Basic and clinical research has underpinned the thesis of Physiological Regulating Medicine: in November 2009, in fact, the journal Pulmonary Pharmacology & Therapeutics published the first paper on the effects of low dose SKA cytokines in an animal model of allergic asthma (Gariboldi et al. Low dose oral administration of cytokines for treatment of allergic asthma. Pulmonary Pharmacology & Therapeutics 22 (2009) 497-510).
Since 2009, new publications have followed the paper published by Pulmonary Pharmacology & Therapeutics.
Low Dose Pharmacology
Collagen Medical Devices
|
Year |
Authors |
Journal |
Research type |
Title |
Medical Device |
|---|---|---|---|---|---|
|
2016 |
Martin-Martin L. S. et al. |
BMC Musculoskeletal Disorders |
Clinical Trial | A double blind randomized active-controlled clinical trial on the intra-articular use of Md-Knee versus sodium hyaluronate in patients with knee osteoarthritis (“Joint”). |
MD-KNEE |
|
2018 |
Randelli F. et al. |
Cells |
Ex vivo basic research | Effect of a Collagen-Based Compound on Morpho-Functional Properties of Cultured Human Tenocytes. |
MD-TISSUE |
|
2018 |
Nitecka-Buchta A. et al. |
Pain Research and Management |
Clinical Study |
MD-MUSCLE |
Physiological Nutraceutical
Synopsis of research on Physiological Regulating Medicine
The analyzed articles report the experimental evidence of the effectiveness of PRM approach on diseases involving the immune system. All the papers show the ability of the signaling molecules to modulate the responses of immune cells in a highly selective fashion; especially, the immunostimulatory and immunomodulatory skills of the tested cytokines are clearly described.
The ability to act in a refined manner on the Th1/Th2 balance is crucial for the management of diseases with diametrically opposed cytokine imbalances such as Bronchial Allergic Asthma (which shows a Th2 predominance), Crohn’s disease and Psoriasis Vulgaris (Th1-driven diseases).
One of the key issues emerging from the analyzed scientific works is the effectiveness of treatment with low dose molecules in spite of the fact that they operate at lower concentrations than those generally considered pharmacologically effective.
The use of cytokines and other signaling molecules has often collided with the need of high dosages, realizing concentrations which show a wide range of side effects in addition to the proper pharmacological effects.
The classical minimum active dose is generally found between the lowest pharmacological one (10-5) and the highest physiological one (10-6) (Figure 4); low dose pharmacology moves within the range of physiological concentrations of signaling molecules acting below the concentrations at which adverse effects appear but equally reaching appreciable therapeutic results.The ligand-receptor binding properties are crucial to explain how low dose SKA signaling molecules can be effective. Receptor affinity for its specific ligand is fundamental for the activation of postreceptorial downstream, in fact ligand saturation generally induces the receptor freezing and/or its down-regulation. Low dose molecules are able to induce a direct physiological receptorial stimulation of immune cells (as described by Gariboldi S. and colleagues) modulating the responses within the homeostatic range; PRM realizes one of the cardinal points of P.N.E.I. approach to the disease: to restore physiological panel of signaling molecules.
From a pharmacological point of view the revised works highlight the importance of the activation of low dose molecules through the process of drug delivery known as SKA (Sequential Kinetic Activation): low dose molecules not processed with this activation procedure are totally ineffective as described by Gariboldi Set al. SKA activation is fundamental in order to overcome the conceptual wall represented by the minimum pharmacologically effective dose inducing an activity release effect exerted by low dose molecules by interaction with the aqueous vehicle.
Conclusions on Physiological Regulating Medicine and related research
Five years of scientific research on Physiological Regulating Medicine have allowed researchers to provide data of a different nature, scientifically relevant, able to demonstrate:
- The validity of the theoretical concepts underlying the PRM;
- The centrality of the pharmaceutical technological process called SKA (Sequential Kinetic Activation);
- The experimental and clinical effectiveness of low dose SKA signaling molecules.
- The immunomodulatory and immunostimulant ability of cytokines and the trophic activity of growth factors;
- The safety of the preparations tested.
