Paper presented at the 6th International Congress on Amino Acids, Bonn 1999
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Renato Cocchi M.D., Ph.D. (Sociology) Paper presented at the 6th International Congress on Amino Acids, Bonn 1999 |
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Reprinted with the permission of Renato Cocchi Via A. Rabbeno, 3 42100 Reggio Emilia, Italy +39 0522 320 716 Mobile +39 348 5145 520 URL: http://www.stress-cocchi.net |
Normal and Down children with easiness to upper respiratory tract infections (URTI) had favourable treatment by Gabaergic drugs. Research showed that stress undermines host resistance to infections through neuroendocrine mediated changes in immuno-competence. It is the same for every kind of stress, even for internal metabolic stress due to a chromosomal anomaly, as it happens in Down syndrome.
Because the immune suppressive action of stress via the GABA impairment and subsequent cortisol hyperincretion or hyperactivity, it has been explained the rationale to counteract this easiness by drugs, one of which is glutamine. This drug is also directly involved in the nucleogenesis of rapid proliferating cells, by this way contributing to a larger production of leukocytes. Key words: Glutamine, URTI easiness, Stress, GABAergic drugs, Nucleogenesis, Leukocytes.
Since the pioneering study in depressed children (Cocchi, 1981) normal and Down children with easiness to upper respiratory tract infections (URTI) had favourable treatment by Gabaergic drugs (Cocchi, 1998a; 1998b). This immune-protective effect in Down children appears early before the age-related decreasing of easiness to upper respiratory tract infections (Cocchi 1997, 1998a).
Profound forms of URTI easiness stop at the 8-10 years' interval in drug-treated Ss, but at the 14-16 years' interval in non treated Ss. Severe forms in non treated Ss are again 10% while they are only 5% in drug-treated Ss, at more than 16 years.
Metabolic stress, in Down Ss, could relate to the "dosage effect" of the third chromosome 21 (Cocchi 1994). Research showed that stress undermines host resistance to infections through neurendocrine mediated changes in immune competence (Boyce et al., 1995). It is the same for every kind of stress of external or internal origin or both. The adrenergic blockade improves also cellular immune responses otherwise depressed by the so called mental stress in humans as one type of internal stresses (Bachen et al.,1995).
Because the immune-suppressive action of stress via the GABA impairment (Horger and Roth, 1995) and subsequent cortisol hyper-incretion or hyper-activity (Dhabhar et al., 1996; Haessig et al., 1996; Dantzer, 1997; Friedman and Irwin, 1997), the rationale of the treatment to counteract this easiness by drugs has its explanation as it follows.
The basic treatment uses Gabaergic drugs like l-glutamine as the precursor of GABA via l-glutamic acid (Laake et al., 1995; Shupliakov et al., 1997). Pyridoxine is the cofactor of all decarboxylases, GAD inclusive (Baxter, 1976).
Finally, a benzodiazepine is the sensitizer of type A Gabaergic receptors and a powerful antistress agent (Bruni et al., 1980; Viukari, 1983; Schoch et al., 1985).
In 1-14 years children we can prescribe the following:
This 3-drugs' prescription works in a synergistic way and can restore the glutamic-GABA pathway impaired by the stress itself. The use of a benzodiazepine aims to resensitize type A Gabaergic receptors, the first metabolic point where stress applies itself. Without doing it we could induce only the increasing of the glutamate with hazardous effects.
This evening use of a benzodiazepine is the best way to restore sleep ( Viukari, 1983) often impaired by excess adrenergic stimulation. Moreover, it can to avoid side-effects like daily drowsiness and muscle relaxation.
On the other hand l-glutamine is directly involved in the nucleogenesis of rapid proliferating cells (Gismondo et al., 1998). Namely it is the donor of the N atoms 3 and 9 of the purinic ring (Stryer, 1988). By this way it contributes to a better production of leukocytes (Heberer et al., 1996; Newsholme & Calder 1997; Yoo, et al., 1997).
A personal anecdotal experience (non yet published) strongly suggests also the use of this antistress therapy in HIV+ Ss. It can lead to increase the leucocytes production both by reducing the metabolic stress due to the illness itself and by favouring the nucleogenesis.
Baxter C.F.: Some recent advances in studies of GABA metabolism and compartmentation. In: Roberts E., Chase T.N., Tower D.B. (eds): GABA in nervous system function. Raven, New York 1976: 61-87.
Boyce W.T. et al.: Psychobiological reactivity to stress and childhood respiratory illnesses: Result of two prospective studies. Psychosom. Med. 1995, 57: 411-422.
Bruni G., Dal Pra P., Dotti M.T., Segre G.: Plasma ACTH and cortisol levels in benzodiazepine treated rats. Pharmacol. Res. Commun. 1980, 12/2: 163-175.
Catsell L.M., Poortmans J.R., Newsholme E.A.: Does glutamine have a role in reducing infections in athletes? Eur. J. Appl. Physiol. 1996, 75: 488-490.
Cocchi R. Susceptibility to infective respiratory diseases in depressed children. Epidemiological survey of 126 subjects, clinical-therapeutic report of 61 cases. Acta Psychiat. Belg. 1981, 81: 350-365.
Cocchi R. Drug therapy in Down's Syndrome: A theoretical context. It. J. Internat. Impair. 1993, 6: 43-154.
Cocchi R.: Easiness to upper respiratory tract infections: An investigation on 510 Down's syndrome persons. It. J. Intellect. Impair 1997, 10: 143-149
Cocchi R.: Drug therapy of upper respiratory tract infections easiness in Downs: A survey on 328 persons. It. J. Intellect. Impair. 1998a, 11: 9-17
Cocchi R.: Drug therapy of stress on respiratory tract infections easiness in Downs: A survey on one-year and two-years results. It. J. Intellect. Impair. 1998b, 11: 161-171.
Cocchi R.: Glutamine as the key amino acid in promoting cell-mediated immunity: 20 years of clinical experience. Amino Acids 1999, 11: 104 (abstract of the paper).
Cynober L.: Glutamine as an activator of immune cells: How does it work? Nutrition 1997, 13: 688-689.
Dhabhar F.F. et al.: Stress-induced changes in blood leukocyte distribution. Role of adrenal steroid hormones. J. Immunol. 1996, 157: 1638-1644.
Dantzer R.: Stress and immunity: What we have learned from psychomeuro-immunology? Acta Physiol. Scand.Suppl. 1997, 640: 43-46.
Friedman E.M., Irwin M.R.: Modulation of immune cell function by the autonomic nervous system. Pharmacol. Ther. 1997, 74: 27-38.
Gennari R., Alexander J.W.: Arginine, glutamine and dehydroepiandrosterone reverse the immuno suppressive effect of prednisone during gut-derived sepsis. Crit. Care Med. 1997, 25: 1207-1214.
Gismondo M.R. et al: Immunostimulating effect of oral glutamine. Dig. Dis. Sci. 1998, 43: 1752-1754.
Haessig A., Wen-Xi L., Staempfli K.: Stress-induced suppression of the cellular immune reactions: On the neurendocrine control of the immune system. Med. Hypotheses 1996, 46: 551-555.
Heberer M. et al.: Role of glutamine in the immune response in critical illness. Nutrition 1996, 12(11-12 suppl): S71-72.
Horger B.A., Roth R.H.: Stress and central amino acid system. In: Friedman M.J., Charney D.S., Deutch A.J. (eds): Neurobiological and clinical consequences of stress: From adaptation to PTSD. Lippincott-Raven, Philadelphia, 1995: 61-81.
Laake J.H. et al.: Glutamine from glial cells is essential for the maintenance of the nerve terminal pool of glutamate: Immunogold evidence from hippocampal slice cultures. J. Neurochem. 1995, 65: 871-881.
Lavoinne A.: Glutamine and the acute phase response: The role of cell swelling. . Amino Acids 1999, 11: 104 (abstract of the paper).
Newsholm E.A., Calder P.C: The proposed role of glutamine in some cells of the immune system and speculative consequences for the whole animal. Nutrition 1997, 13: 728-730.
Oehler R., Roth E.: Influence of glutamine on apoptosis and heat shock protein expression. Amino Acids 1999, 11: 103 (abstract of the paper).
O'Riordain M.G., Be Beaux A., Fearon K.C.: Effect of glutamine on immune function of the surgical patient. Nutrition 1996, 12(11-12 suppl.): S82-84.
Shabert J.K., Wilmore D.W.: Glutamine deficiency as a cause of human immunodeficienci virus wasting. Med. Hypotheses 1996, 46: 252-256.
Shuplakow O. et al.: Glial and neuronal glutamine pools at glutamergic synapses with distinct properties.Neuroscience 1977, 77: 1201-1212.
Stryer L.: Biochemistry. Freeman and Co., New York 1988
Viukari M.: Sleep and benzodiazepines. In: Costa E. (ed): The benzodiazepines.From molecular biology to clinicalpractice. Raven New York, 1983: 279-286.
Werner M.C., Costa Rosa L.F., Romaldini J.H., Curi R.: Metabolism of glucose and glutamine in lymphocytes from Graves' hyperthyroid patients: Influence of methimazole treatment. Cell. Biochem. Funct. 1996, 14: 97-104.
Yacob P.: Glutamine and cytokine production. Amino Acids 1999, 11: 103 (abstract of the paper).
Yoo S.S., Field C.J., McBurney M.I.: Glutamine supplementation maintains intramuscular glutamine concentrations and normalizes lymphocyte function in infected early weaned pigs. J. Nutr. 1997, 127: 2253-2259.