[The effectiveness of a probiotic containing Bifidobacterium longum BB-46 and Enterococcus faecium ENCfa-68 in the treatment of post-infectious irritable bowel syndrome. Prospective randomized comparative study].

BACKGROUND: In the treatment of post-infectious irritable bowel syndrome (PI-IBS), the leading role belongs to the normalization of the composition of the intestinal microbiome, the disturbances of which are associated with previous intestinal infections. AIM: To study the effectiveness of the drug Bifiform in the treatment of PI-IBS. MATERIALS AND METHODS: An open, prospective, comparative, randomized study included 62 patients with PI-IBS. The diagnosis was confirmed by the results of clinical, laboratory and endoscopic examination of the intestine and met the diagnostic criteria for IBS of the Rome Consensus IV. The patients were randomized into 2 groups depending on the therapy. The patients of the main group received an antispasmodic drug (mebeverin 200 mg 2 times a day or trimebutin 200 mg 3 times a day for 4 weeks), an antibiotic (rifaximin 400 mg 3 times a day or nifuroxazide 400 mg 2 once a day for 1 week), a drug that normalizes the consistency of feces (dioctahedral smectite or macrogol 4000) and Bifiform 2 capsules 2 times a day for 2 weeks. For patients of control group similar therapy was performed without the Bifiform. Evaluation of the effectiveness of treatment was carried out at the end of the course of therapy and 6 months after its termination. RESULTS: All included patients with PI-IBS had abdominal pain, flatulence and tenderness to palpation along the bowel, most of them had diarrhea. Disorders of the intestinal microbiota were detected in 77.4% of patients, while excessive bacterial growth in the small intestine occurred in 72.6%, disorders of the colon microbiocenosis with the presence of opportunistic bacteria in 62.9% of patients. A significant part of the patients had a combination of small and large intestinal dysbiosis. Histological examination of the colon mucosa showed signs of low degree of inflammation activity in all patients. The moderate increase in the level of fecal calprotectin was found in 62.2% of patients with colonic dysbiosis. The majority of patients in the main group showed a pronounced positive dynamics of clinical manifestations of the disease, restoration of the normal composition of the intestinal microbiota and normalization of the content of fecal calprotectin at the end of the course therapy. The good result was observed much more often in the main group at the end of the course of treatment and 6 months after its termination. CONCLUSION: The inclusion of Bifiform in the complex therapy of PI-IBS significantly increases its effectiveness both in arresting the clinical manifestations of the disease, and in restoring the normal composition of the intestinal microbiome and reducing the inflammatory process in the intestinal mucosa. In the majority of patients receiving Bifiform, the remission of the disease achieved at the end of the course of treatment and persisted even 6 months after its termination.

Diabetic Nephropathy - possibilities of early laboratory diagnostics and course prediction (review of literature).

The medical and social significance of diabetes mellitus is determined by a progressive increase in the incidence of the disease, as well as the development of disabling and reducing the quality of life of macro- and microvascular complications in patients of working age, in particular, with the development of diabetic nephropathy (DN), which develops in one third of patients with type 1 and 2 diabetes. DN is the third leading cause of death after diseases of the cardiovascular system and oncological pathologies. In this regard, the identification of DN at the early stages is an important task both from the standpoint of prevention and a more favorable prognosis of the course of diabetes. This review presents data on the possibilities of early diagnosis of DN using blood and urine biomarkers, as well as information on their diagnostic and prognostic value. The analysis of the interpretation of the indicator of microalbuminuria in type 1 and 2 diabetes was carried out. In addition, the literature data of recent years on the informative value of determining markers of podocyte damage, on the role of oxidative stress products, immune-inflammatory factors, and vascular endothelial growth factor in the process of the onset and development of DN are presented. The possibility of their practical use for the diagnosis of DN in clinical practice is discussed. The literature search for this review was carried out using the databases of the RSCI, CyberLeninka, Scopus, Web of Science, MedLine, PubMed for the period from 2011 to 2021. using the following keywords: diabetes mellitus, diabetic nephropathy, markers of diabetic nephropathy; kidney damage, early diagnosis of diabetic nephropathy.

[A prospective randomized comparative study of the efficacy and safety of a two-week bismuth-based quadrotherapy of Helicobacter pylori infection with the inclusion of the probiotic containing Bifidobacterium longum BB-46 and Enterococcus faecium ENCfa-68 ].

AIM: To study the efficacy and safety of a two-week bismuth-based quadruple of Helicobacter pylori (Hp) infection with the inclusion of a probiotic Bifiform. MATERIALS AND METHODS: An open prospective comparative randomized study included 68 Hp-positive patients: 22 with a confirmed diagnosis of peptic ulcer disease, 46 with chronic gastritis, gastroduodenitis and erosions in the pylorobulbar zone. The diagnosis and Hp infection were verified by the results of endoscopic and morphological studies, as well as using the 13C-urease breath test and determination of the Hp antigen in the feces. Depending on the therapy, the patients were randomized into 2 groups: the main group was taken 2 times a day for 14 days omeprazole 20 mg + amoxicillin 1000 mg + clarithromycin 500 mg + bismuth tripotassium dicitrate 240 mg + Bifiform 2 capsules 2 times a day; control similar therapy was carried out, but without the inclusion of Bifiform. Repeated testing for Нр was carried out one month after the termination of the course of treatment. RESULTS: When using bismuth-containing quadruple, a high frequency of Hp eradication was noted, which in the ITT analysis was 86.1 and 68.8% (p0.05) and in the PP analysis it was 93.9 and 95.7% (p0.05) in patients of the main and control groups, respectively. Side effects of drug therapy were detected in 16.7 and 43.8% (p0.05), which was the reason for the early termination of therapy as a result of their development in 5.6 and 28% (p0.05) in patients of the main and control groups, respectively. The inclusion of the probiotic Bifiform in the eradication triple therapy of Hp infection reduced the frequency of detection of colonic dysbiosis from 27.8 to 3.6% and had a positive effect on the indices of local immunity (increased content of plasma cells in the inflammatory infiltrate and a stable level of secretory immunoglobulin A in coprofiltrate). CONCLUSION: A prospective, comparative, randomized study has shown that when using a two-week bismuth-based quadruple the eradication rate exceeds 90%. The inclusion of Bifiform in the eradication scheme dramatically reduces the frequency of adverse events and increases patient compliance, and also maintains the protective factors of the gastrointestinal mucosa at a higher level.

[Gender-related dimorphism of changes in adhesive properties of the vascular wall in the dynamics of surgical treatment of chronic generalized periodontitis]. / Polovoi dimorfizm izmenenii adgezivnykh svoistv sosudistoi stenki v dinamike khirurgicheskogo lecheniia khronicheskogo generalizovannogo parodontita.

The purpose of the study was to reveal gender-related dimorphism of changes in adhesive properties of the vascular wall in the dynamics of surgical treatment of chronic periodontitis (CP). A total of 51 persons aged 24 to 39 years were examined, of which 20 were clinically healthy volunteers (10 men and 10 women) and 31 were patients with CP of moderate severity (14 men and 17 women). It has been shown that endothelial dysfunction is more pronounced in men than in women with CP. Surgical treatment of CP is accompanied by a reactive increase in the concentration of soluble forms of adhesive endothelial molecules in early postoperative period more pronounced in women. In the long-term period surgical treatment causes a decrease in the impairment of the endothelial adhesive properties in men to a lesser extent than in women.

Particularities of Bone Regeneration in Rats after Implantation of Polycaprolactone Scaffold Mineralized with Vaterite with Adsorbed Tannic Acid.

We studied the particularities of osteo- and angiogenesis in albino rats after implantation of polycaprolactone scaffolds mineralized with vaterite with adsorbed tannic acid in the femoral bone defect. It was found that the processes of angio- and osteogenesis in the bone tissue after scaffolds implantation depend on their biocompatibility. Implantation of non-biocompatible scaffolds was followed by activation of angio- and osteogenesis aimed at separation of these scaffold from surrounding tissues. Implantation of polycaprolactone/vaterite scaffolds containing tannic acid stimulated angio- and osteogenesis leading to vascularization and bone tissue formation in the matrix. This demonstrate prospects of clinical approbation of these scaffolds for stimulation of bone regeneration in traumatological and orthopedic patients.

[Markers of endothelial dysfunction: pathogenetic role and diagnostic significance.]

Endothelial dysfunction (ED) is considered one of the pathogenetic mechanisms of a whole range of diseases. Detection of specific biochemical markers in the blood is an effective way to ED diagnostics that characterize the vascular endothelium state. This review highlights the pathogenetic role of the factors synthesized by endotheliocytes whose level changes in biological fluids reflect violations of the endothelium basic physiological properties: vasomotor function, thromboresistance, angiogenesis regulation, barrier and adhesion functions. In particular, the participation of nitric oxide metabolites, asymmetric dimethylarginine, endothelin-1, metabolic products of arachidonic acid, von Willebrand factor, thrombomodulin, vascular endothelial growth factor, vasohibine-1 and adhesion molecules in the onset and development of ED are reviewed. The diagnostic significances of factors damaging endothelium, such as C-reactive protein, homocysteine and 8-hydroxy-2'-deoxyguanosine, are discussed. In addition, the literature data of recent years about the prospects of clinical implication the detection of the above-mentioned factors which indicates structural and functional endothelial cells damage are given. Particular attention is paid to the ED markers detection prognostic significance and the possibility of their practical use for the ED diagnosis. The search of literature for the current review was conducted in RSIC, CyberLeninka, Scopus, Web of Science, MedLine and PubMed databases from 2012 to 2018 using the following keywords: endothelial dysfunction, nitric oxide, asymmetric dimethylarginine, endothelin-1, prostacyclin, thromboxane A2, epoxyeicosatrienoic acids, von Willebrand factor, thrombomodulin, vascular endothelial growth factor, vasohibin-1, adhesive molecules, C-reactive protein, homocysteine, and 8-hydroxy-2-deoxyguanosine.

[Soluble forms of adhesive molecules in blood serum as a marker of endothelial dysfunction in chronic generalized parodontitis.]

An important factor in the pathogenesis of chronic inflammation in periodontitis is endothelial dysfunction (ED). Adhesion molecules are markers of impaired barrier function, adhesive properties and vascular permeability. The study of the concentration of soluble adhesion molecules is very promising in the diagnosis of ED. The purpose of this research was to study changes in the concentration of soluble forms of adhesive molecules of the selectin family and the immunoglobulin superfamily when used as markers of systemic manifestations of ED in the dynamics of the treatment of chronic generalized periodontitis (CP) using surgical and therapeutic schemes. 60 patients with CP (33 women and 27 men) and 20 clinically healthy volunteers (10 men and 10 women) were examined. The state of the endothelium was assessed by the content in the serum of soluble forms of adhesive molecules - sP- and sE-selectins, intercellular adhesive molecules of type 1 (sICAM-1), vascular molecules of cell adhesion of type 1 (VCAM-1) by ELISA. The short-term results of non-surgical treatment of CP are more effective in correction of vascular wall adhesive properties disorders compared with surgical treatment. Conservative treatment of chronic hepatitis C effectively adjusted the blood content of adherent endothelium molecules in women than in men. The long-term results of applying this scheme were characterized by partial preservation of a positive effect on the adhesive properties of the endothelium, however, long-term results were inferior to short-term ones. Surgical treatment of CP in women in the early postoperative period was accompanied by reactive impairment of the adhesive properties of the endothelium. The long-term results of this treatment regimen testified to its greater effectiveness. In women, the effectiveness of treatment of CP in restoring the adhesive properties of the endothelium was higher than in men. The results obtained allow us to conclude that the systemic manifestations of ED in CP were characterized by an increase in the concentration in the blood of soluble forms of adhesion molecules. The dynamics of the concentration of adhesive molecules during the treatment of СР testified to the dependence of the sex of patients on the effectiveness of the influence of therapeutic and surgical treatment regimens on the systemic manifestations of ED.

Hybrid PCL/CaCO3 scaffolds with capabilities of carrying biologically active molecules: Synthesis, loading and in vivo applications.

Designing advanced biomaterials for tissue regeneration with drug delivery and release functionalities remains a challenge in regenerative medicine. In this research, we have developed novel composite scaffolds based on polymeric polycaprolactone fibers coated with porous calcium carbonate structures (PCL/CaCO3) for tissue engineering and have shown their drug delivery and release in rats. In vivo biocompatibility tests of PCL/CaCO3 scaffolds were complemented with in vivo drug release study, where tannic acid (TA) was used as a model drug. Release of TA from the scaffolds was realized by recrystallization of the porous vaterite phase of calcium carbonate into the crystalline calcite. Cell colonization and tissue vascularization as well as transplantability of developed PCL/CaCO3+TA scaffolds were observed. Detailed study of scaffold transformations during 21-day implantation period was followed by scanning electron microscopy and X-ray diffraction studies before and after in vivo implantation. The presented results demonstrate that PCL/CaCO3 scaffolds are attractive candidates for implants in bone regeneration and tissue engineering with a possibility of loading biologically active molecules and controlled release.

[The cytoprotective drug rebamipide in therapy for inflammatory and erosive-ulcerative lesions of the gastrointestinal tract]. / Tsitoprotektor rebamipid v terapii vospalitel'nykh i erozivno-yazvennykh porazhenii zheludochno-kishechnogo trakta.

Rebamipide is a cytoprotесtive drug that stimulates the generation of endogenous prostaglandins in the gastric and small intestinal mucosa and accelerates the healing of erosions and ulcers caused by Helicobacter pylori infection and NSAID administration. The major properties of rebamipide include stimulation of prostaglandins and synthesis of muсus glycoproteins, inhibition of reactive oxygen species, inflammatory cytokines, and chemokines, and suppression of neutrophil activation. This paper shows the ability of rebamipide to enhance the efficiency of therapy for Helicobacter pylori-induced infection, to reduce inflammation, including that after infection eradication, to accelerate ulcer healing, and to prevent the progression of preneoplastic lesions.

STRUCTURAL CHARACTERISTICS OF HUMAN AND OTHER MAMMALIAN ENDOTHELIAL CELLS.

Endothelial cells perform a number of important functions in the organism, and their dysfunction plays an important role in pathogenesis of a wide range of diseases. This review deals with the current literature data on structural characteristics of endothelial cells. A special section is devoted to endothelial cells development and differentiation. Structural aspects of endothelial cells cytoplasm and transport structures organization are discussed. Particular attention is paid to the structural heterogeneity of endothelial cells. Data on planar and apical- basal polarity of endothelial cells are reviewed separately.

[IN VIVO EVALUATION OF POLYCAPROLACTONE-HYDROXYAPATITE SCAFFOLD BIOCOMPATIBILITY].

Biocompatibility is one of the main and very important properties for scaffolds. The aim of the present study was to investigate cells population dynamics in vivo in the process of original polycaprolactone-hydroxyapatite scaffold colonization, as well as tissue reactions to the implantation to assess the biocompatibility of the matrix. It has been found that tissue reactive changes in white rats subside completely up to the 21st day after subcutaneous polycaprolactone-hydroxyapatite scaffold implantation. Matrix was actively colonized by connective tissue cells in the period from the 7th to the 21st day of the experiment. However, intensive scaffold vascularization started from the 14th day after implantation. These findings suggest a high degree of the polycaprolactone-hydroxyapatite scaffold biocompatiblilitye.

[Vascular endothelial Barrier Function].

Endothelium is an important regulator of selective permeability of the vascular wall for different molecules and cells. This review summarizes current data on endothelial barrier function. Endothelial glycocalyx structure, its function and role in the molecular transport and leukocytes migration across the endothelial barrier are discussed. The mechanisms of transcellular transport of macromolecules and cell migration through endothelial cells are reviewed. Special section of this article addresses the structure and function of tight and adherens endothelial junction, as well as their importance for the regulation of paracellular transport across the endothelial barrier. Particular attention is paid to the signaling mechanism of endothelial barrier function regulation and the factors that influence on the vascular permeability.

[Role of endothelium dysfunction in microcirculatory disorders by periodontal disease].

This review presents the advanced data about the role endothelial dysfunction in the pathogenesis of inflammatory periodontal diseases. This article describes the mechanisms of endothelial cell damage. Special attention is paid to the role of endothelial dysfunction in the pathogenesis of local microcirculatory changes at inflammatory periodontal diseases. The modern notions of systemic endothelial dysfunction at periodontal tissues inflammation as a risk factor for several diseases.

Gravity resonance spectroscopy constrains dark energy and dark matter scenarios.

We report on precision resonance spectroscopy measurements of quantum states of ultracold neutrons confined above the surface of a horizontal mirror by the gravity potential of Earth. Resonant transitions between several of the lowest quantum states are observed for the first time. These measurements demonstrate that Newton's inverse square law of gravity is understood at micron distances on an energy scale of 10-14 eV. At this level of precision, we are able to provide constraints on any possible gravitylike interaction. In particular, a dark energy chameleon field is excluded for values of the coupling constant ß>5.8×108 at 95% confidence level (C.L.), and an attractive (repulsive) dark matter axionlike spin-mass coupling is excluded for the coupling strength gsgp>3.7×10-16 (5.3×10-16) at a Yukawa length of λ=20 µm (95% C.L.).

[Endothelial cell adhesion molecules].

The review presents current data concerning the functional role of endothelial cell adhesion molecules belonging to different structural families: integrins, selectins, cadherins, and the immunoglobulin super-family. In this manuscript the regulatory mechanisms and factors of adhesion molecules expression and distribution on the surface of endothelial cells are discussed. The data presented reveal the importance of adhesion molecules in the regulation of structural and functional state of endothelial cells in normal conditions and in pathology. Particular attention is paid to the importance of these molecules in the processes of physiological and pathological angiogenesis, regulation of permeability of the endothelial barrier and cell transmigration.

[The possibilities and perspectives of using scaffold technology for bone regeneration].

The article deals with the one of the topical problem of tissue engineering--the design and implementation of biomaterials that could replace and repair bone defects. This review presents the recent studies of the potential of scaffold technology in bone tissue regeneration. This article contains information about the basic parameters and properties of modern scaffold systems. The results of experimental in vitro and in vivo studies on the use of matrices made of various materials are shown. Advantages and disadvantages of various materials used for the production of scaffolds are discussed. Attention is paid to the advantages combinations of different materials to achieve the desired structural and functional properties. Particular attention is paid to technologies and systems of targeted delivery and controlled release of factors that stimulate bone tissue regeneration. Different strategies for modulating tissue reactions and immune responses that take place during scaffold implantation are presented.

[Disorders of gut microflora in the pathogenesis of liver cirrhosis and complications of portal hypertension].

A total of 85 patients with alcoholic and viral cirrhosis were included in study to assess the prevalence of dysbiosis and its relationship with the severity of disease, and with development of dyspeptic disorders. Intestinal bacterial over-growth was measured by means of a lactulose breath test, fecal flora was cultured under aerobic and anaerobic conditions. Intestinal bacterial overgrowth and colon dysbiosis were determined in 82.4% of patients with equal prevalence in alcoholic and viral cirrhosis. Intestinal dysbiosis was found to be risk factor of increasing cirrhosis severity and liver dysfunction, as well as development of complications of portal hypertension. It was documented, that intestinal dyspepsia syndrome in cirrhotic patients is strongly associated with the presence of gut microflora disorders.

Changes in activity of stress-realizing body systems as a result of terahertz irradiation at nitric oxide frequencies in albino rats under conditions of acute stress.

We studied the effects of irradiation with teraherz electromagnetic waves at frequencies corresponding to nitric oxide emission and absorption molecular spectrum (150,176-150,664 GHz) on activity of the sympathoadrenal and pituitary-adrenal axes of the stress response in albino male rats under conditions of acute immobilization stress. It was shown that terahertz waves exert stress-limiting effect and are capable of reducing the levels of catecholamines, corticotropin, and corticosterone in male rats exposed to acute stress.

[Influence of combined lacto-vegetarian diet and selective beta-blocking agents on clinical and metabolic indices in patients with coronary heart disease].

Clinical, hemodynamic and metabolic parameters were investigated for 42 patients with coronary heart disease, after myocardial infarct, recieved selective beta-adrenoblockers. Patients were divided in two groups. The first group (24 patients) were given methoprolol (50 mg/daily) and antiatherogenic lacto vegetarian diet, the second (18 patients)--methoprolol (50 mg/daily) and standard mixed antiatherogenic diet. After the treatment, positive changes clinical and gemodynamic parameters were observed in both groups of patients. Among the clinical symptoms, a more pronounced decrease in blood pressure in the patients on vegetarian diet and a more significant increase in their exercise tolerance. The level of total cholesterol on the serum of blood decreased by 16%, low-density lipoproteins cholesterol decreased by 18%, the atherogenic coefficient (KA) decreased by 31%, only in vegetarian group. High-density lipoprotein cholesterol increased in vegetarian group, by 14% and decreased in control group. Balanced antiatherogenic lacto vegetarian diet in patients with coronary heart disease prevents the hyperlipedemic effect caused by the selective beta-adrenoblockers and it is an agent for preventing its negative effect on lipid metabolism.