[Models of bone defects in rabbits used to evaluate the bone graft materials efficacy]. / Modeli kostnykh defektov u krolikov, ispol'zuemye dlya otsenki effektivnosti kostno-plasticheskikh materialov.

The review deals with the main types of experimental models of bone defects of the skull in rabbits. The information about the types of critical defects, methods of their modeling and the possibilities of application of the described models in the studies of bone graft materials in dentistry and maxillofacial surgery is systematized.

[Study of properties of three-dimensional matrices manufactured by antisolvent 3D printing for reconstruction of extensive bone defects in dentistry and maxillofacial surgery]. / Issledovanie svoistv trekhmernykh matrits, izgotovlennykh metodom antisol'ventnoi 3D-pechati, dlya vosstanovleniya obshirnykh kostnykh defektov v stomatologii i chelyustno-litsevoi khirurgii.

OBJECTIVE: The aim of the study to study of physical, mechanical and biocompatible properties of the matrices manufactured by antisolvent 3D printing from the solutions of polylactide-co-glycolide in tetraglycol. MATERIAL AND METHODS: Three-dimensional scaffolds were made from a solution of polylactide-co-glycolide mixed with tetraglycol using antisolvent 3D printing. The elastic properties and the structure of the obtained matrices were studied. MTT-test and staining with PKH-26, Calcein-AM, DAPI with subsequent fluorescence microscopy were used to study biological properties. RESULTS: The three-dimensional scaffolds had good mechanical properties. Young's modulus value was 18±2 MPa, tensile strength was 0.43±0.05 MPa. The relative survival rate of cells after the first day was 99.58±2.28%, on the 14th day - 98.14±2.22%. The structure of the scaffold promoted cell adhesion and spreading on its surface. CONCLUSION: The polylactide-co-glycolide matrices produced by antisolvent printing have high porosity, biocompatibility and good mechanical properties. It is allowed to use them in the future as a basis for personalized constructions for the replacement of extensive bone defects of the maxillofacial region.

[Advantages and disadvantages of bone graft materials activated by BMP-2 and constructs carrying its gene]. / Preimushchestva i nedostatki kostno-plasticheskikh materialov, aktivirovannykh BMP-2 i nesushchimi ego gen konstruktsiyami.

In the review gene constructs and proteins used to impart osteoinductive properties to bone graft materials are compared. On the basis of clinical and experimental data the experience and prospects of their application in maxillofacial surgery and dentistry are described. Information about complications associated with the use of bone morphogenetic protein-2 (BMP-2) and vectors carrying its gene is provided.

[Characterization and biological activity of new 4-oxo-1,4-dihydrocinnoline-based inhibitors of the tyrosine phosphatase PTP1B and TCPTP]. / Kharakteristika i biologicheskaia aktivnost' novykh ingibitorov tirozinfosfataz PTP1B i TCPTP na osnove 4-okso-1,4-digidrotsinnolina.

Functional disorders in obesity are largely due to a decrease in tissue sensitivity to insulin and leptin. One of the ways to restore it is inhibition of protein phosphotyrosine phosphatase 1B (PTP1B) and T-cell protein phosphotyrosine phosphatase (TCPTP), negative regulators of the insulin and leptin signaling. Despite progress in the development of inhibitors of these phosphatases, commercial preparations based on them have not been developed yet, and the mechanisms of action are poorly understood. The aim of the work was to study the effect of new derivatives of 4-oxo-1,4-dihydrocinnoline (PI04, PI06, PI07) on the activity of PTP1B and TCPTP, as well as to study the effect of their five-day administration (i.p., 10 mg/kg/day) to Wistar rats with diet-induced obesity on body weight and fat, metabolic and hormonal parameters, and gene expression of phosphatase and insulin and leptin receptors in the liver. It has been shown that PI04 is a mild, low selective inhibitor of both phosphatases (PTP1B, IC50=3.42(2.60-4.51) µM; TCPTP, IC50=4.16(3.49-4.95) µM), while PI06 and PI07 preferentially inhibit PTP1B (IC50=3.55 (2.63-4.78) µM) and TCPTP (IC50=1.45(1.18-1.78) µM), respectively. PI04 significantly reduced food intake, body weight and fat, attenuated hyperglycemia, normalized glucose tolerance, basal and glucose-stimulated levels of insulin and leptin, and insulin resistance index. Despite the anorexigenic effect, PI06 and PI07 were less effective, having little effect on glucose homeostasis and insulin sensitivity. PI04 significantly increased the expression of the PTP1B and TCPTP genes and decreased the expression of the insulin and leptin receptor genes. PI06 and PI07 had little effect on these indicators. Thus, PI04, the inhibitor of PTP1B and TCPTP phosphatases, restored metabolic and hormonal parameters in obese rats with greater efficiency than inhibitors of PTP1B (PI06) and TCPTP (PI07). This indicates the prospect of creating mixed PTP1B/TCPTP inhibitors for correction of metabolic disorders.

Development prospects of curable osteoplastic materials in dentistry and maxillofacial surgery.

The article presents classification of the thermosetting materials for bone augmentation. The physical, mechanical, biological, and clinical properties of such materials are reviewed. There are two main types of curable osteoplastic materials: bone cements and hydrogels. Compared to hydrogels, bone cements have high strength features, but their biological properties are not ideal and must be improved. Hydrogels are biocompatible and closely mimic the extracellular matrix. They can be used as cytocompatible scaffolds for tissue engineering, as can protein- and nucleic acid-activated structures. Hydrogels may be impregnated with osteoinductors such as proteins and genetic vectors without conformational changes. However, the mechanical properties of hydrogels limit their use for load-bearing bone defects. Thus, improving the strength properties of hydrogels is one of the possible strategies to achieve the basis for an ideal osteoplastic material.

[Safety and efficacy of BMP-2 and BMP-7 use in dentistry]. / Bezopasnost' i éffektivnost' primeneniia morfogeneticheskikh belkov kosti 2 i 7 v stomatologii.

The article deals with bone morphogenetic proteins BMP-2 and BMP-7 with high osteoinductive potential. The materials containing these proteins are considered. Their safety and efficacy for regeneration of maxillofacial bone defects are evaluated. The prospects of bone tissue regeneration technologies development based on the use of bone morphogenetic proteins are described.

[Biocompatibility and osteoinductive properties of collagen and fibronectin hydrogel impregnated with rhBMP-2]. / Biosovmestimost' i osteogennye svoistva kollagen-fibronektinovogo gidrogelya, impregnirovannogo BMP-2.

The study aimed to demonstrate the biocompatibility and osteoinductive properties of a hydrogel based on highly purified collagen and fibronectin impregnated with rhBMP-2. In vitro and in vivo experiments have shown that the minimum effective dosage of rhBMP-2 is 10 µg/ml. The cytocompatibility of the collagen-fibronectin gel was determined using MTT test and staining with PKH-26. There was no inflammation reaction when the material was subcutaneously implanted in rats (n=30) in vivo. The collagen-fibronectin hydrogel containing 10 µg/ml rhBMP-2 showed high osteogenic properties. By the end of 28 days 8±4% of its volume was replaced by newly formed bone tissue in case of subcutaneous implantation, 17±10% in intramuscular implantation and 26±11% in intraosseous implantation in the calvarial critical-size. The optimal combination of biocompatible and osteogenic properties of collagen-fibronectin hydrogel impregnated with BMP-2 allows us to consider it as a promising basis for creating the new generation of osteoplastic materials for dentistry.

[Chitosan hydrogels biocompatibility improvement with the perspective of use as a base for osteoplastic materials in dentistry]. / Povyshenie biosovmestimosti khitozanovykh gidrogelei s perspektivoi ikh ispol'zovaniya v kachestve osnovy dlya kostno-plasticheskikh materialov v stomatologii.

Using chitosan as the basis for osteoplastic material, we were dealt with its low biocompatibility. The critical assessment of it is poorly presented in the literature and does not have systematic approaches to solving. The aim of the study was to determine the effect of factors affecting chitosan charge and its free amino groups number on the biocompatibility of hydrogels. Biocompatibility of chitosan compositions were studied in male Wistar rats (n=90). The subcutaneous implantation of chitosan discs and hydrogel caused abundant leukocyte infiltration. The addition of ß-glycerophosphate followed by dialysis slightly reduced the inflammatory response. Treatment with a solution of alkali NaOH and NaHCO3 buffer, on the contrary, intensified the inflammatory response. It is confirmed the effect of charged amino groups of chitosan on leukocyte taxis A decrease in the deacetylation degree (DD) of chitosan to 39.0% led to a statistically significant decrease in leukocyte infiltration. Saturation of chitosan hydrogels with PLA granules reduced by 16% the level of leukocyte infiltration, which was supposedly associated with a decrease in the volume of the hydrogel and an increase in the area of its interaction with blood plasma proteins, which reduce the positive charge of chitosan. The most significant reduction in leukocyte infiltration was achieved with a combination of deacetylated to 39.0% chitosan hydrogel with the addition of 16% by weight highly porous PLA granules.

[The prospects of hydrogels usage as a basis for curable osteoplastic materials]. / Perspektivy ispol'zovaniia gidrogelei v kachestve osnovy dlia otverzhdaemykh kostno-plasticheskikh materialov.

The article deals with the main types of the polymers used in hydrogel preparation. Their biological, physical and chemical properties was compared. Ways of polymers hardening and prospects of medical application were considered. The prospect of use of chitosan hydrogels activated by osteoinductors as a material for bone augmentation were concluded.

[The marker of discogenic diseases of the nervous system in the cerebrospinal fluid].

Using a novel diagnostic technology that allows to investigate the structure of a biological fluid formed during its phase transition into a dried film, we revealed a cause of mistaken results of protein concentrations in the cerebrospinal fluid of patients with discogenic radiculitis. The traditional laboratory study does not reveal the elevated content of protein in patients with discogenic radiculitis and hernia of invertebral discs due to its more active binding with salts with the following sedimentation during centrifugation. It can be explained by the involvement of salt crystals in the formation of the inert organic-mineral aggregate with protein molecules which structure was changed by dystrophy, ischemia, hypoxia, mechanic damage, tumor process. The aggregate is characterized by abnormally tight links. This phenomenon is known as biomineralization, the universal mechanism preventing the organism from toxic effects of products of degraded tissues.

[New actinomycin from Actinomyces sp. No. 2]. / Novyi aktinomitsin iz Actinomyces sp. No. 2.

A new actinomycin was isolated from a mixture of actinomycins formed by Actinomyces sp. No. 2, an organism producing auranthin, an actinomycetous antibiotic. The peptide chains of the new actinomycin contain such amino acids as threonine, valine, proline and sarcosine in a ratio of 2 : 4 : 2 : 2. N-Methyl-valine characteristic of all actinomycins is replaced in position 5 of both pentapeptide chains of the new actinomycin by valine. The new actinomycin is actinomycin D undermethylated in position 5 by valine. When the growing culture of Actinomyces olivobrunneus producing actinomycin D was exposed to sulfadimesine, an inhibitor of biological methylation, production of actinomycin D0 (sarcosine replaced by glycine in one of the pentapeptide chains) markedly increased, which indicated impairment of the glycine residue methylation. Still, no impairment of the valine residue methylation in position 5 of the pentapeptide chains was observed an no actinomycin with N-methyl-valine replaced by valine was formed.