The paraoxonase (PON) gene family includes three members: PON1, PON2, and PON3 aligned in tandem on chromosome 7 in humans. All PON proteins share considerable structural homology and have the capacity to protect cells from oxidative stress; therefore, they have been implicated in the pathogenesis of several inflammatory diseases, particularly atherosclerosis. Increased production of reactive oxygen species as a result of decreased activities of mitochondrial electron transport chain complexes plays a role in the development of many inflammatory diseases, including atherosclerosis. PON1 and PON3 proteins can be detected in plasma and reside in the high-density lipoprotein fraction and protect against oxidative stress by hydrolyzing certain oxidized lipids in lipoproteins, macrophages, and atherosclerotic lesions. Paraoxonase 2 (PON2) possesses antiatherogenic properties and is associated with lower ROS levels. PON2 is involved in the antioxidative and anti-inflammatory response in intestinal epithelial cells. In contrast to PON1 and PON3, PON2 is cell-associated and is not found in plasma. It is widely expressed in a variety of tissues, including the kidney, and protects against cellular oxidative stress. Overexpression of PON2 reduces oxidative status, prevents apoptosis in vascular endothelial cells, and inhibits cell-mediated low density lipoprotein oxidation. PON2 also inhibits the development of atherosclerosis, via mechanisms involving the reduction of oxidative stress. In this review we explore the physiological roles of PON in disease development and modulation of PONs by infective (bacterial, viral) agents.
Background Irrational medicine use including excessive use and abuse of antibiotics remains a crucial problem for the healthcare systems. In this regard, studies examining approaches to improving the clinical use of medicines are highly important. Aim to assess the efficacy rate of management for the rational use of antibiotics in surgical departments of a multi-disciplinary hospital. Material and Methods The intervention complex combined the research, educational, and methodological activities: local protocols for perioperative antibiotic prophylaxis (PABP) for various surgical departments were developed; local PABP protocols were discussed with the physicians of specialized surgical departments; official order on implementation of PABP was issued; the list of drug prescriptions for registration of the first pre-operative antibiotic dose was changed; audit and feedback processes were introduced as well as consultations of a clinical pharmacologist were implemented. We assessed the efficacy rate of the interventions basing on the changes in consumption of antibiotics (both quantitatively and qualitatively) at surgical departments of a hospital using ATC/DDD methodology. Comparison of the studied outcomes was performed before and after the intervention implementation and between the departments (vascular and abdominal surgery). The consumption of antibacterial agents (ATCJ01) was measured as a number of defined daily doses (DDD) per 100 bed-days (DDD/100 bed-days, indicator recommended by the World Health Organization, WHO) and DDD per 100 treated patients (DDD/100 treated patients). Results From 2006 to 2012, a decrease in antibacterial consumption in surgical departments by 188 DDD/100 treated patients was observed. We obtained the opposite results when using an indicator of DDD/100 bed-days (increase by 2.5 DDD/100 bed-days) which could be explained by the dependence on indices of overall hospital work and its changes during the examined period. Observed changes in antibacterial consumption varied in different surgical departments. The most pronounced positive changes were noted in the department of vascular surgery: decrease in total antibacterial consumption by 298 DDD/100 treated patients, decrease in the use of cephalosporins of the III generation from 141 to 38 DDD/100 treated patients. These positive changes were accompanied by the same (low) level of consumption/use of reserve antibiotics. In the department of abdominal surgery, there was no decrease in total antibiotic consumption, as well as in consumption of broad-spectrum cephalosporins of the III generation and fluoroquinolones, and we observed an increase in the use of reserve antibiotics (carbapenems) during the study period. Positive changes in antibiotic consumption were associated with the positive attitude of the manager/head of the department towards interventions: we observed the most pronounced decrease in antibiotic consumption straight after the publication of the administrative order on perioperative antibacterial prophylaxis. Conclusion The combination of scientific, educational, and methodological interventions is effective for improving antibiotic application. The study results provide the rationale for analyzing the drug consumption using the DDD/100 treated patients measure in addition to the WHO-recommended indicator of DDD/100 bed-days which depends on overall hospital performance.
Background:The role of the alternative complement pathway (AP) abnormalities in the pathogenesis of aHUS is well studied. Clinical and morphological manifestations of atypical HUS and catastrophic APS are often similar. However, studies on the state of AP in patients with CAPS are virtually absent.Aims:The aim of our study was to assess the state of AP in patients with CAPS and aHUS. Patients and methods: The study enrolled 67 patients (pts) with a diagnosis of CAPS (28 pts) and aHUS (39 pts). Studies of the complement system are made of 10 pts with CAPS and 20 aHUS. Factor H, I, B, D content, functional activity of factor H, and complement components C3, C4 was determined in serum by ELISA kit.Results:Patients with CAPS and aHUS showed similar changes in complement biomarkers. The factor H level in the serum was significantly higher than the standard value. However, the specific activity of factor H reduced, mean rate 59% for aHUS and 26% for CAPS. The median value of factor D was twice higher than the normal range in both groups, indicating the activation of the AP.Conclusions:There are indications of an AP activation not only in pts with aHUS but in CAPS pts too. We suppose that the activity of factor H is a more sensitive indicator of complement system changes than factor H level. Patients with CAPS and aHUS have similar clinical and laboratory characteristics. However, CAPS is more severe, with the involvement of a larger number of vascular beds. Perhaps this is due to the double damaging effects on the endothelium ― of antiphospholipid antibodies (aPL) and activated complement. So we hypothesize that CAPS can be called aPL-mediated TMA in pts with a complement system defect.
It is established that oxidative stress induces insulin resistance of adipocytes, increases secretion leptin, IL-6, TNF-α by adipocytes. Adiponectin secretion by adipocytes is reduced after the action of reactive oxygen species. Metabolic syndrome contributes to oxidative stress in adipose tissue, on the one hand due to the activation of production of reactive oxygen species by adipocyte NADPH-oxidase, and on the other hand by reducing the antioxidant defense adipocytes. It is found that obesity itself can induce oxidative stress. Chronic stress, glucocorticoids, mineralocorticoids, angiotensin-II, TNF-α play an important role in the pathogenesis of oxidative stress of adipocytes. Metformin remains the cure for the treatment of insulin resistance. The positive results in the treatment of metabolic syndrome by losartan were obtained. Antioxidants and flavonoids exhibit a positive impact on the course of the experimental metabolic syndrome.
An antagonist of central cannabinoid CB1 receptors rimonabant causes weight loss in patients with obesity and metabolic syndrome, improves blood lipid parameters, increases the adiponectin level, decreases the rate of glucose and glycosylated hemoglobin in patients with diabetes mellitus type-2. However, rimonabant adverse effects include depression, anxiety, nausea, and dizziness which are apparently due to the blockade of central CB1 receptors. In mice with a high-calorie diet, we defined that the blockade of peripheral CB1 receptors prevents obesity, steatosis of the liver, improves lipid and carbohydrate metabolism. Experimental studies suggest that peripheral CB2 receptor agonists have antiatherogenic effect. To validate the expediency of clinical research of CB2 receptor agonists in patients with atherosclerosis the comparative analysis of antiatherogenic properties of cannabinoids should be performed. In addition, experiments are needed on the combination use of cannabinoids with well-known antiatherogenic agents, such as statins.
Urethral stricture is a disease characterized by a pathological narrowing of the urethra. Treatment for this condition often requires surgery using autologous grafts (urethroplasty). It is common practice to use patient’s own tissue like genital and extragenital skin, tunica vaginalis, buccal mucosa as a source of the graft. Alternative and safer approach is to use tissue-engineered graft created in a laboratory using patient’s autologous cells and biocompatible matrix (scaffold). The article presents the up-to-date achievements in lab-created tissue-engineered graft, describes all components needed to build a tissue-engineered structure of the graft for urethroplasty, and summarizes authors’ thoughts on advantages and disadvantages of various approaches to choose both cellular component and the matrix of future construction. The article reviews clinical studies conducted in the field of tissue engineering of the graft material for urethraplasty.
This paper presents a comprehensive review on the current concept of the diagnosis and treatment of central metatarsalgia on the basis of medical literature analyses. Metatarsalgia is the term for pain in the forefoot. This is a set of symptoms corresponding to a wide range of diseases. Central metatarsalgia is a kind of metatarsalgia which arises from structural-functional changes that lead to excessive pressure in the area of metatarsal heads. The data analysis demonstrated that presently various types of osteotomies of metatarsal bones are the main surgical treatment options with the chance of complication ranging from 6 to 50%. Weil-osteotomy is known to be the most popular type of osteotomy for treatment of central metatarsalgia. The most common complication of Weil-osteotomy is floating toe, the one that doesn’t contact with the supporting surface. In case Weil-osteotomy and intraphalangeal arthrodesis with trans acticular fixation are both performed, the complication of floating toe increases up to 50%. When Weil osteotomy, plantar plate repair, extensor digitorum longum tendon lengthening and triple Weil-osteotomy are performed simultaneously, the complication rate is 15% approximately which is much lower. Using combined osteotomy techniques as well as taking into account structural-functional pathologic changes of the forefoot and ligaments repair of metatarsalphalangeal joint will ensure the most successful development of surgical treatment techniques for central metatarsalgia.
Antidiabetic drugs with incretin activity in addition to pronounced hypoglycemic activity cause moderate reduction in blood pressure and fat mass as well as improve the lipid profile in patients with type 2 diabetes mellitus (T2DM). In clinical trials the addition of glucagon-like peptide-1 (GLP-1) analogues to standart T2DM therapy leads to significantly reduce the risk of fatal and nonfatal cardiovascular complications. According to the results of many experimental and clinical studies it was shown that GLP-1 analogs protect endothelium in diabetic patients and protect cardiomyocytes after ischemia-reperfusion lesion. Pleiotropic effects of GLP-1-based therapies are realized due to the presence of GLP-1-receptor in endothelial cells, cardiomyocytes, neurons, monocytes and macrophages, as well as due to the connection of the receptor with the most important intracellular signaling cascades (through activation of protein kinase A and B). Whereby GLP-1-based therapies affect the functional condition as well as processes of regeneration and apoptosis of target cells. This review presents the results of studies the cardiovascular effects of GLP-1-based therapies of diabetes. Described proposed nowadays mechanisms of endothelium protective and cardioprotective action of GLP-1 analogs that associated with the action on endothelial function, vascular wall inflammation (the expression of adhesion molecules and inflammatory cytokines), and apoptosis of endothelial cells and cardiomyocytes.
Allergic disease is a serious problem in practical healthcare. Over the last 40 years there has been exponential growth in the prevalence. According to the world health organization information, allergic diseases are at the 2nd place in prevalence the children, behind the viral infections. Their frequency and severity are increasing. In this regard, the relevance of timely and skilled diagnostic allergopathology is most important. In this study the current state of the question of allergy diagnostics is considered, the international experience is summarized and the approach to the allergy diagnosis based on use of step-by-step identification of a causal and significant factor of allergic reactions is offered. On the basis of the analysis of relevance and the importance for patients of one or the other allergens (taking into account a source of allergens and age of patients) use of a step-by-step allergy diagnostics algorithm is offered. The first step is definition of clinical implications of an allergy. It means direct contact of the phisition with the patient, clarification of its complaints, clinical symptoms, medical history disease. The second step is the confirmation of IgE-dependent mechanism. It involves the using of screening tests that are selected depending on the clinical symptoms and seasonality manifestations (the screening module). The third step is to identify the source of the allergens that are most meaningful for the patient with using test panels (modules). The panels include the most common and clinically relevant triggers of allergic reactions. The fourth step is the search for an individual significant allergens, which were not included in the diagnostic modules. On the fifth step, we plan to conduct component-divided diagnostics and detect the antibodies to unique components of significant allergens. The developed diagnostics algorithm, corresponds to needs of both the adult, and children’s population and provides the personalized approach to the patients.
Background: Nowadays autologous mesenchymal placental stromal cells (MSCs) may use to treat for various diseases both of the mother and the child. Stroma of the placenta villi is appropriated origin for cell culture isolation. Aim of the study was to evaluate the possibility for selection and use of placental tissue for mesenchymal stromal cells. Materials and methods: The present study was based on 45 placental samples of women aged 27−38 yy. who underwent surgical delivery at 36−40 weeks of gestation. 30 of these women have been enrolled in the basic group including children with congenital abnormalities (CA). The comparison group consisted of 15 patients with physiological pregnancy. We performed histological examination (with hematoxylin and eosin staining), immunohistochemical examination (with use monoclonal antibodies CD90 (1:25; Abcam, UK), СD105 (1:500; Abcam, UK), CD44 (1:25; Dako), СD73 (1:200, Abcam, UK), and electron microscopy (by microscope Philips/FEI Corporation, Eindhoven, Holland). Eclipse 80i microscope (Nikon Corporation, Japan) was used to examine the immunohistochemical reactions as a brown staining. The evaluation of the intensity of reaction was conducted by NIS-Elements Advanced Research 3.2 program (Czech Republic). Student’s t-test and analysis of variance were used to compare the mean values. Differences were considered statistically significant at p0.05. Results: Interstitial cells of the stroma of the villi with CA had fibroblastic differentiation as revealed degenerative changes of the cells. The histologic examination with hematoxylin and eosin staining revealed significant fibrosis of the stroma of the placenta villi in CA group (p0,01). Immunohistochemical study of stem and intermediate chorionic villi revealed no significant differences in staining of CD44+, СD90+, СD73+, and CD105+ cells if compared to the control group (p0.05). Although CD105 expression was significantly lower in the CA group (0.058±0.0049) than in the control group (0.088±0.0039) (p0.05). However, electron microscopy detected the villi interstitial stromal cells with fibroblastic differentiation in CA group. Conclusions: Thus, it is necessary to exclude placenta with obstetrical history, somatic, and congenital pathology of the mother and the child when selecting the placental cell culture. Moreover, choosing a sample the morphological structure of the placenta should be taken into consideration. However, congenital malformations of the fetus, pathology of the mother cultivate mesenchymal stromal cells of placentas is inappropriate and should be taken advantage of the donor cells.
Background:The lesion of skin of the majority atopic dermatitis patients is chronically colonized by bacteria belonging to the species Staphylococcus aureus. Topical antibacterial and anti-inflammatory therapy treatment are often ineffective due to fast recolonization by S. aureus and exacerbation of allergic process.Aims:Our aim was to determine a frequency of S. aureus colonization in skin lesions, mucous membranes of the nasal cavity and intestine of children with atopic dermatitis, to compare the genotypes of Staphylococcus aureus strains isolated from different biotopes of atopic dermatitis patients, and to clarify whether the intestinal and nasal cavities microbiota may act as a source of S. aureus recolonization of skin lesions.Materials and Methods:Bacteriological examination of fecal samples, skin, and nasal swabs was conducted in 38 atopic dermatitis patients. The pure bacterial cultures of S. aureus were identified using API Staph (Biomerieux, France) and Vitek 2 MS (Biomerieux, France). Isolates of S. aureus were subjected to genotyping by analysis of rRNA internal 16S-23S rRNA spacer regions and high resolution melting analysis (HMR) of polymorphic spa X-regions.Results:99% S. aureus strains were successfully identified using MALDI-TOF mass-spectrometry. S. aureus cultures were isolated from all biotopes in 31,6% of children, from skin and nasal cavities — in 42% of cases, from skin and feces — in 2,6% of cases, only from skin — in 10,5%, from nasal cavities and feces — in 2,6%, and only from nasal cavities — in 2,6% of cases. In 8% of children, S. aureus was not detected in any of the biotopes. Genotyping of the isolates enabled the detection of 17 different genotypes. A match between the genotypes of skin and nasal strains, and skin and fecal strains was observed in 88% and 61% of the cases respectively.Conclusions:The observed a high-frequency matching genotypes suggests the possibility of migration of S. aureus strains inside biotopes in humans and the absence of specialization to colonization of any of the niches.
BACKGROUND:Rheumatoid arthritis (RA) is an inflammatory rheumatic disease associated with a dysfunction of the T cell-mediated tolerance and leading to the disability of working population. The regulatory CD4' T cells play an important role in the regulation of autoimmunity and can suppress immune responses. With that, there is no consensus on the content of these lymphocytes and their role in the pathogenesis of RA. Objective: The aim of the study was to assess the content ofperipheral blood regulatory Tcells (Treg) according to the expression of membrane markers CD4, CD25, CD127 and intracellular FOXP3 marker, as well as the expression of two functional molecules (CTLA-4 and CCR4) in Treg cells of patients with RA.METHODS:Peripheral blood samples of RA patients (median age 65,5 years [54;68,3) and healthy controls (median age 58 years [44; 66]) were analyzed. Cell count and the expression level of molecules were assessed by flow cytometry.RESULTS:Peripheral blood samples of 36 RA patients and 20 healthy donors were analyzed. The number of the cells with Treg-associated phenotypes CD4⁺CD25hi and CD4⁺CD25hiCD127low/⁻ was higher in RA patients in comparison with healthy donors. Increased levels of RA CD4⁺ T cells expressing FOXP3 were also observed. This may be due to increasing in the number of CD4⁺FOXP3⁺CD25⁻ lymphocytes, whereas the content of RA CD4⁺FOXP3⁺CD25⁺ Treg cells was at the level of the control. The expression of the functional molecule CTLA-4 in Treg cells of patients with RA was not different from the control, while the expression level of the chemokine receptor CCR4 which provides migration of lymphocytes at sites of inflammation and barrier tissues was significantly increased in RA patients.CONCLUSION:Increase in the levels of certain Treg-associated lymphocyte populations were detected in peripheral blood of RA patients. During the natural course of RA, alterations in the level of the chemokine receptor CCR4 might indicate the enhanced lymphocyte migration.
UNLABELLED The paper presents the system for intelligent analysis of clinical information. Authors describe methods implemented in the system for clinical information retrieval, intelligent diagnostics of chronic diseases, patient's features importance and for detection of hidden dependencies between features. Results of the experimental evaluation of these methods are also presented. BACKGROUND Healthcare facilities generate a large flow of both structured and unstructured data which contain important information about patients. Test results are usually retained as structured data but some data is retained in the form of natural language texts (medical history, the results of physical examination, and the results of other examinations, such as ultrasound, ECG or X-ray studies). Many tasks arising in clinical practice can be automated applying methods for intelligent analysis of accumulated structured array and unstructured data that leads to improvement of the healthcare quality. AIMS the creation of the complex system for intelligent data analysis in the multi-disciplinary pediatric center. MATERIALS AND METHODS Authors propose methods for information extraction from clinical texts in Russian. The methods are carried out on the basis of deep linguistic analysis. They retrieve terms of diseases, symptoms, areas of the body and drugs. The methods can recognize additional attributes such as "negation" (indicates that the disease is absent), "no patient" (indicates that the disease refers to the patient's family member, but not to the patient), "severity of illness", disease course", "body region to which the disease refers". Authors use a set of hand-drawn templates and various techniques based on machine learning to retrieve information using a medical thesaurus. The extracted information is used to solve the problem of automatic diagnosis of chronic diseases. A machine learning method for classification of patients with similar nosology and the methodfor determining the most informative patients'features are also proposed. RESULTS Authors have processed anonymized health records from the pediatric center to estimate the proposed methods. The results show the applicability of the information extracted from the texts for solving practical problems. The records ofpatients with allergic, glomerular and rheumatic diseases were used for experimental assessment of the method of automatic diagnostic. Authors have also determined the most appropriate machine learning methods for classification of patients for each group of diseases, as well as the most informative disease signs. It has been found that using additional information extracted from clinical texts, together with structured data helps to improve the quality of diagnosis of chronic diseases. Authors have also obtained pattern combinations of signs of diseases. CONCLUSIONS The proposed methods have been implemented in the intelligent data processing system for a multidisciplinary pediatric center. The experimental results show the availability of the system to improve the quality of pediatric healthcare.
The review of literature presents the results of recent epidemiological studies in obese people in Russia and abroad taking into account gender, age, ethnic, social, and geographical factors. The increase of obesity prevalence among different population groups including children and adolescents was registered. The risks of health problems associated with overweight and obesity probably leading to disability and mortality were analyzed. It was shown that the energy imbalance played a key role in the etiopathogenesis of obesity among many other factors. This occurs as a consequence of discrepancy between energy consumption and energy discharge especially under the conditions of hypokinesia in all spheres of modern life. Particular attention was paid to the analysis of environmental factors, increasing urbanization, and socio-economic conditions of modern life. The fundamental importance of a multidisciplinary approach in the development of prevention and treatment and rehabilitation programs was accentuated. The attention was paid to the role of economic factors in the development of carbohydrate metabolism disorders. The important role of the goverment was shown in the development of health improvement programs including improvement of the environmental situation, change in anthropogenic environment due to physical activity. The preferred direction of comprehensive programs of prevention and treatment of obesity were defined including optimization of the motor regime, diet correction, increasing the motivation to healthy lifestyle, physical education and sports, as well as increasing the individual’s personal responsibility for their health.
BACKGRAUND Secondary osteoarthritis (OA) adversely affects the underlying disease and can enhance clinical manifestations of articular syndrome. Early detection of comorbid pathology and early treatment with the therapy of underlying condition is of primary importance to preserve adequate functional activity in patients. The Aim is to analyze the efficacy of the application of interleukin-1 inhibitor in the complex treatment of secondary OA in addition to rheumatoid arthritis (RA). MATERIALS AND METHODS 248 patients with secondary OA and RA were divided in 4 groups: patients of group I (n = 62) took interleukin-1 inhibitor (50 mg x 2 times per day) in combination with laser therapy on the basis of methotrexate (10-20 mg per week), group II (n = 60) received interleukin-1 inhibitor in complex with methotrexate, in group III (n = 62)--laser therapy with methotrexate and in group 4--methotrexate. We estimated the treatment efficacy in 3 and 6 months according to the dynamics of pain on VAS, indexes HAQ and KOOS. RESULTS according to VAS group 1 showed statistical significant reduction in pain on movement in 3 and 6 months of 28.53 mm (43.6%) and 31.3 mm (48%) respectively, to values of 36.87 ± 1.56* and 33.11 ± 1.11* (p < 0.05). The results showed the statistically significant advantage of HAQ dynamics in groups I and II in comparison with groups III, IV (p = 0.03). The most prominent statistically significant (p = 0.02) results according to the dynamics of index KOOS were noted in groups of patients who took diacerein (I and II) 6 months after the complex treatment. CONCLUSIONS the inclusion of interleukin-1 inhibitor in the complex treatment of secondary OA in patients with RA contributes to clinical improvement according to VAS (p = 0.03), index KOOS that reflects functional condition of the knee and increases the quality of life by index HAQ (p = 0.03) after 6 months therapy.
UNLABELLED Today the influence of the digestive tract functional violations followed by microaspiration of gastric contents (MAGC) on the incidence, features and outcomes of bronchopulmonary dysplasia BPD) remains little studied. Focusing on this aspect makes the research actual. OBJECTIVE determination of the nature of influence of MAGC on the progress and course of BPD. METHODS 373 newborns exposed to artificial pulmonary ventilation (APV) in the neonatal period were examined. In a tracheobronchial aspirate (TBA) the marker of MAGC-pepsin--was determined. Its activity was measured by extinction value with subsequent analysis of the incidence and nature of the course of bronchopulmonary dysplasia (BPD) in patients against MAGC and without it. During the three years follow-up period outcomes of BPD and features of combined pathology were established. RESULTS it was revealed that in children suffered from MAGC the incidence of BPD was higher and grew in proportion to the increase of pepsin activity in TBA and the reduction of gestational age. The extinction increase in TBA values was followed by the increase in duration of APV and the subsequent oxygen therapy, and also the severity of BPD clinical course. By the end of 3 years clinical recovery was detected in 55.2% of children suffering from BPD without MAGC whereas in patients with BPD against MAGC this outcome occured only in 0.9% of cases. CONCLUSION MAGC is clinically significant for the etiology, pathogenesis and pathomorphism of BPD. The proposed method of early detection of MAGC and algorithm of complex therapy can reduce its severity and improve the forecast accuracy of neonatal adaptation.
OBJECTIVE:To evaluate the damaging effects of cisplatin on MMSCs from adipose tissue in a phase of active proliferation and the state of the monolayer, this was exposed at standard (20%) and reduced to 1% and 5% level of oxygen.METHODS:The effect of cisplatin was detected on monolayer cultures in the active growth phase after 2 passages. Profile surface markers of MMSC was determined by flow cytometry. MMSCs viability after incubation with cisplatin was detected by the number of apoptotic and necrotic cells using ANNEXIN V-FITC--PI Kit (Immunotech, France). Standard culture conditions (~20% O₂) were created in a CO₂ incubator (Sanyo, Japan), 5% O₂--using multigas incubator (Sanyo, Japan), 1% O₂--using an airtight chamber (Stemcell Technologies, USA).RESULTS:Incubation of MMSC monolayer with cisplatin at a concentration of 10 ug/ml for 72 hours leads to death of half of the cells in the culture. Cisplatin increased thefracture of PI⁺-cell, and PI⁺/Ann⁺-cells under all culture conditions. The short-term exposure with cisplatin (24 and 48 hours) did not cause the damaging effect. Effects of cisplatin on the MMSC in the growth phase for 48 hours led to accumulation of Ann⁺-cells and PI⁺/Ann⁺-cells under all culture conditions. However, minimal noci-influence of cisplatin was observed in a culture under hypoxic conditions (1% O₂).CONCLUSION:These data suggest that MMSC monolayer dies primarily through necrosis, whereas MMSCs in the growth phase in response to cisplatin treatment dies by apoptosis, regardless the oxygen tension.
BACKGROUND:one of the reasons of violation of the functional viability of the myocardium is considered to be the oxygen deprivation and lack of energy. The reason is the inhibitory effect of fatty acids on glucose oxidation. Recently, however, new data have been published proving the need for fatty acids and their importance in the maintenance and regulation of the functional activity of the myocardium in chronic pathology.OBJECTIVE:to investigate the influence of free polyunsaturated and saturated fatty acids (FA) on the oxygen uptake of isolated cardiomyocytes in intact rats and animals with ischemic or diabetic heart disease.METHODS:the executed non-randomized controlled study. It includied 3 groups of male rats of Wistar line (weight 250-300g) with 10 animals in each group. Myocardial infarction ("heart attack" group) was caused by ligation of the left coronary artery, diabetes ("diabetes" group)--by intraperitoneal injection of streptozotocin, and "control" group (intact animals). Myocardial infarction caused by ligation of the left coronary artery, and diabetes by intraperitoneal injection of streptozotocin. Isolated cardiac myocytes were obtained by the enzymatic method. Oxygen consumption was assessed polarographically at different saturation incubation medium with oxygen ([O₂] ≤ 8 mg/l and ([O₂] ≥ 16 mg/l). Arachidonic and palmitic acids were applied as fatty acids.RESULTS:It is established that the introduction of the incubation medium 20 µm arachidonic or palmitic fatty acid significantly increased the oxygen consumption of intact cardiomyocytes of rats. Both at the ischemic and at the diabetic injury to the heart the opposite result was obtained. The most pronounced decrease in oxygen consumption was indicated in the group with diabetes mellitus.CONCLUSION:The inhibitory effect of LCD on the rate of oxygen consumption may be associated with the influence of the ischemic or diabetic injury to the heart on the barrierfunction ofmitochondrial membranes of cardiomyocytes, the activity of membrane-associated enzymes and their associated processes.
Purpose of the study. To assess the state of the hepatobiliary system in psoriasis and psoriatic arthritis in order to establish a causal relationship and to identify clinical and functional predictors of psoriatic disease progression.Methods. The study included patients with extensive psoriasis vulgaris (n = 175) from the age of 18 to 66. Divided into 3 groups: 1 – psoriasis patients with isolated skin lesions (n = 77), 2 – patients with psoriatic arthritis (n = 98), 3 – apparently healthy blood donors (n = 30), matched by sex and age. The evaluation of functional state of the hepatobiliary system was performed by analysis of the clinical and anamnestic data and by the laboratory- instrumental methods.Results. Identified predictors psoriasis: triggers (stress and nutritional factor), increased total bilirubin, aspartate aminotransferase, alkaline phosphatase, gamma glutamyl transferase, eosinophilia, giardiasis, carriers of hepatitis C virus, and changes focal ductal formation in the liver , thickening of the walls of the gallbladder by ultrasound. Predictors of psoriatic arthritis: age over 50 years, dyspeptic complaints, the presence of hepatobiliary system diseases, the positive right hypochondrium syndrome, the clinical symptoms of chronic cholecystitis, excess body weight, high levels of bilirubin, cholesterol and low density lipoprotein, hepatomegaly, non-alcoholic fatty liver disease.Conclusion. High activity of hepatocytes cytolysis, cholestasis, inflammation, metabolic disorders can be considered psoriatic arthritis as a severe clinical stage psoriatic disease where the hepatobiliary system, in turn, is one of the main target organs in systemic psoriatic process. Non-alcoholic fatty liver disease and chronic cholecystitis are predictors of psoriatic disease progression.
UNLABELLED:BACKGRAUND. Treponemal tests based on the detection of antibodies against the Treponema pallidum antigens are the most specific methods for serological diagnosis of syphilis. Due to the inability to cultivate this bacterium in vitro, the most promising sources of antigens for diagnostics are recombinant proteins of T. pallidum. Evaluation of the analytical value of certain T. pallidum proteins is the approach to improve sensitivity, specificity, and reproducibility of syphilis serological tests, including possibilities of differential diagnosis of various forms of the disease.OBJECTIVE:The aim of the research was to evaluate the analytical values (sensitivity and specificity) of recombinant protein Tp0965 of T. pallidum as a candidate antigen for serological diagnosis of syphilis.METHODS:tp0965 gene was cloned into the expression vector pET28a and the construct was used for the transformation of E. coli BL-21 (DE3) cells and further expression and purification of the recombinant protein. The collected protein was used as T. pallidum antigen for serum analysis (ELISA) of groups of patients with various forms of syphilis (n=84) and the group of healthy donors (n = 25).RESULTS:High frequency of positive ELISA results was shown with serum of patients with syphilis, compared to the group of healthy donors. The sensitivity of serological reactions using recombinant protein Tp0965 was 98.8%, specificity--87.5%. The highest sensitivity (100%) was detected in the groups of patients with primary, secondary and early latent syphilis while in the group of patients with late latent syphilis it decreased to 95.2%.CONCLUSIONS:We concluded that due to its specificity T. pallidum recombinant protein Tp0965 can be used as a novel perspective antigen for development of syphilis serological diagnostic assays (for primary and early latent forms).
