Proactive anti-inflammatory therapy in the advanced stages of a new coronavirus infection. Main results of the inpatient phase of the COLORIT study (Colchicin vs. Ruxolitinib and secukinumab in an open, prospective, randomized trial in patients with novel coronavirus infection COVID-19).

Aim      To evaluate clinical efficacy of the proactive anti-inflammatory therapy in patients hospitalized for COVID-19 with pneumonia and a risk of "cytokine storm".Material and methods  The COLORIT study was a comparative study with randomization into 4 groups: colchicine (n=21) 1 mg for the first 3 days followed by 0.5 mg/day through day 12 or discharge from the hospital; secukinumab 300 mg/day, s.c., as a single dose (n=20); ruxolitinib 5 mg, twice a day (n=10); and a control group with no anti-inflammatory therapy (n=22). The effect was evaluated after 12±2 days of inpatient treatment or upon discharge, what comes first. For ethical reasons, completely randomized recruitment to the control group was not possible. Thus, for data analysis, 17 patients who did not receive any anti-inflammatory therapy for various reasons not related with inclusion into the study were added to the control group of 5 randomized patients. Inclusion criteria: presence of coronavirus pneumonia (positive PCR test for SARS-CoV-2 RNA or specific clinical presentation of pneumonia; IDC-10 codes U07.1 and U07.2); C-reactive protein (CRP) concentration >60 mg/l or its threefold increase from baseline; at least 2 of 4 symptoms (fever >37.5 °C, persistent cough, shortness of breath with inspiratory rate >20 per min or blood saturation with oxygen <94 % by the 7th-9th day of disease. The study primary endpoint was changes in COVID Clinical Condition Scale (CCS-COVID) score. The secondary endpoints were the dynamics of CRP and changes in the area of lung lesion according to data of computed tomography (CT) of the lungs from the date of randomization to 12±2 days.Results All three drugs significantly reduced inflammation, improved the clinical course of the disease, and decreased the disease severity as evaluated by the CCS score: in the ruxolitinib group, by 5.5 (p=0.004); in the secukinumab group, by 4 (p=0.096); in the colchicine group, by 4 (p=0.017), and in the control group, by 2 (р=0.329). In all three groups, the CCS-COVID score was 2-3 by the end of observation period, which corresponded to a mild process, while in the control group, the score was 7 (р=0.005). Time-related changes in CRP were significant in all three anti-inflammatory treatment groups with no statistical difference between the groups. By the end of the study, changes in CT of the lungs were nonsignificant.Conclusion      In severe СOVID-19 with a risk of "cytokine storm", the proactive therapy with ruxolitinib, colchicine, and secukinumab significantly reduces the inflammation severity, prevents the disease progression, and results in clinical improvement.

Proactive anti-inflammatory therapy with colchicine in the treatment of advanced stages of new coronavirus infection. The first results of the COLORIT study.

Actuality The course of the novel coronavirus disease (COVID-19) is unpredictable. It manifests in some cases as increasing inflammation to even the onset of a cytokine storm and irreversible progression of acute respiratory syndrome, which is associated with the risk of death in patients. Thus, proactive anti-inflammatory therapy remains an open serious question in patients with COVID-19 and pneumonia, who still have signs of inflammation on days 7-9 of the disease: elevated C-reactive protein (CRP)>60 mg/dL and at least two of the four clinical signs: fever >37.5°C; persistent cough; dyspnea (RR >20 brpm) and/or reduced oxygen blood saturation <94% when breathing atmospheric air. We designed the randomized trial: COLchicine versus Ruxolitinib and Secukinumab in Open-label Prospective Randomized Trial in Patients with COVID-19 (COLORIT). We present here data comparing patients who received colchicine with those who did not receive specific anti-inflammatory therapy. Results of the comparison of colchicine, ruxolitinib, and secukinumab will be presented later.Objective Compare efficacy and safety of colchicine compared to the management of patients with COVID-19 without specific anti-inflammatory therapy.Material and Methods Initially, 20 people were expected to be randomized in the control group. However, enrollment to the control group was discontinued subsequently after the inclusion of 5 patients due to the risk of severe deterioration in the absence of anti-inflammatory treatment. Therefore, 17 patients, who had not received anti-inflammatory therapy when treated in the MSU Medical Research and Educational Center before the study, were also included in the control group. The effects were assessed on day 12 after the inclusion or at discharge if it occurred earlier than on day 12. The primary endpoint was the changes in the SHOCS-COVID score, which includes the assessment of the patient's clinical condition, CT score of the lung tissue damage, the severity of systemic inflammation (CRP changes), and the risk of thrombotic complications (D-dimer) [1].Results The median SHOCS score decreased from 8 to 2 (p = 0.017), i.e., from moderate to mild degree, in the colchicine group. The change in the SHOCS-COVID score was minimal and statistically insignificant in the control group. In patients with COVID-19 treated with colchicine, the CRP levels decreased rapidly and normalized (from 99.4 to 4.2 mg/dL, p<0.001). In the control group, the CRP levels decreased moderately and statistically insignificantly and achieved 22.8 mg/dL by the end of the follow-up period, which was still more than four times higher than normal. The most informative criterion for inflammation lymphocyte-to-C-reactive protein ratio (LCR) increased in the colchicine group by 393 versus 54 in the control group (p = 0.003). After treatment, it was 60.8 in the control group, which was less than 100 considered safe in terms of systemic inflammation progression. The difference from 427 in the colchicine group was highly significant (p = 0.003).The marked and rapid decrease in the inflammation factors was accompanied in the colchicine group by the reduced need for oxygen support from 14 (66.7%) to 2 (9.5%). In the control group, the number of patients without anti-inflammatory therapy requiring oxygen support remained unchanged at 50%. There was a trend to shorter hospital stays in the group of specific anti-inflammatory therapy up to 13 days compared to 17.5 days in the control group (p = 0.079). Moreover, two patients died in the control group, and there were no fatal cases in the colchicine group. In the colchicine group, one patient had deep vein thrombosis with D-dimer elevated to 5.99 µg/mL, which resolved before discharge.Conclusions Colchicine 1 mg for 1-3 days followed by 0.5 mg/day for 14 days is effective as a proactive anti-inflammatory therapy in hospitalized patients with COVID-19 and viral pneumonia. The management of such patients without proactive anti-inflammatory therapy is likely to be unreasonable and may worsen the course of COVID-19. However, the findings should be treated with caution, given the small size of the trial.

[Combination therapy at an early stage of the novel coronavirus infection (COVID-19). Case series and design of the clinical trial "BromhexIne and Spironolactone for CoronаvirUs Infection requiring hospiTalization (BISCUIT)"].

The article focuses on effective treatment of the novel coronavirus infection (COVID-19) at early stages and substantiates the requirement for antiviral therapy and for decreasing the viral load to prevent the infection progression. The absence of a specific antiviral therapy for the SARS-CoV-2 virus is stated. The authors analyzed results of early randomized studies using lopinavir/ritonavir, remdesivir, and favipiravir in COVID-19 and their potential for the treatment of novel coronavirus infection. Among the drugs blocking the virus entry into cells, the greatest attention was paid to the antimalaria drugs, chloroquine and hydroxychloroquine. The article addresses in detail ineffectiveness and potential danger of hydroxychloroquine, which demonstrated neither a decrease in the time of clinical recovery nor any improvement of prognosis for patients with COVID-19. The major objective was substantiating a possible use of bromhexine, a mucolytic and anticough drug, which can inhibit transmembrane serin protease 2 required for entry of the SARS-CoV-2 virus into cells. Spironolactone may have a similar feature. Due to its antiandrogenic effects, spironolactone can inhibit X-chromosome-related synthesis of ACE-2 receptors and activation of transmembrane serin protease 2. In addition to slowing the virus entry into cells, spironolactone decreases severity of fibrosis in different organs, including the lungs. The major part of the article addresses clinical examples of managing patients with COVID-19 at the University Clinic of the Medical Research and Educational Centre of the M. V. Lomonosov Moscow State University, including successful treatment with schemes containing bromhexine and spironolactone. In conclusion, the authors described the design of a randomized, prospective BISCUIT study performed at the University Clinic of the M. V. Lomonosov Moscow State University with an objective of evaluating the efficacy of this scheme.

[Proactive anti-inflammatory and anticoagulant therapy in the treatment of advanced stages of novel coronavirus infection (COVID-19). Case Series and Study Design: COLchicine versus ruxolitinib and secukinumab in open prospective randomIzed trial (COLORIT)].

The article is devoted to the treatment of the new coronavirus infection (COVID-19) in the advanced stages of the disease. The types of response of the immune system to the viral load of SARS-CoV-2 with the start of the inflammation process are considered. The situation is analyzed in detail in which the growing autoimmune inflammation (up to the development of a "cytokine storm") affects not only the pulmonary parenchyma, but also the endothelium of the small vessels of the lungs. Simultaneous damage to the alveoli and microthrombosis of the pulmonary vessels are accompanied by a progressive impairment of gas exchange, the development of acute respiratory distress syndrome, the treatment of which, even with the use of invasive ventilation, is ineffective and does not really change the prognosis of patients with COVID-19. In order to interrupt the pathological process at the earliest stages of the disease, the necessity of proactive anti-inflammatory therapy in combination with active anticoagulation treatment is substantiated. The results of the first randomized studies on the use of inhibitors of pro-inflammatory cytokines and chemokines (interleukin-6 (tocilizumab), interleukin-17 (secukinumab), Janus kinase blockers, through which the signal is transmitted to cells (ruxolitinib)), which have potential in the early treatment of COVID- 19. The use of a well-known anti-inflammatory drug colchicine (which is used for gout treatment) in patients with COVID-19 is considered. The design of the original COLORIT comparative study on the use of colchicine, ruxolitinib and secukinumab in the treatment of COVID-19 is presented. Clinical series presented, illustrated early anti-inflammatory therapy together with anticoagulants in patients with COVID-19 and the dangers associated with refusing to initiate such therapy on time.

[Results of Open-Label non-Randomized Comparative Clinical Trial: "BromhexIne and Spironolactone for CoronаvirUs Infection requiring hospiTalization (BISCUIT)].

Introduction The aim of this study was to assess the efficacy and safety of a combination of bromhexine at a dose of 8 mg 4 times a day and spironolactone 50 mg per day in patients with mild and moderate COVID 19.Material and methods It was an open, prospective comparative non-randomized study. 103 patients were included (33 in the bromhexine and spironolactone group and 70 in the control group). All patients had a confirmed 2019 novel coronavirus infection (COVID 19) based on a positive polymerase chain reaction (PCR) for SARS-CoV-2 virus RNA and/or a typical pattern of viral pneumonia on multispiral computed tomography. The severity of lung damage was limited to stage I-II, the level of CRP should not exceed 60 mg / dL and SO2 in the air within 92-98%. The duration of treatment is 10 days.Results The decrease in scores on the SHOKS-COVID scale, which, in addition to assessing the clinical status, the dynamics of CRP (a marker of inflammation), D-dimer (a marker of thrombus formation), and the degree of lung damage on CT (primary endpoint) was statistically significant in both groups and differences between them was not identified. Analysis for the group as a whole revealed a statistically significant reduction in hospitalization time from 10.4 to 9.0 days (by 1.5 days, p=0.033) and fever time from 6.5 to 3.9 days (by 2.5 days, p<0.001). Given the incomplete balance of the groups, the main analysis included 66 patients who were match with using propensity score matching. In matched patients, temperature normalization in the bromhexine/spironolactone group occurred 2 days faster than in the control group (p=0.008). Virus elimination by the 10th day was recorded in all patients in the bromhexine/spironolactone group; the control group viremia continued in 23.3% (p=0.077). The number of patients who had a positive PCR to the SARS-CoV-2 virus on the 10th day of hospitalization or longer (≥10 days) hospitalization in the control group was 20/21 (95.2%), and in the group with bromhexine /spironolactone -14/24 (58.3%), p=0.012. The odds ratio of having a positive PCR or more than ten days of hospitalization was 0.07 (95% CI: 0.008 - 0.61, p=0.0161) with bromhexine and spironolactone versus controls. No side effects were reported in the study group.Conclusion The combination of bromhexine with spironolactone appeared effective in treating a new coronavirus infection by achieving a faster normalization of the clinical condition, lowering the temperature one and a half times faster, and reducing explanatory combine endpoint the viral load or long duration of hospitalization (≥ 10 days).

Dimeric Disintegrins from the Steppe Viper V. ursinii Venom.

Four dimeric disintegrins were isolated from the venom of the steppe viper V. ursinii using liquid chromatography. Disintegrins prevented adhesion of MCF7 cells to fibronectin, which indicates their interaction with integrin receptors of the αVß1 type. According to mass spectrometry data, the molar masses of disintegrins are about 14 kDa. The method of peptide mapping established the structure of a new heterodimeric disintegrin weighing 13 995.5 Da and shows that it belongs to the class of RGD/KGD-containing disintegrins.

EFFECT THE CARDIOMETABOLIC RISK FACTORS ON VASCULAR AGING IN PATIENTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE CONCOMITANT WITH SUBCLINICAL HYPOTHYROIDISM.

The article presents the analysis of the relationship between thyroid function abnormality -subclinical hypothyroidism (SH) and non-alcoholic fatty liver disease (NAFLD), depending on age peculiarities (>50 years and <50 years), and the risk of cardiovascular complications in this category of patients. Research of early predictors of cardiovascular complications: dyslipidemia, insulin resistance, inflammatory marker- C-reactive protein, marker of vascular aging-telomerase activity and marker of endothelial dysfunction (ED) - CDECs and VEGF-A that have been analyzed are on the front burner. In this regard, the effect of the given values on the formation of cardiac risk in patients with NAFLD combined with SH was studied. 74 patients (29 men (39.2%) and 45 women (60.8%)), with verified NAFLD and SH have been examined. Patients were divided into two clinical groups: group 1 (n=31) - patients with NAFLD, with the mean age 47.2±2.6 years; group 2 (n=43) patients with NAFLD in combination with SH, with the mean age 56,8±6,5 years. Results of the performed tests have shown that patients with NAFLD combined with SH aged over 50 years have pro-atherogenic lipid profile and significantly more pronounced manifestations of endothelial dysfunction. The process of age-dependent shortening of telomere length predominantly in the buccal epithelium is an important point to be made. Consequently, the total effect of cardiometabolic risk factors in patients with NAFLD combined with SH probably is the determining factor of the rate of progression of vascular aging.

Expression and purification of an engineered human endothelin receptor B in a monomeric form.

In humans, two endothelin receptors, ETa and ETb, are activated by three endogenous 21-mer cyclic peptides, ET-1, ET-2, and ET-3, which control various physiological processes, including vasoconstriction, vasodilation, and stimulation of cell proliferation. The first stage of this study it to produce a stable solubilized and purified receptor in a monodisperse state. This article is focused on the engineering, expression, purification, and characterization of the endothelin receptor B for subsequent structural and functional studies.

[Dual role of photosensibilizator merocyanine 540 as a bactericidal agent and immune reaction regulator].

AIM: Develop conditions for inactivation of staphylococcus by using photosensibilizator merocyanine 540 (MC540) for the production of antigenic preparation (AP). Study some of immune reactions to AP and the possibility of regulation of DTH reaction to AP under the effect of MC540. MATERIALS AND METHODS: Merocyanine 540 (MC540, Sigma-Aldrich, Switzerland) is used in the study. MC540 and Staphylococcus aureus, strain 78 (Sa78) were irradiated by light of a mercury-quartz lamp DRSH-250 (Zelenograd). C56BL/6 line mice were immunized once by subcutaneous administration of AP. DTH reaction was tested 7 days after the immunization. Functional activity of peritoneal exudate macrophages was determined 1 and 9 days after the immunization. Immune modulating effect of MC540 in DTH was determined after its per os administration to mice 1 hour after AP sensibilization. RESULTS: In order to obtain AP, S. aureus suspension at the concentration of 2.5 x 10(7) CFU/ml in 25 microM MC540 solution and 0.25 M NaCl solution were exposed to irradiation for 5 minutes. During DTH reaction induction its intensity dependence on AP dose was revealed. A persistent increase of a lysosomatic enzyme cathepsin D in macrophages of peritoneal exudate after a single administration of AP was noted. During MC540 irradiation an accumulation of photoproducts that have a pronounced immune suppression effect in DTH reaction had a dose-dependent character. CONCLUSION: Use of saline allows to increase bactericidal potential of a photosensibilizator (PS). However during therapy of localized forms of infection a possible immune modulating effect of PS on macro organism should be considered. By varying PS dose and irradiation time not only maximum bactericidal effect can be achieved but also regulation of inflammatory reactions in the area of PS effect can be ensured.

[Efficacy of ivabradin in combined treatment of patients with postinfarction systolic chronic cardiac failure].

AIM: To study effects of ivabradin on clinicohemodynamic and prognostic parameters in patients after myocardial infarction (MI) with systolic chronic cardiac failure (SCCF). MATERIAL AND METHODS: A population-based randomized prospective trial enrolled 49 patients (40 males--81.6%, mean age 63.1 +/- 8.1 years) with sinus rhythm and a longer than 3 month history of MI. The patients were randomized into 2 groups: 23 patients of group 1 received standard treatment plus ivabradin, 26 patients of group 2 received standard treatment alone. Follow-up was 36.1 +/- 6.2 months. We analysed the trend in heart rate (HR), blood pressure (BP), parameters of echocardiography, ECG, levels of electrolytes, creatinin in blood plasma, frequency of hospitalizations, recurrent non-fatal MI and lethality (combined endpoint). RESULTS: In the end of the trial ivabradin significantly decreased HR from 71 to 64 b/m. Frequency of combined end point of efficacy was 30.4 and 50% in group 1 and 2, respectively. In group 1 primary end point in high baseline HR occurred more frequently than in HR < 70 b/m in 6 (50%) and 1 (9.1%) cases, respectively, but these differences were not significant (p = 0.068). In group 2 the differences were significant--9 (90%) and 4 (25%) cases, respectively (p = 0.004). By none of the parameters of ECG, plasma electrolytes, creatinine level significant intergroup differences were found. CONCLUSION: In the same trend in BP and ECG, group 1 patients showed significant and more pronounced HR lowering than group 2 patients. Addition of ivabradin to standard treatment of SCCF after MI promoted less frequency of hospitalizations, recurrent non-fatal MI, fatal cardiovascular events. This effect was especially strong in high baseline HR.

Effect of Sodium Chloride on Aggregation of Merocyanine 540 and Photosensitized Inactivation of Staphylococcus aureus and Pseudomonas aeruginosa.

Merocyanine 540 (MC540) is used as a photosensitizer for the inactivation of microorganisms. The following is already known about MC540: firstly, MC540 exists in distilled water in both monomeric and dimeric forms, and the addition of salts into a MC540 solution leads to the formation of large aggregates that can be detected by the resonance light scattering technique. Secondly, singlet oxygen can only be photogenerated by MC540 monomers. In the present work, we studied the effect of MC540 in the aggregated state on the rate of photosensitized inactivation ofStaphylococcus aureusandPseudomonas aeruginosa. To this end, bacteria either in MC540-containing distilled water or in a 0.25 M sodium chloride aqueous solution also containing MC540 are irradiated (546 nm). The results show that, in the presence of salt, the aggregation of MC540 greatly increases the efficiency of the MC540-photosensitized inactivation ofP. aeruginosaandS. aureus. In the presence of salt, the rates ofP. aeruginosaandS. aureusinactivation increase by factors of 10 and 30, respectively, in comparison with the rate of inactivation observed in the case of distilled water. Our results suggest that a salt-induced photosensitization mechanism can switch from the singlet oxygen to the free-radical pathway.

[Investigation of aggregates of dyes by the method of resonance light scattering: correction of spectra].

Resonance light scattering, a phenomenon of an abrupt enhancement of Rayleigh light scattering in close proximity to an absorption band, is easily detectable in solutions of strongly absorbing chromophores, which form large aggregates with strong pi-pi-electronic coupling among the chromophores. Resonance light scattering spectra need to be corrected for the sensitivity of spectrofluorimeter as well as for the effects of internal light filter. A method for correcting the measured resonance light scattering is described. It was shown by the method that the addition of KCl induces the formation of extended supramolecular aggregates (probably of H-type) of the anionic dye merocyanine 540 in water. The spectra of the resonance light scattering of the photosensitizer meta-tetra(hydroxyphenyl)chlorin (mTHPC, foscan ) indicate the formation of J-aggregates of this dye in aqueous medium.

[Health improvement in the medical staff of tuberculosis services in the Primorsky Territory].

The authors analyze occupational morbidity rates in the medical personnel of tuberculosis facilities in the Primorsky Territory, as well as the location of the institutions (industrial premises) and the influence of production factors on medical workers. The nature of work and working conditions in the medical workers of a tuberculosis facility where they are exposed to industrial hazards in practically 100% of cases necessitate effective measures to be taken to preserve and promote their health. The absence of standard buildings and premises for tuberculosis facilities and the low efficiency of rehabilitative sanatorium-and-spa treatment, health improvement, and the prevention of occupational diseases are important problems of a tuberculosis service in the Primorsky Territory. The findings serve as the basis for the development of an approach to preventing occupational diseases and recovering the health of medical workers who have experienced tuberculosis.

[Work conditions and health state of female medical staffers].

The authors studied work conditions of medical personnel and health state including reproductivity, according to periodic medical examinations data, transitory disablement morbidity, occupational morbidity, questioning, clinical, laboratory and instrumental investigations. Reproductive health was assessed through gynecologic observations, course of pregnancy and delivery, the authors evaluated their relationships with work and identified risk groups for target prophylaxis.

[Photohemolysis sensitized by psoralen: dependence on pH].

The effect of pH on the hemolysis of erythrocytes photosensitized (366 nm, 23 Wt/m2) by psoralen has been studied. The dependence of the photohemolysis rate (V) on irradiation dose (D) was described by the equation V = Vo + kD, where Vo is the rate of hemolysis without irradiation (dark), and k is the constant. The index of the power at dose x was approximately equal to 2, and its value did not change as the pH of the erythrocyte suspension was changed. It was found that changes in pH led to a sharp change in the value of coefficient k and correspondingly V. The lowest rate of photohemolysis was observed in the pH range from 8.0 to 8.4. As pH was changed from 3.4 to 9.0 or from 8.0 to 7.4, the V value increased approximately twofold. At pH below 7.4, an abrupt increase (approximately fourfold) in V was observed, with the pK value being equal to 7.3. The psoralen molecule lacks titratable acidic and basic groups; therefore, the effects of pH can hardly be assigned to changes in the photophysical properties of the sensitizer. The increase in V in the alkaline region is prohably related to the acceleration of photooxidation of reduced glutathione, whereas the jump of V at pH of about 7.3 may be due to the titration of the product of psoralen photooxidation. The latter assumption is confirmed by the data of hign performance liquid chromatography. In these experiments, psoralen was oxidized in ethanol and mixed with the phosphate buffer at different pH values followed by a qualitative and quantitative analysis by high performance liquid chromatography of photoproducts. Several photoproducts of psoralen have been identified whose content depended on pH. The curve of titration of one photoproduct was similar in shape to the pH dependence of psoralen-photosensitized hemolysis.

[Causes of health disorders in medical personnel in Vladivostok city].

In recent years, occupational morbidity among medical personnel in health care institutions attracts attention of occupational therapists and inspectorate specialists. Increasing occupational morbidity among medical personnel of health care institutions deteriorates efficiency of the activities.

[Epidemiologic and radiobiologic features of neoplasms in respiratory and gastrointestinal tracts among patients who had occupational contact with uranium].

Morbidity structure among workers engaged into main production of nuclear industry had prevailing lung cancer (1.93 per 1,000), gastric carcinoma (1.09) and colon cancer (0.72). The lung cancer patients demonstrated the highest concentrations of uranium in lung tissue (0.8313 g/g) and liver tissue (0.3548 g/g); those with gastric carcinoma and of reference group--in lung radix nodes (0.1855 and 0.3685 g/g respectively).

[Topics of occupational medicine and environment in codes and social accountability standards of business].

The problems of social accountability as applied to the occupational safety, health and environment are discussed. Russian and international codes and standards in the field are reviewed. Legal duties and rights of employers in occupational risk management for workers' health are considered. Some ethical aspects including health protection of female workers are discussed.

[Photobiophysics of furanocoumarins]. / Fotobiofizika furokumarinov.

Furocoumarins (psoralens) are photosensitizers of plant origin, which increase the sensitivity of biological objects to near ultraviolet (UV-A, 320-400 nm). In combination with UV-A, they are successfully used for treating many dermal and autoimmune diseases (PUVA therapy and photophoresis). Along with therapeutic effects, the furocoumarin photochemotherapy induces a number of side-effects (erythema, edema, hyperpigmentation, and premature aging of skin). All photobiological effects of furocoumarins result from their photochemical reactions. Therefore, in order to advance the therapy, it is necessary to know the photochemical mechanisms of induction of both side- and therapeutic effects. The types of photoreactions of furocoumarins classified with respect to reactive photoproducts interacting with substrate were considered. Primary emphasis was placed on reactions proceeding with the participation of photooxidation products of furocoumarins. Among these photoproducts, at least two types can be distinguished. Some of them possess membranotoxic properties, others produce the immunosuppressory action in vivo. The photochemical mechanisms of the formation of the photoproducts of furocoumarins are different. It was found that, by varying the illumination conditions (intensity of UV-A radiation or the concentration of the photosensitizer), it is possible to obtain the photoproducts of furocoumarins that have either membranotoxic or immunosuppressory properties. It was found that the mechanisms of the immunosuppressive action of the photooxidation products of furocoumarins have some features in common with those underlying the PUVA therapy and photophoresis. It is assumed that the photochemical basis of the therapeutic action of furocoumarins is the reactions with the involvement of the products of their photooxidation.