous scientific research data, a model of a single system that regulates and maintains homeostasis, called the neurodynamic generator (NDG) [Moskvin S.V., 2003(2)], was proposed.
The main idea of the NDG model is that the dopaminergic department of the CNS and the sympathetic department of the ANS, combined into a single structure, named by V.V. Skupchenko (1991) phasic motor-vegetative (FMV) system complex, are closely related to another, mirror-cooperative (P.K. Anokhin's term) structure - tonic motor-vegetative (TMV) system complex. The presented mechanism functions not so much as a reflex response system, but as a spontaneous neurodynamic generator that restructures its work according to the principle of self-organizing systems.
The appearance of facts indicating the simultaneous participation of the same brain structures in providing both somatic and autonomic regulation is difficult to perceive, since they do not fit into known theoretical constructions. However, we cannot ignore what is confirmed by everyday clinical practice. Such a mechanism, having a certain neurodynamic mobility, is not only able to provide a continuously changing adaptive adjustment of the regulation of the entire range of energy, plastic and metabolic processes, which was first suggested and brilliantly proved by V.V. Skupchenko (1991), but manages, in fact, the entire hierarchy of regulatory systems from the cellular level to the central nervous system, including endocrine and immunological changes [Moskvin S.V., 2003(2)]. In clinical practice, the first positive results of this approach to the mechanism of neurohumoral regulation were obtained in neurology [Skupchenko V.V., Makhovskaya T.G., 1993] and in the removal of keloid scars [Skupchenko V.V., Milyudin E.S., 1994 ].
The terms "tonic" and "phasic" were originally formulated by the names of the corresponding types of muscle fibers, since the mechanism of interaction between the two types of nervous systems presented for the first time was proposed to explain movement disorders (dyskinesias). Despite the fact that this terminology does not reflect the full significance of NDG, we decided to keep it in memory of the discoverer of such a mechanism for regulating physiological processes - prof. V.V. Skupchenko.
On fig. Figure 3 shows a general scheme demonstrating the concept of GND as a universal regulator of homeostasis, of course, in a “static” state, so to speak. The main idea of such a systematization is to show the unity of all regulatory systems. This is a kind of fulcrum around which the methodology of therapy is built under the motto: “The impact of unidirectional therapeutic factors” [Moskvin S.V., 2003(2)].
The scheme is rather conditional, which is emphasized by the presentation of LILI as the only method for regulating the neurodynamic state. In this case, we only demonstrate the ability of the same therapeutic effect, depending on the EP for the selected wavelength of LILI, to cause multidirectional effects, which is a characteristic property of, if not all, then most non-specific methods of biologically significant influence. However, laser light seems to us to be the most universal therapeutic physical factor, far beyond the scope of just one of the physiotherapeutic methods. And there is every reason for such a conclusion.
The proposed neurodynamic model for maintaining homeostasis allows a new assessment of the systemic mechanisms of mediator and autonomic regulation. The whole set of neurodynamic, neurotransmitter, immunological, neuroendocrine, metabolic, etc. processes reacts as a whole. When it changes to organism level autonomic balance, this means that at the same time neurodynamic restructuring covers the entire complex hierarchically organized system internal regulation. Even more impressive is that a local change in homeostasis at the cellular level also causes a reaction of the entire neurodynamic generator, to a greater or lesser extent involving its various levels [Moskvin S.V., 2003(2)]. The details of the functioning of such a mechanism are not yet fully understood, however, over the past few years, the number of publications devoted to the study of this issue has increased like an avalanche in foreign neurological journals. Still, it is more important for us to analyze the general patterns associated with the body's response to external influences, some of them are already known and are actively used to improve the efficiency of predicting the results of laser therapy.
First of all, we draw attention to the need to use the terms “regulation” and “modulation”, and not “activation” or “stimulation”, in relation to the LILI DB, since it is now completely clear that laser light is not a unidirectional influence factor, but, as shown us, depending on the EP impact, a shift of homeostasis in one direction or another is possible. This is extremely important when choosing the energy parameters of the therapeutic effect, while at the same time correctly assessing the initial state of the body and for the etiopathogenetic substantiation of LT methods based on the proposed concept of the neurodynamic model of disease pathogenesis.
Normally, there are constant transitions from the phasic state to the tonic state and vice versa. Stress causes the inclusion of phasic (adrenergic) mechanisms of regulation, which is described in detail in the works of G. Selye (1960) as a general adaptation syndrome. At the same time, in response to the prevalence of dopaminergic influence, tonic (GABAergic and cholinergic) regulatory mechanisms are launched. The last circumstance remained outside the scope of G. Selye's research, but is, in fact, the most important point explaining the principle of the self-regulatory role of the GND. Normally, two systems, interacting, themselves restore the disturbed balance.
Many diseases appear to us to be associated with the prevalence of one of the states of a given regulatory system. With a prolonged, uncompensated influence of a stress factor, a malfunction occurs in the work of the NDG and its pathological fixation in one of the states: in the phasic, which happens more often, or in the tonic phase, as if moving into a mode of constant readiness to respond to irritation, affecting almost all regulatory physiological processes, in particular metabolic ones. Thus, stress or constant nervous tension can shift homeostasis and fix it pathologically either in a phasic or tonic state, which causes the development of corresponding diseases, the treatment of which should be primarily aimed at correcting neurodynamic homeostasis. The combination of several circumstances - a hereditary predisposition, a certain constitutional type, various exogenous and endogenous factors, etc. - causes the development of any particular pathology in a particular individual, but the true cause of the disease is common - the steady prevalence of one of the conditions of NDG.
Rice. 3. Schematic representation of the concept of neurodynamic regulation of homeostasis by low-intensity laser light
Once again, we draw attention to the most important fact that not only the CNS and ANS regulate various processes at all levels, but, on the contrary, a locally acting external factor, for example, laser light, can lead to systemic shifts, eliminating the true cause of the disease - an imbalance of NDG, and with local illumination to eliminate the generalized form of the disease. This must be taken into account when developing laser therapy techniques.
Now it becomes clear the possibility of multidirectional influence, depending on the energy and spectral parameters of the acting laser light - stimulation of physiological processes or their inhibition. The universality of bioeffects is due, among other things, to the fact that, depending on the EP, LILI both stimulates and suppresses proliferation and the wound process [Kryuk A.S. et al., 1986; Al-Watban F.A.N., Zhang X.Y., 1995; Friedmann H. et al., 1991; Friedmann H., Lubart R., 1992].
Most often, the methods use the minimum, generally accepted EF of laser exposure (1-3 J/cm2 for continuous operation of a laser with a wavelength of 635 nm), but sometimes in clinical practice, it is the conditionally NOT stimulating effect of LILI that is required. For example, in psoriasis, the proliferation of keratinocytes is greatly increased; this disease is typical of a tonic state in which plastic processes are activated. It is clear that minimal EP LILI that stimulates proliferation is inappropriate in this case. It is necessary to act with super-high power at small areas of the illumination zone in order to suppress excessive cell division. The conclusions made on the basis of this model were brilliantly confirmed in practice in the development of effective methods for the treatment of patients with psoriasis [US Pat. 2562316 RU], atopic dermatitis [Pat. 2562317 RU], vitiligo [Adasheva O.V., Moskvin S.V., 2003; Moskvin S.V., 2003], Peyronie's disease [Ivanchenko L.P. et al., 2003].
Now that we have a fairly complete picture of the mechanisms of action of LILI, it is easy to get an answer to some well-known questions. For example, how to explain the biphasic character of the LILI database? With an increase in absorbed energy, the temperature gradient also increases, which causes the release of a larger number of calcium ions, but as soon as their concentration in the cytosol begins to exceed the physiologically permissible maximum level, the mechanisms of Ca2+ pumping into calcium depots are activated, and the effect disappears.
Why is the effect higher in the pulse mode at an average power, 100-1000 times less than in the continuous mode of radiation? Because the time of thermodynamic relaxation of macromolecules (10-12 s) is much shorter than the duration of the light pulse (10-7 s) and a very short, in our understanding, watt pulse has a much greater effect on the state of local thermodynamic equilibrium than continuous radiation in units milliwatt.
Is it effective to use laser sources with two different wavelengths? Absolutely yes! Different wavelengths cause the release of Ca2+ from different intracellular stores, potentially providing a higher concentration of ions, hence a higher effect. It is only important to understand that simultaneous illumination with laser light with different wavelengths is NOT ALLOWED, it must be separated in time or space.
Other ways to increase the effectiveness of laser therapy, known and developed by us on the basis of the proposed concept of the mechanisms of the DL LILI, can be found in the 2nd volume of the series of books "Effective Laser Therapy" [Moskvin S.V., 2014].
So, the application of system analysis made it possible to develop a universal, unified theory mechanisms of biomodulating action of low-intensity laser light. The primary acting factor is local thermodynamic shifts that cause a chain of changes in Ca2+-dependent physiological reactions, both at the cellular level and the organism as a whole. Moreover, the direction of these reactions can be different, which is determined by the energy density, the wavelength of laser light and the localization of the impact, as well as the initial state of the organism itself (biological system).
The concept developed by us allows not only to explain almost all the existing scientific facts, but also to draw conclusions both about predicting the results of the influence of LILI on physiological processes, and about possible ways to increase the effectiveness of laser therapy.
Source: Moskvin S.V., Fedorova T.A., Foteeva T.S. Plasmapheresis and laser illumination of blood. - M.-Tver: Triada Publishing House LLC, 2018. - P. 7-23.
Laser radiation in medicine is a forced or stimulated wave of the optical range with a length of 10 nm to 1000 μm (1 μm = 1000 nm).
Laser radiation has:
- coherence - the coordinated flow in time of several wave processes of the same frequency;
- monochromaticity - one wavelength;
- polarization - orderliness of the orientation of the electromagnetic field strength vector of the wave in the plane perpendicular to its propagation.
Physical and physiological effects of laser radiation
Laser radiation (LI) has photobiological activity. Biophysical and biochemical reactions of tissues to laser radiation are different and depend on the range, wavelength and energy of the radiation photon:
IR radiation (1000 microns - 760 nm, photon energy 1-1.5 eV) penetrates to a depth of 40-70 mm, causes oscillatory processes - thermal effect;
- visible radiation (760-400 nm, photon energy 2.0-3.1 eV) penetrates to a depth of 0.5-25 mm, causes dissociation of molecules and activation of photochemical reactions;
- UV radiation (300-100 nm, photon energy 3.2-12.4 eV) penetrates to a depth of 0.1-0.2 mm, causes dissociation and ionization of molecules - photochemical effect.
The physiological effect of low-intensity laser radiation (LILI) is realized in the nervous and humoral way:
Change in tissues of biophysical and chemical processes;
- change in metabolic processes;
- change in metabolism (bioactivation);
- morphological and functional changes in the nervous tissue;
- stimulation of the cardiovascular system;
- stimulation of microcirculation;
- increasing the biological activity of cellular and tissue elements of the skin, activates intracellular processes in the muscles, redox processes, the formation of myofibrils;
- increases the body's resistance.
High-intensity laser radiation (10.6 and 9.6 µm) causes:
Thermal tissue burn;
- coagulation of biological tissues;
- charring, combustion, evaporation.
Therapeutic effect of low-intensity laser (LILI)
Anti-inflammatory, reducing tissue swelling;
- analgesic;
- stimulation of reparative processes;
- reflexogenic effect - stimulation of physiological functions;
- generalized effect - stimulation of the immune response.
Therapeutic effect of high-intensity laser radiation
Antiseptic action, formation of a coagulation film, protective barrier against toxic agents;
- tissue cutting (laser scalpel);
- welding of metal prostheses, orthodontic appliances.
NILI readings
Acute and chronic inflammatory processes;
- soft tissue injury;
- burns and frostbite;
- skin diseases;
- diseases of the peripheral nervous system;
- diseases of the musculoskeletal system;
- cardiovascular diseases;
- respiratory diseases;
- diseases of the gastrointestinal tract;
- diseases of the genitourinary system;
- diseases of the ear, throat, nose;
- violations of the immune status.
Indications for laser radiation in dentistry
Diseases of the oral mucosa;
- periodontal diseases;
- non-carious lesions of hard tissues of teeth and caries;
- pulpitis, periodontitis;
- inflammation and trauma of the maxillofacial area;
- TMJ diseases;
- facial pain.
Contraindications
Tumors benign and malignant;
- pregnancy up to 3 months;
- thyrotoxicosis, type 1 diabetes, blood diseases, insufficiency of respiratory function, kidneys, liver, blood circulation;
- feverish conditions;
- mental illness;
- the presence of an implanted pacemaker;
- convulsive states;
- individual intolerance to the factor.
Equipment
Lasers are a technical device that emits radiation in a narrow optical range. Modern lasers are classified:
By active substance (source of induced radiation) - solid-state, liquid, gas and semiconductor;
- by wavelength and radiation - infrared, visible and ultraviolet;
- according to the intensity of radiation - low-intensity and high-intensity;
- according to the radiation generation mode - pulsed and continuous.
The devices are equipped with radiating heads and specialized nozzles - dental, mirror, acupuncture, magnetic, etc., which ensure the effectiveness of the treatment. The combined use of laser radiation and a constant magnetic field enhances the therapeutic effect. Three types of laser therapeutic equipment are mainly produced in series:
1) based on helium-neon lasers operating in a continuous mode of radiation generation with a wavelength of 0.63 μm and an output power of 1-200 mW:
ULF-01, "Yagoda"
- AFL-1, AFL-2
- Shuttle-1
- ALTM-01
- FALM-1
- "Platan-M1"
- "Atoll"
- ALOK-1 - apparatus for laser blood irradiation
2) based on semiconductor lasers operating in a continuous mode of radiation generation with a wavelength of 0.67-1.3 μm and an output power of 1-50 mW:
ALTP-1, ALTP-2
- "Izel"
- "Mazik"
- "Vita"
- "Bell"
3) based on semiconductor lasers operating in a pulsed mode of radiation generation with a wavelength of 0.8-0.9 μm, a pulse power of 2-15 W:
- "Uzor", "Uzor-2K"
- "Lazurit-ZM"
- "Luzar-MP"
- "Nega"
- "Azor-2K"
- "Effect"
Devices for magneto-laser therapy:
- "Mlada"
- AMLT-01
- "Svetoch-1"
- "Azure"
- "Erga"
- MILTA - magnetic infrared
Technique and methods of laser radiation
The impact of LI is carried out on the lesion or organ, segmental-metameric zone (cutaneously), biologically active point. In the treatment of deep caries and pulpitis by the biological method, irradiation is carried out in the area of the bottom of the carious cavity and the neck of the tooth; periodontitis - the light guide is inserted into the root canal, previously mechanically and medically treated, and advanced to the top of the tooth root.
The method of laser irradiation is stable, stable-scanning or scanning, contact or remote.
Dosing
Responses to LI depend on dosing parameters:
Wavelength;
- methodology;
- operating mode - continuous or pulsed;
- intensity, power density (PM): low-intensity LI - soft (1-2 mW) is used to influence reflexogenic zones; medium (2-30 mW) and hard (30-500 mW) - on the area of the pathological focus;
- time of exposure to one field - 1-5 minutes, the total time is not more than 15 minutes. daily or every other day;
- a course of treatment of 3-10 procedures, repeated after 1-2 months.
Safety
The eyes of the doctor and the patient are protected with glasses SZS-22, SZO-33;
- you can not look at the source of radiation;
- cabinet walls should be matte;
- press the "start" button after installing the emitter on the pathological focus.
Amirov N.B. // Basic Research. - 2008. - No. 5. - P. 14-16;
The problem of treating coronary heart disease (CHD) continues to be relevant, as it has great social significance due to the increase in morbidity, increased disability and mortality of the working population from cardiovascular diseases. At the same time, there is an increase in allergic reactions to traditional medicines and the development of tolerance to them. That is why the attention of researchers is attracted by one of the methods of non-drug treatment - laser therapy (LT). In the treatment with laser radiation (LI), low-intensity light fluxes are used, not more than 100 mW / cm2, which is comparable to the intensity of the radiation of the Sun at its zenith on a clear day. This type of LT is called low-intensity laser radiation (LILR). The use of LI is based on the interaction of light with biological tissues. The mechanism of interaction between LILI and a biological object seems to be as follows: when a laser acts on tissues, photophysical and photochemical reactions occur associated with the absorption of light energy by tissues and the violation of weak molecular bonds, and the perception and transfer of the effect of laser radiation by body fluids also occur. Among the secondary effects, which are adaptive and compensatory reactions, it is necessary to note the activation of cell metabolism and an increase in their functional activity against the background of laser therapy. The effect of laser biostimulation is realized through the acceptance of light energy by chromatophore substances in the body, amplification and transformation of the received signal in the cell, activation of enzymes and biosynthetic processes in the cell. By enhancing energy metabolism in cells, LI causes an increase in biosynthetic activity, which manifests itself in an increase in carbohydrates, proteins, nucleic acids in blood serum under experimental conditions and in the clinic. Data have been obtained on the selective effect of LT on the activation of catalase, which is involved in the regulation of intracellular peroxide content and in oxidative processes of cell energy supply, which leads to an increase in the phosphorylating activity of cell mitochondria. It has been established that LILI can stimulate the activity of the most important bioenergetic enzymes - dehydrogenase and cytochrome oxidase, ATPase and acetylcholinesterase, acid and alkaline phosphatase and other enzymes of cellular metabolism, which indicates the presence of single points of application of LI energy, which are membranes and other molecular structures. LILI promotes activation of bioenergetic processes in body surface cells, mitochondria nerve cells, as well as a decrease in the level of activity of ceruloplasmin, an improvement in the activity of sulfhydryl groups. There is a decrease in LDH activity and a change in its fractional composition against the background of LT. The absence of LDH2 and LDH5 fractions on the enzymphoregrams on the 7th day indicates the suppression of anaerobic and activation of aerobic processes. Under the influence of LILI, the level of urea and creatinine decreases.
Laser radiation stimulates cell division, which underlies the regeneration of epithelial tissues, and cell proliferation is accelerated. Under the influence of laser therapy, there is an increase in the level of stab neutrophils (stimulation of leukocytosis); eosinophils, basophils, lymphocytes (release of mature cells from the bone marrow, spleen, lungs), a decrease in the level of monocytes, segmented neutrophils (exit to tissues from the circulatory bed). LILI has a direct effect on the blood, and segmented neutrophils are the most sensitive to it. Their decrease in a limited volume of blood is associated with two processes: either their destruction, or the acquisition of the ability to adhere to the surface as a result of activation. Given that segmented neutrophils are a functionally heterogeneous population of cells consisting of cells with different degrees of differentiation, it is logical to assume the phenomenon of "knocking out" the subpopulation of the least resistant cells under the influence of laser therapy. It is possible that these changes underlie the action of LILI. The remaining neutrophils are characterized by a different composition and reactivity of surface glycoprotein receptor determinants, i.e. represented by a different subpopulation than before irradiation. There is a thickening of the submembrane actin layer. The size of the cells and their surface area are significantly reduced, which leads to the alignment of the surface-to-volume ratio. Under the influence of laser therapy, the phases of the inflammatory process are shortened: first of all, the exudative and infiltrative reactions are suppressed. By increasing the rate of redox reactions, metabolic processes, increasing oxygen utilization at a reduced partial pressure, LI leads to a decrease in edema in tissues and relief of inflammatory processes.
Against the background of LILI, activation of blood microcirculation (MC) and an increase in the level of trophic provision of tissues occur: a stimulating effect on MC is shown, including two processes: the actual activation of microcirculation, which occurs due to an increase in local blood flow, and a more prolonged process associated with new formation of capillaries. The vasodilating effect is manifested in the form of improved microcirculation in the affected area, this occurs due to the opening of new capillaries and arterial vessels, accelerating blood flow in the vessels, and improving the rheological properties of the blood. There is a decrease in the adrenoreactivity of the vessels and their sensitivity to the constrictor effect of biologically active substances. There is a stimulation of erythropoiesis, a change in the electrical potential of the cell membranes of erythrocytes, which leads to an increase in their deformability and a decrease in the viscosity of whole blood. When using laser therapy, the permeability of capillary walls is stabilized, oxygen utilization is increased, and intracellular metabolism is stimulated. The experiment showed a significant increase in the diameter of arterioles, venules and lymphatic vessels in the myocardium after laser irradiation of the apex of the heart. An adaptogenic effect was revealed in the form of an improvement in the functioning of the MC system under the influence of laser therapy on the whole organism. The reaction of the microvasculature (MCR) has a two-phase character. During the first 2-3 sessions of laser therapy, only the arterial link of the MCR is actively functioning, the venous and lymphatic links of the MC are switched on during subsequent sessions of laser therapy. The mechanism of the so-called exacerbation of the clinical manifestations of the disease after the first sessions of RT becomes clear: since the activation of the arterial knee of the capillary bed leads to an increase in exudative processes with the development of perivascular edema, irritation of the neuroreflex apparatus, which is clinically manifested by the "exacerbation" of the disease. Activation of venous and lymphatic drainage during subsequent LILI sessions leads to the resolution of the above phenomena. Against the background of LILI, an increase in the reaction of the cellular and humoral immunity, as well as processes of phagocytosis, normalization of nonspecific immune defense, and correction of the immune status were noted. The intensity of division of immunocompetent cells and the rate of formation of immunoglobulins increase, the activity of T- and B-lymphocytes, mononuclear phagocytes and neutrophils increases and restores, the relationship of local and humoral immunity is harmonized.
There is a hypocholesterolemic effect of laser radiation and stabilization of the lipid bilayer of cell membranes. The fact of a regular decrease in the blood level of phospholipids (PL) in patients with coronary artery disease, as well as a decrease in the content of the latter in erythrocytes and their membranes, is emphasized. There is a restoration of the functional specific oxygen transport properties of erythrocytes, including by accelerating the renewal of the structural composition of their membranes by a regular change of phases: I - shifts due mainly to the stress effect of a physical factor; II - mobilization of adaptive mechanisms and restoration of the membrane structure; III - modification of the cell membrane, due to the actual quantum effect. The lipid-lowering effect in patients with coronary artery disease persists for 6-12
months.
The anticoagulant effect of LI manifests itself due to the prolongation of thrombin and fibrin time, a decrease in the level of fibrinogen, an increase in the content of endogenous heparin, antithrombin III and fibrinolytic activity of the blood, a decrease in the degree and rate of platelet aggregation, normalization of the degree of their disaggregation, as well as a decrease in the degree of erythrocyte aggregation (without significant changes in hematocrit). Under the influence of LILI changes electric potential erythrocyte cell membranes, which is accompanied by an increase in their deformability and a decrease in the viscosity of whole blood, and this helps to improve capillary blood flow.
The bactericidal and bacteriostatic effect of LILI is confirmed by an increase in the phagocytosis of bacteria irradiated with laser radiation. The detoxification effect is manifested due to conformational changes in protein and immune structures; under the influence of LT, protein and RNA synthesis is accelerated, i.e. activation of anabolic processes, as well as an increase in the partial pressure of oxygen and intensification of redox processes.
The decrease in paroxysms of cardiac arrhythmia by 6-8 times, and the number of supraventricular and ventricular extrasystoles by 85% or more when using laser therapy proves the antiarrhythmic effect of this method of treatment. At the same time, the effect of the 1st course of LILI persists for 2-6 months, and with subsequent ones - from 8 months to several years. The positive inotropic effect of LI is manifested in a significant decrease in the volume of the left ventricle, an increase in the ejection fraction and the rate of circular shortening of myocardial fibers. The effect of laser therapy on central hemodynamics is noted in the form of a significant decrease in systolic and diastolic blood pressure: moderate in patients with normal blood pressure and up to 15-20 mm. rt. Art. in patients with arterial hypertension (AH).
There is information about the effect of LILI on the endocrine system: an increase in the concentration of catecholamines, serotonin and histamine, activation of the pituitary-adrenal system, and an increase in the level of triiodothyronine are indicated. In experiments with irradiation with LILR, an increase was found, and with an increase in exposure time, a decrease in blood glucose levels. When analyzing the dynamics of changes in testosterone concentration, its increase was revealed, and in patients with low cortisol levels, only a tendency to its increase was noted. The influence of infrared LI on the level of adrenaline and noradrenaline was also noted.
The effect of stimulating lymphatic circulation under the influence of LILI was noted: an increase in the intensity of lymphatic outflow, an increase in the number of lymphatic vessels, an increase in the release of lymphocytes from the depot into the lumen of functioning lymphatic vessels under the influence of LI of the red region of the spectrum of low intensity. This is due to the effect of LILI on globular proteins, leading to a decrease in the optical density of the lymph, and the impact on the processes of energy metabolism in lymphocytes. After laser exposure, there is a faster regeneration of the lymphatic system, which is the basis of the draining, anti-edematous effects of laser therapy.
Against the background of LILI, the level of trypsinemia decreases: the number of pain attacks decreases significantly (up to complete disappearance), the use of medications is sharply reduced, there is an increase in physical performance and a positive dynamics of ECG indicators.
The practice of recent years has shown the effectiveness of the use of LILI in patients with coronary artery disease, positive experience in the treatment of coronary artery disease with angina pectoris, the effect is especially pronounced in patients with angina pectoris FC II-III and in combination with left ventricular diastolic dysfunction (LVD). LILT makes it possible, on average, to lengthen the terms of therapeutic remission of IHD by 2.5 times, while laser therapy lengthens the terms of clinical remission by 2-4 times compared to the traditional method of treatment. the majority of patients.
The foregoing proves the effectiveness of LILI in the complex treatment of patients with coronary artery disease, in particular, angina pectoris II-III FC. At the same time, the relevance of further study of the mechanisms of the influence of LI on the body of patients suffering from coronary artery disease remains relevant. There are a number of questions that remain to be answered, in particular, the need to identify the most effective combinations of complex drug-laser treatment. To do this, using the latest methods of functional and laboratory diagnostics, a comparison is made of the effect of laser therapy on the dynamics of clinical, laboratory and instrumental studies, depending on the combinations of the groups of drugs used in traditional drug therapy.
BIBLIOGRAPHY:
- Korochkin I. M. The use of low-energy lasers in the clinic of internal diseases. Russian Journal of Cardiology 2001; 5:85-87.
- Kozlov V.I., Buylin V.A. Laser therapy. M: Medicine; 1993.
- Agov B.S., Andreev Yu.A., Borisov A.V. et al. On the mechanism of the therapeutic action of a helium-neon laser in coronary artery disease. Clinical Medicine 1985; 10:102-107.
- Kipshidze N.N., Chapidze G.E., Korochkin N.M. Treatment of ischemic heart disease with a helium-neon laser. Tbilisi; 1993.
- Illarionov V.E. Fundamentals of laser therapy. Moscow: Inotekh-Progress; 1992.
- Skobelkin O.K. (ed.) The use of low-intensity lasers in clinical practice. M: Medicine; 1989.
- Amirov N.B. The use of laser exposure for the treatment of internal diseases. Kaz. honey. magazine. 2001; 5:369-372.
The biological effect of low-intensity laser radiation (helium-neon and infrared light) provides a wide range of photochemical and photophysical changes that cause the intensification of structural and metabolic processes that are not associated with a violation of the integrity of the irradiation zones3.
The impact of coherent radiation with a wavelength of 0.63 μm on a biological tissue causes various reactions of the body, namely:
1) an increase in the concentration of alkaline phosphatase in the blood serum;
2) an increase in the content of immunoglobulins O, T-lymphocytes, as well as the phagocytic activity of leu-
3) decrease in the factor that inhibits the migration of macrophages;
4) strengthening of microcirculation and fibrinolytic activity of blood;
5) increase in the mitotic index and nerve action potential;
6) normalization of increased vascular resistance.
The main points in the complex mechanism of the action of laser radiation on biological structures are the perception of light rays by photoreceptors, the transformation of their molecular composition and the change in their physicochemical state. Subsequently, biochemical reactions are activated with the initiation of active and allosteric centers in enzymes and an increase in their number. This is confirmed by a large number of publications on the increase in enzymatic activity after laser therapy4.
The action of coherent light on biological tissue is carried out through specific enzymes - photoreceptors. Schematically, the primary response of biological systems to laser exposure is as follows: the chromophore group of photoreceptors excited by light transfers the energy of electronic excitation to the protein associated with it, and if the latter is attached to the membrane, then to the membrane as a whole. As a result of these processes, the heat that occurs during nonradiative transitions can cause local heating of photoreceptors, which contributes to its reorientation. In this case, the photoreceptor passes through a number of intermediate relaxation states that provide both dynamic and static conformational transformations of the protein and, accordingly, the membrane, with which
a swarm of the photoreceptor is bound, which, in turn, leads to a change in the membrane potential and the sensitivity of the membrane to the action of biologically active substances.
A wide range of biochemical and physiological reactions observed in the body in response to the impact of a low-intensity laser (Fig. 9.1) indicates the promise of its use in various fields of medicine. Analysis of the results of our own observations showed that the use of infrared coherent light in the early postoperative period in patients with genital endometriosis (endometriosis of the ovaries and uterine body [myometrectomy], retrocervical endometriosis) helps to reduce pain, improves blood circulation in the arteries that feed the uterus and ovaries (according to data of transvaginal ultrasound Doppler) and, most importantly, prevents the formation of adhesions in the small pelvis.
During repeated laparoscopy, performed in order to clarify the clinical situation in some patients with ovarian endometriosis, who underwent salpingo-ovariolysis during the previous operation, and in the postoperative period intravaginal low-intensity laser exposure as a rehabilitation treatment, in all cases, no signs of adhesions.
We adhere to the point of view that low-intensity laser is the method of choice for rehabilitation measures at the second (main) stage of physical treatment of patients with genital endometriosis. At the same time, one should not belittle the merits of other highly effective techniques - a low-frequency pulsed electrostatic field, currents of overtonal frequency (ultratonic therapy), alternating and constant magnetic fields.
Research V.M. Strugatsky et al.10 found that the use of a low-frequency pulsed electrostatic field in gynecological patients leads to a decrease in local pain in the small pelvis along the vessels and nerve trunks, as well as correction of hormone-dependent disorders. Despite the fact that the main clinical effects of a pulsed electrostatic field - defibrosing and analgesic - are somewhat less pronounced than in the treatment with traditional physical factors with a similar effect, this method has a significant advantage, namely, the ability to regulate the estrogen-progesterone ratio. Due to this ability, a low-frequency pulsed electrostatic field can be used to treat patients with hyperestrogenia and/or concomitant hormone-dependent formations of the internal genital organs, i.e., when the use of heat-forming or heat-transfer factors is excluded or limited.
Ultratonotherapy is a method of electrotherapy, in which the patient's body is exposed to an alternating current of supratonal frequency (22 kHz) of high voltage (3-5 kV). Currents of ultratonal frequency have a mild effect on the biological tissue, without causing any discomfort. Under the influence of ultratonotherapy, there is an improvement in local blood and lymph circulation, activation of metabolic processes, relief of pain. This method is one of
highly effective means of preventing reocclusion of the fallopian tubes.
The mechanism of action of a magnetic field on a biological tissue is associated with the stimulation of physicochemical processes in biological fluids, biocolloids, and blood elements. It is assumed that anisotropic macromolecules change their orientation under the influence of a magnetic field and, thereby, acquire the ability to penetrate through membranes, thus affecting biological processes. Such biological processes as free radical reactions of lipid oxidation, reactions with electron transfer in the cytochrome system, oxidation of non-heme iron, as well as reactions involving metal ions of the transition group are sensitive to the action of a magnetic field. The magnetic field causes an acceleration of blood flow, reduces the need for tissues and cells in oxygen, has a vasodilating and hypotensive effect, and affects the function of the blood coagulation system. Along with the influence of magnetic fields on physical and chemical processes, the mechanism of their therapeutic action is based on the induction of eddy currents in the tissues, which emit very little heat; the latter, in turn, activates blood circulation, metabolic processes and enhances regeneration, and also provides sedative and analgesic effects5,11.
It should be noted that in the complex of rehabilitation therapy for patients with endometriosis, it is recommended to use radon waters in the form of general baths, vaginal irrigations, microclysters. Radon therapy has a beneficial effect on the body of patients with various allergic reactions, chronic
colitis and neuralgia of the pelvic nerves.
BIBLIOGRAPHY
1. Arslanyan KN., Strugatsky V.M., Adamyan L.V., Volobuev A.I. Early restorative physiotherapy after microsurgical operations on the fallopian tubes. Obstetrics and Gynecology, 1993, 2, 45-48
2. Zheleznoe B.I., Strizhakov A.N. Genital endometriosis. "Medicine", Moscow, 1985
3. Illarionov V.E. Fundamentals of laser therapy. "Respect", Moscow, 1992
4. Kozlov V.I., Builin V.A., Samoilov N.1., Markov I.I. Fundamentals of laser physio- and reflexotherapy. "Healthy" I, Kyiv-Samara, 1993
5. Orzheshkovsky V.V., Volkov E.S., Tavrikov N.A. etc. Clinical physiotherapy. “I am healthy”, Kyiv, 1984
6. Savelyeva G.M., Babinskaya L.N., Breusenko V.1. Prevention of adhesions after surgery in gynecological patients in the reproductive period. Obstetrics and Gynecology, 1995, 2, 36-39