Antimicrobial activity of dietary supplements based on bacterial lysate of Lactobacillus rhamnosus DV.

Introduction: According to WHO, antibiotic resistance is increasing to hazardous levels worldwide. Candidiasis often occurs after taking antibiotics. Therefore, antibiotic resistance is a global problem and searching for antibacterial agents is necessary. Aim: To determine the antimicrobial activity of bacterial lysate of Lactobacillus (L.) rhamnosus DV separately and with plant extracts against bacterial and yeast test cultures. Material and methods: Antimicrobial activity of Del-Immune V® (cell wall and DNA fragments from a L. rhamnosus DV) separately and with cinnamon, beetroot, and blackcurrant extracts was determined by the minimum inhibitory concentration (MIC). Twofold serial dilutions determined the MIC in previously prepared meat-peptone broth (MPB) for bacteria and liquid wort for yeast. In the study, gram-negative (Escherichia coli IEM-1, Proteus vulgaris PА-12, Pseudomonas sp. MI-2, L. rhamnosus 13/2) and gram-positive (Bacillus (B.) subtilis BТ-2, Staphylococcus aureus BМС-1) bacteria, as well as yeast (Candida (C.) albicans D-6, C. tropicalis PE-2, C. utilis BVS-65) were used as test cultures. Results: The MIC for the studied bacterial test cultures after application of L. rhamnosus DV bacterial lysates was from 1.0 ± 0.05 mg/mL to 12.5 ± 0.63 mg/mL, which was significantly less than that of the thermally inactivated control (MIC from 125.0 ± 6.25 mg/mL to 250.0 ± 12.5 mg/mL). B. subtilis BT-2 culture was the least sensitive to the action of the bacterial lysate (MIC-12.5 ± 0.63 mg/mL). It showed the best antibacterial and antifungal effect bacterial lysate with the phytonutrient blackcurrant. Conclusions: It was demonstrated that bacterial lysate of lactic acid bacteria L. rhamnosus DV exhibits antibacterial and antifungal properties during direct contact with pathogenic agents.

EFFECT OF URBANIZATION ON DENSITY OF THE GENERAL PRACTITIONERS, AVERAGE LIFE EXPECTANCY AND MORTALITY FROM THE DISEASES OF CIRCULATORY SYSTEM.

OBJECTIVE: The aim: Comparative analysis of average life expectancy, mortality from diseases of the circulatory system, gross regional product, and density of general practitioners in regions with different levels of urbanization. PATIENTS AND METHODS: Materials and methods: We compared the following characteristics of groups classified by level of urbanization: average density of general practitioners per 10,000, average life expectancy and mortality from diseases of the circulatory system per 1,000, average gross regional product per 1 person. RESULTS: Results: The groups did not differ in average life expectancy. The highest rate of mortality from diseases of the circulatory system- in the group with average level of urbanization, the lowest- in the group with low level of urbanization (p<0.05). The highest value of gross regional product per person is in the group with high level of urbanization, and the lowest is in the group with low level (p<0.05). The lowest density of primary care doctors per 10,000 is in the group with high level of urbanization, and the highest is in the group with low level of urbanization (p<0.05). CONCLUSION: Conclusions: When planning staffing of health care institutions, it is necessary to take into account the level of urbanization of the region and ensure status of the general practitioner as a leading medical specialist responsible for medical care during the first meeting with the patient and his subsequent follow-up.

THE TRENDS OF THE DENSITY OF SURGEONS IN SOME EUROPEAN COUNTRIES AND 16 OECD COUNTRIES DURING 2005-2018.

OBJECTIVE: The aim: To establish that there are differences in the density trends of surgeons in some European countries and 16 OECD countries and to compare the trends of the density of surgeons in some European countries and 16 OECD member countries, 2005 - 2018. PATIENTS AND METHODS: Materials and methods: The study is based on data of the Centre for Medical Statistics of the Ministry of Health of Ukraine obtained during 2005-2020 and OECD data obtained during 2005-2018. The Difference-in-Differences method has been used to determine the density trends differences, the regression analysis method - to predict the number of surgeons in 2020. RESULTS: Results: In 2020, there were 28,559 surgeons (0.687 per 1,000) in Ukraine, which is by 17.7% less than in 2005. From 2005 to 2018, the density of surgeons per 1000 in Ukraine and the United States decreased (-7.45% and -2.5%). In Korea (+ 78.38%), Greece (+ 65.52%), Lithuania (+ 58.57%), Slovenia (+ 45.65%) and other 11 countries the surgeon's density increased. In 2030, Ukraine is predicted to significantly reduce the number of surgeons, general surgeons, ophthalmologists and urologists; as well as to increase the number of cardiovascular surgeons. The number of proctologists, oncologists-surgeons, neurosurgeons, thoracic surgeons, orthopaedists-traumatologists and anaesthesiologists will not change significantly. CONCLUSION: Conclusions: It is possible to state the availability of surgical care according to the density of surgeons in Ukraine, similar to the level of OECD countries. In 2030, the number of surgeons is projected to decrease, with the exception of cardiovascular surgeons.

Changes in Metabolic Parameters in Patients with Diabetic Kidney Disease Depending on the Status of D3.

BACKGROUND: Type 2 diabetes is a metabolic disease characterized by hyperglycemia as a result of insulin resistance and decreased insulin secretion. A relatively large number of patients with this type of diabetes have abdominal obesity, which also affects insulin resistance development. Chronic hyperglycemia can lead to damage and dysfunction of various organs, and a striking example is diabetic nephropathy. Diabetic nephropathy is a specific kind of kidney damage that occurs due to complications of diabetes and is accompanied by the formation of diffuse or nodular glomerulosclerosis, which can lead to terminal renal failure and requires immediate substitution through renal therapy or renal transplantation. Diabetic nephropathy is diagnosed with albuminuria and a decrease in the rate of glomerular filtration. METHODS: This review was based on a literature search for the most important evidence of vitamin D as a possible method of prevention for obesity, type 2 diabetes, and diabetic nephropathy. Collected published articles were summarized according to their overall themes. RESULTS: In this review, we considered vitamin D as a possible method of treatment for type 2 diabetes, as well as its complications, including diabetic nephropathy. CONCLUSION: Studies show that vitamin D inhibits the renin-angiotensin-aldosterone system, resulting in improved renal function in diabetic nephropathy. Vitamin D also has antiinflammatory, antiproliferative, and anti-metastatic effects, which improve endothelial function.

HEALTH CARE EXPENDITURES OF 179 COUNTRIES WITH DIFFERENT GNI PER CAPITA IN 2018.

OBJECTIVE: The aim: To study the difference in health care expenditures in groups of countries with different GNI per capita. PATIENTS AND METHODS: Materials and methods: In 4 groups of countries with different GNI per capita were analyzed indicators of Current health expenditure per capita ($) (СHE), Domestic general government health expenditure per capita, PPP ($) (GGHE $) and GGHE%, Domestic private health expenditure per capita, PPP ($) (PHE) and PHE%, Out-of-pocket expenditure (%) (OOP), Current health expenditure (% of GDP) (CHE% GDP). RESULTS: Results: The group of high-income countries differs by CHE, GGHE $, GGHE%, PHE $, PHE%, OOP, CHE% GDP (p <0.001), the group with incomes above the average - by CHE, GGHE $, PHE $, PHE%, CHE%GDP (p <0.001). Groups with lower average income and low income do not differ in CHE, GGHE$, PHE$, PHE%, OOP (p> 0.05). GNI per capita has a positive effect on GDP%GDP, CHE, GGHE, PHE in the high-income group and negatively affects the OOP (p <0.05), GNI per capita has a positive effect on CHE, GGHE in the above-average income group, GNI per capita has a positive effect on CHE, GGHE, GGHE%, PHE and negatively affects OOP (p <0.05) in the income group below average. GNI per capita has a positive effect on the OOP and negatively affects the CHE%GDP (p <0.05) in the low-income group. CONCLUSION: Conclusions: Each group of countries, depending on per capita income, has its own health care costs.

Probiotic Composition and Chondroitin Sulfate Regulate TLR-2/4-Mediated NF-κB Inflammatory Pathway and Cartilage Metabolism in Experimental Osteoarthritis.

The therapeutic potential of using probiotics to treat osteoarthritis (OA) has only recently been recognized, with a small number of animal and human studies having been undertaken. The aim of this study was to describe the effect of a probiotic composition (PB) and chondroitin sulfate (CS), administered separately or in combination, on Tlr2, Tlr4, Nfkb1, and Comp gene expression in cartilage and levels of cytokines (IL-6, IL-8, TGF-ß1, IGF-1) and COMP, ACAN, CHI3L1, CTSK, and TLR-2 in serum during monoiodoacetate (MIA)-induced OA in rats. Expression of Tlr2, Tlr4, Nfkb1, and Comp in cartilage was analyzed using one-step SYBR Green real-time RT-PCR. The levels of IL-6, IL-8, TGF-ß1, IGF-1, COMP, ACAN, CHI3L1, CTSK, and TLR-2 were measured in serum by enzyme-linked immunosorbent assay. Experimental OA caused an upregulation in Tlr2, Tlr4, Nfkb1, and downregulation of Comp expression in the cartilage. MIA-OA caused a significant increase of TLR-2 soluble form and IL-6, IL-8, TGF-ß1, COMP, ACAN, CHI3L1, and CTSK levels in the blood serum; the level of IGF-1, on contrary, decreased. Separate administration of PB and CS raised expression of Comp and reduced Tlr2, Tlr4, and Nfkb1 expressions in cartilage. The levels of the studied markers of cartilage metabolism in serum were decreased or increased (IGF-1). The combined use of PB and CS was more effective than separate application approaching above-mentioned parameters to control. The outcomes of our research prove that multistrain live probiotic composition amplifies the positive action of CS in osteoarthritis attenuation and necessitates further investigation with large-scale randomized controlled trial.

Circadian Rhythms of Endothelial Nitric Oxide Synthase and Toll-like Receptors 2 Production in Females with Rheumatoid Arthritis Depending on NOS3 Gene Polymorphism.

BACKGROUND: Rheumatoid Arthritis (RA) is an autoimmune polygenic disease characterized by rapid disability progression and high prevalence. Progression of RA is closely associated with chronobiological changes in the production of some hormones and inflammatory mediators, influencing the disease course and therapy efficacy. The main pathogenetic mechanism of RA is angiogenesis, which is controlled by biological clock-genes. Further investigation of circadian rhythms of angiogenic mediators production in RA patients may be considered as important and relevant. The aim of this study was to establish daily variability of serum endothelial Nitric Oxide Synthase (NOS3) and toll-like receptors 2 (sTLR2) levels in female RA patients depending on the NOS3 gene polymorphism. METHODS: We examined 173 RA patients (100% female) aged 43.7 ± 7.35 years and 34 age-matched healthy women without joint diseases and autoimmune diseases (control). RA was diagnosed by ACR/EULAR 2010 criteria. Blood serum NOS3 and sTLR2 levels were determined at 08:00 and 20:00 using Cloud-Clone Corp kits (USA). NOS3 T-786С (rs2070744) polymorphism was determined by Real-Time PCR (Bio-Rad iCycler IQ5) using SNP-express kits. The SPSS22 software package was used for statistical processing of the results. RESULTS: Females with RA demonstrated oppositely directed serum NOS3 and sTLR2 daily changes: NOS3 level in the morning (08:00) was lower than in the evening (+ 45.5 ± 30.7%), and sTLR2 level in the evening (at 20:00) was lower than in the morning (-21.6 ± 13.1%). RA patients had differences in NOS3 and sTLR2 production depending on NOS3 T786C genotype. CC subjects had NOS3 level at 08:00, 20:00 and day average levels lower (16-25%), and sTLR2 level higher (24-27%) than those of TT subjects. RA patients, carriers of CC genotype, had higher chances of NOS3 and sTLR2 aberrant production compared to TT and TC genotype carriers (OR = 2.99 and 4.79, respectively). CONCLUSION: RA patients demonstrated oppositely directed circadian changes of serum NOS3 and sTLR2. CC genotype carriers had lower NOS3 and higher sTLR2 production rates than TT and TC genotype carriers.

Combined effects of probiotic and chondroprotector during osteoarthritis in rats.

BACKGROUND: Osteoarthritis (OA) is a joint affection, defined by articular cartilage demolition, risks of which rise with age. The aim of this study was to compare the efficacy of chondroitin sulfate (CS) course and multistrain live probiotic (LP) administered alone or in combination on the expression of TLR-2, TLR-4, TNF-α and NF-κB in articular cartilage, subchondral bone and synovial membrane during OA in rats. METHODS: OA was induced in male rats by injecting monoiodoacetate (MIA) in right hind knee. Therapeutic groups received 3 mg/kg of chondroprotector (ChP) CS for 28 days and/or 140 mg/kg of LP diet for 14 days. The expression of TLR-2, TLR-4, TNF-α and NF-κB in articular cartilage, subchondral bone and synovial membrane were determined with immunohistochemical staining kits (Thermo Fisher Scientific). RESULTS: It was established that MIA injection is associated with long-term structural changes in joint tissues that corresponded to OA-like features and associated with activation of pathogen-recognizing molecules and proinflammatory signaling pathways expression. Separate therapy with ChP and probiotics slightly decreased OA score limiting cell death and subchondral bone resorption. However, these changes were not associated with a significant decrease in TLR-2, TLR-4, NF-kB and TNF-α expression. On the other hand, the combination of ChP and LP treatment significantly decreased OA score. This correlated with a decrease in TLR-2, TLR-4, NF-kB and TNF-α expression in chondrocytes and synovial cells. CONCLUSIONS: The outcomes of our research prove that ChPs amplify the positive action of LPs in OA attenuation.

The influence of probiotic diet and chondroitin sulfate administration on Ptgs2, Tgfb1 and Col2a1 expression in rat knee cartilage during monoiodoacetate-induced osteoarthritis.

BACKGROUND: Osteoarthritis (OA) is a common worldwide disease induced by a wide range of biochemical processes, mainly inflammation and degradation of collagen. The aim of this study, was to describe the effect of a multistrain probiotic (PB) and chondroitin sulfate (CS), administered separately or in combination, on the expression of Ptgs2, Tgfb1 and Col2a1 during monoiodoacetate-induced OA in male rats. METHODS: OA was induced in male rats by injecting monoiodoacetate in right hind knee. Therapeutic groups received 3 mg/kg of CS for 28 days and/or 1.4 g/kg of multistrain PB for 14 days. Knee cartilage were taken 30 days after monoiodoacetate injection. RNA was extracted and the expression of Ptgs2, Tgfb1 and Col2a1 were analyzed using SYBR Green 1-step real-time quantitative polymerase chain reaction. RESULTS: Induction of OA caused an upregulation in Ptgs2, Tgfb1 expression, and downregulation of Col2a1. Separate administration of PB and CS reduced Ptgs2 and Tgfb1 expressions. Their combined administration significantly decreased the expression of these pro-inflammatory cytokines, comparable to controls. Expression of Col2a1 showed similar behavior, with upregulation in therapeutic group with separate administration and the cumulative effects in case of co-administration. CONCLUSIONS: The multistrain PB diet may offer a perspective to improve the standard treatment of OA and, necessitates further investigation with clinical trials.

Crosstalk between gut microbiota and antidiabetic drug action.

Type 2 diabetes (T2D) is a disorder characterized by chronic inflated blood glucose levels (hyperglycemia), at first due to insulin resistance and unregulated insulin secretion but with tendency towards global spreading. The gut microbiota is recognized to have an influence on T2D, although surveys have not formed a clear overview to date. Because of the interactions between gut microbiota and host homeostasis, intestinal bacteria are believed to play a large role in various diseases, including metabolic syndrome, obesity and associated disease. In this review, we highlight the animal and human studies which have elucidated the roles of metformin, α-glucosidase inhibitors, glucagon-like peptide-1 agonists, peroxisome proliferator-activated receptors γ agonists, inhibitors of dipeptidyl peptidase-4, sodium/glucose cotransporter inhibitors, and other less studied medications on gut microbiota. This review is dedicated to one of the most widespread diseases, T2D, and the currently used antidiabetic drugs and most promising new findings. In general, the gut microbiota has been shown to have an influence on host metabolism, food consumption, satiety, glucose homoeostasis, and weight gain. Altered intestinal microbiota composition has been noticed in cardiovascular diseases, colon cancer, rheumatoid arthritis, T2D, and obesity. Therefore, the main effect of antidiabetic drugs is on the microbiome composition, basically increasing the short-chain fatty acids-producing bacteria, responsible for losing weight and suppressing inflammation.

Effect of Chondroitin Sulfate on Blood Serum Cytokine Profile during Carrageenan-induced Edema and Monoiodoacetate-induced Osteoarthritis in Rats.

BACKGROUND: Blood cytokines affect the development of inflammatory processes in both normal and pathological states. We have studied changes in the concentration of interleukins (ILs) - 1ß, IL-4, IL-10, IL-12B p40, transforming growth factor ß (TGF ß), tumor necrosis factor (TNF-α) in acute carrageenan-induced inflammation and degenerative-dystrophic changes of knee joint caused by monoiodoacetate-induced Osteoarthritis (OA) in experimental models on rats. We also investigated the change in the cytokine profile during prophylactic and therapeutic administration of chondroitin sulfate to animals under experimental conditions. METHODS: The concentration of the cytokines was measured in blood serum by enzyme-linked immunosorbent assay. RESULTS: The manifestation of articular lesions was characterized by a disturbance in the balance between proinflammatory (IL-1ß, IL-12B p40, TNF-α) and anti-inflammatory (IL-4, IL-10, TGF -ß) cytokines. CONCLUSION: A reduction in the concentration of proinflammatory cytokines in blood serum after prophylactic and therapeutic administration of chondroitin sulfate to the rat with experimental models of acute inflammation of the hind limb and degenerative-dystrophic changes in the knee joint with OA is associated with anti-inflammatory and regenerative properties of the drug.