Experimental and clinical studies of the effectiveness of low-intensity laser radiation in oncology. Mechanisms of action and biological effects of low-intensity laser radiation

Low-intensity laser therapy is a treatment method based on the medical use of low-intensity light that does not cause tissue heating from laser sources of optical radiation.

Laser (optical quantum generator) is a device that helps emit a stream of electromagnetic waves in the optical range, which have special physical properties. The term “LASER” is an abbreviation of the English phrase: Ligt Amplification bi Stimulated Emission of Radiation - amplification of light using stimulated radiation. Currently, laser therapy is used radiation from infrared, red, green, blue, ultraviolet regions of the spectrum. Key links in the mechanism of action of low-intensity laser radiation(NILI) on biological tissue:

  1. activation of cell metabolism
  2. stimulation of reparative processes
  3. activation of blood microcirculation and increase in the level of trophic provision of tissues
  4. analgesic effect
  5. immunostimulating effect
  6. reflexogenic effect on the functional activity of various organs and systems

The interaction of low-intensity laser radiation with biological tissues is determined by the wavelength, dose and intensity of the laser flow.

Indications for low-level laser therapy:

  1. treatment of the cardiovascular system: coronary heart disease, hypertension, atherosclerotic disease, vegetative-vascular dystonia;
  2. diseases of the gastrointestinal tract: chronic gastritis, peptic ulcer, chronic cholecystitis, pancreatitis, hepatitis;
  3. diseases of the respiratory system: chronic laryngo-tracheitis, bronchitis, bronchial asthma, chronic pneumonia;
  4. treatment of degenerative-dystrophic diseases of the musculoskeletal system: osteochondrosis, radicular syndrome, arthrosis, arthritis, osteoparosis;
  5. kidney diseases: chronic pyelonephritis;
  6. cerebrovascular insufficiency: consequences of strokes, cerebral atherosclerosis;
  7. gynecological diseases: chronic adnexitis, cervical erosion, menopausal syndrome of varying severity

General contraindications for low-level laser therapy:

  1. pregnancy in all stages;
  2. chronic diseases of internal organs in the stage of decompensation;
  3. blood diseases: leukemia, hemophilia, bleeding tendency;
  4. malignant neoplasms, or benign ones with a tendency to progress, age spots, nevi, hemangiomas;
  5. hemorrhagic stroke;
  6. fever of unknown etiology;
  7. active tuberculosis;
  8. thrombophlebitis.

Temporary contraindications:

  1. signs of bleeding;
  2. anemia with hemoglobin less than 80 g/l.

Low-intensity laser therapy for diseases of the cardiovascular system.
In acute and chronic myocardial ischemia, the effect of the laser is multicomponent in nature: it reduces the ischemic area and increases the myocardial resistance to hypoxia. At the same time, exposure to laser radiation has pronounced analgesic and antiarrhythmic effects and reduces the consumption of antianginal drugs. As a result of laser radiation, patients' tolerance to physical activity increases, angina attacks are reduced and, in some cases, stopped, blood flow speed is normalized, and myocardial contractility increases. All this helps to improve microcirculation processes in the heart muscle and its functional restoration.
In the process of treating coronary heart disease, intravenous drip administration of drugs that improve metabolism in the heart muscle (polyelectrolyte solution + panangin, neoton, mildronate) is possible in the day hospital of our clinic.
The use of low-intensity laser radiation for the treatment of hypertension makes it possible to improve the well-being of patients - headaches, dizziness, and discomfort from the heart decrease or disappear. Normalization of blood pressure (without the use of antihypertensive drugs) occurs in 60-70% of patients. In 80% of patients, a course of low-intensity laser therapy can significantly reduce the dose of antihypertensive drugs taken.
The use of laser radiation for atherosclerotic vascular lesions allows it to influence the state of the blood coagulation system, normalizing it, preventing further development thrombus formation in blood vessels, on the one hand. On the other hand, by influencing the smooth muscles of blood vessels, increasing blood flow, it ensures the supply of a sufficient amount of oxygen to the tissues and, thereby, normalizes the course of metabolic processes, reduces ischemia and leads to the restoration of damaged vessels. Improvement in condition was noted in 70-75% of patients.

Low-intensity laser therapy for diseases of the gastrointestinal tract.
Under the influence of a laser on the tissues of the gastrointestinal tract, regeneration improves due to the accumulation of plastic materials and the elimination of tissue hypoxia, and the activity of redox enzymes increases. The antiulcer effect of laser irradiation also manifests itself under the influence on endocrine cells and peptidergic structures of the gastrointestinal tract. Laser radiation, due to its analgesic, anti-inflammatory effect and ability to improve tissue regeneration, promotes rapid healing of ulcerative defects. As a result of laser therapy, all patients with peptic ulcers and chronic gastritis quickly improve their overall health, restore appetite and sleep, reduce irritability, and restore performance. According to esophagogastroduodenoscopy, 92% of patients experience healing of the ulcer on days 7-10 through epithelization and the formation of a gentle scar.
The revealed hepatotropic, membrane-stimulating, antioxidant and other healing properties of the laser allow its use in clinical practice for the treatment of diffuse lesions of the liver, pancreas, and gall bladder. As a result of treatment, 75-80% of patients experience disappearance of pain and dyspeptic symptoms. In terms of biochemical blood parameters, there is a decrease in the level of bilirubin and the activity of liver enzymes.

Low-intensity laser therapy for diseases of the respiratory system.

Treatment of respiratory diseases using laser reduces the inflammatory response, has a vasodilating effect, restores blood flow in the lung tissues and, therefore, reduces interstitial and cellular edema, and has an immunostimulating effect. The dynamics of subjective symptoms under the influence of a course of laser treatment in 85% of patients becomes positive: well-being improves, shortness of breath decreases or disappears, attacks of suffocation, cough, chest pain. There are also positive changes in respiratory function indicators in the examined patients: the efficiency of pulmonary ventilation increases, bronchial patency improves. In all patients, the blood picture normalizes.

Low-intensity laser therapy for diseases of the musculoskeletal system.
Diseases and injuries of the musculoskeletal system, in particular the spine, are very common and tend to further increase. One of these diseases is spinal osteochondrosis. Neurological manifestations of osteochondrosis have a varied clinical picture due to the involvement of various tissues, organs and systems in the pathological process. A major role in the pathogenesis of neurological disorders in osteochondrosis is played by disruption of microcirculation processes in the area of ​​the affected roots, which often results in reflex vascular and muscle spasms. Osteochondrosis of the spine is accompanied by pain, sensory, motor, vascular, autonomic and emotional disorders. To some extent, osteochondrosis can be considered as a disease that is a combination of disturbances in the functioning of various body systems. Hence the insufficient effectiveness of treatment methods aimed only at “local” manifestations of the process. The use of laser therapy for the treatment of spinal osteochondrosis makes it possible to effectively act on pain points in order to eliminate pathological impulses from the muscle nerve nodes, as well as on microcirculation processes. The effect of a laser beam on the vertebral and paravertebral areas when compressing the roots can improve regional and systemic microcirculation. As a result of treatment, pain disappears in 80-85% of patients, range of motion increases, general condition improves, performance and mental status are restored. At the same time, treatment of osteochondrosis must be carried out using combined, complementary methods that act on different parts of the pathological process. An example of this method is laser therapy in combination with pulsed magnetotherapy and drug treatment.
One of the important links in the development of arthritis is dystrophic changes in the cartilaginous surface with subsequent reactive processes in the epiphyses of bones, as well as disruption of regional blood flow. Laser treatment reduces pain and swelling in the affected joints, normalizes joint temperature, increases range of motion, and improves regional and general microcirculation.

The search for new drugs and methods of treating dermatoses is due to the intolerance of many medicines, the development of allergic reactions of varying severity, side effects of drugs, low therapeutic effectiveness of conventional treatment methods, the need to improve and optimize existing techniques. In this regard, studying the capabilities of various physical factors - ultrasound, cryotherapy, phototherapy, magnetic and laser radiation - is an important practical task of modern dermatology. This article describes the main physical and therapeutic properties of laser radiation, as well as the range of its applications in dermatology and cosmetology.

The term "laser" is an abbreviation for the English Light Amplification by Simulated Emission of Radiation - amplification of light using induced radiation.

A laser (or optical quantum generator) is a technical device that produces electromagnetic radiation in the form of a directed, focused, highly coherent monochromatic beam.

Physical properties of laser radiation

The coherence of laser radiation determines the constancy of phase and frequency (wavelength) throughout the operation of the laser, i.e., this is a property that determines the exceptional ability to concentrate light energy according to different parameters: in the spectrum there is a very narrow spectral line of emission; in time - the possibility of obtaining ultrashort light pulses; in space and direction - the possibility of obtaining a directed beam with minimal divergence and focusing of all radiation in a small area with dimensions on the order of the wavelength. All these parameters make it possible to carry out local effects, down to the cellular level, as well as to effectively transmit radiation through optical fibers for remote effects.

The divergence of laser radiation is a plane or solid angle that characterizes the width of the radiation pattern in the far field at a given level of energy distribution or power of laser radiation, determined in relation to its maximum value.

Monochromaticity is the spectral width of the radiation and the characteristic wavelength for each radiation source.

Polarization is a manifestation of the transversality of an electromagnetic wave, i.e., maintaining a constant orthogonal position of mutually perpendicular vectors of electric and magnetic field strength in relation to the speed of propagation of the wave front.

The high intensity of laser radiation allows significant energy to be concentrated in a small volume, which causes multiphoton and other nonlinear processes in the biological environment, local thermal heating, rapid evaporation, and hydrodynamic explosion.

The energy parameters of lasers include: radiation power, measured in watts (W); radiation energy, measured in joules (J); wavelength, measured in micrometers (µm); radiation dose (or energy density) - J/cm².

Laser radiation differs in its properties from other types electromagnetic radiation(X-ray and high-frequency γ-radiation) used in medicine. Most laser sources emit in the ultraviolet or infrared ranges of electromagnetic waves, and the main difference between laser radiation and the light of conventional thermal sources is its spatial and temporal coherence. Thanks to this, laser radiation energy is relatively easy to transmit over a considerable distance and concentrate in small volumes or in short time intervals.

Laser radiation affecting a biological object for therapeutic purposes is external physical factor. When laser radiation energy is absorbed by a biological object, all processes occurring during this process are subject to physical laws (reflection, absorption, dispersion). The degree of reflection, scattering and absorption depends on the condition of the skin: moisture, pigmentation, blood supply and swelling of the skin and underlying tissues.

The penetration depth of laser radiation depends on the wavelength, decreasing from long-wave to short-wave radiation. Thus, infrared (0.76-1.5 microns) and visible radiation have the greatest penetrating ability (3-5-7 cm), and ultraviolet and other long-wave radiation are strongly absorbed by the epidermis and therefore penetrate into tissues to a small depth (1- 1.5 cm).

Application of laser in medicine:

  • destructive effects on biological structures and processes - coagulation (in ophthalmology, oncology, dermatovenereology) and tissue dissection (in surgery);
  • biostimulation (in physiotherapy);
  • diagnostics - the study of biological structures and processes (Doppler spectroscopy, flow cytophotometry, holography, laser microscopy, etc.).

Application of lasers in dermatology

In dermatology, two types of laser radiation are used: low-intensity - as laser therapy and high-intensity - in laser surgery.

Lasers are divided according to the type of active medium:

  • to solid-state (ruby, neodymium);
  • gas - HE-NE (helium-neon), CO 2;
  • semiconductor (or diode);
  • liquid (based on inorganic or organic dyes);
  • metal vapor lasers (the most common are copper or gold vapor).

Depending on the type of radiation, there are ultraviolet, visible and infrared lasers. At the same time, both semiconductor lasers and metal vapor lasers can be both low-intensity (for therapy) and high-intensity (for surgery).

Low-intensity laser radiation (LILR) is used for laser therapy of skin diseases. The effect of LILI is to activate cell membrane enzymes, increase electric charge proteins and phospholipids, stabilization of membrane and free lipids, increased oxyhemoglobin in the body, activation of tissue respiration processes, increased synthesis of cAMP, stabilization of oxidative phosphorylation of lipids (reduction of free radical complexes).

When exposed to LILI on biological tissue, the following main effects are observed:

  • anti-inflammatory,
  • antioxidant,
  • anesthetic,
  • immunomodulatory.

The pronounced therapeutic effect in the treatment of human diseases of various etiologies and pathogenesis suggests the existence of a biostimulating mechanism of action of low-power laser radiation. Researchers consider the reaction immune systems They react to laser radiation as one of the most important factors in the mechanism of laser therapy, which, in their opinion, is the trigger point in the reaction of the whole organism.

Anti-inflammatory effect

When exposed to LILI on the skin, an anti-inflammatory effect is observed: microcirculation in tissues is activated, blood vessels dilate, the number of functioning capillaries increases and collaterals are formed, blood flow in tissues increases, the permeability of cell membranes and osmotic pressure in cells is normalized, and the synthesis of cAMP increases. All these processes lead to a decrease in interstitial edema, hyperemia, peeling, itching, delimitation of the pathological process (focus) is observed, and acute inflammatory manifestations subside within 2-3 days. The effect of LILI on the area of ​​inflammation in the skin, in addition to the anti-inflammatory effect, provides an antibacterial and fungicidal effect. According to literature data, the number of bacteria and fungal flora is reduced by 50% within 3-5 minutes of laser irradiation of the pathological area.

Taking into account the anti-inflammatory and antibacterial effect of LILI when applied locally to the skin, lasers are used in the treatment of diseases such as pyoderma (folliculitis, boils, impetigo, acne, streptostaphyloderma, chancriform pyoderma), trophic ulcers, allergic dermatoses (true eczema, microbial eczema, atopic dermatitis , urticaria). LILI is also used for dermatitis, burns, psoriasis, lichen planus, scleroderma, vitiligo, diseases of the oral mucosa and red border of the lips (bullous pemphigoid, exudative erythema multiforme, cheilitis, stomatitis, etc.).

Antioxidant effect

When exposed to LILI, an antioxidant effect is observed, which is ensured by reducing the production of free radical complexes, when cellular and subcellular components are protected from damage, as well as ensuring the integrity of organelles. This effect is associated with the pathogenesis of a significant number of skin diseases and the mechanism of skin aging. As studies by G. E. Brill and co-authors have shown, LILI activates the enzymatic component of antioxidant protection in erythrocytes and somewhat weakens the stimulating effect of stress on lipid peroxidation in erythrocytes.

The antioxidant effect of LILI is used in the treatment of allergic dermatoses, chronic skin diseases and during anti-aging procedures.

Analgesic effect

The analgesic effect of LILI is achieved due to the blockade of pain sensitivity along the nerve fibers. At the same time, a slight sedative effect is observed. Also, the analgesic effect is provided by reducing the sensitivity of the skin receptor apparatus, increasing the threshold of pain sensitivity, and stimulating the activity of opiate receptors.

The combination of analgesic and mild sedative effects plays important role, since in various skin diseases itching (as a perverted manifestation of pain) is the main symptom that disrupts the patient’s quality of life. These effects make it possible to use LILI for allergic dermatoses, itchy dermatoses, and lichen planus.

Immunomodulatory effect

Recently, it has been proven that in various skin diseases there is an imbalance of the immune system. Both with local irradiation of the skin and with intravenous irradiation of the blood, LILI has an immunomodulatory effect - dysglobulinemia is eliminated, the activity of phagocytosis increases, apoptosis is normalized and the neuroendocrine system is activated.

Some techniques using LILI

Allergic dermatoses(atopic dermatitis, chronic eczema, recurrent urticaria). LILI irradiation of venous blood is carried out using an invasive or non-invasive method, as well as local laser therapy.

The invasive method consists of venipuncture (venesection) in the area of ​​the radial vein, collecting blood in an amount of 500-750 ml, which is passed through a laser beam, followed by reinfusion of irradiated blood. The procedure is carried out once, once every six months with an exposure of 30 minutes.

The non-invasive method involves applying a laser beam to the projection of the radial vein. At this time, the patient clenches and unclenches his fist. As a result, 70% of the blood is irradiated within 30 minutes. The method is painless and does not require special conditions, involves the use of both continuous and pulsed laser radiation - from 5 to 10,000 Hz. It has been established that vibrations of 10,000 Hz correspond to vibrations on the surface of cell membranes.

Blood irradiation is performed only with a helium-neon laser, wavelength 633 nm, power 60.0 mW and semiconductor lasers with a wavelength of 0.63 microns.

S. R. Utz et al used laser heads with a reflective surface to treat severe forms of atopic dermatitis in children using a non-invasive method; Immersion oil was applied to the skin at the irradiation site, and compression was created with the head. The irradiation zone was the great saphenous vein at the level of the medial malleolus.

The listed methods are supplemented with local laser therapy. Recommended maximum area sizes for laser therapy during one session: for the skin of the face and mucous membranes of the nasal cavity, mouth and lips - 10 cm², for other areas of the skin - 20 cm². For symmetrical lesions, it is advisable to sequentially work on two contralateral zones during one session with an equal division of the recommended area.

When working on the skin of the face, it is strictly forbidden to direct the beam at the eyes and eyelids. It follows that helium-neon laser radiation should not be used to treat eyelid skin diseases.

Helium-neon laser radiation is used mainly in remote mode. To treat skin diseases with a lesion area greater than 1-2 cm², the laser beam spot is moved at a speed of 1 cm/s over the entire area selected for the session so that it is all evenly irradiated. A spiral scanning vector is advisable - from the center to the periphery.

In atopic dermatitis, irradiation is carried out across fields, covering the entire affected surface of the skin according to the configuration of the pathological area from the periphery to the center, with irradiation of healthy tissue within 1-1.5 cm or scanning with a laser beam at a speed of 1 cm/s. The radiation dose per session is 1-30 J/cm², session duration is up to 25 minutes, course of 5-15 sessions. Treatment can be carried out against the background of antioxidant therapy and vitamin therapy.

When irradiating venous blood using LILI in patients with allergic dermatoses, we achieve all the above-mentioned effects of laser radiation, which contributes to a faster recovery and a reduction in relapses.

Psoriasis. For psoriasis, blood irradiation is used, laser inductothermy of the adrenal glands is used, as well as local effects on plaques. It is usually carried out with infrared (0.89 nm, 3-5 W) or helium-neon lasers (633 nm, 60 mW).

Laser inductothermy of the adrenal glands is carried out by contact on the skin in the projection of the adrenal glands, from 2 to 5 minutes, depending on the weight of the patient, the course is 15-25 sessions. Laser irradiation is carried out in the stationary and regressing stages of psoriasis, ensuring the production of endogenous cortisol by the patient's body, which leads to the resolution of psoriatic elements and allows achieving a pronounced anti-inflammatory effect.

The effectiveness of laser therapy for psoriatic arthritis has been shown. During treatment, the affected joints are irradiated, sometimes local therapy is combined with irradiation of the adrenal glands. After two sessions, an exacerbation is noted, which becomes less intense by the 5th session, and by the 7-10th sessions the condition stabilizes. A course of laser therapy consists of 14-15 sessions.

A fundamentally new direction in the treatment of psoriasis and vitiligo is the development and clinical use of an excimer laser based on xenon chloride, which is a source of narrow-band ultraviolet (UVB) radiation with a length of 308 nm. Since the energy is directed only to the area of ​​the plaque and healthy skin is not affected, the lesions can be irradiated using radiation with a high energy density (from 100 mJ/cm² and above), which enhances the antipsoriatic effect. Short pulses of up to 30 ns allow you to avoid vaporization and thermal damage. A narrow monochromatic radiation spectrum with a length of 308 nm acts only on one chromophore, causing the death of mutagenic keratinocyte nuclei and activating T-cell apoptosis. The introduction of excimer laser systems into widespread clinical practice is limited by their high cost and lack of methodological support, insufficient study of long-term results, difficulties associated with calculating the depth of impact as plaques thin out during therapy.

Lichen planus (LP). In case of LLP, the technique of local irradiation of rashes by contact method, sliding movements from the periphery to the center is usually used. Exposure - from 2 to 5 minutes, depending on the affected area. The total dose should not exceed 60 J/cm². Such procedures provide an anti-inflammatory and antipruritic effect. To resolve plaques, the exposure is increased to 15 minutes.

When LLP is localized on the scalp, laser irradiation is carried out with an exposure time of up to 5 minutes. In addition to the above-mentioned effects, stimulation of hair growth in the irradiation zone is achieved.

When applying these methods, infrared, helium-neon and copper vapor laser radiation is used. In case of LP, irradiation of venous blood can also be performed.

Pyoderma. For pustular skin diseases, the technique of LILI irradiation of venous blood and the technique of local irradiation by contact method, sliding movements with an exposure of up to 5 minutes are also used.

These techniques make it possible to achieve anti-inflammatory, antibacterial (bacteriostatic and bacteriocidal) effects, as well as stimulation of reparative processes.

For erysipelas, LILI is used contact, remotely and intravenously. When using laser therapy, body temperature normalizes 2-4 days earlier, regression of local manifestations occurs 4-7 days faster, cleansing and all repair processes occur 2-5 days faster. An increase in fibrinolytic activity, the content of T- and B-lymphocytes and their functional activity, and an improvement in microcirculation were revealed. Relapses with traditional treatment are 43%, with LILI - 2.7%.

Vasculitis. For the treatment of skin vasculitis, V.V. Kulaga and co-authors propose the invasive LILI method. 3-5 ml of blood is taken from the patient’s vein, placed in a cuvette and irradiated with a 25 mW helium-neon laser for 2-3 minutes, after which 1-2 ml of irradiated blood is injected into the lesions. 2-4 injections are given in one session, 2-3 sessions per week, the course of treatment consists of 10-12 sessions. Other authors recommend intravascular irradiation of blood with helium-neon laser energy with a power of 1-2 mW for 10-30 minutes, sessions are carried out daily or every other day, the course consists of 10-30 sessions.

Scleroderma. J. J. Rapoport and co-authors propose to conduct laser therapy sessions using a helium-neon laser through a light guide inserted through a needle at the border of healthy and affected skin. The session lasts 10 minutes, the dose is 4 J/cm³. Another technique involves external irradiation of lesions with radiation at a power of 3-4 mW/cm² with an exposure of 5-10 minutes, a course of 30 sessions.

Viral dermatoses. Laser therapy has been used quite successfully for herpes zoster. A. A. Kalamkaryan and co-authors proposed remote segmental irradiation of lesions with a helium-neon laser with a power of 20-25 mW, in which the laser beam moves along the nerve trunks and to the sites of rashes. Sessions are held daily and last from 3 to 20 days.

Vitiligo. To treat vitiligo, helium-neon laser radiation and external photosensitizers, such as aniline dyes, are used. Immediately before the procedure, a dye solution (diamond green, methylene blue, fucorcin) is applied to the lesions, after which local irradiation is carried out with a defocused laser beam with a power of 1-1.5 mW/cm². The duration of the session is 3-5 minutes, daily, the course is 15-20 sessions, repeated courses are possible after 3-4 weeks.

Baldness. The use of a copper vapor laser in an experiment carried out on the skin, according to electron microscopy, revealed a marked increase in proliferative and metabolic activity in epidermocytes, including hair follicles. An expansion of the microvessels of the papillary dermis was noted. In connective tissue, in particular in fibroblasts, a relative increase in the volume of intracellular structures associated with collagen synthesis was detected. An increase in activity was recorded in neutrophils, eosinophils, macrophages and mast cells. The listed changes are the basis for the treatment of baldness. Already after the 4-5th session of laser therapy, growth of vellus hair on the head is noted.

The vitiligo treatment technique described above is also used to treat patchy baldness.

Scarring. Using light and electron microscopy, changes that occur in skin scars as a result of the use of laser radiation in humans were studied. Thus, the use of ultraviolet and helium-neon LILI did not cause significant changes due to the shallow penetration of laser energy. After using infrared laser radiation, the number of collagen-resorbing fibroblasts increases, while the collagen fibers become thinner, the number of mast cells and the release of secretory granules slightly decrease. The relative volume fraction of microvessels increases to some extent.

When using LILI to prevent severe scarring of skin surgical wounds, a decrease in the content of active fibroblasts and, consequently, collagen was revealed.

Use of high-intensity laser radiation (HILI)

VILI is obtained using CO 2 , Er:YAG laser and argon laser. CO 2 laser is mainly used for laser removal (destruction) of papillomas, warts, condylomas, scars and dermabrasion; Er:YAG laser - for laser skin rejuvenation. There are also combined CO 2 -, Er:YAG laser systems.

Laser destruction. VILI is used in dermatology and cosmetology for the destruction of tumors, removal of nail plates, as well as for laser vaporization of papillomas, condylomas, nevi and warts. In this case, the radiation power can range from 1.0 to 10.0 W.

Neodymium and CO 2 lasers are used in clinical practice. When using a CO 2 laser, surrounding tissues are less damaged, and a neodymium laser has a better hemostatic effect. In addition to the laser physically removing lesions, studies have shown the toxic effects of laser radiation on human papillomavirus (HPV). By varying the laser power, spot size and exposure time, the depth of coagulation can be controlled. Well-trained personnel are required to perform the procedures. Lasers require anesthesia, but topical or topical anesthesia is sufficient, allowing procedures to be performed on an outpatient basis. However, 85% of patients still report mild pain. The method has approximately the same effectiveness as electrocoagulation, but is less painful, causes fewer postoperative side effects, including less pronounced scarring, and provides a good cosmetic effect. The effectiveness of the method reaches 80-90% in the treatment of genital warts.

Laser therapy can be successfully used to treat common warts that are resistant to other treatments. In this case, several courses of treatment are carried out, which allows increasing the cure rate from 55 (after 1 course) to 85%. However, in special cases with many years of ineffective treatment with various methods, the effectiveness of laser therapy is not so high. Even after multiple courses of treatment, it can stop recurrence in only about 40% of patients. Careful studies have shown that such a low rate is due to the fact that the CO2 laser is ineffective in eliminating the viral genome from lesions that are resistant to treatment (according to PCR, molecular biological cure occurs in 26% of patients).

Laser therapy can be used to treat genital warts in teenagers. The method has been shown to be highly effective and safe in treating this group of patients; in most cases, 1 procedure is sufficient for cure.

To reduce the number of relapses of genital warts (recurrence rate from 4 to 30%), it is recommended to use laser “cleaning” of the surrounding mucosa after the removal procedure. When using the “cleansing” technique, discomfort and pain are often observed. In the presence of large condylomas, before laser therapy, their preliminary destruction is recommended, in particular with electrocautery. This, in turn, avoids the side effects associated with electroresection. A possible cause of relapse is the persistence of the HPV genome in the skin near the treatment sites, which was identified both after laser application and after electrosurgical excision.

The most severe side effects laser destruction are: ulceration, bleeding, secondary infection of the wound. After laser excision of warts, complications develop in 12% of patients.

As with electrosurgical methods, HPV DNA is released through smoke, which requires appropriate precautions to avoid contamination of the physician's nasopharynx. At the same time, some studies have shown no difference in the incidence of warts among surgeons involved in laser therapy compared with other groups of the population. There were no significant differences in the incidence of warts between groups of doctors who used and did not use protective equipment and smoke evacuators. However, because the types of HPV that cause genital warts can infect the lining of the upper respiratory tract, laser smoke containing these viruses is dangerous for surgeons performing vaporization.

The widespread use of laser destruction methods is hampered by the high cost of high-quality equipment and the need to train experienced personnel.

Laser hair removal. Laser hair removal (thermal laser hair removal) is based on the principle of selective photothermolysis. light wave with specially selected characteristics passes through the skin and, without damaging it, is selectively absorbed by melanin contained in large quantities in hair follicles. This causes heating of the hair follicles, followed by their coagulation and destruction. To destroy the follicles, the required amount of light energy must be supplied to the hair root. For hair removal, radiation with a power of 10.0 to 60.0 W is used. Since hair is in different stages of growth, complete hair removal requires several procedures. They are carried out on any part of the body, non-contact, at least 3 times with an interval of 1-3 months.

The main advantages of laser hair removal are the comfort and painlessness of the procedures, the achievement of stable and long-term results, safety, high processing speed (hundreds of follicles are removed simultaneously with one pulse), non-invasiveness, and non-contact. Thus, this method represents the most effective and most cost-effective method of hair removal today. Prolonged exposure to the sun and tanning (natural or artificial) significantly reduces the effectiveness of procedures.

Laser dermabrasion. Dermabrasion is the removal of the upper layers of the epidermis. After exposure, a fairly soft and painless laser scab remains. Within 1 month after the procedure, new young skin is formed under the scab. Laser dermabrasion is used to rejuvenate the skin of the face and neck, remove tattoos, polish scars, and also as a treatment for post-acne in patients with severe forms of acne.

Laser skin rejuvenation. The laser provides precise and superficial ablation with minimal heat damage and no bleeding, resulting in rapid healing and resolution of erythema. For this purpose, Er:YAG lasers are mainly used, which are good for superficial skin rejuvenation (including in dark-skinned patients). The devices allow for quick and uniform scanning of the skin, as well as even out color boundaries after treatment with a CO 2 laser.

Contraindications to the use of laser therapy

Laser therapy is used with caution in patients with cancer, diabetes mellitus, hypertension and thyrotoxicosis in the stage of decompensation, severe heart rhythm disturbances, angina pectoris of the 3-4th functional classes and circulatory failure of the 2-3rd stage, blood diseases, threat bleeding, active form of tuberculosis, mental illness, as well as individual intolerance.

Thus, laser radiation is a powerful adjuvant in the treatment of patients with various dermatological diseases and the method of choice in surgical dermatology and cosmetology.

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A. M. Soloviev,Candidate of Medical Sciences, Associate Professor
K. B. Olkhovskaya,Candidate of Medical Sciences

MEMBRANE MECHANISMS OF PHOTOBIOLOGICAL ACTION
LOW-INTENSE LASER RADIATION

G.I. Klebanov

Department of Biophysics
Russian State Medical University, Moscow

Low-intensity laser radiation (LILR), which has been widely used in clinical practice in the last decade, is used in medicine in two main areas:

1) during photodynamic therapy (PDT) of tumors, where the damaging effect of LILI is manifested

,

2) in the treatment of a wide range of various inflammatory diseases with laser therapy (LT), where the stimulating effect of LILI is manifested

.

The mechanism of the damaging effect of LILI during PDT of tumors is based on the initiation of photosensitized free radical reactions (FRR)

, arising as a result of the interaction of laser radiation quanta with photosensitizer molecules in the presence of oxygen. As for laser therapy, despite the widespread use of this laser technology in clinics in Russia, the CIS countries, Israel, China, Japan, Latin America, etc., the mechanism or mechanisms of the stimulating action of LILI are far from understood and are discussed in the literature only in hypothesis level , many of which are contradictory and speculative, do not have experimental evidence of the presence of a specific chromophore, primary reactions leading ultimately to the formation of a physiological response of the body.

It has already been noted that LILI is very successfully used in the treatment of many diseases

. It would be logical to assume that there is some common link in the pathogenesis of all nosological forms of diseases in the treatment of which RT is beneficial. This implies the presence of a single general mechanism of action of LILI in relation to all pathologies, and not many different individual reactions for each specific disease. It is most likely that such a connecting link is a universal pathological process, namely inflammation, which is found in all the above examples of the use of RT and either plays the role of a leading pathogenetic link or is reactive in nature.

One of the significant stages in the pathogenesis of the inflammatory process is a disorder of microcirculation, including a violation of blood rheology. The inflammatory process in its development goes through a change of phases in the cycle(s) of ischemia-reperfusion

with impaired microcirculation. Any effect that can shorten the duration of the ischemic stage will have a beneficial effect on the subsequent development of the disease.

It must be taken into account that the introduction of LILI into clinical practice is carried out mainly empirically. One of the most insidious properties of LILI is the sharp dependence of the magnitude and even sign of the effect on the radiation dose and the functional state of the biological object. The positive, stimulating effect manifests itself, as a rule, in a narrow range of radiation doses, and then disappears or is even replaced by a depressive effect [

21–23]. Since the mechanisms of the therapeutic effect of LILI on the human body have not yet been explained and the nature of the endogenous chromophore of laser radiation has not been determined, There is still no scientifically based method for selecting radiation doses for LILI.

The molecular cellular mechanisms of the therapeutic effect of LILI are currently discussed in the literature only at the level of hypotheses. The main point of any hypothesis of the photobiological effect of laser radiation on the body is the establishment of the primary chromophore-acceptor of the energy of the absorbed LR photon and the target cell of the LILI action. The fact is that the interaction of laser energy with a chromophore is based on the first law of photochemistry: only the quantum that is absorbed is effective. This means that to trigger all subsequent biochemical and physiological responses of the body during LT, a chromophore is required that can absorb strictly defined quanta of laser energy, i.e. having an absorption spectrum that matches the wavelength of the laser source.

The most widely used in medicine and biology is currently the helium-neon laser (HNL), the wavelength of which is 632.8 nm. In relation to this source of laser energy, the literature suggests that chromophores in the red region of the spectrum can be:

  • porphyrins and its derivatives
,
  • molecules of antioxidant enzymes: superoxide dismutase (SOD), catalase, ceruloplasmin
  • ,
  • components of the mitochondrial respiratory chain: flavoproteins and cytochromes
  • ,
  • molecular oxygen
  • .

    Regarding hypotheses

    about the photobiological effect of LILI, then several assumptions about the mechanism of action of laser radiation are considered in the literature:

    1) reactivation of metal-containing antioxidant enzymes

    ,

    2) hypothesis about the interaction of LILI with components of the electron transport chain in mitochondria

    ,

    3) nonspecific effect on biopolymers

    ,

    4) photoexcited formation of singlet oxygen

    ,

    5) nonspecific effect on the structure of water

    .

    Many of the existing hypotheses about the mechanisms of therapeutic action of LILI have shortcomings that can be divided into two groups. Firstly, some authors consider the effects of LILI without taking into account the presence of a chromophore. Obviously, the search for an LILI acceptor is the most important in the problem of LILI action. Secondly, some assumptions about the mechanisms of action of laser radiation are speculative, i.e. are not confirmed by experimental data, or these data are contradictory.

    The essence of the hypothesis proposed by T.Y. Karu is about the interaction of laser radiation with components of electron transfer chains [

    13, 24 ] boils down to the fact that cytochromes can be LILI acceptors in the human body A And A 3 , cytochrome oxidase. The mechanism of action of laser radiation within the framework of this hypothesis implies the following sequence of events:

    1. During hypoxia, in conditions of lack of oxygen, carrier enzymes in the respiratory chain are restored and the transmembrane potential of mitochondria decreases.

    2. LO leads to the reactivation of these enzymes (for example, cytochrome oxidase), which restores the flow of electrons in the respiratory chain and forms trans membrane potential mitochondria, i.e. the transmembrane potential in mitochondria increases, ATP production in cells increases, Ca transport is activated

    2+ . Increased ATP production and Ca ion concentration 2+ in the cell leads to stimulation of intracellular processes .

    This hypothesis about the mechanism of action of LILI suggests a well-thought-out and well-founded chain of events, which may be real. The authors rely on data on an increase in the proliferation of various cells, on the laser-induced respiratory explosion of phagocytes observed

    in vitro etc., that is, on facts that may be a consequence, and not the cause, of the effects of LILI. In addition, using this hypothesis, it is difficult to explain the remoteness and prolongation of the effects of LILI observed in the clinic.

    Previously, at the Department of Biophysics of the Russian State Medical University, the concept of the membrane mechanism of the stimulating action of LILI was formulated

    . Its main provisions can be presented as follows:

    1. Chromophores of laser radiation in the red region of the spectrum are endogenous porphyrins, which are capable of absorbing light in this region of the spectrum and are well known as photosensitizers. The content of porphyrins in the body increases in many human diseases and pathological conditions. The targets of laser energy are cells, in particular leukocytes, and blood lipoproteins containing porphyrins.

    2. Porphyrins, absorbing LILI light energy, induce photosensitized free radical reactions leading to the initiation of lipid peroxidation (LPO) in leukocyte membranes and lipoproteins with the formation of primary and secondary LPO products. The accumulation of LPO products in membranes, in particular hydroperoxides, contributes to an increase in ionic permeability, including for Ca ions

    2+ .

    3. Increase in the content of Ca ions

    2+ in the cytosol of leukocytes triggers Ca 2+ -dependent processes leading to cell priming, which is expressed in an increase in the level of functional activity of the cell, to increased production of various biologically active compounds (nitric oxide, superoxide anion- radical oxygen, hypochlorite anion, etc.). Some of them have a bactericidal effect, others can affect blood microcirculation. For example, nitric oxide is a precursor to the so-called Endothelium Derived Relaxing Factor (EDRF)a factor that relaxes the vascular endothelium, which leads to vasodilation of the latter and improvement of microcirculation, which is the basis for most of the beneficial clinical effects of RT [ 5–8].

    MECHANISMS OF BIOLOGICAL EFFECTS OF LOW-INTENSE LASER RADIATION

    The biological (therapeutic) effect of low-intensity laser radiation (coherent, monochromatic and polarized light) can be divided into three main categories:

    1) primary effects(changes in the energy of electronic levels of molecules of living matter, stereochemical rearrangement of molecules, local thermodynamic disturbances, the emergence of concentration gradients of intracellular ions in the cytosol);

    2) secondary effects(photoreactivation, stimulation or inhibition of biological processes, changes in the functional state of both individual systems of a biological cell and the organism as a whole);

    3) aftereffects(cytopathic effect, formation of toxic products of tissue metabolism, response effects of the neurohumoral regulation system, etc.).

    All this variety of effects in tissues determines the widest range of adaptive and sanogenetic reactions of the body to laser exposure. It was previously shown that the initial triggering moment of the biological action of LILI is not a photobiological reaction as such, but local heating (more correctly, a local thermodynamic disturbance), and in this case we are dealing with a thermodynamic rather than a photobiological effect. This explains many, if not all, known phenomena in this area of ​​biology and medicine.

    Violation of thermodynamic equilibrium causes the release of calcium ions from the intracellular depot, the propagation of a wave of increased Ca2+ concentration in the cytosol of the cell, triggering calcium-dependent processes. After this, secondary effects develop, which are complex of adaptive and compensatory reactions , arising in tissues, organs and the whole living organism, among which the following are distinguished:

    1) activation of cell metabolism and increase in their functional activity;

    2) stimulation of reparative processes;

    3) anti-inflammatory effect;

    4) activation of blood microcirculation and increase in the level of trophic provision of tissues;

    5) analgesic effect;

    6) immunostimulating effect;

    7) reflexogenic effect on the functional activity of various organs and systems.

    It is necessary to pay attention to two important points. Firstly, in each of the listed points, the unidirectionality of the influence of LILI (stimulation, activation, etc.) is a priori specified. As will be shown below, this is not entirely true, and laser radiation can cause exactly the opposite effects, which is well known from clinical practice. Secondly, all these processes are calcium-dependent. Let us now consider exactly how the presented physiological changes occur, citing 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 occurs primarily due to a calcium-dependent increase in the redox potential of mitochondria, their functional activity and ATP synthesis.

    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 free intracellular calcium, protein kinases that take part in the formation of mRNA are activated. Calcium ions are also allosteric inhibitors of membrane-bound thioredoxin reductase, an enzyme that controls the complex process of synthesis of purine disoxyribonucleotides during the period of active DNA synthesis and cell division. In addition, basic fibroblast growth factor (bFGF) is actively involved in the physiology of the wound process, the synthesis and activity of which depend on the Ca2+ concentration.

    Anti-inflammatory effect of LILI and him influence on microcirculation are caused, in particular, by the calcium-dependent release of inflammatory mediators - such as cytokines - as well as the calcium-dependent release by endothelial cells of the vasodilator - nitric oxide (NO) - the precursor of endothelial vascular relaxation factor (EDRF).

    Since exocytosis, in particular the release of neurotransmitters from synaptic vesicles, is calcium-dependent, the process of neurohumoral regulation is completely controlled by the Ca2+ concentration, and therefore is 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 CNS and ANS mediators, which also suggests the participation of effects caused by laser radiation in neurohumoral regulation.

    The interaction between the neuroendocrine and immune systems has been little studied, but it has been established that cytokines, in particular IL-1 and IL-2, act in both directions, playing the role of modulators of the interaction of these two systems. LILI can influence immunity both indirectly through neuroendocrine regulation and directly through immunocompetent cells (as proven in in vitro experiments). Among the early triggers for blast transformation of lymphocytes is a short-term increase in the concentration of free intracellular calcium, which activates a protein kinase involved in the formation of mRNA in T-lymphocytes, which, in turn, is a key point in laser stimulation of T-lymphocytes. The effect of LILI on fibroblast cells in vitro also leads to increased generation of intracellular endogenous g-interferon.

    In addition to the physiological reactions described above, to understand the whole picture it is also necessary to know how laser radiation can influence the mechanisms neurohumoral regulation. LILI is considered as a nonspecific factor, the action of which is not directed against the pathogen or symptoms of the disease, but at increasing the resistance (vitality) of the body. 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 complete confidence that laser radiation is not the main therapeutic agent at the level of the organism as a whole, but it seems to eliminate obstacles, an imbalance in the central nervous system that interferes with the sanogenetic function of the brain. This is accomplished by a possible change in the physiology of tissues under the influence of LILI, both in the direction of strengthening and in the direction of suppressing their metabolism, depending on the initial state of the body and the dose of exposure, which leads to the attenuation of pathological processes, the normalization of physiological reactions and the restoration of regulatory functions nervous system. Laser therapy, when used correctly, allows the body to restore disturbed systemic balance.

    In recent years, the consideration of the central nervous system and the ANS as independent regulatory systems has ceased to suit many researchers. There are more and more facts confirming their closest interaction. Based on the analysis of numerous scientific research data, a model of a unified regulatory and homeostasis-maintaining system, called a neurodynamic generator (NDG), 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 called V.V. Skupchenko (1991) phasic motor-vegetative (FMV) system complex, closely interacts with another, mirror interacting structure - the 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 rearranges its work according to the principle of self-organizing systems.

    The emergence of facts indicating the simultaneous participation of the same brain structures in ensuring both somatic and autonomic regulation is difficult to perceive, since they do not fit into known theoretical constructs. However, we cannot ignore what is confirmed by everyday clinical practice. Such a mechanism, having a certain neurodynamic mobility, is not only capable of providing continuously changing adaptive adjustment of the regulation of the entire range of energetic, plastic and metabolic processes, but essentially controls the entire hierarchy of regulatory systems from the cellular level to the central nervous system, including endocrine and immunological changes. In clinical practice, the first positive results of this approach to the mechanism of neurohumoral regulation were obtained in neurology and in the treatment of keloid scars.

    Normally, there are constant transitions from the phasic state to the tonic state and back. Stress causes the activation of phasic (adrenergic) regulatory mechanisms, as a general adaptation syndrome. At the same time, as a 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 NDG. Normally, the two systems interact to restore the disturbed balance.

    Many diseases seem to us to be associated with the prevalence of one of the states of this regulatory system. With a long-term, uncompensated influence of a stress factor, the functioning of the NDG malfunctions and it becomes pathologically fixed in one of the states, in the phasic state, which happens more often, or in the tonic phase, as if moving into a mode of constant readiness to respond to irritation. Thus, stress or constant nervous tension can displace homeostasis and fix it pathologically in either 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 various reasons (hereditary predisposition, a certain constitutional type, various exogenous and endogenous factors, etc.) leads to the onset of the development of any specific pathology in a particular individual, but the cause of the disease is common - the stable prevalence of one of the conditions of NDG.

    Once again, we draw attention to the most important fact that not only the central nervous system and the autonomic nervous system regulate various processes at all levels, but also, on the contrary, a locally acting external factor, for example LILI, can lead to systemic changes, eliminating the true cause of the disease - imbalance of NDG, and with local action of LILI eliminates 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 effects of LILI depending on the dose of exposure - stimulation of physiological processes or their inhibition. The universality of LILI action is due, among other things, to the fact that, depending on the dose, laser exposure both stimulates and suppresses proliferation and the wound process.

    Most often, the techniques use minimal, generally accepted doses of laser exposure (1–3 J/cm2 for continuous radiation), but sometimes in clinical practice it is the conditionally NON-stimulating effect of LILI that is required. The conclusions drawn from the previously proposed model were brilliantly confirmed in practice when substantiating effective techniques treatment of vitiligo and Peyronie's disease.

    So, in the biological effects of LILI, the primary operating factor is local thermodynamic disturbances, causing a chain of changes in the calcium-dependent physiological reactions of the body. Moreover, the direction of these reactions can be different, which is determined by the dose and localization of the effect, as well as the initial state of the organism itself.

    The developed concept allows not only to explain almost all existing facts, but also, based on these ideas, to draw conclusions both about predicting the results of the influence of LILI on physiological processes, and about the possibility of increasing the effectiveness of laser therapy.

    Indications and contraindications for the use of LILI

    The main indication is the feasibility of use, in particular:

    Pain syndromes of neurogenic and organic nature;

    Violation of microcirculation;

    Impaired immune status;

    Sensitization of the body to drugs, allergic manifestations;

    Inflammatory diseases;

    The need to stimulate reparative and regenerative processes in tissues;

    The need to stimulate homeostasis regulatory systems (reflexotherapy).

    Contraindications:

    Cardiovascular diseases in the decompensation phase;

    Cerebrovascular accident II degree;

    Pulmonary and pulmonary-heart failure in the decompensation phase;

    Malignant neoplasms;

    Benign formations with a tendency to progress;

    Diseases of the nervous system with sharply increased excitability;

    Fever of unknown etiology;

    Diseases of the hematopoietic system;

    Liver and kidney failure in the stage of decompensation;

    Diabetes mellitus in the stage of decompensation;

    Hyperthyroidism;

    Pregnancy in all stages;

    Mental illnesses in the acute stage;

    Increased sensitivity to phototherapy (photodermatitis and photodermatosis, porphyrin disease, discoid and systemic lupus erythematosus).

    It should be noted that There are no absolute specific contraindications for laser therapy. However, depending on the patient’s condition, the phase of the disease, etc., restrictions on the use of LILI are possible. In some areas of medicine - oncology, psychiatry, endocrinology, phthisiology and pediatrics - it is strictly necessary that laser therapy be prescribed and carried out by a specialist or with his direct participation.

    LASER LOW INTENSITY THERAPY

    Today, the situation in laser medicine can be characterized as enriched with new trends. If you go on the INTERNET, more than 27,000 links will pop up on laser medicine, and if you add here the work previously carried out in the USSR and Russia-CIS for 30 years, then the number of publications will confidently exceed 30,000. Until relatively recently, the vast majority of the work was devoted to laser surgery. Today, more than half of all publications are related to the problems of laser therapy. What has changed? First of all, the level of understanding of the mechanisms of action of low-intensity optical radiation (LOI) on living organisms has increased.

    Let us remind you: we divide the therapeutic effects of laser radiation into surgical and therapeutic. Therapeutic, as opposed to surgical, is manager, but not destructive, impact. This means that after exposure the biological object remains alive. Moreover, if the task of controlling objects in a living organism, posed as the main one in laser therapy, is solved correctly, then after exposure the biological object becomes, as it were, “better than it was” - pathological processes in it are suppressed and natural processes that maintain homeostasis are stimulated. Note that for NIE there is a natural “reference point” - the spectrum sunlight(see Figure 21.1).



    Rice. 21.1.

    Dependence of the spectral density of sunlight on wavelength:

    1 - outside the atmosphere; 2 - black body radiation with a temperature of 5900 0 K; 3 - on the surface of the Earth at middle latitudes (altitude 30 0 above the horizon).

    This “benchmark” has already been discussed above (L1). The spectrum-integrated intensity of solar radiation in free space at a distance equal to the average distance between the Earth and the sun is 1353 W/m2. On its way to the Earth's surface, radiation is actively filtered by the Earth's atmosphere. Absorption in the atmosphere is mainly due to water vapor molecules (H 2 O), carbon dioxide(CO 2), ozone (O 3), nitrogen oxide (N 2 O), carbon monoxide (CO), methane (CH 4) and oxygen (O 2).

    Living organisms in the process of evolution have repeatedly adapted to the changing “electromagnetic environment.” About one and a half million species of living organisms live on the surface of the Earth, and they all exist thanks to sunlight.

    In the twentieth century, the situation with the “electromagnetic environment” on Earth turned out to be very different from the one that organisms encountered over many millions of years of evolution. A lot of anthropogenic radiation has appeared. In the optical (UFICOP) range, laser devices have the highest spectral radiation density. The dependence of the spectral density of radiation from medical lasers on wavelength in comparison with a similar dependence for radiation from the Sun and some other light sources is presented in Fig. 21.2.


    Rice. 21.2.

    Emission spectrum of various light sources:

    1 – sunlight on the Earth’s surface in mid-latitudes; 2 – maximum estimated level of natural background; 3 – continuous-mode neon-helium laser, power 15 mW, wavelength 633 nm, spot area 1 cm 2; 4 – superluminescent LED, integrated power 5 mW, maximum intensity 660 nm; 5 – semiconductor laser of quasi-continuous mode, 5 mW, 780 nm; 6 – semiconductor laser of pulse-periodic mode, pulse power 4 W, 890 nm; 7 – household incandescent lamp 60 W, distance 60 cm.

    The solid line, covering the entire spectral range from UV to IR regions, demonstrates the “smoothed” level of sunlight at mid-latitudes on a clear summer day. In relation to the natural level of sunlight, the spectral densities of laser and LED devices used in medicine vary greatly. For example, the spectral maximum of an LED irradiator (curve 4, see below) in the corresponding spectral interval is at the level of solar radiation, and a similar curve of an IR laser device based on a quasi-continuous mode semiconductor laser (curve 5) reaches the maximum estimated level of natural background (curve 2) . At the same time, the maximums of the curves for a pulsed semiconductor laser (curve 6) and especially for a neon-helium laser (curve 3) overlap these values ​​by several orders of magnitude. In this case, the maximum spectral density of sources reflects not so much the energy characteristics of light as the degree of its monochromaticity. Thus, the output power of a neon-helium laser exceeds the power of a red LED by only 3 times, and in terms of maximum spectral density this excess is more than 10 5 (!).

    The increased level of “artificial” EMR compared to the natural background corresponds to the appearance on the Earth’s surface of additional electromagnetic energy, the magnitude of which is continuously increasing. This energy, in principle, can (and, perhaps, should) “interest” biological systems either in terms of developing a general adaptation syndrome (such as a stress reaction), or adapting to the impact like photosynthesis. The past century is obviously too short a period for the implementation of such a large-scale program, but it is necessary to think about the problem now.

    Low-intensity optical radiation, primarily laser, has found wide application in medicine. “It is difficult to name a disease for which laser treatment has not been tested. A simple listing of the forms and variants of pathology in the treatment of which the laser beam has been shown to be effective will take up a lot of space, and the list of diseases for which the therapeutic effect of NOI is beyond doubt will be quite representative.”

    There are many works on studying the mechanisms of action of NOI on biological objects of different levels of organization - from molecular to organismal and supraorganismal. However, there is still no generally accepted concept of the mechanism of action of NOIs on living organisms. There are several alternative points of view that explain particular phenomena or experiments.

    Why do we say not LLLT (low intensity laser radiation) and LIE (low-intensity optical radiation)? Because among the main characteristics of laser radiation, wavelength and spectral density are of primary importance. The coherence and polarization of laser radiation do not influence the biostimulation effect to such a strong extent, although there is no sufficient reason to say that they do not matter at all.

    Among the problems of phototherapy that are in the center of attention of both doctors and biologists, as well as equipment developers, the main one is - elucidation of the mechanisms of action of NOI on biological objects. This problem has been central to the development of LLLT for almost 50 years. So far it is far from being resolved, although the very fact of a sharp increase in interest in LLLT in the last 10 years indicates positive changes in its study. Among doctors and biologists, an idea has formed about the specificity and nonspecificity of the interaction of NOI with living organisms. Exactly, specific call the interaction of light and BO associated with intense molecular absorption of light, i.e. one for which “specific” photoacceptors are installed, which carry out the primary absorption of light and then trigger a series of “specific” photochemical reactions. Typical example such interaction - photosynthesis. Respectively, nonspecific an interaction is considered when the biological response is large and the light absorption is so low that it is not possible to unambiguously identify the primary acceptor. It is this aspect - establishment of primary acceptors in the absence of strong absorption - and causes the most heated discussions, since the transformation of non-specific interaction into specific opens the way to practical application LLLT is not on an empirical, but on a strictly scientific basis.

    The phenomenon of NOI action is studied at various levels. This refers to the hierarchical levels of construction of a living system: molecular, organoid, cellular, tissue, organismal, supraorganismal. Each of these levels has its own problems, but the greatest difficulties are associated with transitions from one level to another.

    If, first of all, spectral density and wavelength should be taken into account, this means that a similar biological effect can be provided by both laser and incoherent sources (primarily LEDs), provided that the specified characteristics coincide.

    The spectral range in which laser therapeutic devices operate corresponds to the “transparency window” of biological tissues (600-1200 nm) and is far from the characteristic electronic absorption bands of all known chromophores of the body (exception - eye pigments that absorb at 633 and 660 nm). Therefore, about no significant absorbed energy is out of the question.

    However, under the influence of NOI, a number of clinical effects are observed, which for a long time serve as the basis of LLLT. If we try to generalize all these effects, we can formulate nonspecific integral effect at the cellular level: laser radiation affects the functional activity of cells. At the same time, it does not change the function itself, but can increase its intensity. That is, the erythrocyte crawled through the capillaries, giving oxygen through its membrane and the walls of the capillaries, and continues to do so, but it after irradiation it can do this better. The phagocyte both caught and destroyed pathogenic guests, and continues to do so, but with different speed. In other words, under the influence of NOI the speed of cellular metabolic processes changes. In physicochemical language, this means that potential barriers to key biological reactions change their height and width. In particular, NOI can strongly influence membrane potential. With increasing membrane field strength, activation barriers enzymatic reactions tied to membrane transport, are reduced, thereby ensuring exponential increase in the rate of enzymatic reactions.

    Key concept when considering the action of the NIE is biological action spectrum (SBA) . The definition of SBD has already been given in the OVFPBO course. Because of its importance, let us remember it again.

    If some new product appears as a result of light absorption, then the time dependence of the concentration of this product c(t) obeys the equation:

    (21.1)

    Where η - quantum efficiency, σ - light absorption cross section per unit quantum, Ι(t) - intensity of incident light, ħω - energy of the absorbed photon.

    Obviously means the number of photons absorbed. If we introduce into consideration the function , which has the meaning of the rate of production of biomolecules of a given type in terms of one photon with wavelength λ, then it is a quantitative expression of the SBD. Qualitatively, the SBD is defined as dependence of the relative efficiency of the studied photobiological effect on the wavelength. SBD, therefore, is that part of the absorption spectrum that is responsible for a certain photobiological effect. At the molecular level, one can consider the SBD in terms of a unit quantum. But SBD is interesting because it can be considered at any system level. In fact, all radiation absorbed by a biological object forms its absorption spectrum (AS). But the spectrum of biological action is being formed only those molecules that initiate this effect. Therefore, it is natural to call the molecules responsible for SBD differential molecules (as opposed to background molecules responsible for the entire SP). Often the SBD is considered as an additive part of the joint venture. But such a consideration can be considered correct only in the case when there is a recipe for isolating the SBD from the SP (similar to how a signal is isolated from noise in case of strong noise due to the difference in correlation functions). If the noise is modulation in nature, i.e. not present as added to the signal magnitude, but how factor, so that the noise amplitude increases as the signal grows, then the selection useful information becomes sharply more complicated. The additivity of SBD in relation to SP can be considered only in the case linearity interaction of laser radiation with a biological environment, or with an obviously negligible interaction of differential molecules with each other. In many cases this does not seem obvious, since, as a rule, any photobiological effect is of a threshold nature, i.e. exhibits nonlinearity. Therefore, to register a SBD, a methodological compromise is required, including transition from one system level to another. Exactly,

    1) selection of a standard and, if possible, well-studied biological object with stable and reproducible characteristics;

    2) selection of the parameter P, which characterizes the biological object at a higher (in this case cellular) level, so that P is linear is associated with the probability of a microevent (the primary act of excitation of a biomolecule), i.e. its measurement would not introduce disturbances into the cell and would allow for acceptable accuracy;

    3) the presence of a radiation source that is tunable in a given spectral range with sufficient monochromaticity and a given intensity to ensure the achievement of the required effect.

    Providing these conditions simultaneously presents great practical difficulties. Therefore, the information provided in the literature about measuring SBD is almost all untenable from a methodological point of view. The exception is the work carried out at the Lebedev Physical Institute (S.D. Zakharov et al.) together with the Oncology Center of the Russian Academy of Medical Sciences named after. N.N. Blokhin (A.V. Ivanov et al.).

    Study of biological action spectra - this is the path from the nonspecific action of light to the specific one. The main “stumbling block” in the search for a primary photoacceptor (“primary photoacceptor problem”) - this is the absence of noticeable absorption of NOI for all wavelengths used in phototherapy. Therefore, within the framework of traditional photobiology, laser biostimulation effects do not find a satisfactory explanation. As for “non-traditional” photobiology, here water (intracellular, interstitial, etc.) comes to the fore as a universal nonspecific photoacceptor, suggesting the presence of primary photophysical processes. This concept assumes that primary The photoacceptor (at the molecular level) is dissolved molecular oxygen, which, upon absorption of a light quantum, passes into the singlet state. Thus, specificity at the molecular level is combined with nonspecificity at subsequent levels of the system hierarchy. The transition 3 O 2 → 1 O 2 occurs at wavelengths 1270, 1060, 760, 633, 570, 480 nm, and this transition is prohibited for an isolated O 2 molecule. However, in an aqueous environment, the formation of singlet oxygen is possible, and this is primarily manifested in the excitation spectrum of the cellular reaction of erythrocytes (as a change in membrane elasticity). The maximum of this effect corresponds to 1270-1260 nm (absorption band of molecular oxygen), and the shape of the spectrum coincides in detail with the line of transition from the ground to the first excited state of molecular oxygen (3 Σ g → 1 Δ g).

    Singlet oxygen plays a key role in almost all processes of cellular metabolism, and a very small change in the concentration of 1 O 2 (within an order of magnitude) is required to change the nature of enzymatic reactions. Experiments recent years(in particular, G. Klima) showed that the rate of cell growth for the most important cell cultures (leukocytes, lymphocytes, fibroblasts, malignant cells, etc.) varies significantly depending on the energy density (ranging from 10 to 500 J/cm2) , mode and wavelength of incident radiation. The transition from the molecular level to the cellular level occurs through a change in the structure of the water matrix. Quenching of singlet oxygen can occur, as is known, either chemically or physically. In the absence of sensitizers (see below, Chapter 24), we can assume that physical quenching predominates (the cells have well-developed protection against chemical quenching). During the physical deactivation of 1 O 2 molecules, energy of the order of 1 eV is transferred to the vibrational sublevels of surrounding molecules. This energy is enough to break hydrogen bonds, creating ionic or orientation effects. The average vibrational energy per degree of freedom at physiological temperature (~ 310 K) is ~ 0.01 eV, so the local release of 1 eV energy leads to a strong perturbation of the structure of the near environment of the dissolved 1 O 2 molecule. Assuming that the medium is within molecular distance scales obeys the laws of thermal conductivity (which, generally speaking, is not true!), then as a result of solving the equation for the spherically symmetric case we obtain:

    Where Q- energy instantly released at the initial moment, D- coefficient of thermal conductivity, H- heat capacity, ρ - density of matter. If we substitute the data for water here and accept Q = 1 eV, then in a time of about 10 -11 s the release of such energy will lead to heating to 100 0 C of a region with a diameter of ~10 Å (10 -7 cm). This estimate, which is obviously incorrect at short distances, can be considered as a lower limit of the spatiotemporal scale for a kind of microhydraulic hammer. In a thermodynamically stable state, a single disturbance at distances of ~10 -7 cm cannot play a significant role and must be guaranteed to be destroyed by thermal fluctuations. However, biofluids cannot, generally speaking, be considered as thermodynamically equilibrium structures. To model processes in biofluids, one should use the metastable state of solutions of biomolecules that arises in initial phases dissolution process. The peculiarity of such metastable states - high sensitivity to local disturbances.

    Let us estimate the volume of the perturbation sphere without resorting to the heat conduction equation. Assuming that the average vibrational energy per molecule of the water matrix is ​​0.01 eV, we obtain that the deactivation energy of 1 O 2 in 1 eV is evenly distributed among 100 water molecules. Intracellular or interstitial water is a structure close to a liquid crystal (one-dimensional long-range order), with a distance between molecules of ~2.7 Å. When such particles are “rolled up” into a spherical layer, 100 molecules are placed inside a sphere with a radius of ~10 Å, which qualitatively coincides with the “anti-estimate” based on thermal conductivity.

    A change in the structure of the aqueous matrix should be reflected in a change in the refractive index of the biofluid solution, which was observed experimentally when irradiating biofluid solutions with He-Ne laser radiation (λ = 632.8 nm).

    Note that dynamic excitations of liquid crystalline water can, under certain conditions, lead to the emergence of collective dynamic states (similar to exceeding the lasing threshold in a laser, where an avalanche-like increase in the predominance of stimulated radiation is indicated). In other words, the dynamics of water becomes coherent, so that the structure of the liquid in the volume of a certain cluster becomes dominant in the entire volume of the solution. According to estimates, 1 cm 3 of water contains an average of 10 16 -10 17 clusters, of which only 10 10 -10 11 contain molecules of photoexcited singlet oxygen (~ 10 -6 from total number). When these clusters relax, nuclei of a new structural phase are formed. Synergy during the growth of embryos gives a change Δn 0, 10 6 times greater than would correspond to the reorientation of an individual cluster. This was precisely observed experimentally (S.D. Zakharov et al., 1989): absorption of light from a laser within 10 -2 -10 -9 J caused such a change in the refractive index of blood plasma, which would correspond to the “cooling” of the entire volume of the medium by ~ 6 J (!). After Zakharov, similar dependences were observed in solutions of proteins, lipids, glycoproteins, etc. The common ingredient for all these substances is water, and this indirectly confirms the conclusion that water is universal nonspecific acceptor for all types of electromagnetic radiation, the “specific” acceptor for which is a dissolved gas from the air (O ​​2, N 2, CO 2, NO, etc.). Thus, primary processes involving air gases (“respiratory chain”) lead to secondary processes associated with the reorientation of the water matrix.

    Secondary processes are otherwise called dark processes, meaning that many reactions at the cellular level caused by irradiation occur long after the irradiation ceases. For example, the synthesis of DNA and RNA after 10 seconds of irradiation is observed after 1.5 hours. The abundance of possible secondary mechanisms today does not allow us to build a more or less convincing “bridge” between the cellular and tissue levels, similar to the “coherence” of the orientation of the water matrix. However, the accumulation of data speaks in favor of the predominance of redox processes.

    When analyzing processes at the tissue level, the characteristics of incident radiation (not only wavelength and dose, but coherence, polarization, spatial power distribution) come to the fore. The role of coherence is particularly controversial.

    The need to take coherence into account is supported by the fact that when laser radiation is scattered from a biological object, a speckle structure is always observed, which carries information about the object (for more details, see below, Chapter 27) and allows one to achieve a therapeutic effect under certain conditions. The speckle structure is observed only at a sufficiently high degree of coherence of the incident radiation. This means that coherence cannot be neglected, especially since for various types laser sources, the degree of coherence can vary quite significantly (see Fig. 21.2, where the spectral density for a neon-helium laser is many times greater than that for a semiconductor laser due to higher monochromaticity; but monochromaticity - a direct consequence of temporal coherence).

    Opponents of taking coherence into account cite in their favor the fact that coherence is almost immediately destroyed when laser radiation interacts with optically anisotropic biological tissues. Numerous experiments at the cellular and subcellular levels show that similar effects are observed both when using a laser and incoherent sources (incandescent lamps equipped with a light filter).

    Apparently, the truth, as usually happens, is hidden somewhere between polar points of view. In the process of re-radiation inside the tissue, coherence is indeed destroyed. But at the same time, zones with a high degree of spatial inhomogeneity of radiation are formed. The degree of emerging spatial inhomogeneity is directly related to the degree of coherence of the incident radiation. High power density causes local nonlinear effects at the level of primary processes. At the cellular level, this nonlinearity will inevitably cause a corresponding nonspecific reaction. Thereby:

    1) biological tissue affects radiation, destroying coherence;

    2) radiation affects biological tissue, changing its characteristics in accordance with the degree of coherence of the incident radiation.

    So, coherence does not disappear in tissues without a trace, but gives rise to a cascade of processes on which the effect at the tissue level depends. A detailed study of the spatial and temporal characteristics of these processes will make it possible to unambiguously establish the role of coherence in specific cases (see literature for L. 27).

    The dose dependence of the effect at the tissue level can also take on a specific character. There are three dose thresholds:

    1) the minimum dose that causes changes at the cellular level;

    2) the optimal dose that causes a) enhancement of morphogenesis processes, b) acceleration of proliferation, c) cell differentiation;

    3) the maximum dose at which stimulation is replaced by inhibition of proliferation activity.

    The quantitative expression of dose thresholds depends on many parameters (laser characteristics, functional state of tissue, general condition of the body). Overall easy to install system communication between the complexity of elucidating the mechanisms and the level of organization at which we wish to establish any patterns: the higher we rise in the hierarchy, the more noticeable the role of empirics. Isolation of the primary photoacceptor at the molecular level makes it possible, albeit with considerable difficulty, to construct a picture of secondary effects at the subcellular and cellular levels. The transition from the cellular to the tissue level is already much more complicated, so recommendations for choosing a dose are no longer made at the level of writing down solutions to certain equations, but at the level of a verbal description of possible processes. The transition from the tissue to the organismal level generally involves a significant amount of shamanism: do as I say, otherwise it will be bad. But, on the one hand, so as not to become like the primitive clergy, and on the other - Without pretending to be a thoughtful theorist who spends his whole life calculating not what is needed for practice, but what he himself likes, let’s try to generalize the problem to supraorganismal level.

    All living systems are open nonequilibrium systems operating on a balance of matter and energy in exchange with environment. Living system constantly self-organizes, i.e. reduces its entropy. The intensity of entropy reduction is directly related to the amount of information entering the system. From this point of view, low-intensity optical radiation acts as an external signal (information), which abruptly transfers the trigger (energy-informational state of the pathological focus with a predominance of entropy) from one stationary state to another. The transfer of the body as a system from one state to another is inextricably linked with biorhythms. The range of biorhythms extends from 10 - 15 s (the time of one period of a light wave, which is of the same order as the time of molecular electronic transitions) to ~ 7 10 10 s (average life expectancy), thereby amounting to about 10 25 Hz in frequency scale. The task of optimizing exposure at the organismal level - bring the impact into line with biorhythms.

    Regarding low-frequency biorhythms, measured in days, weeks, months, years, optimizing exposure means conducting irradiation sessions at those moments when it contributes to streamlining natural processes and failure pathological, which is an increase in the entropy of the body as a system. For example, the treatment of chronic diseases that worsen in accordance with the seasons (spring, autumn) prescribes LLLT courses at the beginning of the corresponding season, even before the next exacerbation of the disease begins. Practice shows that the effectiveness of treatment increases, and this applies not only to phototherapy itself, but also to accompanying medications and other treatment methods. Prevention of long-term consequences of radical treatment also recommends periodic repetition of LLLT courses in accordance with the time characteristics of pathological processes (for more details, see L.23). Sometimes this approach to LLLT at the organismal and supraorganismal level is called chronobiological.

    In relation to high-frequency biorhythms (within one session irradiation), the following features of laser therapy can be noted.

    The high natural frequency of the acting electromagnetic radiation, corresponding to periodic processes in biomolecules at the level of electronic transitions, provides rich opportunities for modulation impact. In addition, it is possible to form information block impact with extremely high capacity. Within such a block it is possible to create multi-frequency influences with a given spectrum of modulation frequencies. Finally, what is especially important from a systemic point of view, it is possible to introduce biosynchronization into the impact itself due to feedback through the biological object.

    The body as a whole has lower biorhythm frequencies (fractions of hertz), its systems and organs - higher (units and tens of hertz). The spectrum of biorhythms is individual in nature and can be considered as a vibrational “portrait” of a specific person. Multi-frequency biosynchronized laser exposure can extremely effectively control all reactions of the body, including protective reactions to external adverse effects of a very different nature.

    Literature for lecture 21.

    1. The effect of electromagnetic radiation on biological objects and laser medicine. Sat. edited by acad. IN AND. Ilyicheva. - Vladivostok: Far Eastern Branch of the USSR Academy of Sciences, 1989, 236 p.

    2. V.M. Chudnovsky, G.N. Leonova, S.A. Skopinov et al. Biological models and physical mechanisms of laser therapy. - Vladivostok: Dalnauka, 2002, 157 p.

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