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Alterarea componenţilor principali stromali ai biostructurilor organismului şi corijarea lor farmacologică

Author: Vladimir Remiş
Degree:doctor habilitat of pharmacy
Speciality: 15.00.01 - Pharmacy
Scientific consultants: Vasile Anestiadi
doctor habilitat
Serghei Gladkih
doctor habilitat în farmacie, profesor universitar, Moscova
Institution: Pathologic Centre of the ASM
Scientific council:


The thesis was presented on the 27 January, 2006
Approved by NCAA on the 27 April, 2006


Adobe PDF document0.44 Mb / in romanian


CZU 615/.2/.3.072

Adobe PDF document 12.74 Mb / in russian
225 pages


metal-ligand homeostasis, ligand pathology, chelate complexes, organism’s connective tissue structure, adhesive disease, atherosclerosis


The present work is dedicated to the efficiency of the systemic biomedical and biopharmaceutical approach to the solution for the problem of creation of new medicinal agents on the basis of the ligand pathology conception and chelate pharmacology and with regard for the activity of the constitutive enzyme the N-acetyltransferase (NAT2).

The retrospective NAT2 phenotyping of people suffering from the pathologies of the basic elements of the stromal biostructures (collagen and elastin) demonstrated a genetic predisposition of some individuals to various diseases.

It was revealed that the “fast” acetylators are predisposed to the pathologic processes associated with the prevailing of the biosynthesis of the noncellular components of the connective tissue over its catabolism (the adhesive disease), and the “slow” acetylators represent a risk group of a number of diseases including the atherosclerosis.

In the pathogenesis of the postoperative adhesive disease one of the leading parts is assigned to the high general acetylating capacity of human and animal organisms.

Since the postoperative adhesive disease is an anomalous outgrowing of the connective tissue in the area of the cavitary surgical intervention (in a “fast” acetylating phenotype), the proposed medicinal agent, used for the prophylaxis and treatment of the adhesive disease, displays its pharmacologic action by means of the blocking the processes of the biosynthesis of the collagen which is the main extracellular component of adhesions.

The particularities of the mechanism of action of the preparation Isonidesum linked with the blocking the active center of the intracellular enzyme lysiloxidase give it considerable advantages over practice up to the present time.

The local action of the preparation in the experiment and in clinic is realized owing the disorganization of the intracellular synthesis and the disturbance of the fibrillogenesis of the noncellular component of the connective tissue bound up with chelating of the active centers of the metal containing enzymes (prolilhydroxydase and lysiloxidase) by the ligand - isoniazide.

The therapeutic efficacy of the Isonidezum also depends on the function of the principal auxiliary component the polyvinylpyrrolidone (PVP). The study of the Isonidezum pharmacokinetics confirmed the role of the PVP as a prolongator of the pharmacologic effect of the isoniaside. The preparation demonstrates the high specific activity. There were no negative consequences of the use of the preparation Isonidesum both in the abdominal and in cosmetic surgery.

It was proved experimentally that the nutritional deficiency of copper and pyridoxine leads to the fibrinogenesis breach of the extracellular component in the vascular wall (aorta). These disturbances were comsed by ligands of endogenous and exogenous origins, which bind the copper in the composition of the lysiloxidases responsable for the fibrinogenesis of the collagen and elastin in the insoluble chelate complecsis. On the basis of the clinical researches of the lysinoprile an original hypothesis of the action mechanism of the blocking agents of the angiotensin – converting enzyme (ACE) from a position of the ligand (chelate) pathology and a conception of the metal-ligand homeostasis which is stipulated by the formation of chelate complecsies with the ions of the biogenic metals necessary for the optimum functioning of the enzymes is suggested.