Dysmetabolism of Peripheral Blood Monocytes in Type 1 Diabetes Mellitus.

The level of ROS (fluorescent probe 2',7'-dichlorodihydrofluorescein diacetate) and lipid content (fluorescent lipophilic dye Nile Red) in the peripheral blood monocyte fraction from patients with type 1 diabetes mellitus and healthy volunteers were assessed by flow cytofluorimetry. The number of CD36+ monocytes was assessed using specific antibodies. In patients with type 1 diabetes mellitus, the levels of ROS and intracellular lipids in monocytes and the number of cells expressing CD36 fatty acid translocase were elevated. These results indicate metabolic changes in the peripheral blood cells of patients with carbohydrate metabolism disorders and can be considered as possible prognostic markers for the development of type 1 diabetes mellitus complications.

[Disseminated ependymal dysembryoplastic neuroepithelial tumor: a case report and literature review]. / Disseminirovannaya vnutrizheludochkovaya dizembrioplasticheskaya neiroepitelial'naya opukhol': klinicheskii sluchai i obzor literatury.

Dysembryoplastic neuroepithelial tumor (DNET) is a benign mixed neuronal-glial neoplasm (WHO grade 1). DNET is most often localized in temporal lobes and found in children and young people with epilepsy. There a few cases of DNET in ventricular system with dissemination along the ependyma in the world literature. MATERIAL AND METHODS: We present a rare case of T1- and T2-negative ventricular system tumor. Only FIESTA imaging revealed dissemination with multiple focal lesions of the third ventricle, its bottom and lateral walls, anterior horns of lateral ventricles, cerebellar vermis, cervical and lumbar spinal cord. RESULTS: The patient underwent transcortical endoscopic biopsy of the third ventricle tumor with simultaneous ventriculoperitoneal shunting. DNET was diagnosed, and radiotherapy was subsequently performed. Literature data on this issue were analyzed. CONCLUSION: To date, disseminated forms of DNET are extremely rare. X-ray features and morphological results allow us to establish the correct diagnosis and determine further treatment strategy.

[Ankle replacement for severe post-traumatic deformation of the distal tibia: a case report]. / Endoprotezirovanie golenostopnogo sustava pri lechenii gruboi posttravmaticheskoi deformatsii distal'nogo otdela bol'shebertsovoi kosti. Klinicheskii sluchai.

OBJECTIVE: To evaluate the immediate results of ankle replacement with original prosthesis in a patient with severe post-traumatic deformation of the distal tibia. MATERIAL AND METHODS: When developing the original design of ankle prosthesis, we considered foreign analogues of classical and revision models of ankle prostheses taking into account their shortcomings. In this case, an integrated approach was used. Extensive work has been carried out to select materials for prosthetic components. Experimental work with mesenchymal stromal cells of bone marrow was aimed at testing cytotoxicity and biological compatibility. The staff of the department of designing biomechanical structures of the Research Institute of Bionics and Personalized Medicine of the Samara State Medical University carefully studied the proposed design of endoprosthesis using the Ansys software. After cadaver tests on full-scale models, we performed surgical intervention in a patient with severe post-traumatic deformity of the lower third of the left tibia. RESULTS: Our studies revealed convenience and certain advantages of intraoperative installation of original ankle prosthesis. Along with this, this clinical example indicated come features that must be taken into account in revision ankle replacement to avoid possible postoperative consequences. CONCLUSION: Original ankle prosthesis makes it possible to replace the distal tibia and preserve limb function.

Functional Phenotype of Alveolar Macrophages Features in Rats with Metabolic Syndrome.

Phenotypic characteristics of alveolar macrophages in the bronchoalveolar lavage fluid as well as their ability to acquire the M1 and M2 phenotypes during in vitro culturing with reprogramming factors were studied in rats with modeled diet-induced metabolic syndrome. A decrease in the number of alveolar macrophages with the M1 phenotype was found in animals with metabolic syndrome. The factors of metabolic syndrome do not affect phenotypic plasticity of cells in culture, but under the action of M2 reprogramming factors, the cells demonstrate a wide range of phenotypic plasticity by the CD80 and CD206 markers. The consistently high level of production of IL-6 and IL-10 by macrophages during culturing under different conditions indicates functional rigidity of the cells, which is probably a consequence of in vivo predetermined functional phenotype of these cells against the background of metabolic disorders.

Anti-Atherosclerotic Action of a New Stimulator of Soluble Guanylate Cyclase in an Experiment.

We studied the effect of an indolinone derivative GRS on the development of experimental atherosclerosis in C57BL/6 mice. Atherosclerosis was modeled by intraperitoneal administration of endothelial lipoprotein lipase inhibitor Kolliphor P 407 micro Geismar over 5 months. GRS was administered orally in a dose of 10 mg/kg once a day throughout the experiment. In 5 months, the levels of total cholesterol, LDL, and triglycerides in blood serum, as well as histological composition of the ascending aorta were studied. In mice with experimental atherosclerosis, we observed pronounced dyslipidemia with an increase in serum cholesterol, LDL, and triglycerides and accumulation of xanthoma cells in the aorta wall. Repeat administration of GRS did not eliminate dyslipidemia, but prevented an increase in the number of xanthoma cells in the aorta wall (p<0.05). The stimulator of soluble guanylate cyclase GRS did not exhibit hypolipidemic activity, but restored impaired endothelial function in the atherosclerosis model and prevented atherosclerotic damage to blood vessels and vascular wall remodeling.

Intracellular Lipid Levels and Oxidative Stress in Peripheral Blood Mononuclear Cells in Experimental Type 1 Diabetes Mellitus.

Type 1 diabetes mellitus was modeled in Wistar rats by intraperitoneal injection of streptozotocin (25 mg/kg for 5 days), which led to the appearance of the main symptoms of insulin-dependent diabetes. In peripheral blood mononuclear cells isolated by centrifugation on a Ficoll density gradient, the production of ROS and the level of intracellular lipids were evaluated by flow cytofluorimetry. In rats with type 1 diabetes mellitus, an increase in ROS levels in isolated peripheral blood monocytes, but not in the lymphocytic fraction was revealed. Incubation of isolated monocytes in a medium containing 1 mM oleic acid led to a 1.5-fold increase of intracellular lipid levels. After incubation of the lymphocyte fraction in this medium, no differences from the control were revealed. Disorders of carbohydrate and lipid metabolism in type 1 diabetes mellitus leading to an increase of free fatty acids and ROS levels can be detected ex vivo in isolated peripheral blood mononuclear cells.

Hypolypidemic Activity of L-Rhamnopyranosyl-6-O-Methyl-D-Galacturonan, a Polysaccharide Isolated from Birch Leaves (Betula pendula L.).

In male Syrian hamsters fed a synthetic high-fat diet enriched with cholesterol (0.3%), administration of a polysaccharide from birch leaves L-rhamnopyranosyl-6-O-methyl-D-galacturonan (3 g/100 g of diet) resulted in a decrease in total cholesterol levels, mainly due to the LDL fraction, triglycerides, and bile acids in blood serum; the content of triglycerides and cholesterol in the liver also decreased, while excretion of bile acids with feces increased. Thus, the lipid-lowering effect of L-rhamnopyranosyl-6-O-methyl-D-galacturonan is related to its ability to bind bile acids in the intestine and interrupt their enterohepatic circulation.

[Biomechanics of the first metatarsophalangeal joint after replacement]. / Analiz biomekhaniki pervogo plyusnefalangovogo sustava posle endoprotezirovaniya.

OBJECTIVE: Analysis of biomechanics of the first metatarsophalangeal joint after arthroplasty, interaction between bones and two implants of the first metatarsophalangeal joint using skeletal model of the foot. MATERIAL AND METHODS: We developed anatomically adapted all-ceramic non-coupled endoprosthesis of proximal interphalangeal joint between 2016 and 2021. To create a model of the foot, we used diagnostic computed tomography whose images were applied in 3D sculpting system and computer-aided design system for final geometric modeling of the joint. RESULTS: In dorsal flexion of the first metatarsophalangeal joint under 45° with the presence of implant, cortical bone tissue can withstand a load of up to 40 kg. Cortical bone tissue with implant can withstand a load of up to 305 kg without dorsal flexion. Strength of implant elements made of zirconium ceramics significantly exceeds strength of bone tissue within implant-bone tissue connection. CONCLUSION: Postoperative axial load on the first metatarsophalangeal joint up to 35 kg with maximum dorsal flexion up to 45° is the most appropriate. Higher load and hyperextension over 45° may be followed by postoperative complications such as implant instability, dislocation and periprosthetic fracture.

Insulin Resistance in Experimental Type 1 Diabetes Mellitus.

Experimental type 1 diabetes mellitus (T1DM) was induced in rats by daily intraperitoneal injections of alloxan in a dose of 90 mg/kg for 4 days. For verification of insulin resistance, insulin tolerance test was performed in 2 weeks and the glucose utilization rate constant (KITT) was calculated. The rats demonstrated the main symptoms of T1DM: hypoinsulinemia, hyperglycemia, ketonemia, glucosuria, ketonuria, polydipsia, polyphagia, weight loss, and insulin resistance, as evidenced by a decrease in KITT. The serum content of free fatty acids and triacylglycerols significantly increased. The content of triacylglycerols increased in skeletal muscles and decreased in the liver. A negative linear correlation was found between KITT and triacylglycerol content in muscles. Thus, the development of insulin resistance in experimental T1DM in rats is associated with accumulation of triacylglycerols in skeletal muscles.

Airway Smooth Muscles Contractions in Metabolic Syndrome.

We studied contractile responses of isolated airway smooth muscle segments from rats with metabolic syndrome. Metabolic syndrome was induced in rats by high-fat and high-carbohydrate diet. It was shown that metabolic syndrome was associated with an increase of bronchoconstrictor action of cholinergic receptor activator carbacholine (0.1-100 µM) and a decrease of the dilatory effect of ß2-adrenoreceptor activator salbutamol (0.1-100 µM). The observed effects of agonists are epithelium-dependent. Disorders in contractile activity in the airway smooth muscles were accompanied by bronchial epithelium destruction, immune inflammation in the bronchial wall, muscular and peribronchial adipose tissue hypertrophy.

A study of kudurs used by wild animals located on the water sources high in REE content in the Caucasus Nature Reserve.

One of the theories explaining the reasons for geophagy, which was proposed earlier by the authors of the article, consists in the assumption that animals need rare-earth elements (REE). In order to test this hypothesis, we studied the chemical composition of spring waters in the territory of the Caucasus Nature Reserve at three kudurs along the Achipsta River, as well as at the Mamaevsky kudur (southwestern slope of the Pshekish mountain). At the Mamaevsky kudur, we also studied the chemical composition of earth consumed by animals, and the species, age and gender composition, seasonal and daily activity of ungulate animals-visitors of the kudur. It was determined that the most active visitors of the Mamaevsky kudur were European bison (Bison bonasus) with one activity peak during the rut, in July. The frequency of visits to the kudur by red deer (Cervus elaphus) was 4 times lower with the highest peak activity in April and a lower peak in August. Only in one of four water sources at the Mamaevsky kudur there was an elevated concentration of Na (by 7 times). In the other three the concentration was comparable to the local river water. The waters of two "sodium-free" springs had increased concentrations of REE (by 5-8 times). Geophagic earths near the Mamaevsky springs are decomposition products of siltstone and sandstone shale rocks of the Jurassic age consisting of clay minerals (illite mixed with smectite, and chlorites)-from 42 to 45%, and quartz and feldspar (in total up to 50%) mixed with Fe and Ca carbonates. The chemical composition of acid extracts (0.1 N HCl, pH = 1.0) from consumed earth showed the highest extractability of Ca and Fe. In trace elements, Sr, Ba, Zn, Cu, Ni, Co, V, light lanthanides, and Y are most actively extracted. Na is extracted at 0.03-0.1 g/kg. The sodium bicarbonate spring water consumed by animals at kudurs on the Achipsta River had Na contents 70-300 times, and REE contents 25-40 times higher than that in the river water. The revealed facts do not contradict the hypothesis that the desire for geophagy in animals in the Caucasus (in addition to the long-known "urge" for Na) can be also related to the properties of lanthanides group elements exchange in the body.

Role of H2S in Regulation of Vascular Tone in Metabolic Disorders.

We studied the effect of the H2S donor (NaHS, 1-500 µM) on the contractile responses of isolated aortic smooth muscle segments from rats with metabolic syndrome induced by high-fat, high-carbohydrate diet. It was found that the vasorelaxing effect of NaHS (5-100 µM) decreased in under conditions of MS. The endothelial NO synthase inhibitor L-NAME (100 µM) suppressed the effect of NaHS, while cystathionine-gamma-lyase inhibitor PAG (100 µM) decreased the vasodilating effects of acetylcholine (0.1-100 µM). Application of endogenous NO precursor L-arginine (1 mM) potentiated in the effects of H2S donor NaHS. Thus, the contractile activity of vascular smooth muscles in metabolic syndrome is determined by not only the effect of H2S, but also the influence of NO.

Radiolabeled Complex of Antimicrobial Peptides UBI29-41 and UBI18-35 Labeled with 99mTc for Differential Diagnosis of Bone Infection of the Limbs.

We studied an original radiolabeled complex of antimicrobial peptides UBI29-41 and UBI18-35, ubiquicidin derivatives, for distinguishing between bacterial and aseptic inflammation. For radiolabeling of the peptides with technetium-99m, a bifunctional chelating agent succinimide-1-yl 6-(bis(pyridin-2-ylmethyl)amino)hexanoate was used. The obtained complexes 99mТс-DPAH-UBI29-41 and 99mТс-DPAH-UBI18-35 had radiolabeling yield >80% and radiochemical purity >96%. Accumulation of the complexes in the focus of bacterial inflammation in bone structures and the absence of this complex in the site of aseptic inflammation was confirmed in a rat model of traumatic osteomyelitis by single-photon emission computed tomography.

[Zn-CysHis Protein Factor Families: Role of Electrostatic Interaction of Zn-Domains in Factor Functions].

The large amount of the DNA- and RNA-binding protein regulatory factors contain Zn-domains. Total six Zn-CysHis factor families with different functions were considered. Among them the transcription factors of family PF00096, complex type Zn-Cys2His2, is the most important because it includes over 340.000 members of 365.000 total members listed at present in the Zn-containing factor families. The role of electrostatic potential of Zn-domains in the structure and function of factors from different factor families has been considered. We have shown that the positive electrostatic potential of Zn-domains plays an essential role in forming contact of factors' Zn-domains with DNA/RNA in three protein factor families PF00096, PF12874, and PF09329. While in other three families PF03119, PF08996, and PF01258 Zn-domains do not contact with nucleic acids, and electrostatic interactions do not play a distinctive role, consequently.

Regulation of Vascular Smooth Muscle Contractions in the Model of Metabolic Syndrome.

Reduced glucose tolerance, hyperglycemia, and imbalance in lipid levels were found in rats with metabolic syndrome induced by a high-fat, high-carbohydrate diet. The contractile responses of intact and endothelium-denuded aortic smooth muscle segments from rats with metabolic syndrome to application of acetylcholine, phenylephrine, sodium nitroprusside, and forskolin were studied by mechanographic method. It was found that endothelial dysfunction develops against the background of metabolic and hemodynamic disorders in metabolic syndrome. It was shown that the regulation of vasoconstrictor reactions of vascular smooth muscles in metabolic syndrome is due to a decrease in Ca2+ entry, mainly voltage-independent, as well as changes in the function of cGMP- and cAMP-activated K+-channels.

[Relationship between masticatory muscles activity and motor cortex activation during treatment of patients with distal malocclusion]. / Vzaimosviaz' izmeneniia aktivnosti zhevatel'nykh myshts i motornykh zon kory golovnogo mozga pri lechenii patsientov s distal'noi okkliuziei.

The processes of neuroplasticity of the motor cortex of the brain were evaluated in the treatment of 20 (12 women and 8 men) patients aged 18-35 years (22.5±1.5 years) with distal occlusion using functional magnetic resonance imaging (fMRI), as well as comparison of surface myography (EMG) data to assess the adaptive capabilities of the tooth-jaw system and the central nervous system against the background of orthodontic correction. Correction of distal occlusion was carried out using ceramic braces 'Damon' (f. 'Ormco', USA). The advancement of the lower jaw forward with bite enhancement was carried out using the Twin force device ('Ortho Orgonizers GmbH', Germany). The study was conducted in five stages: 1) before orthodontic correction; 2) before installing the Twin force device; 3) after anterior displacement of the lower jaw and bite enhancement on the Twin force device; 4) after removing the brackets; 5) 1.5 months after the treatment. FMRI proved to be a useful tool for orthodontic treatment efficacy assessment and neuromuscular adaptation of maxillofacial structures to changing functional status.

Using biological-physical modelling for informing sea lice dispersal in Loch Linnhe, Scotland.

Sea lice are a constraint on the sustainable growth of Scottish marine salmonid aquaculture. As part of an integrated pest management approach, farms coordinate procedures within spatial units. We present observations of copepodids being at relatively greater density than nauplii in upper waters, which informs the development of surface layer sea lice transmission modelling of Loch Linnhe, Scotland, for informing farm parasite management. A hydrodynamic model is coupled with a biological particle-tracking model, with characteristics of plankton sea lice. Simulations are undertaken for May and October 2011-2013, forced by local wind data collected for those periods. Particles are continually released from positions representing farm locations, weighted by relative farm counts, over a 2-week period and tracked for a further 5 days. A comparison is made between modelled relative concentrations against physical and biological surveys to provide confidence in model outputs. Connectivity between farm locations is determined in order to propose potential coordination areas. Generally, connectivity depends on flow patterns in the loch and decreases with increased farm separation. The connectivity indices are used to estimate the origins of the sea lice population composition at each site, which may influence medicinal regimens to avoid loss of efficacy.

Glycolysis Inhibitors Monoiodoacetate and 2-Deoxyglucose as Antitumor Agents: Experimental Study on Lewis Lung Carcinoma Model.

Antitumor effects of glycolysis inhibitors monoiodoacetate and 2-deoxyglucose were studied on Lewis lung carcinoma model. Monoiodoacetate exhibited antitumor and antimetastatic activities, being not inferior of methotrexate (reference drug); however, the preparation also demonstrated high systemic toxicity. 2-Deoxyglucose exhibited only antitumor effect, while its antimetastatic activity did not differ from the result in the group without treatment.

Evaluation of Regenerative Potential of Cryopreserved Adenosine-Modified Monocytes on the Model of Burn Wounds.

We studied viability of adenosine-modified monocytes after cryopreservation and their regenerative potential. The optimal method of cell cryopreservation was the use of serum-free medium followed by storage in liquid nitrogen. Injections of adenosine-modified monocytes after 12-week cryopreservation around grade IIIB burn wound accelerated healing of the skin defect and significantly improved the histological pattern of the damage area at delayed terms.

[Sphincter-sparing treatment of anal fissure]. / Sfinkterosokhraniaiushchaia taktika lecheniia patsientov s anal'noi treshchinoi.

Surgical treatment of the anal fissure is associated with unreasonably high risks of delayed development of fecal incontinence to gas or liquid stool. Standardized sphincter-preserving therapy, based on the pharmacological reduction of increased internal anal sphincter tone (chemical sphincterotomy) allows to improve significantly the results of the non-surgical approach of treating one of the most common pathology in proctological practice. Our work presents a retrospective analysis of the treatment of 295 patients with anal fissure treated with diltiazem ointment, nifedipine ointment, nitroglycerin ointment and botulinum toxin A. Significant improvement or disappearance of complaints was noted in 84% of patients. The use of botulinum toxin A was successfull in 10 out of 11 patients without the need of surgical intervention. High efficiency (91% of patients) of the sphincter-preserving approach with a significant decrease in the need for aggressive surgical manipulation allows to decrease sphincterotomy rate and reduces the risk of delayed fecal incontinence.