Results of Experimental Hernioplasty with Acellular Dermal Matrix.

We performed a comprehensive assessment of the acellular dermal matrix obtained during the detergent-enzymatic treatment of the porcine dermis. Acellular dermal matrix was used for the experimental treatment of a hernial defect in a pig using the sublay method. Sixty days after the surgery, biopsy specimens were obtained from the area of hernia repair. The acellular dermal matrix can be easily modeled depending on the size and shape of the defect during surgical procedures, can eliminate the defect of the anterior abdominal wall, and is resistant to cutting by the suture material. Histological examination demonstrated replacement of the acellular dermal matrix with newly formed connective tissue.

Use of natural products in anticytokine therapy.

This work was designed to study direct anticytokine activity of natural products on the cell model of inflammation. We developed a combination of medicinal plants (calendula, elder, and pansy) with maximum antiinflammatory activity. This combination can be used for pathogenetic therapy of various inflammatory diseases, including atherosclerosis.

Desialylation decreases the resistance of apo B-containing lipoproteins to aggregation and increases their atherogenic potential.

Subfractions of apo B-containing lipoproteins (VLDL and intermediate-density lipoproteins) with reduced content of sialic acid were found in human blood. These lipoproteins are characterized by high capacity to spontaneous association (aggregation) and stimulated accumulation of cholesterol in smooth muscle cells of human aortic intima. In vitro treatment of apo B-containing lipoproteins with alpha-2,6-sialidase and alpha-2,3-sialidase stimulated aggregation and increased the ability of these particles to potentiate cholesterol accumulation in smooth muscle cells of the intact human aortic intima. Probably, desialylation of various apo B-containing lipoproteins can occur in the blood; this process decreases their resistance to aggregation, and increases the ability of these particles to stimulate accumulation of cholesterol in human aortic intima cells, i.e. increases their atherogenic potential.

Phospholipid hydrolysis with phospholipases A2 and C impairs apolipoprotein B-100 conformation on the surface of low density lipoproteins by reducing their association resistance.

Modification of apolipoprotein B-100 conformation on the surface of LDL isolated from human blood was demonstrated by enzyme immunoassay with a panel of monoclonal antibodies to this protein. The study by the light transmission fluctuation method showed that incubation of LDL with phospholipases A2 or C led to association of LDL particles. This lipolytic modification seems to impair LDL surface properties inducing association of these particles, which can play an important role in lipid accumulation in the vascular wall and at early stages promote the development of atherosclerosis.

Proteolysis of apoprotein B-100 impairs its topography on LDL surface and reduces LDL association resistance.

Serine proteinases (trypsin and chymotrypsin) cause destruction of apolipoprotein B-100 on the surface of human blood LDL. Incubation of LDL with these enzymes increases the mean size of LDL particles. Proteolysis of apolipoprotein B-100 induces changes in surface structure, destabilizes LDL particles, and reduces their association resistance. Presumably, this proteolytic modification of LDL with subsequent association of these particles plays an important role in accumulation of cholesterol in the vascular wall and in the development of early stages of atherosclerosis.

Antigenic differences between apo-B in native and circulating modified low-density lipoproteins.

The state of apo-B in native and circulating modified low-density lipoproteins was studied by solid-phase enzyme immunoassay. We studied the interaction of these particles with monoclonal antibodies to apo-B of low-density lipoproteins. Native and circulating modified low-density lipoproteins had different affinity for the studied antigens. Our results illustrate conformational changes in apo-B of circulating modified low-density lipoproteins compared to native low-density lipoproteins. These changes probably contribute to increased accumulation of particles in vascular cells and their transformation into foam cells giving way to atherosclerotic vascular lesions.

Low ionic strength promotes association of circulating modified LDL in human blood.

The resistance to association of circulating multiply-modified low-density lipoproteins (LDL) isolated from human blood and characterized by a decreased content of sialic acids in comparison with native LDL was studied by analysing light transmission fluctuations. LDL association was stimulated by decreasing environmental ionic strength. It is established that circulating modified LDL are less resistant to association than native LDL. Association of LDL in a medium with low ionic strength was irreversible. Probably, increased capacity to irreversible association determines the atherogenic properties of circulating modified LDL subfraction.

Resistance of native and circulating modified low-density lipoproteins in human blood to association.

The resistance of native and circulating modified low-density lipoproteins from human blood to spontaneous and polyethylene glycol-induced association was studied by recording light transmission fluctuations. Circulating modified low-density lipoproteins were less resistant to association than native low-density lipoproteins. Polyethylene glycol-induced association of low-density lipoproteins was irreversible. Our results suggest that atherogenic activity of circulating modified low-density lipoproteins is associated with their increased predisposition to irreversible association.

[Comparative evaluation of the antioxidant and antiatherogenic effect of natural and selenoorganic substances]. / Sravnitel'naia otsenka antioksidantnogo i antiaterogennogo deistviia preparatov prirodnogo i selenorganicheskogo proiskhozhdeniia.

The antioxidant and atherogenic effects of naturally occurring compounds (soya isoflavones) and of the synthetic organic compounds of selenium (selenopyran and dimethyl-pyrosalyl-selenide) on the primary cell culture of human aortic subendothelial intima and on macrophage cell culture were investigated. Our results suggest that soya isoflavones exhibit mainly antiatherogenic effect and organic compounds of selenium exhibit mainly antioxidant effect.

The content of lipoperoxidation products in normal and atherosclerotic human aorta.

To evaluate the role of lipid oxidation in atherogenesis the levels of lipid- and protein-bound products of peroxidation in normal and atherosclerotic areas of human aorta were investigated. The level of fluorescent (360/430 nm) lipid products was measured in chloroform-methanol extracts of aortic tissue. Normal intima, initial lesions and fatty streaks had a similar content of fluorescent substances. On the other hand, high level of fluorescent products was found in atherosclerotic plaques. Cholesterol covalently bound to proteins, which serve as a marker of lipoperoxidation, was measured by high performance liquid chromatography after mild alkaline hydrolysis of delipidated tissue protein samples. The levels of protein-bound cholesterol in initial lesions and fatty streaks were close to its content in uninvolved intima (59 +/- 18 and 92 +/- 18 vs. 70 +/- 13 nmol/g protein). The content of covalently bound cholesterol in atherosclerotic plaques was dramatically higher (90-fold) than in the normal tissue. In addition to protein-bound cholesterol, considerable amount of lipofuscin was revealed in the cells of atherosclerotic plaques, but not in the cells of normal intima, initial lesions or fatty streaks. Thus, the contents of all investigated lipid- and protein-bound products of lipoperoxidation in earlier atherosclerotic lesions were similar to their levels in normal tissue. It can be due to a low rate of oxidized product formation and/or high rate of its degradation in or elimination from the vessel wall.