Results and Prospects of Using Activator of Hematopoietic Stem Cell Differentiation in Complex Therapy for Patients with COVID-19.

The paper presents the results of a standard and complex treatment method using the peptide drug thymus thymalin in patients with COVID-19. One of the mechanisms of the immunomodulatory effect of thymalin is considered to be the ability of this peptide drug to influence the differentiation of human hematopoietic stem cells (HSCs). It was found that, as a result of standard treatment, patients in the control group showed a decrease in the concentration of the pro-inflammatory cytokine IL-6, C-reactive protein, D-dimer. The addition of thymalin to standard therapy accelerated the decline in both these indicators and the indicators of the T cell system. This has helped reduce the risk of blood clots in COVID-19 patients. The revealed properties of the thymus peptide preparation are the rationale for its inclusion in the complex treatment of coronavirus infection. Peptideswith potential biological activity against SARS-CoV-2 virus [29]. Note: Nitrogen atoms are shown in blue, oxygen atoms - in red, carbon atoms - in gray, hydrogen atoms - in white, and phosphorus atoms - in yellow.

Effect of Thymalin on the Tumor and Thymus under Conditions of Activation Therapy In Vivo.

Pronounced antitumor effect of Thymalin in doses lower than the therapeutic doses was shown in experiments on albino outbred male rats with transplanted sarcoma 45. Tumor growth arrest and its regression were observed in more than half of animals and in other cases, the growth was suppressed by 78%. Microstructural changes in the thymus were analyzed. Significant increase in lymphoproliferative activity and the content of tissue basophils and plasmocytes in the thymus lobules was observed. Tumor regression was accompanied by the development of stable antistress adaptation reactions of calm and elevated activation. High efficiency of Thymalin can be attributed to the use of lower doses of the substance and their modulation during the treatment course in accordance with the regimes of activation therapy.

Thymus hormones as prospective anti-inflammatory agents.

IMPORTANCE OF THE FIELD: Inflammatory diseases are characterized by severe immune imbalances, leading to excessive or inappropriate release of mediators, which, in turn, result in massive damage to organs and systems. Effective means to control inappropriate immune reactions are often life-critical needs. Available data on the role of thymus-derived hormones in inflammation show their great potential. AREAS COVERED IN THIS REVIEW: The review aims to systematize information for the last two decades on immune system regulation by thymic peptide hormones, with a primary focus on the role of these hormones in the systemic inflammatory response and inflammatory diseases. Anti-inflammatory potential of three thymic hormones - thymulin, thymosin-alpha, and thymopoietin - is discussed, reviewing recently published clinical and experimental studies. WHAT THE READER WILL GAIN: Our analysis revealed the regulation of inflammatory processes via thymic hormones that could be prospective for therapeutic application. This regulation may be mediated through thymic hormone effects on peripheral immune cell activities and bidirectional coupling between thymic hormones and the hypothalamic-pituitary-adrenal axis. TAKE-HOME MESSAGE: In view of the role of thymic hormones in immune and neuroendocrine systems, they could be suitable as therapeutic agents for inflammation.

[Immunological correction in progressive pulmonary tuberculosis].

The authors used their immunological correction method to treat 154 patients with progressive pulmonary tuberculosis. Of them, 38 patients received standard antituberculosis therapy (Group 1), 39 had additionally paravasal lymphotrophic immunological correction (Group 2), and 38 took antituberculous drugs in accordance with individual regimens (Group 3), and 39 patients were treated by individual regimens during immunological correction (Group 4). After termination of the basic course of chemotherapy, clinical cure was achieved in 61.1, 76.3, 72.2, and 94.7%, respectively (p < 0.05). During the basic course, mortality was 11.1, 5.3, and 5.5% in the first three groups. By taking into account the immunological status of patients with caseous pneumonia, disseminated, and multicavernous pulmonary tuberculous lesion, immunological correction is indicated early in the basic course of therapy.

[The application efficacy of immunomodulators in complex of treatment of an acute necrotic pancreatitis]. / Efektyvnist' zastosuvannia imunomoduliatoriv v kompleksi likuvannia hostroho nekrotychnoho pankreatytu.

Analysis of efficacy of the immunomodulators application, thymalin in particular, in complex treatment algorhythm in 18 patients with an acute necrotic pancreatitis was conducted. Efficacy of immunocorrecting therapy in the immune state improvement, purulent-septic complications prophylaxis, the abortive course of the disease promotion was established In 12 (66.7) patients the disease regression was noted, in 2 (11.1%)--the inflammatory process delineation with pancreatic pseudocyst formation was observed, 4 (22.2%) patients were operated on. All the patients survived.

[Possibilities of immunomodulation in patients with chronic bronchitis during physiotherapeutic impacts on the thymic area]. / Vozmozhnost' immunomoduliatsii pri fizioterapevticheskikh vozdeistviiakh na oblast' timusa u bol'nykh khronicheskim bronkhitom.

Immune effects of galvanic current (GC) and ultrasound (US) applied on the thymic area were studied in 66 patients with chronic bronchitis (CB) on rehabilitation treatment. 64 control CB patients either receive an immunomodulating drug thymalin or were treated without immunomodulation. It was found that GC and US are effective in disorders of cellular immunity and result in closer interaction between separate components of immune system. The immunomodulating effect of GC and US was comparable with that of thymalin.

[Effect of thyroxin and thymalin on proliferation and apoptosis of thymocytes in rats after thyroidectomy]. / Vplyv tyroksynu i tymalinu na proliferatsiiu ta apoptoz tymotsytiv u shchuriv pislia tyreoïdektomiï.

It is found that 3 months after removal of thyroid gland in rats, a suppression of thymic endocrine function, loss of weight and cellularity occurs. These changes are mainly caused by a weakening of index of proliferative activity. In animals that postoperatively received substitutive thyroxin hormonotherapy and courses of thymulin these disorders don't occur or they are not expressed significantly.

[Use of testosterone preparations in complex therapy of severe herpetic keratitis in male patients]. / Primenenie preparatov testosterona v kompleksnoi terapii tiazhelykh form gerpeticheskogo keratita u lits muzhskogo pola.

Data are reported on the efficiency of using the testosterone preparations in male patients with severe herpetic keratitis concomitant with a reduced concentration of the hormone in blood serum; simultaneously, zovirax (an antiviral drug) and immunocorrector tymalin were administered. The above drugs normalized the testosterone content in blood serum in 46.9% of patients; they stabilize the count of CD95+ lymphocytes in peripheral blood, which is manifested clinically by an improved visual acuity and a shorter treatment of the above patients in hospital.

[Effect of a levopromazine-thymalin combination on the development of toxic edema and swelling in the brain]. / Vliianie kombinatsii levomepromazina i timalina na razvitie toksicheskogo oteka-nabukhaniia golovnogo mozga.

The development of toxic edematous brain swelling in rats is accompanied by disproteinemia of the blood plasma and buildup of the gamma-globulin fraction. The administration of levopromazine (5 mg/kg), thymalin (1.2 mg/kg), or their combination reduces this disorder in the blood protein fractions. The antiedematous effect of the levopromazine--thymalin combination has an additive synergistic interaction.

[Lipid peroxidation and activity of antioxidant enzymes in thyroidectomized rats]. / Perekysne okysnennia lipidiv i aktyvnist' antyoksydantnykh fermentiv u shchuriv pislia tyreoïdektomiï.

The effect of thymalin on peroxidation of lipids in thyroidectomized rats that received thyroxin at a dose 2 mg/ kg was examined. It was found that 3 months after operation a decrease in body weight (over 2 times), weight of spleen and amount of cells in it took place. An increase of TB-activated products in livers and spleens of thyroidectomized rats 3 month later was not essential. Indices of enzyme activity of antioxidant system in liver were within normal ranges while indices of activity of catalase and superoxidedysmuthase in spleen increased by 4,3 and 1,3 times, respectively. Simultaneous administration of thyroxin and thymalin promotes more effective normalization of POL peroxidation, inhibits development of pathologic changes in organism after removal of thyroid gland.

[Geroprotective effect of thymalin and epithalamin]. / Geroprotektornaia éffektivnost' timalina i épitalamina.

Researchers of the St. Petersburg Institute of Bioregulation and Gerontology of the North-Western Branch of the Russian Academy of Medical Sciences and the Research Institute of Gerontology of the Ukrainian Academy of Medical Sciences (Kiev) clinically assessed the geroprotective effects of thymic and epiphyseal peptide bioregulators (Thymalin and Epithalamin, correspondingly) in 266 elderly and older persons during 6-8 years (the bioregulators were applied for the first 2-3 years of observation). The obtained results convincingly confirmed the ability of the bioregulators to normalize the basic functions of the human organism, i.e. to improve the indices of the cardiovascular, endocrine, immune, and nervous systems, homeostasis, and metabolism. The restoration of homeostasis in the patients was accompanied by a 2.0-2.4-fold decrease in acute respiratory disease incidence, reduced incidence ischemic heart disease clinical manifestations, hypertension, deforming osteoarthrosis, and osteoporosis, as compared to the control group. Such a significant improvement in the somatic state of the peptide-treated patients corresponded to a decrease in their mortality rate during the observation period: 2.0-2.1-fold among the Thymalin-treated patients, 1.6-1.8-fold--in the Epithalamin-treated group, and 2.5-fold--in the patients treated with Thymalin combined with Epithalamin, as compared to the control group. A separate group of patients was treated with Thymalin combined with Epithalamin annually for 6 years. We registered a 4.1-fold mortality decrease in this group as compared to the control level. The results of our research confirmed the conclusion on the high geroprotective efficacy of Thymalin and Epithalamin and the expediency of their application in medicine and social care as the means of health maintenance and age-related pathology prevention in persons over 60 years old enabling the prolongation of the active period of their lives.

[Comparative study of the effects of thymalin and vitamin E on certain indices for local pulmonary protection in rheumatoid arthritis]. / Sravnitel'noe izuchenie vliianiia timalina i tokoferola atsetat na nekotorye pokazateli mestnoi zashchity legkykh pri revmatoidnom artrite.

In experimental rheumatoid arthritis, certain indices for local defence of the lung were studied together with effects on these of preparations of vitamin E and thymalin. Noted in experimental rheumatoid arthritis are manifest changes in quantitative indices for cellular population of the bronchoalveolar space and disturbances in humoral mechanisms of defence of the lungs. The drugs employed for the treatment of the affliction have a positive effect on quantitative indices for the cell population of the lung local defence factors. But no significant effects could be demonstrated of thymalin on humoral factors of defence of the lungs. Unlike thymalin, tocopheroli acetas is noted to augment the secretion of lysozyme, to decrease the activity of phospholipase A2, to improve the surface-active properties of the lung surfactant. It is suggested that its antioxidant, membrane-stabilizing action may be responsible for the positive effect on indices for local defence of the lung.

[Changes in the immune status parameters and their correction in various forms of tick-borne encephalitis]. / Izmenenie pokazatelei immunnogo statusa i ikh korrektsiia pri raznykh formakh kleshchevogo éntsefalita.

Comparative investigation of immune status indices in patients with fever form of vernal encephalitis (group 1), with inapparent form with prolonged antigenemia (group III) and with short-term antigenemia (group II) was performed for the first time. Total 99 patients were under investigation. It was shown that in group I selective damage of immune system at T-level took place. In patients of group III immune system at all levels was less involved and humoral factor were changes. In patients in group II no significant change in immune system were registered. Activity of different immune correctors (thimalin, 4-iodoantipirine, leukinferon) was investigated in vitro. This preparations had stimulating effect in blood samples of patients with decreased immune status. In the patients with unchanged immune status no effect was demonstrated. The most prominent effect was revealed in the case of 4-iodoantipirine--interferon inducer.

[Immune and enzyme disorders in patients with acute pancreatitis]. / Immunnye i fermentnye narusheniia u bol'nykh ostrym pankreatitom.

Analysis of immune and enzyme disorders in 85 patients with acute pancreatitis shows that persistent imbalance of immunoregulatory T-lymphocytes with suppression predominance; reduction of all immunoglobulines number, imbalance in phagocytic immunity with height of absorbing activity of neutropils and stimultaneous decrease of their digestive capacity are prognostically unfavourable for high risk of pyonecrotic complications and lethal outcome. It is necessary to include immunocorrectors in combined therapy. Direct assessment of leukocytic elastase activity and alpha-IP level in blood plasma permits to evaluate spreading of inflammatory process and it severity, efficacy and prognosis of treatment.

[Clinical and immunological characteristics and specific features of the treatment of patients with recurrent sarcoidosis of respiratory organs]. / Kliniko-immunologicheskaia kharakteristika i osobennosti lecheniia bol'nykh s retsidiviruiushchimi formami sarkoidoza organov dykhaniia.

In the past 35 years, the authors have followed up 5600 patients with sarcoidosis of respiratory organs (SRO), among whom 1.2 and 10.7% were found to have single and multiple recurrences. The clinical manifestations of recurrent sarcoidosis were moderate, by showing a drastic reduction in the count of T and T"a" lymphocytes, as well as helper lymphocytes, and an increase of circulating immune complexes and immunoglobulins G, A, and M. Poor adaptive responses (AR) defined by the blood leukocyte and lymphocyte counts that reflect the body's nonspecific responsiveness were concurrently diagnosed. In chronic recurrent SRO, poor AR as stress and superactivation amount to as much as 86.1%. To optimize treatment, the patients were given adaptogens (thymaline, levamisole, dibasole, etc.) that make AR better, by enhancing the efficiency of treatment, reducing its duration, and improving prognosis.

[Changes in cell immunity indexes under the influence of thymalin, thyroxine and fibronectin in patients with hyperplastic diseases of thyroid gland before and after the surgery]. / Izmenenie pokazatelei kletochnogo immuniteta pod vliianiem timalina, tiroksina i fibronektina u patsientov s giperplasticheskimi zabolevaniiami shchitovidnoi zhelezy do i posle operatsii.

Changes in the cell immunity indexes under the influence of thymalin, thyroxin and fibronectin in vitral loading models were studied up in patients with hyperplastic diseases of the thyroid gland. Disbalance of the cell link immunity was revealed before the operation and, in particular, in the main subpopulations of lymphocytes as well as immunoregulating index lowering, which had intensified after the operation. In patients with toxic, nodose euthyroid goiter and chronic autoimmune thyroiditis the existence of (thyroxin- and thymalin) dependent control of the cell link immunity was determined. Application of fibronectin substituting therapy for correction of the hormone depending functional activity of lymphocytes in the early postoperative period in patients with hyperplastic diseases of thyroid gland was pathogenetically substantiated.

Immunomodulatory agents for prophylaxis and therapy of infections.

The advent of the antibiotic era ushered in a shift towards non-pathogen-specific therapy of infectious diseases. This led to an overt emphasis on targeting microbial pathogens while strategies directed towards enhancing host immunity were neglected. In an effort to decrease sole reliance on antimicrobials, the time has come for a critical reappraisal of nonantibiotic, albeit immune response-enhancing substances. The diverse array of natural, synthetic, and recombinant immunomodulators discussed in this review succinctly demonstrate the potential of these agents to stimulate host defense mechanisms for prophylaxis and treatment of various microbial infections.

Review of thymic hormones in cancer diagnosis and treatment.

The thymus is an endocrine organ. A unified, physiological concept of humoral regulations of the immune response has emerged in the last three decades. The thymus is the major site of production of immunocompetent T lymphocytes from their hematopoietic stem cells. This complex process required direct cell to cell, receptor based interactions, as well as in situ paracrine information via the numerous cytokines and thymic hormones produced by the cells of thymic microenvironment. Thymic hormones induce in situ T-cell marker differentiation, expression and functions. These polypeptide hormones have also been shown by means of immunocytochemistry to localize in the reticulo-epithelial (RE) cells of the thymic cellular microenvironment. Due to the great complexity of the intrathymic maturation sequence of T lymphocytes and the diverse immunophenotypically unique subpopulations of T lymphocytes, it is quite unlikely that a single thymic humoral factor could control all of the molecular steps and cell populations involved. It is much more likely that an extremely rich and diverse, but genetically determined, milieu is present within the thymus, and that thus the control of intrathymic T lymphocyte maturation and the functional maturation of T cells involves the orchestral interaction of various thymic-specific factors and other molecules during the differentiation process. Thymosin fraction 5 and its constituent peptides influence several properties of lymphocytes including cyclic nucleotide levels, migration inhibitory factor production, T-dependent antibody production, as well as the expression of various cell surface maturation/differentiation markers. Recently, derivatives of thymic hormones, mostly of thymosins, have been detected as products of neoplastically transformed cells and employed in the early diagnosis of neoplasms. In clinical trials, thymic hormones strengthen the effects of immunomodulators in immunodeficiencies, autoimmune diseases, and neoplastic malignancies. Combined chemo-immunotherapeutical anti-cancer treatment seems to be more efficacious than chemotherapy alone, and the significant hematopoietic toxicity associated with most chemotherapeutical clinical trials can be reduced significantly by the addition of immunotherapy.

[Circulating immune complexes in acute concussion of the brain]. / Tsirkuliruiushchie immunnye kompleksy v ostrom periode sotriaseniia golovnogo mozga u detei.

The aim of the study was to study the count of circulating immune complexes (CIC) in the blood of children with acute concussion of the brain. The fact that CIC at high concentrations that can penetrate into the brain through the blood-brain barrier and cause complications as vasculitis, microangiopathy, proliferative processes in the meninges, enlarged ventricles of the brain, and atrophy of its tissue was borne in mind. The studies revealed a significant progressive CIC increase within 3 weeks. For correction of blood CIC levels, laser exposure was applied to the carotid and vertebral arteries and acupuncture points. For comparison, thymaline in age-specific doses was used. Laser radiation showed a significant fall of CIC at days 19-21, particular when applied to the acupuncture points. Thymaline did not affect blood CIC levels. Laser application to the acupuncture points in children with acute brain concussion should reduce the incidence of complications of brain injury disease.

[Effects of thymalin on blood coagulation and contents of proinflammatory and anti-inflammatory cytokines in patients with burns]. / Vliianie timalina na svertyvaemost' krovi i soderzhanie provospalitel'nykh i protivovospalitel'nykh tsitokinov u bol'nykh s ozhogovoi bolezn'iu.

The authors share their experiences with treatment of 32 patients with burns of the III-IV degrees using an immunomodulator Thymalin which promoted liquidation of the syndrome of disseminated intravascular coagulation, normalization of fibrinolysis, influenced the content of pro-inflammatory and anti-inflammatory cytokins. It allowed to shorten the terms of the first autodermoplasty at an average by 5 days and to make staying of burned patients at the hospital 11 days shorter.