Recovery of minor movements in ICP and ACCI patients is another Neurovit application. In the concluding phase the course of treatment lasts 14-18 days.

Hence, as far as the effectiveness and the manifestation speed of the therapeutic effect are concerned, the drug has no likes in world practice. Its area of application as well as that of other pathogenic preparations is limited, however.

On the contrary, the hypothesis on genetic determination of the decay of nerve cells (the apoptosis phenomenon) still remains universal and wins an ever growing number of supporters. In 1988, a gene was identified whose derepression leads to the generation of a specific protein that destroys DNA cells and triggers apoptosis (16).

It is hard to identify in vivo the apoptosis characteristics: DNA fragmentation and a change of neuron membrane permeability. All the more so that, depending on the amount of the protein produced, the process may be prolonged and occasionally go on for many years. Injuries, hypoxia, frequent convulsive seizures, neuroinfectious diseases and other factors can significantly accelerate the cell decay program implementation which modern medicine is unable to prevent despite the impressive armamentarium of therapeutic drugs.

Postmortal studies of the brain of patients who died of traumas or somatic diseases point to the possibility of a similar mechanism of the death of nerve cells. Yet it should not be ignored that apoptosis is a physiological process. In this fashion, 3-5% of nerve cells with metabolic defects are rejected in the prenatal (and, partially, in the postnatal) period. However, the process of the decay of nerve cells risks (under the influence of certain etiologic factors) to degenerate into a large-scale process and then large cell groups may lose their viability (16).

In these conditions, moderate hypoxia, birth traumas, neuroinfection, etc. produce irreversible changes precisely in these regions.

In this case, the cell decay process may last for a long time and gradually form a clinical picture of infantile cerebral palsy. Many years ago, Prof. K.A. Semyonova proved such a possibility although the development and prolongation mechanism of the pathologic process remained unclear.

One could think: should the hypothesis be confirmed, the treatment tactics for neurologic diseases would have to be radically revised. Yet, this is unfeasible in the present stage; it is advisable to perform the therapy along the following three lines:

1) suppression of the apoptosis process;

2) correction of the disturbed metabolism processes (pathogenic therapy);

3) elimination of factors stimulating apoptosis (prevention).

Examples and significance of the pathogenic therapy were mentioned above. Apoptosis pharmacology is still in its infancy and most of pharmaceutical preparations are being experimentally tested.

As our experiments and two-year clinical studies have shown, the application of the drug Provit permits not only to arrest apoptosis but to simultaneously correct the disturbed metabolic processes as well.

It is recommended to administer Provit in children of the "risk group" aged 5-60 days when the nonformed hematoencephalitic barrier does not limit penetration of amino acids through nerve cells. The course of treatment lasts 20 days. The treatment results are presented below.

Another problem. Is it possible to prevent apoptosis development in adults? To do so, it is necessary to identify in every specific case factors stimulating this process, that is, an in-depth study of the pathogenesis of disease at the molecular level is required.

Take, for instance, multiple sclerosis, a severe demyelinating autoimmune disease. Etiology is unknown. Specificity, as compared with other autoimmune diseases, was not revealed. The pathogenesis at the molecular level, though, was established in sufficient detail.

Furthermore, genetic predisposition of individuals to multiple sclerosis has been established in the recent years. This applies not only to the immune component.

Apoptosis in oligodendrocytes triggered at a certain developmental stage severely inhibits remyelination processes preparing the ground for myelin loss (1).

Under these conditions, myelin loses the set of antiinflammatory means: antioxidants, proteolytic enzyme inhibitors, unique lipids; the flammatory reaction produced by autoimmune mechanisms can therefore be indefinitely long.

Yet, the process is not of total nature. For some unclear reasons, single cell groups are affected which contributes to the formation of separate foci. Apoptosis is stimulated by the following factors: g-interferon produced by T-lymphocytes; tumor necrosis factor (TNF) produced by astrocytes and macrophages; interleukin-I and others.

The cited biologically active compounds stimulate apoptosis in lesioned oligodendrocytes closing the vicious circle. This is why the disease is continually progressing. In these conditions, drugs of the b-interferon group, g-interferon and TNF antagonists, may substantially inhibit the pathologic process activity, yet they are unable of suppressing apoptosis.

The triggered cell death mechanism in oligodendricytes is going on and there are no guarantees against repeated exacerbation.

For this purpose, we suggest the following preparations.

"Halovit" that inhibits the activity of macrophages, T-lymphocytes and astrocytes and restores the myelin’s antioxidant background. Until recently, the drug was used to suppress the activity of macrophages in patients with intestinal infections. The use of the drug in the treatment of demyelinating patients will allow cell death suppression and will vigorously strengthen the remyelinating process.

The application areas of other drugs, cholamine and dechol, are T-lymphocytes. The drugs stimulate the triggering of apoptosis in these immunocompetent cells by restricting their activity.

Primavit, being an activator of ATP activity, was used as a pathogenic drug in treating multiple sclerosis patients.

The drug produced a pronounced therapeutic effect 3-4 days following the beginning of its intake. Its main destination is elimination of pyramidal symptoms and pelvic disorders. In this respect, Aminocomposit surpassed other preparations (especially, hormones) used to this end.

Combined application of the enumerated drugs made it possible to arrest the pathologic process in 83% of multiple sclerosis patients. Over a 4-year period of supervision of the group of patients concerned, not more than 2 exacerbations were reported while prior to treatment most of the patients were considered as those with progredient disease form.

As of today, the determined cell death hypothesis prevails both in terms of experiment and practice. The fight against apoptosis is complicated and requires a detailed knowledge of fine pathogenesis mechanisms and adequate metabolic therapy.

REFERENCES

1. Boiko, A.N.; Favorova, O.O. Multiple sclerosis: molecular and cellular mechanisms. Molecular Biology, 29(4), p. 727, 1993 (in Russian).

2. Gusev, Ye.I.; Skvortsova, V.I. et al. Neuroprotective therapy in the acute period of cerebral and ischemic insult. Clinical Messenger, issue 2, p. 6, 1995 (in Russian).

3. Karlov, V.A. in the book "Therapy of Nervous Diseases". M., 1996, p. 437 (in Russian).

4. Reutov, V.I.; Orlov, S.N. Physiological importance of guanylacyclase and the role of nitric oxide and nitrocompounds in the control of the activity of this enzyme. Physiology of Man, 19, #1, pp.114, 1993 (in Russian).

5. Khokhlov, A.P.; Savchenko, Yu.S. "Myelopathics and demyelinating diseases". M., 1991 (in Russian).

6. Beckman, I.S. The double-edged role of nitric oxide in brain function and superoxide-mediated injury. J. Dev. Physiol., 15, p. 53, 1991 (in English).

7. Bensimon, O.; Lacombler, L.; Meiningce, V. A control trial of riluzole in amyotrophic lateral sclerosis. N. Engl. J. Med., 330, 9, p. 585, 1994 (in English).

8. 8. Chenais et al. Hydroxy-Larginine as reactional intermediate in nitric oxide byosynthesis-induced cytostasis in human and murine tumor cells. Bioch. Biophys. Res. Communications, 196, p. 1558, 1993 (in English).

9. Ellis, R.E. et al. Mechanisms and functions of cell death. Annu. Rev. Cell Biol., 7, p. 663, 1991 (in English).

10. Oluffro, M.E. et al. Milacemide therapy for Parkinson’s disease. Mov. Disord. 8, p. 47, 1993 (in English).

11. Kathleen, M. Microglial-produced nitric oxide and reactive nitrogen oxides mediate neurol cell death. Brain Research 587, p.250, 1992 (in English).

12. Knowles, R.C.; Moncada, S. Nitric oxide syntheses in mammals. Biochem. J., 298, p. 249, 1994 (in English).

13. Moncada, S.; Hileos, E. Molecular mechanisms and therapeutic strategies related to nitric oxide. Fasseb J. 9, p. 1319, 1995 (in English).

14. Rand, M.I. Nitrergic transmission: nitric oxide as mediator of non-adrenergic, non-chlorinergic neuro-effector transmission. Clin. Exp. Pharmacol. Physiol. 19, p. 147, 1992 (in English).

15. Testa, D. et al. Chronic treatment with L-threonine in amyotrophic lateral sclerosis. Clin. Neurol., Neurosurgery 94(1), p. 7, 1992 (in English).

16. Vaux, D. et al. An evolutionary perspective on apoptosis. Cell. 76, p. 777, 1994 (in English).