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The objective was to assess the prognostic value of D-dimer level in peripheral venous blood and arterial blood to the risk of developing complications in the short-term period after open reconstructive surgery on the aortoiliac segment.Methods and materials. The study included 89 patients who were determined the D-dimer level in peripheral venous blood, as well as arterial blood intraoperatively.Results. Statistically significant differences in the D-dimer level were established depending on the presence or absence of early postoperative complications.Conclusions. The intraoperative D-dimer level in arterial blood has a predictive ability in relation to the development of early postoperative complications.

Introduction. Ph-positive acute lymphoblastic leukemia (ALL) is a high risk group of B-lineage acute lymphoblastic leukemia (B-ALL). Since tyrosine kinase inhibitors (TKIs) were introduced, controversial data have been obtained on the efficacy of allogeneic hematopoietic stem cell (allo-HSCT) in the first complete remission.The objective was to evaluate the efficacy of allo-HSCT in the first complete remission of Ph-positive ALL in adult patients after remission induction with continuous chemotherapeutic exposure in combination with TKIs.Methods and materials. The retrospective analysis included 74 patients with a median age of 32 years (range 18–59) after allo-HSCT in the first complete remission and 58 patients with a median age of 39 years (range 18–65) in the first complete remission after conservative therapy. Ninety-one per cent and 83 % of patients received imatinib as TKIs in remission induction in the allo-HSCT and conservative therapy groups, respectively. The median time from the first complete remission to allo-HSCT was 7 months (range 2–33). Thirty-six patients (49 %) had positive minimal residual disease (MRD) status prior to allo-HSCT. Eighteen patients (14 %) over 40 years underwent allo-HSCT in the first complete remission.Results. Allo-HSCT improves overall survival (OS) and relapse-free survival (RFS) and by 9 months since the achievement of the first complete remission, they were 70.1 (95 % CI 56.4–88.6) in the allo-HSCT group versus 45.1 (95 % CI 33.4–61.0) in the conservative group, p=0.025 and 63.3 % (95 % CI 47.6–84.1) in the allo-HSCT group versus 44.8 % (95 % CI 33.2–60.4) in the conservative therapy group, p=0.04, respectively. Allo-HSCT in patients over 40 years does not improve 5-year OS and RFS and were 57.2 % (95 % CI 30.0–84.4) versus 59.8 % (95 % CI 36.9– 82.7), p=0.69, and 42.6 % (95 % CI 14.0–71.2) vs. 50.9 % (95 % CI 29.5–72.3), p=0, 88, respectively.Conclusion. Allo-HSCT performed before 9 months from achievement of the first complete remission after induction with imatinib is the preferred method of remission consolidation in patients from 18 to 40 years old. The optimal therapy for patients older than 40 years in the first complete remission is a conservative approach in combination with TKIs.

Scientific relevance. Hypromellose phthalate is a component of enteric coatings used to modify active substance release from oral medicinal products in the small intestine. The release rate directly depends on the non-stoichiometric composition of the polymer, first of all, on the proportion of phthalate groups in the macromolecule. It is therefore necessary to develop reliable analytical procedures for determining the structure of hypromellose phthalate to evaluate the dissolution rate of medicinal products containing the polymer.Aim. The study aimed to develop an analytical procedure for quantifying the proportion of phthalate groups in hypromellose phthalate samples using NMR spectroscopy and to determine the relationship between the polymer dissolution rate in aqueous buffer solutions and its structural features (degree of molar substitution and molecular mass).Materials and methods. The study examined hypromellose phthalate samples isolated from enteric coatings of proton-pump inhibitors and used the reference standard for hypromellose phthalate. The non-stoichiometric composition of the polymer was determined by 13C NMR spectroscopy.Results. The authors established the conditions required to separate hypromellose phthalate from the other coating components and identified the characteristic 13C NMR signals that may be used to differentiate between the structural fragments of hypromellose phthalate. The study demonstrated the relationship between the dissolution rate and the structure of the polymer. Commercial grades of hypromellose phthalate were shown to differ in composition and, as a result, in their dissolution kinetics (in particular, the threshold pH for the onset of dissolution (5.0–5.5), as well as the dissolution rates at the same pH).Conclusions. The authors developed NMR-based procedures to determine the proportion of phthalate groups on the basis of their mass fraction in a weighted hypromellose phthalate sample and the degree of molar substitution of the polymer. The results support the applicability of these analytical procedures to the characterisation of sample composition in polymer dissolution rate studies. In principle, it is possible to derive a multiple linear regression equation that describes the dissolution rate of hypromellose phthalate as a function of the molecular mass and the molar substitution with phthalate groups. Further investigation of a larger number of polymer samples with different compositions is needed to improve the regression model and demonstrate its statistical significance. In addition to the proportion of phthalate groups, the pharmacopoeial analysis of hypromellose phthalate should also control the molecular mass of the polymer.

Objectives: The most important phase in the endometrial pathologies diagnostics is the histological examination of tissue biopsies obtained under visual hysteroscopic control. However, the unclear visual diagnostics characteristics of subtle focal endometrial pathologies often lead to selection errors regarding suspicious endometrial lesions and to a subsequent false pathological diagnosis/underestimation of precancer or early-stage cancer. Methods: In this study, we investigate the potential of Multimodal Optical Coherence Tomography (MM OCT) to verify suspicious endometrial lesion regions before biopsy collection. We study the polarization (by cross-polarization OCT, CP OCT) and elastic (by compression OCT-elastography, C-OCE) properties of ex vivo endometrial tissue samples in normal conditions (proliferative and secretory phases to the menstrual cycle, atrophic endometrium) with endometrial hyperplasia (non-atypical and endometrial intraepithelial neoplasia) and endometrial cancer subtypes (low-grade, high-grade, clear cell and serous). Results: To the best of our knowledge, this is the first quantitative assessment of relevant OCT parameters (depth-resolved attenuation coefficient in co-[Att(co) values] and cross-[(Att(cross) values] polarizations and Young’s elastic modulus [stiffness values]) for the selection of the most objective criteria to identify the clinically significant endometrial pathologies: endometrial intraepithelial neoplasia and endometrial cancer. The study demonstrates the possibility of detecting endometrial pathologies and establishing optimal threshold values of MM OCT criteria for the identification of endometrial cancer using CP OCT (by Att(co) values = 3.69 mm−1, Sensitivity (Se) = 86.1%, Specificity (Sp) = 92.6%; by Att(cross) values = 2.27 mm−1, Se = 86.8%, Sp = 87.0%) and C-OCE (by stiffness values = 122 kPa, Se = 93.2%, Sp = 91.1%). The study also differentiates endometrial intraepithelial neoplasia from non-atypical endometrial hyperplasia and normal endometrium using C-OCE (by stiffness values = 95 kPa, Se = 87.2%, Sp = 90.1%). Conclusions: The results are indicative of the efficacy and potential of clinical implementation of in vivo hysteroscopic-like MM OCT in the diagnosis of endometrial pathologies.

Scientific relevance. Hypromellose phthalate is used in enteric coatings for oral medicinal products. The proportion of phthalate groups in the polymer is standardised because it has a significant effect on solubility. Whereas, the molecular mass of hypromellose phthalate is not controlled, and its impact on solubility in media with different pH values is understudied.Aim. The study aimed to employ NMR spectroscopy to investigate the effect the molecular mass of hypromellose phthalate may have on the dissolution kinetics at the pH value declared by the polymer manufacturer.Materials and methods. The study analysed hypromellose phthalate isolated from proton-pump inhibitor enteric coatings and the hypromellose phthalate reference standard. The molecular mass of the polymer was estimated by diffusion-ordered NMR spectroscopy (DOSY) with polyethylene glycols of known molecular masses for calibration. The authors studied the dissolution profiles of hypromellose phthalates of different molecular masses using 1H NMR spectra.Results. The authors developed a procedure for estimating the average molecular mass of hypromellose phthalate by DOSY. The procedure showed variations in the molecular mass of the polymer in the test samples; the molecular mass scatter amounted to 10 kDa. The dissolution profile of the test samples in an aqueous buffer solution (pH 5.59) was described by a linear function during the first hour. The slope characterising the dissolution rate varied from 10° to 36°.Conclusions. The variation in the molecular mass of hypromellose phthalate significantly affects the dissolution rate of the test samples. The function of the dissolution rate against the molecular mass of hypromellose phthalate is non-linear. The article provides a compelling reason for further research to derive a correlation equation for the dissolution rate of hypromellose phthalate as a function of two variables (molecular mass and proportion of phthalate groups in the polymer).

Gentamicin sulfate is a broad-spectrum bactericidal aminoglycoside antibiotic produced by Micromonospora purpurea and used in clinical practice as an active substance containing a mixture of gentamicins C1 and C2. Gentamicin content is a standardised parameter controlled as part of a pharmaceutical product review. Currently, the quality control of the active substance gentamicin sulfate involves the use of high-performance liquid chromatography (HPLC) for the indirect identification of the component composition by comparison with a reference standard and for its quantification by calibration against the reference standard.The aim of the study was to develop a procedure for identifying and quantifying the components of the active substance gentamicin sulfate using nuclear magnetic resonance (NMR) spectroscopy that would not require reference standards.Materials and methods. The authors studied a sample of the active substance gentamicin sulfate using an Agilent DD2 NMR spectrometer operating at 600 MHz to record NMR spectra and an Agilent 1200 HPLC system equipped with a multiple wavelength detector (MWD) to obtain chromatograms.Results. Having determined the spectral properties of the C1, C1A, C2, C2A and C2B gentamicins comprising the active substance, the authors observed characteristic signals of the same type that corresponded to each of the gentamicins and did not overlap with other signals in the 1H and 13C spectra. These characteristic signals provided spectral markers indicative of the gentamicins of interest in the sample, with normalised integrated intensities equal to the mole fractions of the analytes. The authors compared NMR and HPLC measurements of the active substance composition.Conclusions. The authors developed a procedure for identifying and quantifying the constituents of the active substance gentamicin sulfate by 1H and 13C NMR spectroscopy, which requires less effort than HPLC procedures and no reference standards for the intended applications.

The purpose of the study is to investigate the clinical significance of determination of serum FGF-23 and Klotho in patients with different stages of chronic kidney disease (CKD). Materials and Methods: The study included 70 patients with CKD stages 1–5D (30 men and 40 women, mean age 41,0–6,7 years), in whom the serum levels of FGF-23 and Klotho, as well as work Ca х P and the content of intact parathyroid hormone (iPTH). Results: the progression of CKD from stage 1 to 5D serum concentration of FGF-23 was increased, and the concentration of Klotho decreased. Glomerular filtration rate (GFR) was directly correlated with the serum concentration of FGF-23 (r=0,693, p

Recently, data have been published on the leading role of endothelial dysfunction in the development of severe COVID-19, including acute renal failure (AKI) and poor prognosis in this group of patients.Aim. To define the role of angiopoetin-1(Ang-1) as a marker of endothelial dysfunction in development of AKI in patients, hospitalized with COVID-19.Materials and methods. 76 patients with confirmed coronavirus infection were included in the study. AKI was diagnosed according to KDIGO 2012 criteria in 44 patients (group 1), 32 patients without sings of kidney disfunction were in group 2. Beside standard clinical and laboratory markers on admission we evaluated serum Ang-1 level with ELISA. We used regression analysis for AKI risk factors evaluation, we calculated odds ratio (OR) and 95% confidence intervals (CI). We used Cox regression for evaluation of risk of death.Results. The serum level of angiopoietin-1 was significantly higher in patients with COVID-19 with AKI: 1.8 (1.5; 2.1) ng/ml vs 1.58 (1.29; 1.7) ng/ml in group 2, р < 0.01. In deceased patients, the level of Ang-1 at admission was significantly higher than in patients who was discharged: 1.91 (1.71; 2.32) ng/ml vs 1.58 (1.34; 1.67) ng/ml, respectively, p = 0.0001. In unifactorial regression analysis we confirmed, that increase of serum Ang-1 level >1.66 ng/ml on admission is the risk factor for AKI development in patients with COVID-19 (OR 5.7, 95% CI 1.7–19.1, р < 0.01). In Cox regression development of AKI increased the absolute risk of death: Hazard ratio = 5.159 (95% CI 1.839–14.469), p = 0.002.Conclusion. The high serum level of Ang-1 in patients with COVID-19 at hospital admission is the marker of systemic endothelial dysfunction and the risk factor for AKI and poor prognosis.

Relevance. Evidence exists that infrarenal aortic aneurisms and aortoiliac occlusive disease in women are different than in men in terms of anatomical features and more severe clinical course. Gender differences in histopathology of abdominal aorta are not fully studied.The objective was to study gender based differences in histopathology of abdominal aorta in patients with aortic aneurisms and aortoiliac occlusive disease.Methods and materials. The study included 96 biopsy specimens from 71 patients with aorto-iliac lesions (23 women and 48 men). A number of morphological characteristics and expression of matrix metalloproteinase 9 (MMP-9) were analyzed. The data obtained were processed statistically.Results. Adventitial infiltrate and medial sclerosis are more intense in the aneurysm than in occlusive-stenotic lesions, differences in the grade of fibrosis were proven only in men. Regardless of the patients’ gender, adventitial infiltration is denser in the aneurysmal body than in the neck; other changes in the anatomic parts of the aneurysm are similar. MMP-9 expression in the adventitia in the aneurysmal neck is higher in women, than in men. MMP-9 expression in the media and adventitia is higher in men with aneurysm, then with occlusive or stenotic lesion. Almost all indices of the aortic wall remodeling and MMP-9 expression correlate with each other in men with the aneurysm, in contrast to women.Conclusion. Gender based features in histopathology of abdominal aorta and the degree of their correlation may determine differences in the anatomy and course of abdominal aortic aneurysm and aortoiliac occlusive disease in women and men.

BackgroundMinimal change disease and focal segmental glomerulosclerosis are primary podocytopathies that are clinically presented in adults presenting with severe nephrotic syndrome. The pathogenesis of these diseases is not clear and many questions remain to be answered. A new concept about the role of changes in the antigenic determinant of podocytes and the production of anti-podocyte antibodies that cause podocyte damage is being developed. The aim of the study is to evaluate the levels of anti-CD40 and anti-ubiquitin carboxyl-terminal hydrolase L1 (anti-UCH-L1) antibodies in patients with podocytopathies in comparison with other glomerulopathies.MethodsOne hundred and six patients with glomerulopathy and 11 healthy subjects took part in the study. A histological study revealed primary FSGS in 35 patients (genetic cases of FSGS and secondary FSGS in the absence of NS were excluded), 15 had MCD, 21 - MN, 13 - MPGN, 22 patients - IgA nephropathy. The effect of steroid therapy was evaluated in patients with podocytopathies (FSGS and MCD). The serum levels of anti-UCH-L1 and anti-CD40 antibodies were measured by ELISA before steroid treatment.ResultsThe levels of anti-UCH-L1 antibodies were significantly higher in MCD patients and anti-CD40 antibodies were higher in MCD and FSGS than in the control group and other groups of glomerulopathies. In addition, the level of anti-UCH-L1 antibodies was higher in patients with steroid-sensitive FSGS and MCD, and anti-CD40 antibodies were lower than in patients with steroid-resistant FSGS. An increase in anti-UCH-L1 antibody levels above 6.44 ng/mL may be a prognostic factor of steroid-sensitivity. The ROC curve (AUC = 0.875 [95% CI 0.718–0.999]) for response to therapy showed a sensitivity of 75% and specificity of 87.5%.ConclusionAn increase in the level of anti-UCH-L1 antibodies is specific for steroid-sensitive FSGS and MCD, while an increase in anti-CD40 antibodies – for steroid-resistant FSGS, compared with other glomerulopathies. It suggests that these antibodies could be a potential factor for differential diagnosis and treatment prognosis.

Vaginal wall prolapse is the most common type of pelvic organ prolapse and is mainly associated with collagen bundle changes in the lamina propria. Neodymium (Nd:YAG) laser treatment was used as an innovative, minimally invasive and non-ablative procedure for the treatment of early-stage vaginal wall prolapse. The purpose of this pilot study was to assess connective tissue changes in the vaginal wall under prolapse without treatment and after Nd:YAG laser treatment using cross-polarization optical coherence tomography (CP OCT) with depth-resolved attenuation mapping. A total of 26 freshly excised samples of vaginal wall from 26 patients with age norm (n = 8), stage I–II prolapses without treatment (n = 8) and stage I–II prolapse 1–2 months after Nd:YAG laser treatment (n = 10) were assessed. As a result, for the first time, depth-resolved attenuation maps of the vaginal wall in the B-scan projection in the co- and cross-polarization channels were constructed. Two parameters within the lamina propria were target calculated: the median value and the percentages of high (≥4 mm−1) and low (−1) attenuation coefficient values. A significant (p < 0.0001) decrease in the parameters in the case of vaginal wall prolapse compared to the age norm was identified. After laser treatment, a significant (p < 0.0001) increase in the parameters compared to the normal level was also observed. Notably, in the cross-channel, both parameters showed a greater difference between the groups than in the co-channel. Therefore, using the cross-channel achieved more reliable differentiation between the groups. To conclude, attenuation coefficient maps allow visualization and quantification of changes in the condition of the connective tissue of the vaginal wall. In the future, CP OCT could be used for in vivo detection of early-stage vaginal wall prolapse and for monitoring the effectiveness of treatment.

Diffusion-ordered nuclear magnetic resonance spectroscopy (DOSY) is a molecular transport method in analytical chemistry, based on experimental recording of the molecules’ translational mobility at thermodinamic equilibrium in a solution. The translational mobility is characterised quantitatively by a self-diffusion coefficient. The aim of the study was to summarise the main trends in application of DOSY for the analysis of natural and modified natural polysaccharides used in pharmaceuticals and pharmaceutical biotechnology. The review shows that this method is an effective instrument for monitoring fractionation during isolation of polysaccharides from a natural mixture, for estimating their average molecular weight and molecular weight distribution, and for studying the formation of supramolecular systems based on polysaccharides. The paper describes main issues of the precise measurement of polysaccharide macromolecules self-diffusion coefficients and provides the correction factors to compensate for errors caused by fluctuations in temperature and viscosity of solutions. The observed scatter of self-diffusion coefficients of narrowly dispersed polymer macromolecules nuclei is explained using the polyphase concept. The paper illustrates ways of describing translational mobility of a polyphase polymer macromolecule as a whole. The authors summarise values of the gradient pulse sequence parameters used in quantitative measurements of self-diffusion coefficients of linear, low-branched, and branched polysaccharides.

The ongoing development of the Pharmacopoeia of the Eurasian Economic Union and the current trend for harmonisation of the Russian Pharmacopoeia with the world leading pharmacopoeias suggest the necessity of studying how different pharmacopoeias use nuclear magnetic resonance (NMR) for quality control of medicinal products. The aim of the study was to compare the extent of medicine quality characteristics assessed by NMR in the Russian and foreign pharmacopoeias. The review summarises the experience of various national and world pharmacopoeias in using the NMR method for quality control of medicines and certification of pharmacopoeial reference materials. The comparative analysis covered the following quality parameters: active ingredient identification, determination of the composition of non-stoichiometric compounds, determination of the average polymer chain length in polymers and block copolymers, determination of the absolute content of the active ingredient, identification and quantification of impurities, polymorphism, and crystallinity. It was shown that the United States and Japanese Pharmacopoeias are leading the way in introducing the NMR method into pharmacopoeial analysis. There have been some positive trends in the introduction of the NMR method in the State Pharmacopoeia of the Russian Federation as well. It was concluded that changes are needed in the general chapters “Nuclear Magnetic Resonance Spectroscopy” and “Reference Standards” of the State Pharmacopoeia of the Russian Federation, 14th ed. in order to harmonise the texts with those of the Eurasian Pharmacopoeia and the European Pharmacopoeia and to allow for the possibility of direct identification of a substance by complex analysis of NMR spectral data, without comparing the test sample and the reference standard spectra. The NMR method should be included in the list of absolute methods used for determination of purity of primary chemical reference substances during certification.

Cardiovascular disease (CVD) is the leading cause of death worldwide. The main contribution to the structure of mortality from CVD is made by atherosclerosis. Indications for surgical treatment of patients with diseases caused by atherosclerotic lesions of the arteries are set taking into account the degree of their stenosis. Angiography has been considered the gold standard for screening patients with CVD for many years. Numerous studies carried out over the past several decades have revealed the weak side of this method in assessing the significance of borderline stenosis. Therefore, to analyze such changes, functional tests were introduced to clarify the indications for surgical intervention. Currently, criteria for the significance of stenosis of the iliac, renal and coronary arteries have been determined. The significance of stenosis of the arteries supplying the brain and intestines is still a matter of debate and requires further study.

Near-infrared spectrometry (NIRS) is a new pharmacopoeial method. It is widely used in the pharmaceutical industry for quality control of medicinal products at various production stages (control of raw materials and finished products), and for detection of substandard and counterfeit drugs.The aim of the study was to assess the feasibility of using NIRS as an identification test for active ingredients during pre-marketing quality control of medicinal products.Materials and methods: 327 drugs samples represented as solid and semisolid dosage forms were tested by NIRS following their examination by well-established pharmacopoeial Identification methods during pre-marketing laboratory evaluation. The NIR spectra of the test samples were compared with the spectral library classification models.Results: NIRS confirmed the identity of 3.1% of the tested medicinal products. It was demonstrated that library classification models could be used for identification of only those medicines that were produced by a specific manufacturer, i.e. for confirmation of medicine identity.Conclusions: the NIRS method is unpractical as an Identification test for active ingredients in medicinal products during the pre-marketing laboratory evaluation stage. The main limitations of NIRS are lack of complete sets of library classification models for all medicinal products available in the market and non-reproducibility of spectral library data obtained with a different instrument.

Introduction.The biological heterogeneity of chronic lymphocytic leukemia (CLL) is reflected in the rate of progression, the need for therapy, and the response to treatment. Analysis of prognostic factors contributes to improving the quality of treatment and rational distribution of healthcare resources.Materials and methods. Among 890 patients with documented stage of CLL, 405 (45.5 %) received treatment. As the first-line of treatment, 173 patients received intensive regimens (FCR or BR), 6 – new agents, and 226 – all other regimens. The initial stage of the disease, mutation status of IGHV, del17p with or without complex karyotype were analyzed as prognostic markers.Results. Immunochemotherapeutic regimens were shown to be highly effective in case planned amount of treatment was completed. The combination of such prognostic parameters as the initial stage of the disease, the mutation status of IGHV, and the presence of del17p and/or complex karyotype allows us to clearly identify a group of patients with an unfavorable prognosis, for which it is advisable to use either intensive programs or new agents in the first-line therapy.

Direct-acting antivirals (DAAs) therapy is associated with fibrosis regression in patients with hepatitis C virus liver cirrhosis.Aim. To study the dynamic of liver fibrosis in cirrhotic patients with a DAAs-induced sustained virological response (SVR).Materials and methods. The retrospective cohort study included 80 cirrhotic patients (male — 43%, median age 54 years). Liver stiffness (LS) was measured by transient elastography before treatment and after SVR. Patients with LS improvement ≥30% were included in group 1, other patients — in group 2. Clinical, laboratory and instrumental parameters were assessed. Independent risk factors for the absence of LS improvement ≥30% were determined by binary logistic regression with the definition of odds ration (OR) and 95% confidence interval (CI).Results. LS reduced from 21.35 (15.2; 27.7) to 13.5 [10.1; 20.0] kPa (p < 0.001), the median reduction was 5.1 [2.6; 11.0] kPa. Regression of fibrosis from F4 to F2 and F3 stages was observed in 16 (20%) and 19 (24%) of cases, respectively. Overall, 36 patients were included in group 1, 44 patients — in group 2. Platelet counts increased in group 1 compared to group 2 by 24.5% vs 5.2% (p = 0.014), a disappearance or reducing the size of esophageal varices were observed in 72% vs. 35% of cases (p = 0.035). Significant differences in ALT, AST, albumin, prothrombin time dynamics were not observed. Baseline albumin level ≤35 g/l is an independent risk factor for the absence of significant improvement of LS: OR 6.7 (95% CI 1.7–25.9, p = 0.006).Conclusion. SVR leads to fibrosis regression to F2-F3 stages in 44% of patients. Baseline albumin level ≤35 g/l is an independent risk factor for the absence of significant improvement of LS.

The number, shape and position of NMR spectral lines depend on dynamic processes, and this creates certain difficulties in identification of pharmaceutical substances by NMR spectroscopy. The aim of the paper was to study instances of manifestation of intramolecular dynamic processes that affect identification of organic compounds by NMR, and to illustrate the potential of the methods used for their reduction, as well as associated problems.Materials and methods: 1H and 13C spectra of the following pharmaceutical substances: «buserelin acetate», «valsartan», «goserelin acetate», «iopromide», «clopidogrel hydrogensulfate», «omeprazole», «proroxan», «risperidone», «triptorelin acetate», and «enalapril maleate» were used to demonstrate negative effects of dynamic processes. The spatial structures of conformers were established by 1H-1H ROESY experiments. The quantum-chemical calculation of geometric and thermodynamic characteristics of different conformers was carried out by the PM3 method, and electronic characteristics—by the AM1 method with the help of the HyperChem software.Results: the authors analysed intramolecular dynamic processes which are most commonly encountered in expert work: pyramidal inversion of nitrogen in a heterocyclic compound (risperidone, proroxan, clopidogrel), rotation of molecular fragments around the amide bond (valsartan, iopromide, enalapril), prototropic rearrangements (buserelin, goserelin, omeprazole, triptorelin). The change in exchange rates was explained from the perspective of the change in the system of intra- and intermolecular nonvalent interactions.Conclusions: the use of traditional methods for increasing the rate of dynamic processes (increasing the temperature and changing the solvent) does not always eliminate the negative effects of intramolecular transformations. Methods of smoothing the spectral manifestations of dynamic processes have limited application due to strong intramolecular nonvalent interactions which prevent the conversion of the dynamic process rate into fast exchange. Experts and manufacturers should take into account the manifestation of dynamic processes during identification of pharmaceutical substances by NMR spectroscopy.

Abstract Common diagnostic approach in patients with suspected cardiac amyloidosis includes cardiac magnetic resonance imaging and scintigraphy. We report the first clinical case of false‐positive results of scintigraphy in a patient with Danon disease.

The work is a continuation of the research on the use of NMR spectroscopy in the quality control of natural peptide hormone-based active substances and their synthetic analogues. The aim of the paper was to develop identification test methods for triptorelin acetate and goserelin acetate substances using NMR spectroscopy that does not require reference standards ‒ with the aim of using the newly developed test methods in pharmacopoeial analysis. Materials and methods: the procedure was developed using two-dimensional NMR spectroscopy (1H-1H gCOSY, 1H-13C gHSQC, 1H-13C gHMBC). Results: thestudy made it possible to assign 1H and 13C NMR signals to a specific molecular fragment, and to determine the amino acid composition of each oligopeptide. Conclusions: the authors drew up a table showing structural assignment of NMR signals, which makes it possible to use the NMR method for identification testing of triptorelin acetate and goserelin acetate substances without the use of pharmacopoeial reference standards. The study helped to determine the optimal temperature conditions for recording 13C NMR spectra (27 °С and 50 °С for triptorelin acetate and goserelin acetate, respectively). It was demonstrated that 13C NMR spectroscopy could be used for identification testing in pharmacopoeial analysis.

Introduction. Steroid-refractory graft-versus-host disease (srGVHD) is one of the most severe and life-threatening complications of allogeneic hematopoietic stem cell transplantation. Currently, there is no standard treatment for this complication. In addition, there is no data on the pharmacoeconomics of various methods in the Russian Federation. The objective is to compare the effectiveness and cost of treatment of acute and chronic srGVHD, as well as the use of different approaches in therapy. Material and methods. We have conducted a pilot study in 12 srGVHD patients treated with ruxolitinib and in 24 patients of wellmatched historical control, who treated with etanercept for the acute srGVHD and with extracorporeal photopheresis for chronic srGVHD. Results. The 6-month therapy of acute GVHD was associated with significantly higher cost than therapy of chronic GVHD (4.138±2.672 vs 1.862±1.122 thd. rub., р=0.004). The major factors driving up the costs were bacterial infections (р=0.022), opportunistic viral infections (р

The article illustrates the prospects of using nuclear magnetic resonance spectroscopy for complex, fast and reliable determination of key quality attributes of drug substances while performing pharmacopoeial analysis.

The article describes a newly developed procedure of quantitative determination of fluorine which is present in residual trifluoroacetates in glatiramer acetate pharmaceutical substances by19F NMR spectroscopy. Test parameters (the relaxation delay and the number of scans) were selected to minimize errors in quantitative measurements. Comparative analysis of available water-soluble fluorine-containing compounds showed that trifluoroethanol could be reasonably used as an internal standard for the determination of the absolute content of trifluoroacetic acid residues in glatiramer acetate. It was demonstrated that the new method could be used for quantitative determination of trifluoroacetates with no need for a series of reference standards and without destruction of glatiramer acetate.

The article describes validation of the procedure for determination of amino acids composition of glatiramer acetate by C-13 NMR spectroscopy. The procedure makes it possible to determine the molar ratio of amino acids present in glatiramer acetate with no need for a reference standard. The authors evaluated the accuracy, linearity, repeatability, intermediate precision and specificity of the validated procedure. The analysis of extraction factors for L-Glu, L-Ala, L-Tyr и L-Lys helped to calculate the systematic errors, standard deviations, confidence intervals, variation coefficients, confidence intervals, Fisher’s test and Student’s t-test for the results of amino acids molar ratio determination. It was shown that the obtained statistical data satisfy the acceptance criteria for validation parameters described in the national and foreign quality standards.

The article describes a simple method for purifying N-(5-amino-2-methylphenyl)-4-(3-pyridyl)-2-pyrimidineamine for further use as a standard for quantitative determination of genotoxic impurities substance imatinib mesylate. Experimentally proved choice of sorbent used for purification of N-(5-amino-2-methylphenyl)-4-(3-pyridyl)-2-pyrimidineamine. The advantage of column chromatography on neutral alumina prior to crystallization methods presented in the literature. Comparative chromatographic and spectral characteristics of N-(5-amino-2-methylphenyl)-4-(3-pyridyl)-2-pyrimidineamine before and after purification. NMR spectroscopy evaluated quantitative content of the target substance in the purified sample.

Optical coherence tomography (OCT) has been recently suggested as a promising method to obtain in vivo and real-time high-resolution images of tissue structure in brain tumor surgery. This review focuses on the basics of OCT imaging, types of OCT images and currently suggested OCT scanner devices and the results of their application in neurosurgery. OCT can assist in achieving intraoperative precision identification of tumor infiltration within surrounding brain parenchyma by using qualitative or quantitative OCT image analysis of scanned tissue. OCT is able to identify tumorous tissue and blood vessels detection during stereotactic biopsy procedures. The combination of OCT with traditional imaging such as MRI, ultrasound and 5-ALA fluorescence has the potential to increase the safety and accuracy of the resection. OCT can improve the extent of resection by offering the direct visualization of tumor with cellular resolution when using microscopic OCT contact probes. The theranostic implementation of OCT as a part of intelligent optical diagnosis and automated lesion localization and ablation could achieve high precision, automation and intelligence in brain tumor surgery. We present this review for the increase of knowledge and formation of critical opinion in the field of OCT implementation in brain tumor surgery.

The purpose of the research was to study the diagnostic possibilities of the use of the active radiometry method for localized scleroderma (LS), both for monitoring the results of therapy, and for a comprehensive assessment of the functional state of body tissues in the study area, as well as the possibility of determining new foci of the disease. Material and Methods. In a pilot study, patients were presented with different forms of lesions and their different localization, as well as with different disease activity. The method of resonance wave diagnostics is implemented in the diagnostic complex "Aquafon". Results. The primary registration of wave activity in different types of foci may differ. The activity of the foci and the possibility of the appearance of new foci can be said not so much by the data of the initial measurements as by the integral data on their difference before and after the illumination procedure, which requires further study. Conclusion. It is necessary to improve the measurement technique, avoid places where the sensor is not well attached to the skin or minimize this effect. The research also aimed to conduct studies with simultaneous use of other methods.

Study Objective . To evaluate the correlation between cytokine synthesis and organ involvement in patients with granulomatosis with polyangiitis (GPA). Methods. The study involved 60 patients with GPA diagnosed following the ACR criteria and the CHCC-2012 definition. Cytokines genes expression was studied in blood samples from 57 patients with reverse transcription polymerase chain reaction. We evaluated mRNA for the following cytokines: interferon (IFN)-α, IFN-γ, interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-18, tumor necrosis factor (TNF)-α production. Also, we investigated the serum concentration of IFN-α, IL-1β, IL-8 IL-18 and TNF-α by ELISA in 40 patients with GPA. Results . Markers for granulomatous disease were detected in 45 (75,0%) GPA patients, markers for vasculitis - in 23 (38,3%) patients. GPA affected eyes in 33 patients (55,0%), ears in 29 (48,3%), nose and sinuses in 57 (95,0%), lungs in 35 (58,3%) and kidneys in 28 (46,7%). There was total positive correlation between eye disease and IL4 and IL12 genes expression ( r =1,00). Total negative correlations were between ear disease and IL-12 gene expression; glomerular filtration rate reduction more than 50% and serum IFN-α ( r =-1,00). Conclusion. Cytokines may upregulate the direct immune response in organ damage in GPA patients. Markers for granulomatous disease correlated with cytokines, that suppressed Th2 type immune response and promoted Th1 type immune response. Correlation between vasculitis markers and cytokines showed that IFN-α, TNF-α, IL-1β and IL-6 participated in vascular damage in GPA patients.

Aim ― development of a hardware-software system allowing to treat infected superficial wounds in a liquid environment, designed to provide continuous flow of various irrigation solutions (depending on the wound healing stage) under airtight and water-resistant film tightly fixed over the wound. Methods ― in this experiment wound irrigation with antiseptic, oxidizing antiseptic and osmotically active agents with subsequent exposure and drainage was performed using the novel device. Efficacy of the proposed hardware-software system was evaluated by comparing it with standard wound dressings by planimetry and wound biopsy results. Results ― according to study results the novel device reduces the time of wound healing by 26.1%, while the time to wound proliferation is 1.7 times shorter when compared with standard wound dressings. Conclusion ― the proposed method stimulates wound repair and limits purulent inflammation in infected wounds. Using the novel method of superficial wound management helps to prevent the development of re-infection and suppuration.

Introduction: Despite the introduction of increasingly multifaceted diagnostic techniques and the general advances in emergency abdominal and vascular surgery, the outcome of treatment of patients with acute impaired intestinal circulation remains unsatisfactory. The non-invasive and high-resolution technique of optical coherence tomography (OCT) can be used intraoperatively to assess intestine viability and associated conditions that frequently emerge under conditions of impaired blood circulation. This study aims to demonstrate the effectiveness of multimodal (MM) OCT for intraoperative diagnostics of both the microstructure (cross—polarization OCT mode) and microcirculation (OCT angiography mode) of the small intestine wall in patients with acute mesenteric ischemia (AMI). Methods and Participants: A total of 18 patients were enrolled in the study. Nine of them suffered from AMI in segments II-III of the superior mesenteric artery (AMI group), whereby the ischemic segments of the intestine were examined. Nine others were operated on for adenocarcinoma of the colon (control group), thus allowing areas of their normal small intestine to be examined for comparison. Data on the microstructure and microcirculation in the walls of the small intestine were obtained intraoperatively from the side of the serous membrane using the MM OCT system (IAP RAS, Russia) before bowel resection. The MM OCT data were compared with the results of histological examination. Results: The study finds that MM OCT visualized the damage to serosa, muscularis externa, and blood vessels localized in these layers in 100% of AMI cases. It also visualized the submucosa in 33.3% of AMI cases. The MM OCT images of non-ischemic (control group), viable ischemic, and necrotic small intestines (AMI group) differed significantly across stratification of the distinguishable layers, the severity of intermuscular fluid accumulations, and the type and density of the vasculature. Conclusion: The MM OCT diagnostic procedure optimally meets the requirements of emergency surgery. Data on the microstructure and microcirculation of the intestinal wall can be obtained simultaneously in real time without requiring contrast agent injections. The depth of visualization of the intestinal wall from the side of the serous membrane is sufficient to assess the volume of the affected tissues. However, the methodology for obtaining MM OCT data needs to be improved to minimize the motion artefacts generated in actual clinical conditions.

Modeling of allogeneic bone marrow transplantation and graft-versus-host disease (GVHD) plays a crucial role in the improvement of transplantation procedures and testing novel immunosuppressive drugs. In this study we evaluated the feasibility of busulfan and cyclophosphamide conditioning with posttransplantation cyclophosphamide (150 mg/kg) in donorrecipient pairs C57Bl/6-Balb/с and Balb/с-C57Bl/6. We observed that Balb/с mice as opposed to C57Bl/6 mice can’t be the recipients because of the unacceptably high acute mortality from acute toxicity of chemotherapeutic drug. Histological studies in the C57Bl/6 recipients revealed acute GVHD in 93 % of animals. All animals had only grade I–II severity of GVHD. This model has the potential for future studies in the field of transplantology, nonetheless a decrease in the intensity of prophylaxis is required to augment the manifestations of GVHD.

Refractory chronic graft-versus-host disease (cGVHD) is the complication of allogeneic hematopoietic stem cell transplantation (HCT) that signi ficantly impacts quality of life, may be associated with morbidity and mortality and has limited treatment options. 16 adult pts (median age 22, range 16 - 51 y.o.) with refractory cGVHD were enrolled. 6 pts were on steroids upon inclusion. 11 patients had severe (NIH) cGVHD, 6 - moderate, and have received 1-3 anti-cGVHD treatments before IL-2. Pts received IL-2 sc injections 1 MIU 3 times a week. Median duration of treatment was 2.5 moths (range 1 - 8 months). Partial clinical response was observed in 5 pts, complete response in 2 pts with overall response of 44 %. There was an improvement of Karnofsky in 25 % of pts, reduction in NIH severity scores in 37.5 % of and any objective response also in 44 % of pts. With median follow-up of 14 months overall survival was 62.5 %, non-relapse mortality was 12.5 % (2 pts), 25 % of patients had a relapse of underlying disease.

The aim of the study was to compare the efficacy of allogeneic hematopoietic stem cell transplantation (alloHSCT) and chemotherapy (CT) of acute myeloid leukemia (AML) in first remission (CR1), to identify factors influencing the results. We compare the efficacy alloHSCT in CR1 (n = 70) and CT (n = 52). Patients were stratified by age, the level of leucocytes, the origin of AML, cytogenetic risk group and response to induction CT. Five-years overall and disease-free survival (OS and DFS) were higher in the group alloHSCT (67 and 65 % vs 46 and 30 % (p = 0.02 and p = 0.001)). Benefits of DFS after alloHSCT was in standard and high-risk cytogenetic groups (78 % versus 29 % (p = 0.001), and 34 % vs 17 % (p = 0.007)). The risk of relapse (RR) was 24 % in patients after alloHSCT vs. 57 % for CT (p = 0.003). Comparing the RR after alloHSCT and CT depending on the cytogenetic risk groups: standard (HR0.2(CI95 %0.07 - 0.56) p = 0.002), and high (HR0.27(CI95 %0.08-0.86) p = 0.03). Additional factors affect the RR were the origin of AML (de novo) (HR0.47 (CI95 %0.3-0.74) p = 0.001), the hyperleukocytosis (HR1.91 (CI95 %1.09 - 3.32) p = 0.02), and no remission after the first course CT (HR3.32(CI95 %1.57-7.0) p = 0.002). The efficacy of alloHSCT compared with CT is higher both in standard and high-risk cytogenetic group.

The retrospective analysis of the data of 197 patients who had undergone elective abdominal aortic aneurysm (AAA) repair showed that almost half of them (43.1 %) had impaired passability of the inferior mesenteric artery (IMA), 19.3 % – of the internal iliac artery (IIA) and both arteries were affected in 8.3 % of the patients. IMA after elective AAA repair was ligated in 130 patients, 65 patients had it implanted into prosthesis and 2 patients underwent stenting of the aorta. The operation resulted in preserved antegrade and retrograde blood flow in the IIA in a quarter (25.4 %) and a third (32.1 %) of the patients, respectively. In the early postoperative period ischemic colitis was found in 8 patients (4.1 %), and more than a third of them (37.5 %) developed infarction in the left side of the colon with a lethal outcome. To objectify the intraoperative assessment of the blood supply in the left colon after elective AAA repair the methods of direct manometry and ultrasonography were used in 41 and 40 patients, respectively, and both methods were applied in 21 patients. The level of statistical significance and the positive values of the coefficients of correlation between the values of the peak systolic velocity and the indices of pressure intraoperative ultrasonography as a reliable and noninvasive method for assessing perfusion in the left side of the colon after electively AAA repair.

We report the case of young patient, whose cause of death was generalized syphilitic cerebrospinal meningitis. The results of autopsy and histological examination are presented. The possibility of using magnetic resonance imaging to verify the form of neurosyphilis is discussed.

Objective: to determine the effectiveness of the Atlas of Ophthalmic Instruments for Smartphones (the application for smartphones) in optimization of the educational process of students, residents, and ophthalmologists. Material and methods. On the Android platform there had been created and placed in the Google Play an application "Ophthalmic Instruments" with illustrations and description of ophthalmic surgical instruments. Next, a survey had been conducted of users of the application (1005 respondents). To this was applied a specially designed questionnaire in English. Results. According to the survey, the average score among students (652 users) is 4.9; among residents (281) 4.7 and doctors (72) and 4.6. Conclusion. Obtained data allow to conclude that the use of interactive mobile applications positively influences the optimization of the educational process and can be considered as a new and effective form of tutorials.