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Proceedings of the National Academy of Sciences of Belarus, Medical series

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Vol 17, No 4 (2020)
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https://doi.org/10.29235/1814-6023-2020-17-4

CLINICAL AND EXPERIMENTAL MEDICINE 

391-400 672
Abstract

Ulcerative colitis is an inflammatory disease of the mucosa of the colon and rectum. The clinical practice of cell therapy programs based on mesenchymal stem cells allows to limit patient data on the use of hormonal or immunosuppressive drug therapy. The article presents a clinical case of 52 years man with ulcerative colitis, which was treated by autologous multipotent mesenchymal stromal cells that pass through the inferior mesenteric artery. Treatment control was carried out 43 days after the procedure. The following results were obtained: a decrease in the diseases activity index with a severe degree (DAI = 9) to mild (DAI = 4), refusal of steroid therapy, patient satisfaction according to SF-36 questionnaire and diary.

401-408 6386
Abstract

The aim of the study is to compare the structure of the lumbosacral transitional vertebra, which were detected by computed tomography (CT) and identified on dried human sacral, and to discuss possible pathogenetic mechanisms of this congenital malformation. The article presents 9 cases of lumbosacral transitional vertebra, including 6 cases of L5 sacralization and 3 cases of S1 lumbarization. The formation of the transitional lumbosacral vertebra is genetically determined. All types of such developmental anomaly can be detected only on CT. L5 sacralization repeats the process of fusion of the sacral vertebra into a single bone. A lack of the costotransverse bars of the first sacral vertebrae fusion results in the S1 lumbarization.

409-416 1166
Abstract

A sufficient number of facts testifying the importance of liver arginase and nitrogen monoxide in the life processes in the normal and pathological conditions have been accumulated to date. The aim of the study was to determine the significance of the relationship and interaction of liver arginase and L-arginine-NO system in the processes of detoxification, lipid peroxidation and the formation of the thyroid status in rats with chronic ethanol intoxication. In rat experiments using the modern physiological, biochemical research methods and a pharmacological approach, it was found that chronic ethanol intoxication leads to a decrease in the liver arginase activity and the triiodothyronine concentration. At the same time, the increase in the level of “average molecules”, NO3 – /NO2 –, the content of lipid peroxidation products in the plasma, as well as the increase in the blood toxicity degree, the activity of alanine amino transferase, aspartate amino transferase and the narcotic sleep duration were observed. Hyperthyroid rats demonstrated the increased liver arginase activity, the processes of detoxification, lipid peroxidation and body temperature while rats with the experimental hypothyroidism showed the opposite results. The liver arginase depression caused by the injection of Nω-hydroxy-nor-L-arginine (Nor-NOHA), or L-valine into the body prevents the body temperature increase and the development of characteristic changes in the detoxification and lipid peroxidation processes acted upon by exogenous triiodothyronine. Under the conditions of the liver arginase inhibition by Nor-NOHA or L-valine, the ethanol action is accompanied by a more significant inhibition of the liver detoxification function and an increase of NO3 – /NO2 – levels in blood plasma. The preliminary injection of an NG-nitro-L-arginine methyl ester inhibitor of NO-synthase into the animal’s body weakensthe toxic ethanol effect on the liver, as well asthe development of characteristic changes in the liver arginase activity, in the processes of detoxification and lipid peroxidation in rats with chronic ethanol intoxication. Apparently, the activity of liver arginase and L-arginine-NO system determines the severity of detoxification, lipid peroxidation processes and the formation of the thyroid status in the conditions of chronic alcoholization, which is important in the ethanol intoxication pathogenesis.

417-426 844
Abstract

Laryngotracheal stenosis is a serious pathological process that leads to the narrowing of the airways because of damage of the mucous membrane and the formation of pathophysiological mechanisms of regeneration. Mesenchymal stem cells (MSCs) are known to be able to suppress the inflammatory response and to stimulate tissue regeneration; that is why, they are a promising biomedical cell product for treatment of laryngotracheal stenosis. The aim of this study was to evaluate the safety, tolerability, and long-term clinical efficacy of cell therapy of laryngotracheal stenosis using autologous MSCs of the olfactory lining (OL). The clinicalstudy included patients with a diagnosis of laryngotracheal stenosis (J38.6 and J95.5 according to ICD-10) without compromising the integrity of the cartilage frame with or without a tracheostomy/laryngostomy, including patients after surgical interventions to restore the lumen of the larynx and trachea. Clinical trials of laryngotracheal stenosis using autologous olfactory mucosa-derived mesenchymal stem cells were carried out. Cell therapy was safe and well tolerated, and prevented the restenosis and formation of scar granulation tissue during 2 years of observation in all patients included in the clinical study. The restoration of the larynx and trachea lumen, the improved respiratory function and the increased exercise tolerance were observed in 6 patients who had no cartilage disorder. The data obtained indicate the high clinical efficacy of the method of cell therapy of laryngotracheal stenosis using autologous olfactory mucosa-derived mesenchymal stem cells.

427-436 984
Abstract

The objective was to improve the results of surgical treatment of vesicoureteral reflux in children, using laparoscopic access. The prospective study was performed in 111 children (137 ureters) with the primary III–IV grade vesicoureteral reflux. The mean age was 34.7 months. The modified laparoscopic antireflux technique was performed on 73 children (91 ureters). We compared the perioperative complications and the medium-term outcome with a group of 38 children (46 ureters) who underwent classical laparoscopic extravesical reimplantation.3 In the modified group, the mean surgery time was 109.8 ± 31.5 minutes for unilateral cases and 176.5 ± 47.6 minutes for bilateral cases; in the classical group, it was 118.6 ± 34.3 and 209.5 ± 51.2 minutes respectively (p > 0.05). Postoperative vesicoureteral reflux had 2 (2.7 %) patients in the main group and 8 (21.1 %) children in the control group (p  =  0.002). There was no ureteral obstruction in the both groups. The success rate for ureters was 97.8 % with modified technique versus 82.6 % after classical laparoscopic reimplantation (p = 0.003). Laparoscopic extravesical ureteral reimplantation is a safe and effective surgical procedure. The modified technique may improve the surgical treatment results.

444-451 3674
Abstract

The article presents the analysis of the morphological changes of the periodontal tissues of laboratory animals using mesenchymal stem cells (MSCs). The goal of the study is to create a model of experimental periodontitis and to identify the characteristics of morphological changes in the periodontal tissues using a biomedical cell product based on the allogeneic adipose tissue of MSCs (AT MSCs). The application of a mixture of AT MSCs and osteoinduced AT MSCs (in the ratio of 1:1) allows reducing the time of bone defect regeneration in comparison to that of bone tissue regeneration when AT MSCs and osteoinduced AT MSCs are used separately, which is expressed in the filling of the bone defect with a fibroreticular osteogenic tissue, as well as with a muscle tissue one month after surgery. In 2 months, in the defect area filled with a collagen membrane with a mixture of AT MSCs and osteoinduced AT MSCs, the initial signs of the formation of trabecula of bones were detected, which is evident of a more comprehensive osteosynthesis process compared to the blood clot use.

452-460 573
Abstract

The aim of the study was to investigate the features of clinically suspected myocarditis complicated by the left ventricular systolic dysfunction development. 93 patients with clinically suspected myocarditis were examined. The average age was 36.63 ± 1.15 years. In 43.01 % of patients the disease was accompanied by a decrease in left ventricular systolic function. In the group of patients with left ventricular systolic dysfunction in comparison with those with preserved left ventricular ejection fraction, a significantly lower proportion of men (75 % versus 81 %, respectively, χ2 = 9.3, p < 0,01) and a higher average group age (40.7 ± 1.87 versus 33.6 ± 1.3 years, respectively, p <  0,01) were revealed. The course of the disease in patients with left ventricular systolic dysfunction was characterized by a more frequent development of rhythm disturbances (65 % versus 43.3 %, respectively, χ2  = 4.3, p  < 0,05) and a higher heart rate at admission (94.5 (75‒100) and 85 (70‒89) beats per minute, respectively, p = 0.006). The structural and functional state of the heart according to echocardiography in patients with a reduced left ventricular ejection fraction versus comparison group was characterized by larger heart chambers sizes, more pronounced violations of local left ventricular contractility, more frequent involvement of the right ventricle in the pathological process (56.3  % versus 22.2  %, respectively, χ2   =  6.4, p  < 0,05). The relationships between the left ventricular ejection fraction Весці Нацыянальнай акадэміі навук Беларусі. Серыя медыцынскіх навук. 2020. Т. 17, № 4. C. 452–460 453 and the patient’s age (r = ‒0.36), the value of the heart rate at admission (r = ‒0.32), the severity of heart failure at admission, the degree of impaired local contractility of the left ventricle, the degree of right ventricular function (TAPSE, r  =  0.58), the severity of myocardial fibrosis according to cardiovascular magnetic resonance imaging (r = ‒0.32) were revealed.

461-469 701
Abstract

The effect of methionine overload on the state of the pool of sulfur-containing amino acids and their metabolites was studied in the various brain structures determined by reverse phase high performance liquid chromatography (HPLC). In all regions of the brain studied, methionine led to a unidirectional imbalance of sulfur-containing compounds: there was an increase in the concentrations of methionine, cystathionine and hypotaurine. The most pronounced increase in methionine and hypotaurine levels was observed in the striatum, cystathionine in the hemispheres. A significant increase in taurine concentration was observed only in the hypothalamus and striatum. In other parts of the brain a tendency to increase its level was shown. In all brain regions studied except the striatum, serine levels were decreased. In the cerebellum, in comparison with other regions, an increase in the level of cysteic acid and a decrease in the level of cysteinesulfinic acid were observed, which indicates that taurine synthesis is occurred mainly through the cysteine sulfinate oxidation.

470-479 488
Abstract

The article presents data assessment of the severity of the clinical condition and a number of biochemical parameters in 51 patients with aneurysmal intracranial hemorrhage on the 10th day, on average, after the rupture of the arterial aneurysm and after treatment with the additional use of magnesium sulfate to standard therapy in the postoperative period. It is shown, that at the time of hospitalization, 75 % of patients in the control group and 50 % of patients in the main group had cerebral vascular spasm according to transcranial dopplerography; activation of lipid peroxidation processes, a decrease in superoxide dismutase activity, an increase in the content of vascular endothelial growth factor and highly sensitive C-reactive protein (CRP) with a decrease in the level of stable nitrogen monoxide exchange products were detected. A statistically significant improvement in the clinical condition of patients on the Hunt-Hess scale, the modified Fisher scale, and an increase in the score on the Glasgow coma scale with normalization of pro- and antioxidant status of the blood were revealed in the main group after neurosurgical treatment and course use of magnesium sulfate. At the same time, high levels of highly sensitive CRP and low levels of nitrates/nitrites in the patients blood of both groups are maintained. Consequently, the additional use of magnesium sulfate improves the clinical condition of patients with intracranial hemorrhage and increases the antioxidant potential of the blood in the postoperative period.

480-492 858
Abstract

Vitamin D plays an important role in bone metabolism and pathology. Although the VDR gene is one of the most studied determinants of bone mineral density (BMD) and osteoporosis (OP), its exact effects have yet to be established. Prediction of OP and/or fracture risk, based on individual genetic profile, is of high importance. The aim of our study was to develop prognostic model for postmenopausal OP individual risk evaluation in Belarusian women, based on the analysis of VDR gene variants. Case group included women with postmenopausal OP (n = 350), the control group comprised of women with normal BMD and without previous fragility fractures (n  =  243). VDR gene ApaI rs7975232, BsmI rs1544410, TaqI rs731236, FokI rs2228570 and Cdx2 rs11568820 variants were determined using TaqMan genotyping assays. We revealed a significant association of single ApaI A/A (p = 0.045), BsmI T/T (p = 0.015) and TaqI G/G (p = 0.005) variants and their A-T-G-haplotype (OR  =  4.6, p  =  0.003) with increased OP risk. Together with Cdx2 rs11568820, these variants correlated with BMD (p <0.05 in all cases). For the bearers of non-favorable alleles of VDR gene variants, the serum 25(OH)D level was significantly increased. The constructed from informative VDR gene variants model of individual OP risk evaluation possessed a good prognostic value (AUC = 0.79) with high sensitivity level (82.9 %) and average specificity (69.4 %). Our findings highlight the importance of analyzed VDR gene variants for personalized OP risk prediction.

493-499 514
Abstract

The pleiotropic effects of vitamin D (VD), whose active form is synthesized in the kidneys, play a certain role both in forming and functioning the feto-placental system, including various pregnancy complications. The aim of the study was to evaluate the vitamin D status in pregnant women with placental dysfunction (PD) and chronic inflammatory kidney disease (CIKD). During 24–34 pregnancy weeks, 56 pregnant women with PD were examined (main group ‒ I); 24 patients (42.85 %) had chronic pyelonephritis (group IA). The control group (group II) had 31 conditionally healthy pregnant women. The total VD level in the blood was determined by ELISA; in addition to the general clinical standard examination, the urine also underwent bacteriological examination. The VD mean level in pregnant women with PD and CIKD was significantly lower than that in the control group (31.08 ± 7.2 and 45.42 ± 9.67 ng/ml (p <0.01)). Only 33.33 % of pregnant women in group IA had a VD optimum, as well as 93.55 % (p < 0.01) in the control group and 17.86 % in group I. 8.33 % of pregnant women had a VD deficiency in group IA (RR = 2.09; CI 95 % ‒ 1.8‒2.42). The patients with a VD-deficiency were absent in the control group. 58.33 % of women in group ІА had a suboptimal VD level and 6.45% in the control group (RR = 3.57; CI 95 % ‒ 1.62‒7.88). Bacteriuria was observed in all pregnant women with a VD-deficient or suboptimal level. At the optimum VD level, bacteriuria was diagnosed twice less (χ2 = 66.67; p <0.01). In patients with an inadequate VD level, CIKD was diagnosed 3.8 times more (RR = 3.57; CI 95 % ‒ 1.62‒7.88). 494 Proceedings of the National Academy of Sciences of Belarus. Medical series, 2020, vol. 17, no. 4, pp. 493–499 A significantly calcitriol reduction in pregnant women with placental dysfunction suggests that the deficiency or the suboptimal level of vitamin D and inflammatory kidney diseases may be the interdependent processes that play a decisive role in the formation of placental dysfunction.

REVIEWS 

500-508 516
Abstract

The following review summarizes the latest studies on in vitro osteogenic mesenchymal stem cell differentiation and selection of scaffolds that can maintain the viability and functional activity of these cells for bone tissue repair. In the last time, there have been investigated a lot of issues such as the stimulation and development osteogenic differentiation of MSCs, the growth factors – inducers of osteogenesis in MSCs, the creation of 3D constructions of cells in different scaffolds. A deeper understanding of the osteogenic differentiation mechanisms can result in the novel therapeutic opportunities of bone disease treatment. Special attention is given to materials for scaffold designs and template–cell interactions, which is of great importance for the structuring and functioning of an engineered tissue.

SCIENTISTS OF BELARUS 



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ISSN 1814-6023 (Print)
ISSN 2524-2350 (Online)