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Degenerative and dystrophic changes of joints and ligaments are among the most prevalent disorders in professional athletes. Specification of a complex system for these diseases is an important task in sports medicine. Extracorporeal shock wave therapy is a modern and highly effective method of rehabilitation.

The article covers individual coaching program specified by specialists in Sports Medicine and Rehabilitation Center in Bournazian FMBC of the FMBA of Russia, to improve functional durability of highly qualified athletes.

The bone marrow myelopeptides Phe-Arg-Pro-Arg-Ile-Met-Thr-Pro (MP-4) and Val-Asp-Pro-Pro (MP-6) have been synthesised by a classical method and by a solid phase synthesis. The differentiating activity of MP-4 and MP-6 in human leukemia cells HL-60 and K-562 has been studied. Both peptides induce terminal differentiation of these cell lines but the mechanism of action of peptides MP-4 and MP-6 is distinguished.

The review describes structure and functions of bone marrow-derived peptides (myelopeptides). The final biological effects of these endogenous bioregulators (antitumor, antiviral, anti-infectious, antileukemia etc.) are due to their immunocorrecting and differentiating activity. Myelopeptides are the integral parts of the immune homeostasis maintenance system. Nowadays, medical preparations with no side effects and natural mechanisms of action are being developed on the basis of synthesized myelopeptides.

The Val-Val-Tyr-Pro-Asp bone marrow peptide (MP-5) and an analogue (MP-5-Lys) were synthesized. Fluorescent derivatives, Ftc-MP-5 and MP-5-Lys(Ftc), were prepared. The biological activity of MP-5 and MP-5-Lys was studied in vitro and in vivo. The MP-5 peptide caused 60-84% inhibition of growth of the following mouse cancers: lymphatic leukemia P-388, melanoma B-16, and cervical carcinoma CUC-5. These peptides also restored functional activity of T lymphocytes that was inhibited by metabolic products of the HL-60 leukemic cell line. MP-5-Lys(Ftc) was shown to preserve the functional properties of MP-5 toward T lymphocytes, but Ftc-MP-5 was practically inactive.

Combined application of mumps and measles vaccine strains in equal doses results in significant decrease of immune response to the former component in humans. It is possible that this phenomenon is related with well-known immunodepressive effect of measles virus, which was demonstrated both in vivo and in vitro. It was previously shown that myelopeptide-2 (MP-2) partially neutralizes suppressive effect of measles vaccine on blast transformation of activated human lymphocytes in vitro. Partial supression of immune response to mumps vaccine by live measles vaccine was reproduced in laboratory animals. It was shown that in experiment MP-2 partially neutralized suppressive effect of measles vaccine.

Myelopeptide-4 (MP-4) (Phe-Arg-Pro-Arg-Ile-Met-Thr-Pro), inducing the terminal differentiation of HL-60 leukemia cells, was labeled with fluorescein isothiocyanate. The specific binding of this modified peptide to the surface of HL-60 cells and its ability to penetrate into the cells were studied. It was shown by cytometry and confocal microscopy to be bound on the HL-60 cell surface, to penetrate into their cytoplasm, and finally to concentrate around the cell nucleus. These phenomena are probably necessary for the exhibition of MP-4 differentiating activity.

A model is suggested to study the effects the myelopeptide 2 (MP2) immunomodulator on the results of live measles rash immunized by vaccine. Guinea pigs were found to respond to live measles vaccine L-16 the way man does, i.e. the antibodies' level in their sera was increasing until days 28-56 after a single intramuscular vaccine injection. An intramuscular injection of the MP2 immunomodular, made alongside with vaccination, was demonstrated to enhance the immune response to the measles vaccine and to induce its action. Finally, it was for the first time, that the possibility was proven to enhance the action of the live measles vaccine by an immunomodulator.

Previously unknown bioregulators from bone marrow, myelopeptides, were isolated, identified, and synthesized, and their biological properties and mechanism of action were studied in detail. Phe-Leu-Gly-Phe-Pro-Thr (MP-1) manifests an immunocorrecting effect by restoring the level of antibody production in animals suffering from immunodeficiencies of various etiologies; Leu-Val-Val-Tyr-Pro-Trp (MP-2) manifests an antitumor effect by abolishing the inhibitory action of tumor cells on the functional activity of T-lymphocytes; Leu-Val-Cys-Tyr-Pro-Gln (MP-3) stimulates phagocytosis by macrophages and, in this way, protects animals from infections caused by pathogenic microorganisms; and Phe-Pro-Arg-Ile-Met-Thr-Pro (MP-4) is a new factor of cell differentiation inducing terminal cell differentiation in the HL-60 and K-562 leukemic cell lines.

The paper summarizes the data available on the structural and functional characteristics of the brain marrow immunoregulatory peptides myelopeptides (MPs). It describes the amino acid sequences of 6 individual MPs, their biological properties and mechanism. MP-1 is a hexapeptide having an immunocorrective effect. MP-2 has antitumor action, MP-3 stimulates the phagocytic activity of macrophages, M-4 is a new differentiating factor. The endogenous origin of the MPs isolated, their structure, and the pattern of their biological effects lead to the conclusion that MPs represent a new group of regulatory peptides that are promising for clinical application.

Two hexapeptides affecting pain sensitivity were isolated from the bone marrow cells supernatant, shown to have primary structure Leu-Val-Val-Tyr-Pro-Trp and Phe-Leu-Gly-Phe-Pro-Thr, and synthesized by the solid phase method. In physico-chemical and biological properties the synthetic peptides were identical to the peptides isolated.

Penicillin, streptomycin and gentamicin, when introduced into mice in a single injection in doses of 0.5-500,000 U/kg, produced different changes in the phagocytic activity of mouse peritoneal macrophages. Bactericidal doses of these antibiotics either suppressed the activity of macrophages or left it unchanged. Their sub-bactericidal doses enhanced the phagocytic activity of macrophages. Combined use of penicillin and streptomycin produced a synergic effect.

The study investigated immunocorrecting properties of penicillin G, streptomycin, gentamycin in cyclophosphamide--induced immunodeficiency in mice. It was determined, that antibiotics in sub-bactericidal doses possess pronounced immunocorrecting properties. This effect was observed in both humoral and cell-mediated immune response.

Forty-one neurotic patients with pronounced depressive-hypochondriac symptomatology were treated by acupuncture. A decrease in the psychoemotional and algetic symptoms (sleep restoration, increased working capacity) following acupuncture was attended by certain changes in the nocturnal and diurnal EEG with the prevailing activation of the synchronizing mechanisms of nonspecific brain systems which suggests that the structures of the thalamo-cortical and nonspecific cerebral level are involved in the realization of the acupuncture therapeutic effect and that it is advisable to activate the synchronizing cerebral mechanisms.

The injection of the marrow stimulator of antibody-producing cells (SAPC) into animals infected with Japanese encephalitis and tick-borne encephalitis viruses stimulated the formation of virus-specific antibodies in the infected animals, increasing antibody production 8- to 16-fold. Such SAPC-induced stimulation of the formation of virus-specific antibodies is observed in cases of both acute and chronic virus infection. The prospects of using the preparation of SAPC are discussed.

The status of the serotoninergic and catecholaminergic systems was studied in patients with neurotic depressive disorders before and after acupuncture (AP). The parameters studied included blood serotonin levels, monoamine oxidase (MAO) activity in the blood serum, as well as urinary excretion of adrenaline, noradrenaline, dopamine, DOPA and 5-HOIAA. Prior to AP patients with anxiety-depressive, depressive-hypochondriac or asthenodepressive manifestations showed different changes in the parameters studied. Following a course of AP they presented a compensatory increase in MAO activity, normalization of blood serotonin levels and of the urinary excretion of noradrenaline, dopamine and DOPA. Improvement in biochemical parameters indicates that this type of therapy is an effective means of the treatment of patients with neuroses with the predominance of depressive disorders.

Hormones and mediators of the immune system influencing the growth, differentiation and effector functions of immunocompetent cells, were described. Lymphokines and monokines produced by lymphocytes and cells of a monocytic series in response to antigenic stimulation, mediate intercellular interrelationships in the process of development of immune reactions, thus providing for intersystemic regulation. Mediators of the central immunity organs, thymus peptides and bone marrow peptides (myelopeptides) influence the formation and normal functioning of T and B lymphocytes. Peptides with opiate-like properties were detected among bone marrow mediators. The involvement of thymus and bone marrow mediators in intersystemic interrelationships is discussed.

The results of clinico-psychological examination of 121 patients have demonstrated that acupuncture is a fairly effective method of treating asthenic states in neurotic patients. Thus, considerable improvement and improvement has been observed in 67% of the patients. The absence of positive effect in the remaining cases is explained by an aggravated history, a stubborn course of the disease, and depletion of the functional activity of the sympathoadrenal system (SAS) and the adrenal cortex. Normalization of EEG rhythm is effected through activation of the synchronizing and inactivation of the desynchronizing cerebral systems; the positive dynamics of the structure of nocturnal sleep is reflected in an increased duration of slow sleep and rapid sleep which were initially reduced, in more regular alternation of the cycles and phases of sleep, and in a shorter period of falling asleep. Biochemical examinations have revealed activation of the mediatory component of the SAS and elevation of the function of the adrenal cortex, while baroalgesimetric studies have shown that acupuncture is characterized by antinociceptive and activizing effects. On the whole the efficacy of acupuncture in controlling asthenic conditions related to neuroses is due to its integral action.

Different fractions of bone marrow cell culture supernatant effects on pathological pain have been studied. It is shown that all studied fractions have analgesic effect and inhibit strong pain syndrome induced by generator of pathologically enhanced excitation. In distinction from commercial drug myelopid bone marrow supernatant fractions with high and low molecular weight exert analgesic effect in low concentrations not having muscle-relaxant and narcotic influence. It suggests the possibility of creation of some new highly effective analgesic drugs to abolish pain syndromes.

Using double 3H-thymidine/14C-amino acid label, the influence of myelopeptides (MP) on chromosomal DNA and total protein (without histones) synthesis has been studied in vitro in mouse lymphoid organ cells. It has been shown that MP cause a decrease in DNA labelling and a parallel increase in protein labelling in bone marrow cells and have practically no effect on these two parameters in thymus, lymph node and spleen cells. It has been found that MP have only mitogenic effect on the above-mentioned organ cells, but in combination with 2-mercaptoethanol. The data obtained show that MP possess the properties of cell-differentiating factors.