The aim of this work is to study the possibility of using blood serum (BS) fatty acids (FA) and erythrocytes (ER) as diagnostic markers of the severity of NAFLD. Materials and methods. We examined 52 patients with NAFLD (51.8 ± 3.9 years), confirmed by the NLFS index, and 20 apparently healthy men (49.2 ± 4.5 years). The degree of liver fibrosis was established by indirect elastometry (FibroScan® 502 Echosens, France). 27 patients had an initial degree of fibrosis (F0-1), 25 had severe fibrosis (F2-4). The study of the composition of fatty acids of Er and BS was carried out using a GC / MS system based on three Agilent 7000B quadrupoles (USA). Results. Significant differences in the levels of fatty acids in blood serum and erythrocyte membranes in patients with NAFLD were revealed, associated with the degree of fibrosis and necroinflammatory activity. To distinguish between mild and severe fibrosis in NAFLD, the levels of saturated fatty acids (myristic, pentadecane, margarine) and omega-3 PUFAs (eicosapentaenoic, docosapentaenoic, docosahexaenoic) were found to be significant (p = 0.002-0.0003). Saturated and monounsaturated FAs (palmitelaidic, palmitoleic, vaccenic) played a key role in differentiating the degree of necroinflammatory activity (minimal versus pronounced) (p = 0.03-0.005). The created diagnostic panels (FA of blood serum and erythrocyte membranes) made it possible to differentiate patients with NAFLD with varying degrees of fibrosis. Correlations of FA levels in erythrocyte membranes and blood serum with manifestations of metabolic syndrome, indicators of liver damage in patients with NAFLD were revealed. Conclusions. The established differences in fatty acid profiles of blood serum and erythrocyte membranes in patients with NAFLD, associated with the degree of fibrosis, necroinflammatory activity, manifestations of metabolic syndrome and indicators of liver damage, should be considered as promising biomarkers for assessing the severity of NAFLD.
Aim. The clinical guidelines are intended to supplement specialty decision-making for improved aid quality in patients with gastritis and duodenitis though acknowledging the latest clinical evidence and principles of evidencebased medicine.Key points. Gastritis is an inflammatory disease of stomach mucosa, with a separate definition of acute and chronic gastritis. Chronic gastritis is a cohort of chronic diseases uniting a typical morphology of persistent inflammatory infiltration, impaired cellular renewal with emergent intestinal metaplasia, atrophy and epithelial dysplasia of gastric mucosa. Oesophagogastroduodenoscopy (OGDS) or high-resolution OGDS with magnified or non-magnified virtual chromoendoscopy, including targeted biopsy for atrophy and intestinal metaplasia grading and neoplasia detection, are recommended to verify gastritis and duodenitis, precancer states and/or gastric mucosal changes. All chronic gastritis patients positive for H. рylori should undergo eradication therapy as aetiological and subsidiary for gastric cancer prevention. Chronic gastritis patients with symptoms of dyspepsia (epigastric pain, burning and congestion, early satiety), also combined with functional dyspepsia, are recommended proton pump inhibitors, prokinetics, rebamipide and bismuth tripotassium dicitrate in symptomatic treatment. With focal restricted intestinal metaplasia, follow-up is not required in most cases, mainly when advanced atrophic gastritis is ruled out in high-quality endoscopy with biopsy. However, a familial history of gastric cancer, incomplete intestinal metaplasia and persistent H. pylori infection render endoscopy monitoring with chromoendoscopy and targeted biopsy desirable once in three years. Patients with advanced atrophic gastritis should have high-quality endoscopy every 3 years, and once in 1–2 years if complicated with a familial history of gastric cancer.Conclusion. The recommendations condense current knowledge on the aetiology and pathogenesis of gastritis and duodenitis, as well as laboratory and instrumental diagnostic techniques, main approaches to aetiological H. pylori eradication and treatment of dyspeptic states.
Aim of work is to study the compositional features of fatty acids (FA) of erythrocyte membranes in patients with diff erent localization of the tumor in colorectal cancer (CRC). Materials and methods . Using a chromatography-mass spectrometric system (GC/MS) Agilent 7000B based on three quadrupoles (USA), the composition of erythrocyte (Er) membranes of 129 patients with CRC was studied: (average age 63.2±9.4 years, of which 68 men and 61 women; 25 with proximal, 98 with distal tumor localization) and 35 people in the comparison group. Results . A greater degree of decrease in the levels of saturated, monounsaturated FAs (MUFAs), and, conversely, an increase in the levels of polyunsaturated FAs (PUFAs) in patients with distal tumor localization compared to healthy ones, was established than the same ratio in the pair “proximal localization of tumor RCC — healthy”. A greater degree of increase in the level of omega-3 PUFAs was noted than omega-6, which aff ected the ratio n-6 / n-3, which was signifi cantly reduced in cancer patients, to a greater extent with distal tumor localization. The most signifi cant for distinguishing tumors located in diff erent parts of the intestine were: saturated fatty acids — myristic C14:0 (p<0,001) and pentadecanoic C15:0 (p=0,012), omega-3 a-linolenic (C18:3; n-3) (p=0,02), whose levels were signifi cantly higher and, conversely, most of the omega-6 PUFAs (C18:2 n-6, C20:3 n-6, C20:4 n-6) and one omega-3 PUFAs — C22:6 n-3 (p<0,05), whose levels were signifi cantly lower with proximal localization of the tumor than with distal. Conclusion . The results obtained indicate the importance of taking into account the localization of the tumor in patients with CRC when conducti ng studies of metabolic profiles.
Background : some researchers have demonstrated a link between the genetic polymorphism of certain pro-infl ammatory cytokines (IL-1β, IL-6) and the risk of developing precancerous diseases of the stomach and gastric cancer (GC). Aim : to study the genotypes and alleles frequency of polymorphisms of –511C/T (rs16944) of the IL1B gene and 174G/C (rs1800795) of the IL6 gene in patients with serologically detected atrophic gastritis (AG) — the main precancerous lesions of the stomach. Materials and methods . the study included 55 people (45 females and10 males) with an average age of 58.2 ± 11.5 years with signs of obvious or possible atrophy of diff erent parts of the gastric mucosa revealed by enzyme-linked immunosorbent assay (ELISA) with determination of pepsinogen levels I (PGI), PGII, the PGI / PGII ratio, gastrin-17 and IgG antibodies to H. pylori using the “GastroPanel” diagnostic kit (Biohit Plc, Helsinski, Finland). DNA was isolated from venous blood using the phenol-chloroform extraction method. DNA samples were genotyped according to published methods. Results : in patients with severe AG (PGI level less than 30 μg/l), the combined variant with the rare T allele (T/T + C/T) was detected signifi cantly more often (68.8%) than the common homozygous C/C variant (31, 3%, p = 0.004). In individuals with a low PGI/PGII ratio (less than 3), which is also evidence of fundamental atrophy, the homozygous T/T variant was more common (29.6%) than the C/C genotype (7.4%, p = 0.04) The average PGI values were signifi cantly lower with the C/C genotype of the IL-6 gene compared with the heterozygous C/G variant (p = 0.03), however, in patients with morphologically confi rmed atrophy, the combined variant with the rare G allele (G/G + C/G) of the IL6 gene was more common than the homozygous C/C variant (71.4% versus 28.6%, p = 001). Conclusions : in patients with signs of corpus atrophy (low PGI, PGI PGII ratios), the homozygous variant with a rare T allele, which is associated with increased IL-1β production and the development of a hypoacid state, was 4 times more likely than the homozygous C/C variant (p = 0.04). The results obtained suggest a possible association of IL1B polymorphism (carriage of a rare T allele) with the formation of a cancer phenotype of gastritis. The contribution of IL6 polymorphism requires further refi nement.
The aim of the work was to study the compositional features of fatty acids of erythrocyte membranes and blood serum in patients with fatty liver disease of alcoholic (AFLD) and nonalcoholic (NAFLD) genesis for possible use for differential diagnosis. A total of 80 men (51.8±3.9 years) with AFLD (n = 28) and NAFLD (n = 52), as well as 20 conditionally healthy individuals were examined. The composition of erythrocyte membrane and serum fatty acids (FA) was studied using a chromatography mass spectrometry system based on three Agilent 7000B quadrupoles (USA). Differences in levels and ratios of FA in blood serum and erythrocyte membranes were revealed in patients with alcoholic and nonalcoholic fatty liver disease. Increased esterification of FA, increased synthesis of polyunsaturated (PUFA), enhancing liver damage caused by ethanol, a significant role of oleic and linoleic acids are associated with AFLD. Patients with NAFLD showed elevated levels of potentially lipotoxic saturated FA (margarine, stearic, arachinic, pentadecanoic) with a decrease in monounsaturated (palmitoleic, elaidic, oleic). A decrease in the content of docosahexaenoic n-3 PUFAs against the background of a compensatory increase in the level of docosapentaenoic FA n-6 with an omega-3 deficiency, increased consumption of omega-6 PUFAs suggest defective desaturation of unsaturated fatty acids and increased longchain PUFA peroxidation followed by oxidative stress, especially insulin resistance. The synthesis of triglycerides provides a protective mechanism against toxic accumulation of free FA in the liver. Correlation was established between the levels of FA erythrocyte phospholipids and components of the metabolic syndrome, markers of alcohol consumption. Pilot diagnostic models have been obtained that make it possible to distinguish patients with NAFLD and AFLD from healthy patients (AUC 0.892, sensitivity 0.82, specificity 0.88 for NAFLD; AUC 0.811, sensitivity 0.74, specificity 0.80 for ASFLD), as well as NAFLD from AFLD (AUC 0.790, sensitivity 0.73, specificity 0.78). FA profiles of erythrocyte membranes and blood serum are reliable biomarkers of disorders in lipid metabolism in patients with fatty liver disease of various genesis and are promising from the point of view of differential diagnosis.
В статье представлен клинический случай пациента 63 лет с анемией на фоне хронического атрофического гастрита и неэффективностью лечения препаратами железа. На примере данного наблюдения проанализированы ошибки, возникающие при диагностике и ведении пациентов с аутоиммунным (атрофическим фундальным) гастритом (АИГ). Параллельно обсуждаются вопросы патогенеза АИГ, связи с Helicobacter рylori (H. pyloi) инфекцией. Актуализируется проблема своевременной диагностики АИГ и преимуществ неинвазивных методик оценки функционального состояния желудка.
The aim of the work is to study the possibilities of distinguishing between men with fatty disease of alcoholic and non-alcoholic origin using the viscoelastic parameters of erythrocytes - deformation amplitude, summerized indicators of viscosity and rigidity (baseline and after exposure to ethanol in vitro) obtained using the method of erythrocyte dielectrophoresis; to determine associations of the amplitude of deformation, summerized viscosity and rigidity of erythrocytes with blood lipid levels. The study involved 54 men (44,62±1.52 years) with fatty liver disease according to ultrasound of the abdominal organs, the severity of fibrosis corresponded to 0-1 (FibroScan® 502 Echosens, France). All patients underwent a study of the viscoelastic parameters of erythrocytes - the amplitude of deformation, summerized indicators of viscosity and rigidity by the dielectrophoresis method: the baseline level of indicators was determined, as well as their values after exposure of red blood cells with 10 μl of 0,0 2% ethanol solution in vitro for 300 s. The dynamics of changes in the viscoelastic parameters of erythrocytes during the experiment with alcohol in patients with fatty liver disease of unknown origin made it possible to highlight two groups with diametrically opposite trends in erythrocyte indices. The group with a decrease in the amplitude of erythrocyte deformation against the background of an increase in summerized viscosity and rigidity (n = 26) consisted mainly of patients with metabolic syndrome who do not drink or occasionally consume alcohol in low doses (less than 20 g in terms of pure ethanol). Group with increased erythrocyte deformability and decrease in summerized viscosity and rigidity (n = 28) includes systematic alcohol consumers who were in a state of abstinence. Ethanol exposure, important energy substrate of this group, built into metabolic processes, led to an increase in the amplitude of cell deformation. Correlations of the viscoelastic parameters of erythrocytes with the style of alcohol consumption, components of the metabolic syndrome, lipid profile indicators, and liver tests were established. Direct associations of the amplitude of erythrocyte deformation with the level of HDL cholesterol and inverse - with the values of total cholesterol, LDL cholesterol, triglycerides were identified. Summarized viscosity and rigidity correlated with the levels of these lipid indicators inversely compared with the amplitude of deformation. The diagnostic accuracy of distinguishing between NAFLD and AFLD using models, including the viscoelastic parameters of erythrocytes and their changes after exposure to ethanol, using Random Forest and SVM methods reached 99 %, sensitivity of 98 % and specificity of 99 %.
Atherosclerotic cardiovascular diseases are the leading cause of death worldwide. In recent decades, the influence of many microorganisms involved (directly or indirectly) in provoking the process of atherogenesis, including cell adhesion, cytokine-associated damage, release of reactive oxygen species, etc. has been shown. Others, such as the influenza virus, can cause systemic inflammation that can damage vascular wall (for example, by cytokines and proteases). In addition, another indirect mechanism by which some infectious agents (such as Helicobacter pylori, Chlamydia pneumoniae, periodontal pathogens, etc.) that may play a role in the pathogenesis of atherosclerosis is molecular mimicry. Given the complexity of the mechanisms by which each pathogen can contribute to the development and progression of atherosclerosis, it is obvious that ongoing research and new data will be useful for improving our understanding of the infectious component of atherosclerosis.
Background. Atrophic gastritis (AG), being the basic premalignant condition for the stomach cancer (SC), is commonly diagnosed and screened for by noninvasive biomarkers (pepsinogens, gastrin-17), however the data on those biomarkers at SC is inconsistent. Aim of investigation. To evaluate the markers of stomach atrophy along with risk factors of SC of different localization, histological type and stage in the «case series» study. Material and methods. Original investigation was designed as «case series», that included 85 patients with SC (48 m and 37 f, mean age 61.2±13,6 years) who were consistently referred to two medical institutions. All patients underwent interviewing the questionnaire concerning smoking and alcohol consumption, presence of gastroenterological symptoms and family history. Blood serum samples were analyzed using ELISA test kits «GastroPanel» («Biohit Plc», Finland). Manufacturer recommended threshold levels were used at diagnostics of AG. Results. The diagnosis of SC of the III to IV stage was established in 67.9% of patients. The most common location of the neoplasm was the stomach body (63,5%). Helicobacter pylori (H. pylori) infection was revealed by serological method in 74.1% of cases, of which in 15.1% the attempt of eradication treatment was carried out. In 90.6% of patients the adenocarcinoma of different differentiation grade was diagnosed, low degree of differentiation was the most common (57.6%). Signet-ring cell carcinoma was diagnosed in 7.1% of patients, undifferentiated tumor - in 2.4%. Pepsinogen-I (PGI) level under 50 mcg/l was found in 43.2% of patients, indicating different degrees of fundic atrophy. Significantly lower PGI scores were detected in SC patients with histologically verified atrophy. No significant differences in biomarker levels according to tumor location, histological type of SC and tumor stage were found. Conclusions. The «case series» study demonstrated high rate of late SC diagnostics with predominance of corpus location and the most malignant types. H. pylori infection was diagnosed in serologically in the most of patients, however attempts for eradication therapy was carried out only in 15% of patients. Fundic atrophy was diagnosed by serological tests in over 40% of patients, however no association with location, stage and morphological type of the tumor was established. Blood serum samples were analyzed using ELISA test kits «GastroPanel» («Biohit Plc», Finland). Manufacturer recommended threshold levels were used at diagnostics of AG.
Background. A functionally significant TP53Arg72Pro polymorphism can contribute to the development of gastric cancer (GC). The aim: to study the associations of genotypes and alleles of the TP53Arg72Pro 4 polymorphism with GC and biomarkers of gastric ucosal atrophy in population-based prospective and case-control clinical trials among the population of Siberia. Material and methods. As a part of the epidemiological study, data of the international multicenter HAPIEE project for 2003–05, based on a population sample of residents of Novosibirsk city (serum and DNA samples) and data of the population-based registry of GC (2012) were compared. Gastric cancer patients were matched by age and sex to HAPIEE population controls. A total of 156 serum samples (GC – 52, control – 104) and 146 DNA samples (GC – 50, control – 96) were available for prospective analysis. DNA samples from 80 gastric cancer patients (45 men and 35 women, mean age 61.0 ± 13.4 years) and from 87 age-and sex-matched controls were analyzed. DNA samples from venous blood were genotyped according to standard methods. Serum samples were tested using diagnostic kit for enzyme-linked immunosorbent assays to determine the levels of pepsinogen I (PGI), PGII, PGI/PGII ratio, gastrin-17 and IgG antibodies to H. pylori. Results. No differences in genotype and allele frequencies of the TP53 gene between the case group and the control group were found. A decreased frequency of the Pro allele in female gastric cancer patients compared with controls indicated that the Pro allele is protective against the development of gastric cancer, but this effect was not observed in male patients. No associations of TP53 genotypes with the risk of diffuse or intestinal gastric cancer, as well as with the age and sex of patients were found. A high frequency of genotypes with the Pro allele in patients with stage III–IV gastric cancer indicated the relationship between Arg/Pro TR53 and tumor progression, in particular, the contribution of the minor Pro allele to the unfavorable prognosis. A prospective study showed high risk of reducing the level of pepsinogen for assessing predisposition to gastric cancer. Conclusion. Two case-control studies (population and clinical) conducted in the Western Siberia found no relationship between the TP53Arg72Pro polymorphism and the risk of gastric cancer. However, the TP53 genotype with a rare Pro allele was associated with atrophic gastritis and severity of gastric cancer.
Background. A functionally significant TP53Arg72Pro polymorphism can contribute to the development of gastric cancer (GC).The aim: to study the associations of genotypes and alleles of the TP53Arg72Pro 4 polymorphism with GC and biomarkers of gastric ucosal atrophy in population-based prospective and case-control clinical trials among the population of Siberia.Material and methods. As a part of the epidemiological study, data of the international multicenter HAPIEE project for 2003–05, based on a population sample of residents of Novosibirsk city (serum and DNA samples) and data of the population-based registry of GC (2012) were compared. Gastric cancer patients were matched by age and sex to HAPIEE population controls. A total of 156 serum samples (GC – 52, control – 104) and 146 DNA samples (GC – 50, control – 96) were available for prospective analysis. DNA samples from 80 gastric cancer patients (45 men and 35 women, mean age 61.0 ± 13.4 years) and from 87 age-and sex-matched controls were analyzed. DNA samples from venous blood were genotyped according to standard methods. Serum samples were tested using diagnostic kit for enzyme-linked immunosorbent assays to determine the levels of pepsinogen I (PGI), PGII, PGI/PGII ratio, gastrin-17 and IgG antibodies to H. pylori.Results. No differences in genotype and allele frequencies of the TP53 gene between the case group and the control group were found. A decreased frequency of the Pro allele in female gastric cancer patients compared with controls indicated that the Pro allele is protective against the development of gastric cancer, but this effect was not observed in male patients. No associations of TP53 genotypes with the risk of diffuse or intestinal gastric cancer, as well as with the age and sex of patients were found. A high frequency of genotypes with the Pro allele in patients with stage III–IV gastric cancer indicated the relationship between Arg/Pro TR53 and tumor progression, in particular, the contribution of the minor Pro allele to the unfavorable prognosis. A prospective study showed high risk of reducing the level of pepsinogen for assessing predisposition to gastric cancer.Conclusion. Two case-control studies (population and clinical) conducted in the Western Siberia found no relationship between the TP53Arg72Pro polymorphism and the risk of gastric cancer. However, the TP53 genotype with a rare Pro allele was associated with atrophic gastritis and severity of gastric cancer.
Background: Genetic polymorphism of some inflammatory cytokines is associated with the risk of developing specific, H. pylori-associated diseases, including gastric cancer (GC). Aim: To study the genotypes and alleles frequencies of polymorphism 174G / C (rs1800795) of the IL6 gene and polymorphism -511C / T (rs16944) of the IL1B gene, as well as their association with biomarkers of atrophy in patients with GC in the clinical «case-control» study. Materials and methods: 80 patients with GC (45 mails and 35 females with an average age of 61.0 ± 13.4 years) from two medical centers were studied. In the control, DNA samples from 87 subjects were matched by sex and age from the base of the multicenter cohort study HAPIEE. DNA was isolated from venous blood using phenol-chloroform extraction. DNA samples were genotyped according to published methods. Serum samples were tested using a diagnostic kit for enzyme-linked immunosorbent assays to determine the levels of pepsinogen I (PGI), PGII, PGI/PGII ratios, gastrin-17 and IgG antibodies to H. pylori. Results: In the general group, association of polymorphisms of 174 G/C of the IL6 gene and the -511C/T gene of the IL1B gene with the GC was not found. However, in women, the frequency of the G/G genotype of the IL6 gene was 2 times higher in the group with G/C than in the control (p=0.03). In patients with corpus atrophy, the G/G genotype was revealed twice as often as homozygous C/C variant of the IL6 gene (p=0.002). In patients with GC, the genotype with a rare T allele (C/T + T/T) of the IL1B gene was significantly more frequent than the common homozygous C/C variant (p=0.03). The rare homozygous T/T genotype was significantly less frequent in patients with GC and no signs of corpus atrophy (PGI >30 μg/l): 11.3% vs 47.2% (C/T genotype) and vs 41.5% (genotype C/C) (p <0.001). Conclusions: The received data allow assuming the possible connection of studied polymorphisms with the formation of a cancer phenotype of the gastritis, which requires further study of their significance (weight) in the GC riskometry.
Aim of investigation. To study antisecretory activity of the first dose of esomeprazole (20 or 40 mg) (Emanera®, «KRKA», Slovenia) by long-term intragastric pH monitoring. Material and methods. Long-term intragastric pH monitoring was carried out in 20 patients with acidrelated diseases by «Gastroskan-24» device («IstokSistema», Fryazino, Russia). In the first 24 hours patients received no antisecretory agents, in the morning of the next day - they received esomeprazole 20 or 40 mg orally 30 min. prior to the breakfast. Median pH, both time with various pH values and area under pH distribution curve, percent of this time with values from 1,0 to 10,0 per day before and after esomeprazole administration were estimated. The respective scores were compared, using Wilcoxon criterion. Differences were considered to be significant at р
Under supervision there were 151 men (age from 35 till 60 years) with diffuse hepatic diseases (97 with chronic hepatitis, 33 with liver cirrhosis, 21 with fatty liver disease). Alcohol liver disease (ALD) was determined in 66 men. Biochemical and instrumental studies, ultrasonic examination of liver, spleen as well as portal vessels were performed for determination stadia of disease. Moreover, liver biopsy was performed in 19 patients for verification of diagnosis. To all men were carried out inspections of structure-functional erythrocyte characteristics by methods of dielectrophoresis, thin-layer, gas chromatography, GC/MS system. Is experimentally established: rigidity, viscosity, electric conductivity of a membrane of erythrocytes, indexes of agregation and destruction are increased, but the amplitude of deformation of erythrocytes, polarizability are decreased in ALD. An abnormally high content of cholesterol, saturated fatty acids and low levels of total lipids, phospholipids, triglyceridies, ethers of cholesterol, unsaturated fatty acids were found in red cell membranes from patients with ALD. The molar ratio cholesterol/phospholipids was increased at the expense of decreased level of total phospholipids (fractions of phosphatidylcholine, phosphatidylserine, phosphatidylethanolamine and sphingomieline). In patients with fatty liver disease, unidirectional changes in the spectrum of fatty acids in the membranes of erythrocytes and serum (increased level of saturated with decreasing unsaturated) were detected, associations with the manifestations of atherogenic dyslipidemia were established. Correlations between amplitude of deformation of erythrocytes, rigidity, viscosity, electric conductivity of a membrane of erythrocytes, polarizability, index of destruction and levels of total cholesterol, lysophospholipids, polyunsaturated fatty acids in red cells can be used as additional characteristics with a view of early diagnostics of alcoholic liver disease.
The presented method of integrated assessment of liver fibrosis degree based on the comparison of the data obtained in the study of electric and viscoelastic parameters of erythrocytes by the dielectrophoresis method using the electro-optical system of the detection cells and method for indirect elastometry. A high degree of comparability of the results of the above-described methods was established when the degree of fibrosis F 2-4 in the absence of marked cytolysis, cholestasis, inflammatory syndrome, metal overload. It is shown that parallel using the methods of dielectrophoresis and indirect elastography is needed in the presence of a rise of transaminases, gammaglutamyltranspeptidase more than 5 norms, expressed dysproteinemia, syndromes of iron overload, copper to increase the accuracy in determining the degree of liver fibrosis. The evaluation of dynamics of changes of the degree of fibrosis during antiviral therapy is more accurate by the method of indirect elastometry, and the method of dielectrophoresis is preferable in the treatment of nonalcoholic fatty liver disease. In cases of restrictions on the use of the method for indirect elastography (marked obesity, ascites, cholelithiasis, pregnancy, presence of pacemaker, prosthesis) to determine the degree of fibrosis the method of dielectrophoresis of red blood cells can be used. Simultaneous use of both methods (using the identified discriminatory values) allows to reduce or to neutralize their disadvantages, dependence on associated syndromes, to expand the possibilities of their application, to improve the diagnostic accuracy in determining each of the degrees of liver fibrosis. Integrated application of both methods — indirect elastography and dielectrophoresis of red blood cells — for determining the degree of liver fibrosis allows to achieve high levels of sensitivity (88.9 percent) and specificity (100 percent) compared to the “gold standard” — biopsy of the liver.
Differences in the rate constants of specific interactions between serum tumor M2-pyruvate kinase (Tumor M2-PK) and highly specific monoclonal antibodies deposited on the surface of biochips were found in colorectal cancer patients using surface plasmon resonance enhanced ellipsometry. Scanning ellipsometry revealed a significant increase in the biomolecular layer thickness caused by antigen-antibody reaction in patients with hepatic and extra-hepatic metastases compared to that in healthy subjects (p<0.001–0.042).The specificity of the interaction was confirmed by fluorescence optical spectrometry. The Raman spectra of serum samples revealed differences in the intensity of peaks appeared at 1005–1520 cm-1 in the same groups of patients (p<0.0001–0.05) with a predictive accuracy of 90 % for early-stage disease. The pilot experiments with a nanowire biosensor based on SOI (silicon on insulator), for example Tumor M2-PK, were carried out. High sensitivity (10-13–10-15M) and specificity in identifying antigens in serum samples of patients with colorectal cancer were demonstrated. The results obtained were useful for detecting early-stage disease, metastases and recurrence as well as for monitoring the quality of treatment in colorectal cancer patients.
The metabolic syndrome and visceral obesity have an increasing prevalence and incidence in the generalpopulation. The actual prevalence of the metabolic syndrome is 24% in US population and between 24,6% and 30,9% in Europe. As demonstrated by many clinical trials (NAHANES III, INTERHART) the metabolic syndrome is associated with an increased risk of both diabetes and cardiovascular disease. In addition to cardiovascular disease, individual components of the metabolic syndrome have been linked to the development of cancer, particularly to colorectal cancer. Colorectal cancer is an important public health problem; in the year 2000 there was an estimated total of 944717 incident cases of colorectal cancer diagnosed world-wide. This association is sustained by many epidemiological studies. Recent reports suggest that individuals with metabolic syndrome have a higher risk of colon or rectal cancer. Moreover, the clusters of metabolic syndrome components increase the risk of associated cancer. The physiopathological mechanism that links metabolic syndrome and colorectal cancer is mostly related to abdominal obesity and insulin resistance. Population and experimental studies demon trated that hyperinsulinemia, elevated C-peptide, elevated body mass index, high levels of insulin growth factor-1, low levels of insulin growth factor binding protein-3, high leptin levels and low adiponectin levels are all involved in carcinogenesis. Understanding the pathological mechanism that links metabolic syndrome and its components to carcinogenesis has a major clinical significance and may have profound health benefits on a number of diseases including cancer, which represents a major cause of mortality and morbidity in our societies.
The aim; to evaluate the clinical manifestations and data of instrumental methods in patients with Gilbert's syndrome and different genotype UGT1A1. MATERIALS AND METHODS:Clinical manifestations and results of instrumental methods were studies in 104 patients with Gilbert's syndrome (UGIlAl gene mutation rs8175347), including 75 with the homozygous variant (genotype 7TA*7TA) and 29 - with heterozygous variant (genotypes 6TA*7TA or 6TA*STA). RESULTS:The most frequent clinical manifestation was asthenovegetative syndrome. The promoter of the appearance/intensification ofjaundice were physical activity, stress and viral infections. Homozygotes exhibit an earlier manifestation of the disease, higher rates of bilirubin (sometimes not only due to deconjugating), a greater variety of stigmas undifferentiated dysplasia of connective tissue, more frequent detection of biliary sludge or gallstones. The clinical observation of a family case of Gilbert's syndrome where the mother is a homozygote, and the son - heterozygotes on UGT1A1 mutation is presented, which shows the above differences associated with genotype. CONCLUSION:Patients with asthenic constitution and the stigma dysplasia of connective tissue have to be examined by the presence of mutations rs8175347 gene UGT1A1. The carrier not only homozygous but with the heterozygous variant mutations may require changes in the interpretation of symptoms, lifestyle, medication, etc.