Age-related blood biochemical changes (lipid metabolism) in healthy young and mature men living under the North conditions

Metabolic disorders (dyslipidemias) are currently crucial since they develop cardiovascular diseases. The work was aimed at studying age dynamics and its correlation with severity of dyslipidemia in basic lipid metabolism variables (in different age groups). Materials and methods: Examinees were Caucasians born and permanently residing in Magadan region: 55 mature men and 147 young men (mean ages were 36.8±0.8 and 18.7±0.8 yr, respectively). Blood serum lipid metabolism was examined by colorimetric and photometric method using AU 680 (Beckman Coulter, USA). Results: The data of obtained lipidogram showed dependence of rise in all indicators on subjective older age with higher percentage of dyslipidemia and increase in calculated indices reflecting degree of the lipid profile atherogenicity. Conclusion: Overall, the North study revealed a safer lipid profile in group of younger men, while biochemical picture of older residents demonstrated increased values. Lipid atherogenicity is a very alarming factor in developing cardiovascular diseases, and a predictor of risks for metabolic syndrome.

Clinical significance of acetylcholinesterase activity in brain tumors

It has been established that the non-neuronal cholinergic system is related to the oncogenesis which increases the attractiveness of its components as the promising markers of oncologic diseases. The purpose of this work is to evaluate the clinical significance of the analysis of the activity of acetyl cholinesterase as a new marker of gliomas. The activity of acetyl cholinesterase was assessed by photo colorimetric analysis according to the Hestrin method recalculating the activity of the enzyme in the tumor tissue per 1 g of protein, and in the blood - by 0.1 g of hemoglobin. The data obtained in the primary tumors of the brain (28) in the tissue of the brain of persons who died as a result of injury (6) and in whole blood of patients with gliomas (28) and practically healthy people (10) were compared with the use of a number of statistical programs. A significant decrease in the activity of acetyl cholinesterase in tumor tissue and in whole blood is revealed as the degree of anaplasia of tumors increases, starting with Grade II. It is for the first time that a significant direct correlation was noted showing the consistency between the decrease in the activity of acetyl cholinesterase in the tumor tissue of the brain and blood. Bioinformatic analysis showed the connection of the enzyme of acetyl cholinesterase with proteins of the PI3K-AKT and Notch signaling pathways providing antiapoptotic and proliferative effects. The found dependences provide new insights into understanding of the mechanisms of gliomas genesis and can be used for selection of new diagnostic markers of brain tumors.

Clinical implication of detecting sensitization to iodinated radiocontrast media in the basophil activation test by flow cytometry

The use of iodinated radiocontrast media is necessary for visualization. A number of patients have adverse effects of various nature and severity when these drugs are administered. Routine allergy tests do not provide adequate diagnosis of reactions to drugs in this group. The aim of this work is to assess the capabilities of the basophil activation test to confirm sensitization to non-ionic iodinated radiocontrast media, as well as to select a safe alternative drug in patients with a burdened history. Basophil activation test by flow cytometry was performed in 184 patients The Nikiforov Russian Centre of Emergency and Radiation Medicine» EMERCOM of Russia and 32 volunteers using ultravist, omnipack, and optiray. The presence of sensitization was assessed based on the basophil activation index, as well as spontaneous and anti-IgE antibody-induced activation of basophils and the population of T-lymphocytes type 2 immune response. The volunteers showed no sensitization to iodinated radiocontrast media. In patients with a medium degree of hypersensitivity reaction in vivo, in vitro sensitization to drugs was detected 4 times more often than in patients with a mild degree (51% versus 13.5%). In patients with systemic reactions to the administration of a known drug, in vitro sensitization was confirmed in 86% of cases, while the frequency of detection of sensitization to drugs did not differ. Spontaneous activation of basophils in patients and type 2 T-lymphocytes were 2 times higher than in volunteers. Patients were more likely to have low (less than 30%) activation of basophils for anti-IgE antibodies. The specificity of the basophil activation test with iodinated radiocontrast media was 100% with a sensitivity of 94.1%. Most patients were able to select a non-sensitizing contrast. Inclusion in the algorithm of spontaneous and anti-IgE antibody-induced activation of basophils and a population of T-lymphocytes type 2 immune response will allow the doctor to carry out a personalized approach to the management of patients with a burdened history.

Clinical significance of gene polymorphisms for hereditary predisposition to breast and ovarian cancer (review of literature)

The review presents classical and modern views on the molecular genetic causes underlying hereditary predisposition to breast and ovarian cancer. A computerized literature search was carried out in the electronic databases MEDLINE, Scopus, and Web of Science, published between January 1994 and May 2021, using the keywords: «hereditary breast and ovarian cancer», «BRCA» and «DNA repair». Current views on the role of germline mutations in genes for susceptibility to breast cancer (BC): BRCA1, BRCA2, PALB2, TP53, CHEK2, PTEN, ATM, and PPM1D are presented. The role of a complex of genes involved in homologous DNA repair and causing other hereditary oncological diseases is considered. The role of the loss of heterozygosity in these genes, which increases the level of chromosomal instability and leads to an increased risk of malignant transformation, is considered. Germinal mutations in the genes under consideration in 90% of clinical cases are the cause of initiation of tissue malignancy and greatly increase the risk of developing hereditary breast cancer and OC. The review emphasizes the complex nature of pathogenesis and significant polymorphism of genetic targets for hereditary breast cancer and OC. It is concluded that it is necessary to use NGS panels for complex screening of genes of hereditary susceptibility to these oncological diseases. The review provides data on the clinical significance of each group of genes of hereditary predisposition in the pathogenesis of breast cancer and OC, and also demonstrates the possible role of methylation of the promoter regions of genes and the state of mitochondrial DNA in the development of these pathologies. The purpose of this review was to broaden the horizons of specialists in the field of oncology and clinical diagnostics in the context of the rapidly expanding spectrum of molecular genetic markers of hereditary breast and ovarian cancers.

Experience in the diagnosis of group B Streptococcus infections in pregnant women and newborns in a perinatal center

Serogroup B streptococci (Streptococcus agalactiae) are one of the main etiological agents responsible for the occurrence of severe perinatal infections in both postpartum women and newborns. The experience of microbiological diagnostics of infections caused by streptococcus serogroup B (GBS) according to the data of the microbiological laboratory of the perinatal center is generalized. In the study of biomaterial from patients, the proportion of positive cultures of Streptococcus agalactiae was 2.2% in cervical samples, 8.8% in vaginal contents, 6.6%; 2.8% and 0.7% in amniotic fluid, placenta and urine, respectively. In 57% of cases, GBS was released at a concentration of more than 5 lg / ml and in 73% of cases as part of polymicrobial associations with other opportunistic microorganisms. In the biomaterial from newborns, GBS was found in 2.5% of positive findings in blood samples, 4.6% in tracheobronchial lavages and 2.7% in detachable skin of the armpit when taking material immediately after childbirth and 1, 1% and 0.7%, respectively, during examination in the second stage of nursing. 5 cases of GBS isolation in newborns ended in early neonatal mortality with definitive diagnoses of congenital pneumonia and IUI of newborns, while there was only partial coincidence of the results of microbiological studies of the genital tract of the mother and biomaterials from the newborn. Relatively frequent findings of GBS in newborns of the high-risk group in intensive care unit indicate intrauterine infection with this pathogen. The examination of smears from the cervical canal is not informative in relation toGBS infection in comparison with the examination of the vaginal contents and recto-vaginal smears. The results of the introduction of microbiological screening and its effectiveness in real practice to prevent the development of early and late forms of GBS infections in newborns require further analysis.

Validation of the infrared spectroscopy method for analysis of the composition of urine concretes

The aim of this study was to validate the method for analyzing the composition of calculus using infrared (IR) spectroscopy by studying model mixtures of salts. Study was made with an ALPHA-P IR Fourier spectrometer with OPUS software (Bruker, Germany). The samples of pure chemical salts manufactured by Sigma-Aldrich USA were used to validate the method. Salt mixtures were prepared in ratios of 10/90, 50/50 and 90/10. To assess the effect of the fraction size on the calculus component results, were used calculi of patients with urolithiasis. For each mixture were used 10 repeated measurements. Analysis of the composition of model salts showed that in the study of pure cystine salt CV(%) was 0,79%, calcium carbonate - 0,92%, sodium urate - 0,97%, calcium oxalate monohydrate - 4,94%, magnesium ammonium phosphate - 5,59%. And the most common components were analyzed in the composition of complex mixtures, including 90%, 50% and 10% of the investigated component. Calcium oxalate monohydrate has CV(%) 5.70% in mixture 9 part of it to one part of impurities, in mixture 50/50 - 21.57% and in 10/90 - 5.70%. For uric acid in 90/10 - 2.20%, in 50/50 - 10.09%, in 10/90 - 31.94%. For calcium carbonate in 90/10 - 9.02%, in 50/50 - 11.98%, in 10/90 - 24.70%. The dispersion analysis showed that the weighed portions of salts with a particle diameter of more than 0.8 mm provide reproducibility with a CV - 11.48%, with a diameter of 0.2-0.8 mm - 5.35%, and finally less than 0.1 mm - 2.28%. The accuracy of the method is high, but the reproducibility of the IR-spectroscopy method is relatively low in the analysis of stones of mixed composition, due to the greater error in the determination of impurities. Laboratories should pay special attention to optimizing sample preparation to ensure particle fineness less than 0.1 mm.

Lipid peroxidation functional state changes in patients with obstructive jaundice depending on the level of bilirubin in the blood

Obstructive jaundice (OJ) is the most common syndrome among diseases of the hepatopancreatoduodenal region and is found in 12-45% of cases. OJ may be benign and malignant etiology. Despite the evidence of the participation of bilirubin in reducing the bactericidal properties of neutrophils, there are no data currently on changes in the functioning of the antioxidant defense system depending on the level of bilirubin in the blood of patients with OJ of various origins. Research in this direction reveals the possibility for the development of pathogenetic recommendations for influencing these links of the pathogenesis of the disease. The study included men with OJ of non-malignant (OJNMG) (n = 47; mean age - 52.02 ± 5.18 years) and OJ of malignant genesis (OJMG) (I-II stages of the malignant process) (n = 45; mean age - 53.02 ± 4.8 years), divided into three subgroups, depending on the level of bilirubin in the blood. The indicators of practically healthy men as a control (n = 50, average age - 48.7 ± 3.9 years) were used. Spectrophotometric and statistical research methods were used. A statistically significant decrease of superoxide dismutase, glutathione-S-transferase, glutathione-peroxidase, ceruloplasmin, an increase in the values of diene conjugates, malondialdehyde in the group of patients with OJNMG relative to the control was revealed, regardless of the level of bilirubin in the blood. The presence of malignant genesis of the disease with more intense changes in the studied parameters relative to control is accompanied. Comparison of indicators between groups of patients with OJ of different genesis showed a decrease in the values of glutathione-S-transferase and an increase in the level of diene conjugates in patients with OJMG and the level of bilirubin less than 60 μmol / L, as well as an increase in the content of diene conjugates in patients with OJNMG and a level of bilirubin 60- 200 μmol / L in comparison with the corresponding groups of patients with OJNMG. Thus, both in the groups with OJNMG and in the groups with OJMG, there is a significant decrease in the activity of the main antioxidant enzymes and an increase in lipid peroxidation products, regardless of the level of bilirubin in the blood. The presence of malignant genesis is characterized by more intense differences. The revealed changes can serve as additional criteria for optimizing the diagnosis and treatment of this cohort of patients.

Homoarginine test for evaluation of metabolic renal dysfunction

Low plasma L-homoarginine (hArg) concentration is an independent predictor of adverse cardiovascular outcomes and overall mortality, as well as the progression of chronic kidney disease (CKD). The enzyme L-arginine:glycinamidinotransferase (AGAT, EC 2.1.4.1) acts in the mitochondrial membrane of the renal tubular epithelium, forming the precursor of creatine, guanidinoacetic acid, and additionnaly by-product hArg. As it was shown recently, there is a decreased level of hArg in the late stages of CKD, however, the the level of hArg in the early stages of CKD remained unexplored. The aim of this study was to determine the diagnostic threshold levels of hArg in the blood of patients with stages 1 and 2 of CKD. In patients with the initial stages of CKD (n = 44) at the age of 58 (45-67) years, compared with the group of donors of 55 (42-58) years (n = 30), a significant decrease of hArg level was found. In the subgroup with stage CKD 2, the cut-off point of 1.59 μM threshold was characterized by greater sensitivity and specificity than in the subgroup with stage CKD 1 with 1.66 μM threshold level of hArg. For the full group, the hArg cut-off threshold was 1.60 μM, which is about to 0.2 μM lower than the lower limit of the reference interval for healthy individuals. It can be assumed that even before the formation of symptoms of proteinuria and albuminuria, a significant part of individuals from population cohort develops a state of decreased AGAT activity, since the expression of this enzyme is associated with a certain regulatory feedback inhibition at the body level. As a result of the study, it can be noted that in patients with early stages of CKD in the age group 45-67 years, there is a disturbance of the kidneys metabolic function. These metabolic changes can be detected by testing the level of hArg.

Diagnostic value of platelet parameters and megakaryocyte formula of bone marrow in idiopathic thrombocytopenic purpura

The parameters of the megakaryocyte formula and peripheral blood platelet indices were studied in 237 people with diagnoses of idiopathic thrombocytopenic purpura (ITP) and myelodysplastic syndrome (MDS). A correlation analysis was performed between megakaryocyte subpopulations and platelet counts. The threshold values for MPV, PCT and PDW were determined by ROC analysis with the construction of the ROC curve, the calculation of the area under the curve (AUC) and the cutoff threshold. The obtained values make it possible to make a differential diagnosis between ITP and MDS by platelet parameters of peripheral blood without examining the bone marrow.

Clinical and diagnostic manifestations of tickborne mixed infection in combination with COVID-19

The coexistence of various pathogens inside the patient’s body is one of the poorly studied and current issues. The aim of the study is to identify the relationship between the indicators of complex laboratory diagnostics and the clinical manifestations of a mixed disease during subsequent infection with the SARS-CoV-2 virus using the example of a case of chronic encephalitis-borreliosis infection. Seven blood serum samples were collected from the patient over the course of a year. For the etiological verification of the causative agents of TBE, Lyme disease and COVID-19, the methods of ELISA and PCR diagnostics were used. The patient was diagnosed with Lyme disease on the basis of the detection of IgG antibodies to Borrelia 5 months after the onset of the disease, since she denied the tick bite. In the clinical picture, there was an articular syndrome and erythema migrans. Later, IgG antibodies to the TBEV were found in the blood. Throughout the study, IgM antibodies to Borrelia were not detected. The exacerbation of Lyme disease could be judged by the clinical manifestations of this disease and by the growth of specific IgG antibodies. A feature of this case was that during an exacerbation of the Lyme disease, an infection with the SARS-CoV-2 virus occurred. Treatment (umifenovir, hydroxychloroquine, azithromycin, ceftriaxone) was prescribed, which improved the condition of the underlying disease, decreased joint pain, decreased IgG levels to borrelia. However, during this period, serological markers of TBEV appear: antigen, IgM antibodies, and the titer of IgG antibodies increases. Most likely, this was facilitated by the switching of the immune system to the SARS-CoV-2 virus, with the simultaneous suppression of borrelia with antibiotics and the appointment of hydroxychloroquine, which has an immunosuppressive effect. Despite the activation of the virus, clinical manifestations of TBE were not observed in the patient, which is most likely associated with infection with a weakly virulent TBEV strain. The further course of tick-borne infections revealed the dominant influence of B. burgdorferi in relation to TBEV. Laboratory studies have shown that suppression of the activity of the borreliosis process by etiotropic treatment subsequently led to the activation of the persistent TBEV.