Specific properties of probiotic strains: relevance and benefits for the host.

BACKGROUND: Probiotics have tremendous potential to develop healthy diets, treatment, and prevention. Investigation of in vitro cultural properties of health-promoting microorganisms like lactic acid bacteria (LAB) and bifidobacteria is crucial to select probiotic strains for treatments based on gut microbiota modulation to justify individualized and personalized approach for nutrition and prevention of variety of diseases. The aim was to study the biological properties of LAB and bifidobacteria probiotic strains, namely adhesive properties; resistance to antibiotics; and biological fluids (gastric juice, bile, pancreatic enzymes), and to overview the literature in the field. MATERIALS AND METHODS: We studied six LAB strains (Lactobacillus acidophilus ІМV В-7279, L. casei ІМV В-7280, L. delbrueckii subsp. bulgaricus ІМV В-7281, L. rhamnosus LB-3 VK6, L. delbrueckii LE VK8, L. plantarum LM VK7), and two bifidobacteria strains (Bifidobacterium animalis VKL, B. animalis VKB). We characterized tinctorial, culturally morphological, physiological, and biochemical properties of probiotic strains of LAB and bifidobacteria by commonly used research methods. Determination of the resistance to antibiotics was carried out using disc-diffusion method. The effects of gastric juice, bile, and pancreatin on the viability of LAB and bifidobacteria were evaluated. Adhesive properties of LAB and bifidobacteria to epithelial cells were assessed calculating three indicators: average adhesion rate (AAR), participation rate of epithelial cells (PRE), and adhesiveness index of microorganisms (AIM). Electron microscopy of LAB and bifidobacteria cells was conducted. RESULTS: The studied strains of LAB and bifidobacteria did not form spores, were positively stained by Gram, grow on medium in a wide range of pH (1.0-9.0, optimum pH 5.5-6.5), were sensitive to a wide range of antibiotics; and showed different resistance to gastric juice, bile, and pancreatic enzymes. The most resistant to antibiotics were L. rhamnosus LB-3 VK6 and L. delbrueckii LE VK8 strains. The most susceptible to gastric juice was L. plantarum LM VK7, which stopped its growth at 8% of gastric juice; L. acidophilus IMV B-7279, B. animalis VKL, and B. animalis VKB strains were resistant even in the 100% concentration. Strains L. acidophilus IMV В-7279, L. casei IMV В-7280, B. animalis VKL, B. animalis VKB, L. rhamnosus LB-3 VK6, L. delbrueckii LE VK8, and L. delbrueckii subsp. bulgaricus IMV В-7281 were resistant to pancreatic enzymes. Adhesive properties of the strains according to AIM index were high in L. casei IMV В-7280, B. animalis VKL, and B. animalis VKB; were moderate in L. delbrueckii subsp. bulgaricus IMV В-7281; and were low in L. acidophilus IMV В-7279, L. rhamnosus LB-3 VK6, L. delbrueckii LE VK8, and L. plantarum LM VK7. CONCLUSION: We recognized strain-dependent properties of studied LAB and bifidobacteria probiotic strains (adhesive ability, resistance to antibiotics, and gut biological fluids) and discussed potential for most effective individualized treatment for gut and distant sites microbiome modulation.

High regenerative capacity of the liver and irreversible injury of male reproductive system in carbon tetrachloride-induced liver fibrosis rat model.

BACKGROUND: Liver fibrosis (LF) is a chronic disease, associated with many collateral diseases including reproductive dysfunction. Although the normal liver has a large regenerative capacity the complications of LF could be severe and irreversible. Hormone and sex-related issues of LF development and interactions with male reproductive have not been finally studied. The aim was to study the reproductive function of male rats in experimental CCl4-induced liver fibrosis rat model, and the capability for restoration of both the liver and male reproduction system. MATERIALS: Studies were conducted on 20 3-month old Wistar male rats. The experimental animals were injected with freshly prepared 50% olive oil solution of carbohydrate tetrachloride (CCl4). On the 8th week after injection we noted the manifestations of liver fibrosis. The rats were left to self-healing of the liver for 8 weeks. All male rats underwent ultrasound and biopsy of the liver and testes on the 8th and 16th weeks. The male rats were mated with healthy females before CCl4 injection, after modeling LF on the 8th week, and after self-healing of the liver. Pregnancy was monitored on ultrasound. RESULTS: On the 8th week of experiment we observed ultrasound manifestation of advanced liver fibrosis, including hepatosplenomegaly, portal hypertension. Ultrasound exam of the rat testes showed testicular degeneration, hydrocele, fibrosis, scarring, petrifications, size reduction, and restriction of testicular descent; testes size decreased from 1.24 ± 0.62 ml to 0.61 ± 0.13, p < 0.01. Liver histology showed granular dystrophy of hepatocytes, necrotic areas, lipid inclusions in parenchyma. Rats with liver fibrosis demonstrated severe injury of the reproductive system and altering of fertility: the offspring of male rats with advanced LF was 4.71 ± 0.53 born alive vs 9.55 ± 0.47 born from mating with healthy males, p < 0.001. Eight weeks after last CCl4 injection, we revealed signs of liver regeneration, significant recovery of its structure. The ALT and AST levels significantly decreased and reached background measurements. As a result of the second interbreeding after liver self-healing no significant difference was found vs previous mating. CONCLUSION: Carbohydrate tetrachloride induces injury of liver parenchyma evoking fast and severe liver fibrosis, and is associated with irreversible structural and functional changes in testes, reducing fertility, decreasing potential pregnancy rate, and affecting its development. Liver showed high potential to regenerate, however the self-restoring after liver fibrosis was not accompanied with recovery of the reproductive system.

Efficacy of Fenugreek-based bionanocomposite on renal dysfunction and endogenous intoxication in high-calorie diet-induced obesity rat model-comparative study.

BACKGROUND: Worldwide obesity spread is a global health problem and needs to be further studied. Co-morbidities of obesity include insulin resistance, diabetes mellitus type 2, and dyslipidemia, which are the most frequent contributing factors for metabolic syndrome (MetS), as well as non-alcoholic fatty liver disease and chronic kidney disease. The aim was to study renal function and endogenous intoxication panel on high-calorie diet-induced obesity rat model and perform comparative study of the treatment efficacy of Fenugreek-based bionanocomposite vs antiobesogenic drugs (Orlistat). MATERIALS: We included 60 male rats and equally divided them to 6 groups of 10 animals in each group: the experimental groups were firstly assigned as controls and high caloric diet (HCD)-fed groups, and each group further was subdivided to remain untreated, Fenugreek bionanocomposite (BNC)-treated, and Orlistat-treated. Normal control rats (groups 1, 2, 3) were fed by a standard chow, while the others (groups 4, 5, 6) were fed with HCD ad libitum during 98 days. From days 77 to 98, groups 2 and 5 were treated with BNC based on Fenugreek (150 mg/kg body weight, orally) and groups 3 and 6 were treated with antiobesogenic drug Orlistat (10 mg/kg body weight, orally). Food and water consumptions were measured daily and body weights were measured once a week. On day 99, blood was collected; the creatinine, urea, and uric acid were estimated in serum according to the standard protocols. Levels of low and middle molecules (MMs) were measured; the quantity of oligopeptides was estimated by Bradford method. We performed the liver and kidney ultrasonography in rats. RESULTS: We revealed an increase in the levels of endogenous intoxication syndrome markers (MM and oligopeptides) in all animals with experimental obesity. Ultrasound data showed injury of the liver and kidneys in obese rats. We observed significant decreasing of MM levels after Orlistat treatment vs controls (p < 0.05). However, this effect was more pronounced in Fenugreek BNC-treated group vs both Orlistat-treated and controls (p < 0.05). Orlistat treatment evoked rising of serum creatinine and oligopeptides in control animals and failed to normalize these markers in experimental group. Fenugreek-based BNC treatment did not evoke signs of kidney failure and changes in the studied indices in control group. We noticed normalization levels of uric acid and urea in the blood under the use of BNC and Orlistat. CONCLUSION: High-calorie diet-induced obesity evokes endogenous intoxication syndrome and kidney dysfunction in rats. Application of Orlistat- and Fenugreek-based BNC decreases MM content to the normal level. Orlistat induces increasing levels of oligopeptides in both groups, likely due to adverse side effects on renal function and its pro-oxidant activity.

Comparative study of probiotic effects of Lactobacillus and Bifidobacteria strains on cholesterol levels, liver morphology and the gut microbiota in obese mice.

BACKGROUND: Microbiome-modulating interventions are promising for treatment and prevention of metabolic syndrome. The number of probiotic strains demonstrated ability to decrease cholesterol level in vivo, however, it was poorly confirmed in a clinical setting. The aim was to study the effects of L. acidophilus IMV B-7279, L. casei IMV B-7280, B. animalіs VKL and B. animalіs VKB separately and in various compositions on the level of serum cholesterol, gut microbiota contents and liver morphology on a high-calorie-induced obesity model in BALB/c mice. MATERIALS AND METHODS: We used for the study female BALB/c mice 6-8 weeks old (18-24 g). Experimental animals were fed by a fat-enriched diet (FED), and 8 experimental groups were formed (12 mice in each group) to test strains of probiotic bacteria L. delbrueckii subsp. bulgaricus IMV B-7281, L. casei IMV B-7280, B. animalіs VKL and B. animalіs VKB and compositions. We used ultrasound for in vivo assessment of the liver and visceral (mesenteric) fat size. In the blood serum of the obese mice, the level of cholesterol was estimated. The liver morphology and gut microbiota of obese mice were studied. RESULTS: We revealed that after treatment with all of the studied probiotic bacteria and compositions of B. animalis VKL/B. animalis VKB/L. casei IMV B-7280, the weight of obese mice decreased, and cholesterol and its fraction levels in serum were reduced. The size of the liver slightly decreased after treatment with L. delbrueckii subsp. bulgaricus IMV B-7281, B. аnimalis VKB or probiotic compositions; we observed reduction of the mesenteric fat size after injection of all these probiotic bacteria (separately) and probiotic compositions. We defined the strain-dependent effects on serum lipid profiles, liver morphology and the gut microbiota. The B. animalis VKL/B. animalis VKB/L. casei IMV B-7280 composition effectively recovered the liver morphological structure of obese mice. The number of Lactobacillus spp., Bifidobacterium spp. and coliform bacteria increased, the number of staphylococci and streptococci reduced, and the number of microscopic fungi significantly decreased in the gut of obese mice after treatment with L. casei IMV B-7280, L. delbrueckii subsp. bulgaricus IMV B-7281, B. animalis (separately) or their compositions. CONCLUSION: L. casei IMV B-7280 (separately) and a composition of B. animalis VKL/B. animalis VKB/L. casei IMV B-7280 are effective at decreasing the weight of obese mice, decreasing cholesterol level, restoring the liver morphology and beneficially modulating the gut microbiome in high-calorie-induced obesity.

Efficacy of nanoceria for periodontal tissues alteration in glutamate-induced obese rats-multidisciplinary considerations for personalized dentistry and prevention.

BACKGROUND: Nowadays, we face the global epidemic of obesity, that is known to contribute to the development of many diseases, such as the oral cavity pathologies. Dental and oral pathologies are frequently caused by and overlapped with systemic multifactorial diseases such as obesity being its early indicators and risk factors. The aim was to study the influence of nanoceria on periodontal tissues alteration in glutamate (MSG)-induced obese rats. METHODS: We included 52 Wistar rats of both genders and divided into four groups: newborn rats in group 1 (control) received subcutaneously 8 µl/g saline. Group 2 received 3 to 4 mg/g MSG subcutaneously on the second, fourth, sixth, eighth, and tenth day of life; group 3-intragastric administration of nanocrystalline cerium dioxide at a dose of 1 mg/kg volume of 2.9 ml/kg against the background of glutamate-induced obesity; the fourth group of animals was treated with a solution of sodium citrate intragastric volume of 2.9 ml/kg (solvent of nanocrystalline cerium). We determined the total proteolytic activity, the total antitrypsin activity, the content-free fucose and glycosaminoglycanes (GAG), content of TBA-active of products, the content of oxidation-modified proteins (OMB), and catalase activity in the homogenate of soft periodontal tissues of rats. RESULTS: Intragastric injection of nanoceria prevents activation of proteolytic processes, reducing the catabolism of glycoproteins and proteoglycans of periodontal tissue in MSG-induced obese rats. Injection of nanoceria prevents activation of proteolytic processes, significantly decreases the total proteolytic activity, and inhibits the activation of free radical oxidation in periodontal tissues of rats compared with MSG-induced obesity model without corrections. Further, it significantly increases the total antitrypsin activity in periodontal tissues by 1.7 times, TBA-reagents by 1.7 times, and content of OMB by 1.4 times compared with glutamate-induced obese animals. CONCLUSIONS: MSG-induced obesity triggers periodontal tissue alterations in the rat model. Nanoceria contributes to the corrections of pathological changes in periodontal tissues in glutamate-induced obese rats via balancing protein-inhibitory capacity and reducing the depolymerization of fucosylated proteins and proteoglycans and antioxidative activity.

Innovative payer engagement strategies: will the convergence lead to better value creation in personalized medicine?

BACKGROUND: As reimbursement authorities are gaining greater power to influence the prescription behavior of physicians, it remains critical for life science companies focusing on personalized medicine to develop "tailor-made" payer engagement strategies to secure reimbursement and assure timely patient access to their innovative products. Depending on the types of such engagement, pharmaceutical and diagnostic companies may benefit by obtaining access to medical and pharmacy claims data, getting invaluable upfront inputs on evidence requirements and clinical trial design, and strengthening trust by payers, therefore avoiding uncertainties with regards to pricing, reimbursement, and research and development reinvestment. This article aims to study the evolving trend of partnering among two interdependent, yet confronting, stakeholder groups-payers and producers-as well as to identify the most promising payer engagement strategies based on cocreation of value introduced by life science companies in the past few years. We analyzed the recent case studies from both therapeutic and diagnostic realms considered as the "best practices" in payer engagement. The last 5 years were a breakout period for deals between life science companies and reimbursement authorities in the area of personalized medicine with a number of felicitous collaborative practices established already, and many more yet to emerge. We suggest that there are many ways for producers and payers to collaborate throughout the product life cycle-from data exchange and scientific counseling to research collaboration aimed at reducing healthcare costs, addressing adherence issues, and diminishing risks associated with future launches. CONCLUSIONS: The presented case studies provide clear insights on how successful personalized medicine companies customize their state-of-the-art payer engagement strategies to ensure closer proximity with payers and establish longer-term trust-based relationships.

Erratum to: Antarctica challenges the new horizons in predictive, preventive, personalized medicine: preliminary results and attractive hypotheses for multi-disciplinary prospective studies in the Ukrainian "Akademik Vernadsky" station.

[This corrects the article DOI: 10.1186/s13167-016-0060-8.].

Antarctica challenges the new horizons in predictive, preventive, personalized medicine: preliminary results and attractive hypotheses for multi-disciplinary prospective studies in the Ukrainian "Akademik Vernadsky" station.

BACKGROUND: Antarctica is a unique place to study the health condition under the influence of environmental factors on the organism in pure form. Since the very beginning of the scientific presence of Ukraine in the Antarctic, biomedical research has been developed for the monitoring of individual biomarkers of winterers and medical accompaniment in Antarctic expeditions. The aim of the study was to analyze and discuss the retrospective data of long-term monitoring and observations in Ukrainian Antarctica station "Akademik Vernadsky," providing multi-scale biomedical information with regard to conditions of a perfect isolation from technological and social influences and under extreme environmental factors. METHODS: Medical and biological studies have been performed with the participation of all 20 Ukrainian wintering expeditions. We surveyed 200 males aged 20-60 years (mean age 37 years). Extensive medical examinations were carried out before the expedition, during the selection of candidates, and after returning, and particular functions were monitored during the entire stay in Antarctica. The medical records were analyzed to study the reaction of the human organism on phenomena like "Antarctic syndrome," dysadaptation, anxiety, desynchronosis, photoperiodism, influence of climatic and meteofactors like "Schumann resonance," infrasound, "ozone hole," and "sterile" environment; important aspects of its role on human health were precisely studied and discussed. RESULTS: The examinations showed the multi-level symptoms of the processes of dysregulation and dysadaptation, as functional tension in the sympathetic-adrenal system rights, especially during urgent adaptation to the Antarctic (1-month stay at the station) and, to a lesser extent, after returning from an expedition to Kyiv. At the initial, adaptation to the conditions of the Antarctic levels of urinary catecholamines (epinephrine, norepinephrine, dopamine, DOPA) increased compared with the start of the expedition (23.2 ± 4.3 and 53.3 ± 5 2 mmol/l, p < 0.001; 67.1 ± 12.3 and 138.3 ± 16.9 mmol/l, p < 0.01; 1749.6 ± 476.5 vs 7094.6 ± 918.3 mmol/l, p < 0.001; 129.6 ± 12.3 and 349.9 ± 40.6 mmol/l, p < 0.001, respectively). In the blood serum of 100 % of the expedition, we found an increase of oxidative stress markers-the level of TBARS increased by 41.2 %, i.e., the activation of free radical peroxidation. Thus, in 80 % of the participants, we observed a reduction in the activity of the SOD antiradical enzyme vs 58 % in the controls. Changes in brain electrical activity after a long stay at the Antarctic stations showed increasing delta rhythms, signs of CNS protective inhibition, likely due to hypoxia. We found changes in the concentrations of microelements (iron, copper, zinc, etc.) in the blood of winterers after the expedition. The polychrome-adaptive method of correcting the changes of the psycho-emotional state in a monochrome Antarctic environment was successfully applied. CONCLUSIONS: The preliminary results of the retrospective study and our own observations of the fundamental physiological mechanisms of the negative influence of extreme environmental factors on an organism in the absence of man-made origin factors allow the determination of many mechanisms of "pre-pathology" processes which promise to develop the pathogenetically based pro-active prevention methods for a number of common diseases to set prospective interdisciplinary research in predictive, preventive, and personalized medicine.

Assessing value of innovative molecular diagnostic tests in the concept of predictive, preventive, and personalized medicine.

Molecular diagnostic tests drive the scientific and technological uplift in the field of predictive, preventive, and personalized medicine offering invaluable clinical and socioeconomic benefits to the key stakeholders. Although the results of diagnostic tests are immensely influential, molecular diagnostic tests (MDx) are still grudgingly reimbursed by payers and amount for less than 5 % of the overall healthcare costs. This paper aims at defining the value of molecular diagnostic test and outlining the most important components of "value" from miscellaneous assessment frameworks, which go beyond accuracy and feasibility and impact the clinical adoption, informing healthcare resource allocation decisions. The authors suggest that the industry should facilitate discussions with various stakeholders throughout the entire assessment process in order to arrive at a consensus about the depth of evidence required for positive marketing authorization or reimbursement decisions. In light of the evolving "value-based healthcare" delivery practices, it is also recommended to account for social and ethical parameters of value, since these are anticipated to become as critical for reimbursement decisions and test acceptance as economic and clinical criteria.

Probiotics and immunity: provisional role for personalized diets and disease prevention.

There is great interest in the interaction between diet and immune system and concomitantly in the potential of probiotic bacteria, especially given recent advances in understanding of gut microbiota effects on health in the context of microbiome research. Following our recent study on bacterial wall elasticity as a predictive measure of phagocytic cellular reactions and related outcomes, a question was raised regarding the scope of the application of these findings in various medical conditions in the context of predictive, preventive, and personalized medicine (PPPM). This summarizing review of the data describes the contributions, both observed and potential, of probiotics to the gut-brain axis and various medical conditions, including immune and atopic states, metabolic and inflammatory diseases-including liver disease and diabetes mellitus-cancer, and more. It also suggests novel insights for a number of beneficial applications of probiotics and advances in development of novel probiotic-based treatments and personalized diets, as well as application of sophisticated imaging techniques and nanobiotechnologies that can be adopted in the near future by innovative medical experts, warranting further research and practical translation.

Antioxidative effects of cerium dioxide nanoparticles ameliorate age-related male infertility: optimistic results in rats and the review of clinical clues for integrative concept of men health and fertility.

BACKGROUND: Male infertility has largely idiopathic, multifactorial origin. Oxidative stress is a major factor that affects spermatogenesis, in particular in aging. Cerium dioxide nanoparticles (CNPs) due to their antioxidative properties are promising to impact on the development of male infertility. The aims of this study were to investigate the effects of CNPs on fertility parameters in 24-month male rats and to overview relevant literature in the field of personalized treatments, predictive diagnosis, and preventive measures for male health and fertility. METHODS: We included 30 24-month-old male rats. After a week of adaptation to the standard diet, the rats were randomly divided into three groups with ten rats in each. Group 1 (controls) received only a standard diet. The rats of group 2 and 3 in adjunct to the standard diet during 10 days received intragastrically 10 % sodium citrate and citrate-coated CNPs in dose 1 mg/kg, respectively. We assessed sex hormones, epididymal sperm parameters and spermatogenesis, ultrasound, and morphological data of rat reproductive organs. RESULTS: After a 10-day administration of CNPs, we revealed significant decrease of lipid peroxidation product levels in serum and increase of catalase and SOD activity, associated with increase of sperm count (p < 0.001) and improvement in quantitative sperm parameters (motility, viability, and percentage of spermatozoa). We found no significant changes between sperm quantitative parameters in citrate-treated rats and controls and observed age-related decrease of activated Leydig cell number and focal atrophy of the seminiferous tubules. In CNP group, we observed regeneration of seminiferous tubules, increase number and activation of Leydig cells, and 2.5-fold significant increase of serum testosterone. Ultrasound data showed the slight increase of linear measurement and volume of rat testes in CNP group. Review highlights the benefits for predictive diagnosis, preventive measures, and personalized approaches to manage male infertility in the general concept of male health also related to aging. CONCLUSION: Citrate-coated 2-5-nm CNPs lead to increase in sex hormones levels, sperm count, and quality, as well as the activation of spermatogenesis in 24-month-old male rats. Nanoceria demonstrated the perspectives to be an effective infertility treatment via reduction of oxidative stress in male reproductive organs, in particular in aging.

The role of beneficial bacteria wall elasticity in regulating innate immune response.

BACKGROUND: Probiotics have great potential to contribute to development of healthy dietary regimes, preventive care, and an integrated approach to immunity-related disease management. The bacterial wall is a dynamic entity, depending on many components and playing an essential role in modulating immune response. The impact of cell wall elasticity on the beneficial effects of probiotic strains has not been sufficiently studied. The aim was to investigate the effect of lactic acid bacteria (LAB) and bifidobacteria strains on phagocytic system cells (macrophages) as related to bacterial wall elasticity, estimated using atomic force microscopy (AFM). METHODS: We conducted studies on Balb/c line mice 18-20 g in weight using lyophilized strains of LAB-Lactobacillus acidophilus IMV B-7279, Lactobacillus casei IMV B-7280, Lactobacillus delbrueckii subsp. bulgaricus IMV B-7281, and bifidobacteria-Bifidobacterium animalis VKL and Bifidobacterium animalis VKB. We cultivated the macrophages obtained from the peritoneal cavity of mice individually with the strains of LAB and bifidobacteria and evaluated their effect on macrophages, oxygen-dependent bactericidal activity, nitric oxide production, and immunoregulatory cytokines. We used AFM scanning to estimate bacterial cell wall elasticity. RESULTS: All strains had a stimulating effect on the functional activity of macrophages and ability to produce NO/NO2 in vitro. Lactobacilli strains increased the production of IL-12 and IFN-γ in vitro. The AFM demonstrated different cell wall elasticity levels in various strains of LAB and bifidobacteria. The rigidity of the cell walls among lactobacilli was distributed as follows: Lactobacillus acidophilus IMV B-7279 > Lactobacillus casei IMV B-7280 > Lactobacillus delbrueckii subsp. bulgaricus IMV B-7281; among the strains of bifidobacteria: B. animalis VKB > B. animalis VKL. Probiotic strain survival in the macrophages depended on the bacterial cell wall elasticity and on the time of their joint cultivation. CONCLUSION: LAB and bifidobacteria strains stimulate immune-modulatory cytokines and active oxygen and nitrogen oxide compound production in macrophages. Strains with a more elastic cell wall according to AFM data demonstrated higher resistance to intracellular digestion in macrophages and higher level of their activation. AFM might be considered as a fast and accurate method to assess parameters of probiotic strain cell wall to predict their immune-modulatory properties.

Nanocrystalline cerium dioxide efficacy for gastrointestinal motility: potential for prokinetic treatment and prevention in elderly.

BACKGROUND: Constipation is a common condition, with prevalence after 65 years, is a major colorectal cancer risk factor. Recent works have demonstrated advances in personalized, preventive nanomedicine, leading to the construction of new materials and nanodrugs, in particular, nanocrystalline cerium dioxide (NCD), having strong antioxidative prebiotic effect. The aim of our study was to investigate the influence of NCD on motor function of the stomach and colon in vivo and contractive activity of smooth muscles in different year-old rats. METHODS: We included 80 rats: 3- (weight 130-160 g, n = 40) and 24-month old (weight 390-450 g, n = 40), divided into four groups as follows: І-control group; rats of II-ІV groups were injected intragastrically one injection per day during 10 days, 3 ml of water 3 ml/kg stabilizing solution, аnd 1 mmol/ml NCD, respectively. In all animals, we recorded spontaneous and carbachol-stimulated (0.01 mg/kg) gastrointestinal tract motor activity. We used the index of motor activity (IMA), expressed in cmH2O, for characterization of the motor function. We investigated smooth muscle contraction by tenzometric method, studied the spontaneous and stimulated motility by ballonographic method. RESULTS: IMA reduced by 21.1 + 0.2% (p < 0.01) in the old rats of the control group compared with the young rats. A 10-day administration of NCD increased IMA in the stomach of young rats by 9.3% (р < 0.001) vs the control group. The exposure of NCD increased the amplitude of contraction to 34.2 ± 5.4 mN (n = 10) in the stomach of old rats and increased by 32.1 ± 2.4% vs the control group (p < 0.05). NCD did not influence acetylcholine (ACh) contractions in the stomach of young rats; however, in the stomach of old rats, V nr increased by 90 ± 15.2% (р < 0.001). CONCLUSIONS: The index of motor activity is decreased in old rats. Nanocrystalline cerium dioxide increased the index of motor activity in all groups of rats and also evoked a significant increase of colon contractions in old rats.

Development of biomarker panel to predict, prevent and create treatments tailored to the persons with human papillomavirus-induced cervical precancerous lesions.

INTRODUCTION: Human papillomavirus (HPV) induce many cancer conditions and cause cervical cancer, second in frequency of malignant disease in women.The aim was to develop biomarker panel for HPV-induced cervical precancerous diseases in patients infected with herpes simplex virus (HSV). MATERIAL AND METHODS: The study involved 71 women with cervical precancerous diseases (mean age 26 ± 5 years) revealed by colposcopic, cytomorphological, and ultrasound signs which were assessed according to the following: first group, 44 patients infected with HPV; second group, 27 HPV-negative patients; and third group, 30 healthy patients (controls). In cervical specimen, we identified HPV DNA of different oncogenic risk types by polymerase chain reaction (PCR). Enzyme-linked immunosorbent assay (ELISA) kits (JSC SPC 'DiaprofMed') were used for detecting antibodies to HSV1 and/or HSV2 and for determining the avidity index. The production of pro-inflammatory cytokines, interferon-γ (IFN-γ), IFN-α, TNF-α, and interleukin-1ß (IL-1ß), and anti-inflammatory cytokines, IL-4, IL-10, and transforming growth factor-ß1 (TGF-ß1), were studied by ELISA. RESULTS: In HPV-induced cervix precancerous diseases, we identified low-avidity IgG antibodies to HSV serum of 20 patients; in the serum of 17 patients, we identified average-avidity antibodies, and high-avidity antibodies were found in 2 patients only. In 14 HPV-negative patients, we found low-avidity IgG antibodies to HSV; in 10 patients, medium avidity. Patients with low-avidity IgG antibodies to herpes virus showed high and medium oncogenic risk HPV types and a decrease of IFN-γ compared to patients with medium-avidity IgG antibodies. Production of IFN-γ was suppressed also in HPV-negative patients with cervical precancers, but we found low- and medium-avidity IgG antibodies to herpes virus. In patients with low-avidity antibodies, we observed increased level of IL-10. Level of IFN-α, IL-1ß, IL-2, and IL-4 did not change in patients of all groups, but TGF-ß1 increased. CONCLUSIONS: In HPV-positive patients, those with low-avidity IgG antibodies to HSV had immunosuppression, confirmed by increased TGF-ß1 and violation of IFN-γ production. Therefore, in pro- and anti-inflammatory cytokines and IgG antibodies to HSV, their avidity is an important diagnostic biomarker of HPV-induced precancerous cervical diseases. Low-avidity IgG antibodies may be an indication for treatment with immunomodulators and antiviral drugs.

The efficacy of probiotics for monosodium glutamate-induced obesity: dietology concerns and opportunities for prevention.

INTRODUCTION: Obesity becomes endemic today. Monosodium glutamate was proved as obesogenic food additive. Probiotics are discussed to impact on obesity development. AIMS AND OBJECTIVES: The aim was to study the effects of probiotics on the development of monosodium glutamate (MSG)-induced obesity in rats. MATERIAL AND METHODS: We included 45 Wistar male rats and divided into three groups (n = 15). Newborn rats of group 1 (control) received subcutaneously 8 µl/g saline. Group 2 received 3 to 4 mg/g MSG subcutaneously on the second, fourth, sixth, eighth and tenth day of life. Within 4 months after birth, rats were on a standard diet. Group 3 received an aqueous solution of probiotics mixture (2:1:1 Lactobacillus casei IMVB-7280, Bifidobacterium animalis VKL, B. animalis VKB) at the dose of 5 × 109 CFU/kg (50 mg/kg) intragastrically. Administration of probiotics was started at the age of 4 weeks just after weaning and continued for 3 months during 2-week courses. Group 2 received intragastrically 2.5 ml/kg water. Organometric and biochemical parameters in all groups of rats were analyzed over 4 months. The concentration of adiponectin was determined in serum, and leptin - in adipose tissue. RESULTS: Administration of MSG led to the development of obesity in rats; body weight had increased by 7.9% vs controls (p < 0.05); body length had increased by 5.4% (p < 0.05). Body mass index and Lee index and visceral fat mass had increased (p < 0.001). Under the neonatal injection of MSG, the concentration of total cholesterol, triglycerides, VLDL cholesterol and LDL cholesterol significantly increased (p < 0.001), in comparison with controls. Adipose-derived hormones changed in MSG obesity rats: adiponectin decreased by 58.8% (p < 0.01), and leptin concentration in adipose tissue had increased by 74.7% (p < 0.01). The probiotic therapy of rats from group 3 prevented obesity development. Parameters of rats treated with probiotic mixture did not differ from that in the control. CONCLUSIONS: The introduction of MSG to newborn rats caused the obesity in adulthood. Periodic administration of probiotic mixture to rat injected with MSG neonatally resulted in recovery of lipid metabolism and prevention of the obesity development.

Predictive diagnosis of endometrial hyperplasia and personalized therapeutic strategy in women of fertile age.

INTRODUCTION: Endometrial hyperplasia has a high risk for malignant transformation and relapses; existing mini-invasive treatments may lead to irrevocable endometrium destruction. The aims were to analyze receptor systems in endometrial hyperplasia, to evaluate the capabilities of ultrasonography, sonoelastography for diagnosis and treatment control, and to develop treatment algorithm. MATERIALS AND METHODS: We included 313 women (20-45 years), assessed into the following: group 1 (n = 112) with glandular cystic hyperplasia, group 2 (n = 98) endometrial polyps, and group 3 (n = 103) atypical hyperplasia; and 82 controls who have undergone hysteroscopy before in vitro fertilization in tubal origin infertility were also included. Patients underwent clinical examination, transvaginal ultrasound, immunohistochemical study, and hormonal therapy/hysteroresectoscopy. RESULTS: In patients with glandular hyperplasia, we registered increase of endometrium estrogen receptors (75.6% in the epithelium and 30.9% in the stroma; in controls, 43.3% and 29.6%, respectively); in polyps, there was a significant estrogen receptor increase in the stroma (48.2% vs 29.6% in controls), and in atypical hyperplasia, progesterone receptors significantly increased in the stroma. Ki-67 increased (40% to 50%) in the epithelium without changes in the stroma. Ultrasound has a sensitivity of 96% and a specificity of 85% for early detection of endometrial pathology and prediction outcome of intervention, and sonoelastography has a sensitivity of 91% and a specificity of 83% for polyp diagnosis. Personalized treatment was effective in 88.8%, relapse was diagnosed in 11.2% after 6 months, and conservative treatment of atypical hyperplasia was effective in 45%: in 25.8%, ablative hysteroresectoscopy was performed, while in 22.6% with comorbidities, hystero/oophorectomies were performed. CONCLUSIONS: The evaluation of receptor status with ultrasound data in patients with endometrial hyperplasia allows for a clear definition of the treatment policy, avoidance of relapse, treatment optimization, and observation of such patients.

Development and testing of gold nanoparticles for drug delivery and treatment of heart failure: a theranostic potential for PPP cardiology.

INTRODUCTION: Nanoscale gold particles (AuNPs) have wide perspectives for biomedical applications because of their unique biological properties, as antioxidative activity and potentials for drug delivery. AIMS AND OBJECTIVES: The aim was to test effects of AuNPs using suggested heart failure rat model to compare with proved medication Simdax, to test gold nanoparticle for drug delivery, and to test sonoporation effect to increase nanoparticles delivery into myocardial cells. MATERIAL AND METHODS: We performed biosafety and biocompatibility tests for AuNPs and conjugate with Simdax. For in vivo tests, we included Wistar rats weighing 180-200 g (n = 54), received doxorubicin in cumulative dose of 12.0 mg/kg to model advance heart failure, registered by ultrasonography. We formed six groups: the first three groups of animals received, respectively, 0.06 ml Simdax, AuNPs, and conjugate (AuNPs-Simdax), intrapleurally, and the second three received them intravenously. The seventh group was control (saline). We performed dynamic assessment of heart failure regression in vivo measuring hydrothorax. Sonoporation of gold nanoparticles to cardiomyocytes was tested. RESULTS: We designed and constructed colloidal, spherical gold nanoparticles, AuNPs-Simdax conjugate, both founded biosafety (in cytotoxicity, genotoxicity, and immunoreactivity). In all animals of the six groups after the third day post-medication injection, no ascites and liver enlargement were registered (P < 0.001 vs controls). Conjugate injection showed significantly higher hydrothorax reduction than Simdax injection only (P < 0.01); gold nanoparticle injection showed significantly higher results than Simdax injection (P < 0.05). AuNPs and conjugate showed no significant difference for rat recovery. Difference in rat life continuity was significant between Simdax vs AuNPs (P < 0.05) and Simdax vs conjugate (P < 0.05). Sonoporation enhances AuNP transfer into the cell and mitochondria that were highly localized, superior to controls (P < 0.01 for both). CONCLUSIONS: Gold nanoparticles of 30 nm and its AuNPs-Simdax conjugate gave positive results in biosafety and biocompatibility in vitro and in vivo. AuNPs-Simdax and AuNPs have similar significant cardioprotective effects in rats with doxorubicin-induced heart failure, higher than that of Simdax. Intrapleural (local) delivery is preferred over intravenous (systemic) delivery according to all tested parameters. Sonoporation is able to enhance gold nanoparticle delivery to myocardial cells in vivo.

Gold nanoparticles - the theranostic challenge for PPPM: nanocardiology application.

The article overviews the potential biomedical applications of nanoscale gold particles for predictive, preventive and personalised nanomedicine in cardiology. The review demonstrates the wide opportunities for gold nanoparticles due to their unique biological properties. The use of gold nanoparticles in cardiology is promising to develop fundamentally new methods of diagnosis and treatment. The nanotheranostics in cardiovascular diseases allows the non-invasive imaging associated with simultaneous therapeutic intervention and predicting treatment outcomes. Imaging may reflect the effectiveness of treatment and has become a fundamental optimisation setting for therapeutic protocol. Combining the application of biomolecular and cellular therapies with nanotechnologies foresees the development of complex integrated nanodevices. Nanocardiology may challenge existing healthcare system and economic benefits as cardiovascular diseases are the leading cause of morbidity and mortality at present.

Evidence-based pain management: is the concept of integrative medicine applicable?

This article is dedicated to the concept of predictive, preventive, and personalized (integrative) medicine beneficial and applicable to advance pain management, overviews recent insights, and discusses novel minimally invasive tools, performed under ultrasound guidance, enhanced by model-guided approach in the field of musculoskeletal pain and neuromuscular diseases. The complexity of pain emergence and regression demands intellectual-, image-guided techniques personally specified to the patient. For personalized approach, the combination of the modalities of ultrasound, EMG, MRI, PET, and SPECT gives new opportunities to experimental and clinical studies. Neuromuscular imaging should be crucial for emergence of studies concerning advanced neuroimaging technologies to predict movement disorders, postural imbalance with integrated application of imaging, and functional modalities for rehabilitation and pain management. Scientific results should initiate evidence-based preventive movement programs in sport medicine rehabilitation. Traditional medicine and mathematical analytical approaches and education challenges are discussed in this review. The physiological management of exactly assessed pathological condition, particularly in movement disorders, requires participative medical approach to gain harmonized and sustainable effect.

The use of trigger point "dry" needling under ultrasound guidance for the treatment of myofascial pain (technological innovation and literature review).

The aim of the study was to examine the use of trigger point dry needling under ultrasound guidance and myofascial release for the treatment of myofascial pain and to increase the provability of the puncture treatment by visual verification. A review of modern and traditional approaches to myofascial pain treatment is presented in the article. For the first time the trigger point was visualized by ultrasound (US) in this study and ultrasound guided needling therapy of muscles was performed as well. The group of 91 patients, suffered from myofascial pain of different location was included in the study. The patients were treated during last year by patented method (UA patent A 2010 06283). The pain relief effect was registered in 93.3% patients.