Structure, properties, and decomposition in biological systems of a new nitrosyl iron complex with 2-methoxythiophenolyls, promising for the treatment of cardiovascular diseases.

A new promising binuclear tetranitrosyl iron complex with 2-methoxythiophenolyl of the composition [Fe(CHOS)(NO)] (complex 1), which acts on the therapeutic targets of cardiovascular diseases, guanylate and adenylate cyclase, has been synthesized. X-ray diffraction data show the presence of two isoforms of complex 1; according to quantum chemical calculations, the structure of only the trans isomer is stable in solutions. The processes of transformation of complex 1 in DMSO, in aqueous solutions, as well as in the presence of bovine serum albumin, reduced glutathione, and mucin were studied.

Effect of Pyridoxine Derivative B6NO on Transcription Factor Nrf2 Activity and Cytotoxic Properties of Doxorubicin In Vitro.

The effect of a new pyridoxine derivative B6NO on doxorubicin cytotoxicity and Nrf2-dependent cellular processes in vitro was studied. Antioxidant B6NO enhances the cytotoxic effect of doxorubicin on tumor cells, which is associated with G2/M cell division arrest and an increase in activity of proapoptotic enzyme caspase-3. The antioxidant promotes intracellular accumulation and nuclear translocation of Nrf2 transcription factor in non-tumor and tumor cells.

Cationic dinitrosyl iron complexes with thiourea exhibit selective toxicity to brain tumor cells .

The cytotoxic activity of a series of dinitrosyl iron complexes (DNICs) with thioureas against cells of different origin has been studied in this work. The cytotoxicity of the studied DNICs proved to be substantially different depending on the structure of the complexes and cell line. Complexes with thiourea and 1,3-dimethylthiourea were found to induce notable cell death in different cell lines of both cancerous and non-cancerous origin, while the -ethylthiourea-bearing complex induced cell death in cells derived from brain tumors.

Amphiphilic chitosan-polyaminoxyls loaded with daunorubicin: Synthesis, antioxidant activity, and drug delivery capacity.

The binding of aminoxyls to polymers extends their potential use as antioxidants and EPR-reporting groups and opens up new horizons for tailoring new smart materials. In this work, we synthesized and characterized non-sulfated and N-sulfated water-soluble amphiphilic chitosans with a critical micelle concentration of 0.02-0.

Preparation, Antioxidant Properties and Ability to Increase Intracellular NO of a New Pyridoxine Derivative B6NO.

In the case of various pathologies, an imbalance between ROS generation and the endogenous AOS can be observed, which leads to excessive ROS accumulation, intensification of LPO processes, and oxidative stress. For the prevention of diseases associated with oxidative stress, drugs with antioxidant activity can be used. The cytotoxic, antioxidant, and NO-donor properties of the new hybrid compound B6NO (di(3-hydroxy-4,5-bis(hydroxymethyl)-2-methylpyridinium) salt of 2-(nitrooxy)butanedioic acid) were studied.

Novel potent bifunctional carboxylesterase inhibitors based on a polyfluoroalkyl-2-imino-1,3-dione scaffold.

An expanded series of alkyl 2-arylhydrazinylidene-3-oxo-3-polyfluoroalkylpropionates (HOPs) 3 was obtained via Cu(OAc)-catalyzed azo coupling. All were nanomolar inhibitors of carboxylesterase (CES), while moderate or weak inhibitors of acetylcholinesterase and butyrylcholinesterase. Steady-state kinetics studies showed that HOPs 3 are mixed type inhibitors of the three esterases.

Anatomy of the Bezymianny volcano merely before an explosive eruption on 20.12.2017.

Strong explosive eruptions of volcanoes throw out mixtures of gases and ash from high-pressure underground reservoirs. Investigating these subsurface reservoirs may help to forecast and characterize an eruption. In this study, we compare seismic tomography results with remote sensing and petrology data to identify deep and subaerial manifestations of pre-eruptive processes at Bezymianny volcano in Kamchatka shortly before its violent explosion on December 20, 2017.

Conjugates of tacrine and 1,2,4-thiadiazole derivatives as new potential multifunctional agents for Alzheimer's disease treatment: Synthesis, quantum-chemical characterization, molecular docking, and biological evaluation.

We synthesized conjugates of tacrine with 1,2,4-thiadiazole derivatives linked by two different spacers, pentylaminopropene (compounds 4) and pentylaminopropane (compounds 5), as potential drugs for the treatment of Alzheimer's disease (AD). The conjugates effectively inhibited cholinesterases with a predominant effect on butyrylcholinesterase (BChE). They were also effective at displacing propidium from the peripheral anionic site (PAS) of acetylcholinesterase (AChE), suggesting that they could block AChE-induced β-amyloid aggregation.

Anticancer Activity of Dinitrosyl Iron Complex (NO Donor) on the Multiple Myeloma Cells.

The results of the study of the effect of a mononuclear dinitrosyl iron complex (DNIC7) with functional sulfur-containing ligands (NO donors) on the viability of multiple myeloma cells are presented. It was shown that DNIC7 decreased cell viability and inhibited the proliferation of multiple myeloma cells, i.e.

Applicability of histopathological osteomyelitis evaluation score (HOES) in chronic osteomyelitis of the foot - A feasibility study.

Background: Diagnosis and classification of chronic osteomyelitis is not based on any objective criteria. None of the available methods for this is completely reliable. Tienmann et al.

[Variants of clinical course of Dupuytren's contracture and palmar aponeurosis tissue composition in patients of different age groups.].

For the purpose of comparative analysis of the clinical course of fascial fibromatosis and tissue composition of the palmar aponeurosis in patients of different age groups сase reports and histological surgical material from 179 Dupuytren's contracture patients treated in 2014-2018 were analyzed. Patients were distributed in age groups: the 1st - younger than 50 years, the 2nd - 50-65 years, the 3rd - over 65 years old. In all groups four variants of Dupuytren's contracture clinical course were noted: swift, fast, benign and deffered.

Assessment of palmar subcutaneous tissue vascularization in patients with Dupuytren's contracture.

Aim: To investigate the structural and functional characteristics of palmar hypodermal tissue vascularization in Dupuytren's contracture patients of different age groups.

Methods: Eighty-seven Dupuytren's contracture patients underwent partial fasciectomy. Twenty-two of them were less than 55 years old (Y-group, = 22); the others were 55 and older (O-group, = 65).

Benefits of Ilizarov automated bone distraction for nerves and articular cartilage in experimental leg lengthening.

Aim: To determine peculiarities of tissue responses to manual and automated Ilizarov bone distraction in nerves and articular cartilage.

Methods: Twenty-nine dogs were divided in two experimental groups: Group M - leg lengthening with manual distraction (1 mm/d in 4 steps), Group A - automated distraction (1 mm/d in 60 steps) and intact group. Animals were euthanized at the end of distraction, at 30 day of fixation in apparatus and 30 d after the fixator removal.

Electron probe microanalysis оf experimentally stimulated osteoarthrosis in dogs.

Aim: To develop methods of articular cartilage preparation for X-ray-electron probe microanalysis and to study its elements content in experimental osteoarthrosis.

Methods: Twenty dogs aged 2-8 years were divided in research (aged 2 years, induction of osteoarthrosis - IOA) and intact group. Intact group included three subgroups (aged 2, 5 and 8 years).

NO-Donor Iron Nitrosyl Complex with N-Ethylthiourea Ligand Exhibits Selective Toxicity to Glioma A172 Cells.

We studied effects of NO-donor iron nitrosyl complex with -ethylthiourea ligand (ETM) on normal or tumor-derived cell lines. ETM was mildly toxic to most cell lines studied except the human glioma cell line A172 that proved to be highly sensitive to the complex and underwent cell death after ETM exposure. The high susceptibility of A172 cells to ETM was attributed to its NO-donor properties since no toxicity was detected for the -ethylthiourea ligand.

Preparation of Articular Cartilage Specimens for Scanning Electron Microscopy.

We developed and adapted a technology for preparation of articular cartilage specimens for scanning electron microscopy. The method includes prefixation processing, fixation, washing, and dehydration of articular cartilage specimens with subsequent treatment in camphene and air-drying. The technological result consists in prevention of deformation of the articular cartilage structures.

HISTOLOGICAL CHANGES IN THE KNEE JOINT SYNOVIAL FLUID IN EXPERIMENTAL MODELING OF OSTEOARTHROSIS AND ORTHOPEDICBONE LENGTHENING IN DOGS.

The experiment was aimed at studying the structural reorganization of the knee joint synovium in dogs with modeling of primary osteoarthrosis (MOP) and tibial lengthening (TL). The methods of light microscopy and histomorphometry of semithin epoxy sections were used to assess the thickness of synovial surface layer, number of synoviocyte layers, characterize the cells, to measure the numerical density of vessels, and to define the changes of the nerves and cell composition of the subsynovial layer. In MOP-group, the predominance of type А synoviocytes, hypovascularity and irreversible changes in the nerves of subsynovial sheath were observed.

[STUDY OF CHONDROCYTE PROLIFERATIVE ACTIVITY IN THE CANINE ARTICULAR CARTILAGE DURING LENGTHENING OF THE ADJACENT LIMB SEGMENT].

To assess the effect of orthopedic lengthening on proliferative activity of chondrocytes in the articular cartilage, dosed tibial lengthening by 28 mm was performed in 15 dogs at the rate of I mm/day divided into 4 sessions. Experiment time-points - 28 days of distraction, 30 days of fixation in the apparatus and 30 days after the apparatus removal. Methods of light microscopy of paraffin sections, immunohistochemistry, histomorphometry of semithin epoxide sections were used.

Role of subchondral bone in the restoration of articular cartilage.

The role of subchondral bone in the restoration of the articular cartilage was determined in experiments on mongrel dogs subjected to gonarthrosis modeling followed by subchondral zone tunneling and introduction of bone marrow suspension into the canal. Light microscopy, computer histomorphometry, and electron probe microanalysis showed that stimulation of functional activity of chondrocytes was achieved via correction of homeostasis of the cartilage and subchondral bone and improvement of tissue trophic. Restoration of the microarchitecture of the subchondral bone and improving its vascularization after tunneling with the introduction of bone marrow suspension into the drill holes enhances chondrocyte metabolism and recovers their functionality.

A method for making preparations from nondecalcified articular cartilage with sublying subchondral bone for multipurpose studies.

A method for making preparations from nondecalcified articular cartilage and subchondral bone for multipurpose studies is developed. Semithin and ultrathin sections of nondecalcified articular cartilage and subchondral bone prepared by this method are used for light and transmission electron microscopy. The method can also be used for studies of the qualitative and quantitative characteristics of the articular cartilage, scanning electron microscopy, and microanalysis of chemical elements in the articular cartilage and subchondral bone.

[Structural reorganization of the main joint components during the experimental modeling of osteoarthrosis with reduced blood supply].

The reactive changes in the knee synovium, articular cartilage, and subchondral bone during osteoarthrosis modeling were studied in dogs (n = 5). The results of histomorphometry, scanning electron microscopy, and electron probe microanalysis have demonstrated that the osteoarthrosis model used (femoral artery ligation and the knee immobilization) lead to marked synovitis, axonal atrophy and nerve fiber degeneration in subsynovial nerves, as well as synovial membrane hypovascularization. Subchondral bone vascularization was shown to deteriorate, while calcium content was reduced.

[Changes in the knee joint synovial membrane and articular cartilage during shin lengthening by autodistractor at increased daily rate].

Light microscopy and computerized morpho- and stereometry were used to examine the changes in the knee joint articular cartilage and synovial membrane studied during experimental canine shin lengthening by 15% of initial length by autodistraction at increased rate - 3 mm per day with switching on the automatic device 120 times. By the end of distraction period (10 days) the destructive changes in articular cartilage were more marked in the superficial and deep zones, synovitis of moderate and mild degree was observed accompanied by the destructive changes in the blood vessels and nerves of the subsynovial layer. Regeneration of articular cartilage was incomplete, and regressive neurovascular changes persisted in synovial membrane 30 days after the device removal.