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IV.5.3.2.1. AN EXAMPLE OF CLINICAL SYNERGY IN AUTOIMMUNITY

 

It is well known the role of the beneficial intervention in the immune response of the PMN granulocytes for the neutralization of the exogenous or endogenous antigens.

We could choose any other examples on other diseases, where the synergistic action of the complex of bioactive substances contained in the honey bee therapeutic products we produce has a clear beneficial role. We chosed an example of the field of autoimmune diseases in which the intervention of PMN, one of the most effective means of action of the body in the injuries caused by the autoantibodies that positivated themselves by the antigens action, for two reasons. First, because the autoimmune diseases are a definite offensive, affecting a growing number of humans. The second reason are the successes that, by apitherapy, we have obtained in various autoimmune diseases. In medical premiere, by apitherapy, we have been able to negativate the autoantibodies synthesized as a result of exogenous or endogenous antigens action.

That was possible thanks to the researches that we conducted on the cell disorders caused by autoimmunity, the way and substances of intervention in atiinflamatory steroid medication (AIS) and non-steroid medication (NSAIDs). These were combined with the study of the immunosuppressive, immunomodulators factors contained in honey bee therapeutic products, which have the potential to interfere beneficially in the mechanism of autoimmunity. We dedicated to the immunomodulatory potential of the honey bee therapeutic products a significant number of studies already published (see Appendix 1), and a PhD thesis in medical sciences. And in this paper the apitherapy in autoimmune diseases will occupy a large space, not only thanks to the  successes obtained in this extended chapter of the human pathology, but also due to other medical firsts which belong to us: the negativation of the autoantibodies through apitherapy. Through length comparative studies, also as medical firsts, we demonstrate the theory of the apiprophylaxis in autoimmune diseases.

The antigenic action of PMN is stimulated by soluble mediators on the type of the cytokines TNF and IL-1β. These cells with cytoplasmic grains – as they are supported by a rich enzymatic equipment and a large number of adhesion molecules (ICAM) - in cooperation with T cells, B cells and antigen-presenting (APC), intervene against the antigen (by phagocytosis / pinocytosis) and destroy it. With a high oxidative potential, they release large amounts of RLO, degrading not only the antigens, but also the epitopes. After the destruction of the antigen, in the possible absence of antioxidants that can control them, limit and stop their actions, the PMN continue to release proteolytic enzymes and RLO which can result in severe injury, self harm, autoimmunity, premature aging.

The honey bee therapeutic products produced by the Apytherapy Medical Center are beneficially involved in this process  for protecting the immunity and / or for preventing the onset of the autoimmunity because:

1) they ensure the action synergy through the presence synergy of an important number of substances that support, but also limit the anti-inflammatory actions of PMN;

2) they ensure, also sinergically, the substances that may protect the neighboring cells from any aggressive actions of PMN, which would act without limitation;

3) they provide all the substances needed for the reconstruction of the possibly destroyed cells.

We are recalling the fact of great importance especially for the organisms whose metabolism is deficient that this offer has a character of duality: it includes both the primary necessary precursor substances from which the body can synthesize the substances it needs, but also a variety of preformed biomolecules, directly available to the body which struggles to maintain or regain its immunity.

In a brief and incomplete summary of the reports Apitherapy-PMN-physiological immunity, we may hold several significant aspects of the intervention of honey bee therapeutic products  in regulating their anti inflammatory functions, the honey bee therapeutic products  comprising:

- substances that help regulate the homeostasis of  the functions of the bone marrow, where are synthesized and start their maturation the PMN from where they come through the bloodstream and diapedese to the affected antigens;

- substances that facilitate the PMN locomotion to the affected area;

- full range of enzymes that forms the rich and varied proteolytic enzyme-oxidative equipment of PMN;

- all the antioxidants known in the medical sciences, including all the enzymes that control, limit and stop the activity of PMN after the neutralization of the antigen, the last also playing the role of   inactivating the RLO, preventing the occurrence of the injuries with the destruction of their own cells and tissues;

- all the primary substances precursor of the glycoproteins, but also the glycoproteins as biomolecules directly available, contributing to the synthesis of antibodies which, of the biochemical point of view, are glycoproteins and have important tasks in the human physiological  immunity;

- all the substances which contribute to the reconstruction of possibly damaged cells, such as raw material for its own biosynthesis and as biomolecules: amino acids, lipids, carbohydrates, solubilized minerals, amino acids DNA and RNA, growth factors etc.etc.;

Bringing us closer to the subject of the present issue, we are joining to the above the statement - which we are supporting by the results of clinical research – about the importance of the albumin and of restoring the A/G physiological ratio, in close relation to ionic serum calcium, both in prohibiting the onset of the inflammatory diseases and  in the neutralization of the autoimmune processes.

The immunologist Andrew Olinescu appreciatse that, compared to any other therapy, the systemic administration of the enzymes superoxide dismutase (SOD) and catalase in cases of self harm, is "the only effective therapy" (Olinescu, 2005).

It is well known, that the SOD and catalase are ubiquitous in the bee products, as in the honey bee therapeutic products A.M.C. The  SOD, as oxidoreducing enzyme, catalyzes the dismutation reaction of the superoxide radical, with formation of hydrogen peroxide, limiting the aggressive actions of RLO:

O2-+ O2-+ 2H + = H2O2 + O2

The honey bee therapeutic products offer not only SOD, as directly active biomolecules, but also minerals Cu, Zn and Mn necessary to the organic biosynthesis of this enzyme. The SOD antioxidant action is supported, in synergy of presence and action by the catalase, an enzyme with hemoprotein structure, with an important role in the decomposition of H2O2 formed in peroxisomes:

2H2O2 = 2H2O + O2

The honey bee therapeutic products offer biomolecules of catalase and also Mn needed to its biosynthesis in the human body. The synergy of presence and action of the SOD and catalase, each other but also with other bioelements, is much broader.

The bee glucocorticoids, well represented in A.M.C. honey bee therapeutic products have a significant anti-inflammatory action without any of the drawbacks present in the corticotherapy  with corticosteroids of pharmacochemical synthesis. Acting synergistically with PMN, they limit their involvement in too high number to the site of the inflammation by their own anti-inflammatory action, reducing both quantitatively the RLO and the exposure time of the body to their actions. In addition to the direct anti-inflammatory action, they stabilize the lysosomal membranes, preventing the release of hydrolytic action enzymes, suppresse the phagocytosis and T cell activation, reduce the synthesis of IL-1, in turn increasing the synthesis of lpocortin (Annex I) - inhibiting the phospholipase A2, which has itself an anti-inflammatory action.

The vitamin A, in synergy with vitamins C and E, as well as with some metal ions participate in the oxydoreduction of the RLO. The troponin acts synergistically with the vitamin C etc.etc.

 

Table no. 5. Intervention of Honey Bee Therapeutic Products in Polymorphonuclear Granulocytes (PMN) Actions.

They support / prohibitthe PMN movementto the site of infection

They support PMN action of antigen degradation on the affected site

RLO produced by the oxidative action of PMN

They protect the cells against  RLO / help the cell reconstruction

-Glycoproteins - for antibodies synthesis

- Arachidonic Acid – for leukotriene and prostaglandin synthesis

-Amino-acids - for synthesis of molecular compounds (as fMLP, methionine, leucine, phenylalanine).

-Albumin:

a) plays the role of shipping role bioactive substances;

b) prohibits the self-aggresions onset

-Ca2 +:

a) synergistically supports

the albumin actions

b) ionic hypocalcemia

favors the

synthesis of auto-antibodies

pylorus, hipoalbumi-

nemia and onset of

autoimmunity.

* Lysosomal enzymes

* Proteinases, elastase,  collagenase, cathepsin G

* Acid hydrolases

   of gucuronidases, glicerophosphates type, etc…

* Oxidases - type NADPH oxidase- with composing source in nicotinic acid and flavoproteins: it initiates the oxidation.

* Holoproteins ​​and hetero-proteins making up molecular complexes on the surface of PMN  or damaged cells.

 

 

 

 

 

By oxidative metabolism it generates:

 

O2 - Superoxide anion

 

H2O- Hydrogen peroxide

 

1O2- Oxygen singlet 

 

OH  - Hydroxyl radical

 

ROO - peroxiradical

 

HOCl - hypochlorous acid, roduced in the presence of MPO           

 

 

 

 

 

 

 

 

1) Control / limit

PMN action:

- Superoxide dismutase

-Catalase

-Glutathione

- Glutathione peroxidase

-Glutathione transferase

-Glucocorticoids of honey bee products

  well represented in

CENTAUR I, II, III     

- Albumin- it bans -1O2 synthesis

- Ca2 + - support inclusively  the

   biologicalactions

  of  albumin

-Other antioxidants

2) Honey Bee Steroids Anti-inflammatory

3) All substancesdesigned for the   protectionand / or reconstruction of the cell.      

(Adapted from Andrițoiu V., 2006, 2012; Andrițoiu și Andrițoiu, 2010)

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