The impact of Gam-COVID-Vac, an Adv5/Adv26 COVID-19 vaccine, on the biomarkers of endothelial function, coagulation and platelet activation.

COVID-19 vaccines have played a critical role in controlling the COVID-19 pandemic. Although overall considered safe, COVID-19 vaccination has been associated with rare but severe thrombotic events, occurring mainly in the context of adenoviral vectored vaccines. A better understanding of mechanisms underlying vaccine-induced hypercoagulability and prothrombotic state is needed to improve vaccine safety profile. We assessed changes to the biomarkers of endothelial function (endothelin, ET-1), coagulation (thrombomodulin, THBD and plasminogen activator inhibitor, PAI) and platelet activation (platelet activating factor, PAF, and platelet factor 4 IgG antibody, PF4 IgG) within a three-week period after the first (prime) and second (boost) doses of Gam-Covid-Vac, an AdV5/AdV26-vectored COVID-19 vaccine. Blood plasma collected from vaccinees (n = 58) was assayed using ELISA assays. Participants were stratified by prior COVID-19 exposure based on their baseline SARS-CoV-2-specific serology results. We observed a significant post-prime increase in circulating ET-1, with levels sustained after the boost dose compared to baseline. ET-1 elevation following dose 2 was most pronounced in vaccinees without prior COVID-19 exposure. Prior COVID-19 was also associated with a mild increase in post-dose 1 PAI. Vaccination was associated with elevated ET-1 up to day 21 after the second vaccine dose, while no marked alterations to other biomarkers, including PF4 IgG, were seen. A role of persistent endothelial activation following COVID-19 vaccination warrants further investigation.

Experimental study on clinical and morphological determination of the optimal cannula diameter for lipoaspirate harvest from rabbit inguinal fat pad.

Determining the most appropriate cannula diameter for lipoaspirate harvesting is important, both in terms of the quality and composition of the material obtained, and the ease of practical use of the cannula. The size of the cannula is one of the main factors affecting the qualitative characteristics of the obtained lipoaspirate sample for further use of adipose tissue. The purpose of the investigation was to clinically and histomorphometrically determine the optimal cannula diameter for lipoaspirate samples collection from rabbit inguinal fat pad in an experimental study. The methods of Animal models, Surgical procedures, Macroscopic examination, Histological examination, and Morphometric study were applied. There is a direct correlation between the percentage of connective tissue fibres in the lipoaspirate and the diameter of the cannula. The lack of clear criteria for selecting a lipoaspiration cannula is one of the limitations to obtaining generally accepted lipoaspiration protocols with subsequent use of adipose tissue. In this study, the animal experiment determined the most ideal cannula diameter suitable for collecting the largest amount of lipoaspirate for subsequent use.

Bacterial Co-Infections and Antimicrobial Resistance in Patients Hospitalized with Suspected or Confirmed COVID-19 Pneumonia in Kazakhstan.

Our study was carried out to characterize respiratory tract microbiota in patients with "COVID-like pneumonia" in Kazakhstan and analyze differences between COVID-19 positive and negative groups. Sputum samples were collected from hospitalized patients, ≥18 years old, in the three cities in Kazakhstan with the highest COVID-19 burden in July 2020. Isolates were identified by MALDI-TOF MS. Susceptibility testing was performed by disk diffusion. We used SPSS 26 and MedCalc 19 for statistical analysis. Among 209 patients with pneumonia, the median age was 62 years and 55% were male. RT-PCR-confirmed SARS-CoV-2 cases were found in 40% of patients, and 46% had a bacterial co-infection. Co-infection was not associated with SARS-CoV-2 RT-PCR test results, but antibiotic use was. The most frequent bacteria were Klebsiella pneumoniae (23%), Escherichia coli (12%), and Acinetobacter baumannii (11%). Notably, 68% of Klebsiella pneumoniae had phenotypic evidence of extended-spectrum beta-lactamases in disk diffusion assays, 87% of Acinetobacter baumannii exhibited resistance to beta-lactams, and >50% of E. coli strains had evidence of ESBL production and 64% were resistant to fluoroquinolones. Patients with a bacterial co-infection had a higher proportion of severe disease than those without a co-infection. The results reinforce the importance of using appropriate targeted antibiotics and effective infection control practices to prevent the spread of resistant nosocomial infections.

Assessment of Adipokines, CXCL16 Chemokine Levels in Patients With Rheumatoid Arthritis Combined With Metabolic Syndrome.

OBJECTIVE: Rheumatoid arthritis (RA), which is a chronic systemic inflammatory disease, is associated with accelerated atherosclerosis and an increased risk of cardiovascular disease (CVD), but the causal factors have yet to be completely elucidated. The studies show that the prevalence of metabolic syndrome (MtS) was significantly higher in RA patients compared to the population. In RA and MetS inflammation and atherosclerosis are closely linked. The level of chemokines and adipokines, which may play a role in the development of atherogenesis in RA with MetS patients is currently unknown. In this study, we investigated the level of chemokine C-X-C motif chemokine ligand 16 (CXCL16) and adipokine in RA with MetS patients and assessed the association of biomarkers with clinical and biochemical activity scores of RA and components of MetS. METHODS: Blood serum of 298 people (48-patients with RA and MetS, 82-with RA without MetS, 105-with MetS, 63-control group without both RA and MetS) was tested for (CXCL16), Resistin, Leptin and Fibroblast Growth Factor 21 (FGF21) levels by fluorescent antibody technique. Statistical analysis was performed using SPSS version 18.0. RESULTS: The biomarker study showed the highest level in the RA with MetS patient group; but as compared with the RA group the differences were insignificant. CXCL16 (Me = 426.2 pg/ml (Q25-75 250.5-527.6), resistin (Me = 8685.4 pg/ml (Q25-75 6480.8-13 629.1), and FGF21 (Me = 443.6 pg/ml (Q25-75 772.9-916.3) proved to be significantly augmented in RA with MetS patients group, and in RA without MetS patients group (Me = 312.7 (Q25-75 199.4-517.7) pg/ml; Me = 8265.3 (Q25-75 5779.7-13 340.5) pg/ml; Me = 412.4 (Q25-75 300.4-497.4) pg/ml, respectively) as compared with MetS patients group (Me = 189.4 (Q25-75 130.3-280.6) pg/ml; Me = 5364.8 (Q25-75 2368.9-10 160.9) pg/ml; Me = 133.2 (Q25-75 76.2-268.6) pg/ml, respectively; P = <.001). Leptin level in all groups was higher than in the control group, but there were no differences between groups. The correlation analysis found a positive relationship between the leptin level and the waist circumference (rs = 0.39; P = .007) in the RA with MetS patients, the association of biomarkers with DAS28 score and ESR did not have any statistical significance. Conclusions: The augmented chemokine, resistin and FGF21 in the RA with MetS patients proves the systemic inflammation which is the basis of RA; the augmented leptin is linked to the abdominal obesity. These data are somewhat of an explanation of the increased risk of the CVD development in RA with MetS people. A differentiated specification can be useful to assess the cardiovascular risk of patients and justify prompt personalized treatment.

The Levels of Hepcidin and Erythropoietin in Pregnant Women with Anemia of Various Geneses.

AIM: The purpose of the present research was to study the content of erythropoietin and hepcidin in serum in pregnant women with iron deficiency anaemia and anaemia of chronic inflammation. METHODS: The authors examined 98 pregnant women who were observed in LLP (Regional obstetric-gynaecological centre) in Karaganda. The including criteria for pregnant women in the study was the informed consent of the woman to participate in the study. Exclusion criteria were oncological diseases, HIV-infection, tuberculosis, severe somatic pathology, mental illness, drug addiction. The design of the study was by the legislation of the Republic of Kazakhstan, international ethical norms and normative documents of research organisations, approved by the ethics committee of the Karaganda State Medical University. RESULTS: As a result of the study, it was determined that the content of erythropoietin and hepcidin in pregnant women with anemias of different genesis varies ambiguously. In the main group of pregnant women with IDA, the erythropoietin content rises, and the hepcidin level decreases. In pregnant women with ACI, on the contrary, the level of hepcidin increases, and in one subgroup it is significant. However, in pregnant women and with IDA and anemia of chronic inflammation, there is a subgroup of women in whom erythropoietin is either comparable with hepcidin, or their changes are of opposite nature. CONCLUSION: The authors concluded that the obtained data indicate ambiguous changes in the level of erythropoietin and hepcidin in pregnant women with anaemias of various origins. In all likelihood, there are still unaccounted factors affecting the content of these protein-regulators of iron metabolism, which require further definition and interpretation in anaemia of pregnant women.

Characteristic of the Oxidative Stress in Blood of Patients in Dependence of Community-Acquired Pneumonia Severity.

BACKGROUND: At the present time the alternation of the oxidative metabolism is considered as one of the leading pathogenic mechanisms in the development and progression of community-acquired pneumonia (CAP). However the nature and direction of the oxidative protein changes in CAP patient's blood had been almost unexplored. AIM: To define oxidative and modified proteins in erythrocytes and blood plasma of CAP patients. MATERIAL AND METHODS: Blood plasma and erythrocytes obtained from: 42 patients with moderate severity pneumonia, 12 patients with grave severity pneumonia and 32 healthy volunteers. Content of advanced oxidation protein products, malondialdehyde and reactive carbonyl derivatives were estimated as indicators of the oxidative stress and oxidative damage of proteins. RESULTS: In patients with grave severity the level of oxidative proteins and MDA in erythrocytes exceeded both: control values and similar meanings in CAP patients with moderate severity. The further growth of MDA in this group patients' blood plasma was observed, but the level of oxidative proteins decreased in comparison with those in CAP patients with moderate severity. CONCLUSION: To sum up, our derived data show, that injury of erythrocytes' redox-status and blood plasma components plays an essential role in development and progression CAP.

The modified proteins in erythrocytes at hemodialysis patients.

The main goal of our research was to study the modified proteins and activity of integral band 3 protein in erythrocytes of patients with end-stage renal failure during hemodialysis. Depending on the starting nosological variant 2 groups were formed. The first group included 27 patients with end-stage renal failurein the outcome of chronic pyelonephritis, the second - 20 patients with end-stage renal failure, developed on a background of chronic glomerulonephritis. The control group consisted of 15 healthy subjects. The patients of 1-th and 2-nd groups were treated with hemodialysis. The concentration of reactive protein carbonyl derivates, membrane-binding hemoglobin were detected in erythrocytes. Activity of band 3 protein was detected following the protocol of I. Mindukshev et al. (2010). Comparison the results obtained was performed using non-parametric Mann-Whitney U-test (for independent variables). Before hemodialysis the significant increasing of concentration of reactive protein carbonyl derivates and membrane-binding hemoglobin in erythrocytes of both group patients in comparison with healthy ones was observed. During hemodialysis the further augmentation of modified proteins in erythrocytes took place. Different changes in the activity of the protein band 3 in erythrocytes of patients during hemodialysis were found. The similar type of protein band 3 activity changing was determined in erythrocytes of 1-th group patients. There was positive pair correlation between concentration of the reactive protein carbonyl derivates and protein band 3 activity (r= 0,31, p<0,05). Two different types of protein band 3 activity changing were determined in erythrocytes of 2-th group patients. Thus, the differences in modified proteins concentration and protein band 3 activity that occurred in the erythrocytes of patients during hemodialysis were established.

Characteristic of oxidative metabolism in patients with chronic kidney disease depending on etiological nosology.

Development of chronic kidney disease (CKD) is accompanied by change in the oxidative metabolism. The aim of the study was to assess the parameters of oxidative stress in erythrocytes and plasma of patients with CKD 1 and 2 stages depending on the etiological nosology. Two groups were formed. 1(st) - patients with chronic glomerulonephritis (CG), CKD 1, 2. 2(nd) - patients with chronic pyelonephritis (CP), CKD 1, 2. The concentration of carbonyl derivatives was determined by the method of Levine R.L. Malondialdehyde (MDA) concentration - by the method of Goncharenko M.S. and Lapytova A.M. Median and quartiles of parameters were calculated. Statistically significant difference of data in the comparison groups were assessed using the Mann-Whitney test. In group of patients with CG there is the tendency to reduce the concentration of carbonyl derivatives in erythrocytes Md=12.861nmol/ml (12.468, 15.177) as compared with patients with CP Md=14.346nmol/ml (14.130, 14.537). Significant differences in this indicator in these groups were not detected, p=0.715. The concentration of MDA in erythrocytes in these groups varied in the opposite way. In patients with CG concentration of MDA in erythrocytes Md=5.513 µmol/ml (4.487, 6.282) was higher than this indicator in patients with CP Md=4.744 µmol/ml (3.974, 5.256), these changes were not significant, p=0.256. The concentrations of carbonyl derivatives and MDA in plasma in the compared groups were almost identical. In patients with CG concentration of carbonyl derivatives in plasma was Md=0.390nmol/ml (0.381, 0.528), the content of MDA Md=0.846 µmol/ml (0.714, 1.005). In patients with CP concentration of carbonyl derivatives in plasma was Md=0.424nmol/ml (0.312, 0.485) (when comparing 2 groups p=0.668), the content of MDA Md=0.820 µmol/ml (0.740, 0.979) (p=0.886). Thus, in patients with CKD 1, 2 depending on the etiological nosology features of oxidative metabolism were not found.

Myeloperoxidase activity and the oxidized proteins in blood neutrophils of patients with pneumonia.

The main purpose of our investigation was to study myeloperoxidase activity and concentration of oxidized proteins in blood neutrophils of patients with ambulant pneumonia and secondary pneumonia which has arisen on a background of chronic obstructive pulmonary disease (COPD). Patients were divided into 2 groups. 17 patients with ambulant pneumonia moderate severity and respiratory insufficiency of grade 2 were included in the 1-st group. 20 COPD patients with secondary pneumonia moderate severity and with respiratory insufficiency of grade 2 were included in the 2-nd group. The control group consisted of 15 healthy subjects. The reactive protein carbonyl derivates, advanced oxidation protein products (AOPP) and myeloperoxidase activity were detected in neutrophils. In neutrophils of 1-st group patients the augmentation of reactive protein carbonyl derivates was observed in comparison with healthy ones. In neutrophils of 2-nd group patients the slight decrease of reactive protein carbonyl derivates was observed in comparison with healthy ones (by 17%). In neutrophils of 2-nd group patients the significant increasing AOPP in comparison with healthy ones (p <0.01) and 1 group patients (p <0.05) was fixed. Myeloperoxidase activity was higher in neutrophils of 1-th group patients in comparison with healthy ones. In neutrophils of 2-nd group patients myeloperoxidase activity was higher in comparison with the same of 1 group patients (by 67%, p <0.05). Our results showed the different direction of oxidized proteins formation neutrophils of patients with primary and secondary pneumonia. Besides that the varied degree of myeloperoxidase activity was fixed. Our results require more detailed understanding because they can reflect peculiar mechanisms of pneumonia development and determine the characteristics of their progression.