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Fundamental and Clinical Medicine

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Vol 9, No 2 (2024)
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EDITORIAL

ORIGINAL RESEARCH

8-19 213
Abstract

Aim. To evaluate the activity of autophagy and apoptosis in the myocardium of rats with different
stress resistance after the modeling of myocardial contusion.

Materials and Methods. The study was performed on 106 white male rats weighing 250-300 g. The rats were ranked according to stress tolerance, and medium-resistant individuals (n = 42) were excluded from the experiment. Control (n = 16) and experimental (n = 48) groups were formed from the remaining animals; the control group included subgroups with high and low stress resistance, and the experimental group included 6 subgroups (rats with high and low stress resistance; 6, 12, and 24-hour time points). Each of the subgroups included 8 animals. Myocardial contusion was modeled in the experimental group. At 6-, 12- and 24-hour time point, rat hearts have been excised and 5×5 mm myocardial fragments were dissected from the areas with the most prominent traumatic effects (interventricular septum, anterior walls of the left and right ventricles). Tissues were then sectioned and stained with antibodies to Beclin-1 and caspase-3.

Results. We have documented a significant expression of Beclin-1 and Caspase 3 expression in rat hearts after myocardial contusion. From 6 to 24 hours upon the myocardial contusion, Beclin-1 expression has been increased in rats with high stress resistance but was reduced in rats with low stress resistance. Expression of caspase-3 expression was registered exclusively at 24-hour time point in rats with high stress resistant but increased along the time points in rats with low stress resistance.

Conclusion. Expression of Beclin-1 and caspase-3 in rat myocardium indicated autophagy and apoptosis upon the myocardial contusion. Temporal patterns of Beclin-1 and caspase-3 expression were opposite in rats with high and low stress resistance.

20-27 216
Abstract

Aim.To evaluate the cytotoxicity of poly(ε-caprolactone) and polyurethane scaffolds in vitro.

Materials and Methods. Polymer scaffolds were made by electrospinning from a 12% solution of poly(ε-caprolactone) or a 12% solution of polyurethane. Surface structure was examined by scanning electron microscopy, whilst cytotoxicity was evaluated by seeding EA.hy 926 endothelial cells on scaffold surface for 72 hours. Cell culture viability and proliferation was assessed by MTT assay and by quantifying cell culture density. On the xCELLigence device, cells were cultured in the presence of the studied matrix samples, and the dynamics of cell culture growth was evaluated in real time.

Results. Poly(ε-caprolactone) scaffolds were characterised by a higher variability in the filament thickness and by a significantly larger pore size. Polyurethane filaments formed a dense web with a smoother surface. Poly(ε-caprolactone) scaffolds had significantly higher biocompatibility in comparison with polyurethane. Adhesion of cells to poly(ε-caprolactone) scaffolds did not differ from the cell culture plastic, and poly(ε-caprolactone) supported cell proliferation in the MTT test. Poly(ε-caprolactone) and polyurethane did not differ significantly in terms of inducing cell proliferation. Both poly(ε-caprolactone) and polyurethane scaffolds did not pose considerable cytotoxicity.

Conclusion. Poly(ε-caprolactone) and polyurethane scaffolds did not exhibit cytotoxic effects and can be used for manufacturing polymer scaffolds of vascular grafts.

28-36 201
Abstract

Aim. To study the effect of malignant tumor growth on level of cAMP in mitochondria of cardiomyocytes in mice with chronic neuropathic pain.

Materials and Methods. С57ВL/6 mice (n = 336) have been grouped as follows: intact mice (♂n = 21; ♀n = 21), mice with chronic neuropathic pain (♂n = 21; ♀n = 21), mice with melanoma В16/F10 (♂n=63; ♀n=63), and mice with melanoma В16/ F10 and chronic neuropathic pain (♂n=63; ♀n=63). After 1, 2, and 3 weeks of the melanoma growth, cardiac mitochondria of abovementioned mice have been isolated by the centrifugation with the following measurement of cAMP.

Results. Chronic neuropathic pain has induced a 3.6-fold reduction in cAMP in cardiac mitochondria of female mice. In mice with melanoma В16/ F10, cardiac cAMP showed 4-fold average increase from the 2nd week of the tumor growth, while in mice with melanoma В16/F10 and chronic neuropathic pain a 2-4-fold increase in cAMP was recorded as soon as from the 1st week of tumor growth, eventually leading to the depletion of cAMP by the 3rd week of the experiment. Serum cAMP concentration did not correlate with the cAMP level in cardiac mitochondria and was reduced in both males and females.

Conclusion. Alterations in cAMP concentration in cardiac mitochondria were gender-specific, as female mice responded to a chronic neuropathic pain without other triggers. In mice with melanoma and chronic neuropathic pain, cAMP level raised significantly earlier than in mice without chronic neuropathic pain, resulting in full cAMP depletion by the 3rd week of the experiment.

37-54 336
Abstract

Aim. Placental abruption is a severe complication of pregnancy, which is often accompanied by pre-eclampsia and early delivery. Here we aimed to study maternal and neonatal outcomes in patients with placental abruption depending on the severity of pre-eclampsia.

Materials and Methods. The study included 509 patients with placental abruption and pre-eclampsia from 22 medical centers in 16 regions of the Russian Federation, which were divided into two groups: patients with placental abruption and severe pre-eclampsia (n = 369) and patients with placental abruption and moderate pre-eclampsia (n = 140).

Results. Regardless of the severity of pre-eclampsia, average term of placental abruption was 34 weeks of pregnancy. Among the adverse maternal outcomes in patients with placental abruption and severe pre-eclampsia were coagulopathy (OR = 5.01; 95% CI = 1.17–21.46) and near miss proportion (OR = 2.95; 95% CI =1.22 –7.08) which were significantly more common as compared to a moderate pre-eclampsia. Neonatal outcomes were accompanied by a high perinatal mortality (12.8%) and neonatal morbidity due to a high prevalence of premature birth (65%), asphyxia (64%), and small for gestational age (40%). Groups with severe and moderate pre-eclampsia had no statistically significant differences in neonatal outcomes, excepting congenital malformations which were found less frequently (OR = 0.32; 95% CI 0.13–0.79) in severe pre-eclampsia.

Conclusion. Severity of pre-eclampsia did not affect neonatal outcomes in women with placental abruption. Maternal outcomes were significantly worse in patients with severe pre-eclampsia in comparison with those with moderate pre-eclampsia.

55-65 259
Abstract

Aim. To evaluate the effectiveness of an integrated approach to the prevention of postpartum hemorrhage (PPH) in high-risk patients using uterine balloon tamponade with a double-balloon system, double-sided compression suture on the lower uterine segment, and administration of a uterotonic drug.

Materials and Methods. Here we performed an open-label, comparative, controlled clinical trial aimed at establishing superiority. 144 pregnant patients with a high risk of PPH were randomised into 2 groups of 72 patients each. When implementing the study protocol, 22 patients were excluded from the treatment group, and 1 patient was excluded from the control group. In the treatment group, in addition to routine prevention, we applied an original technique which included uterine balloon tamponade with a double-balloon system, double-sided compression suture in the lower uterine segment, and intravenous administration of carbetocin. Control group received routine prevention of PPH. Statistical data analysis was carried out using Python version 3.11.

Results. The volume of blood loss ranged from 500 to 1900 mL in the treatment group and from 400 to 3900 mL in the control group (p = 0.375). In the treatment group, the incidence of PPH was significantly lower than in the control group (10.00% and 49.30%, respectively, p < 0.0001), as well as the frequency of blood loss > 1000 mL (20.00% and 39.44%, respectively, p = 0.002). Blood loss > 2000 mL was recorded exclusively in the control group (12.69% patients). Among the secondary outcomes, blood products were used significantly less frequently in patients of the treatment group compared to the control group (12.00% and 29.58%, respectively, p = 0.027); hysterectomy was performed only in 6 (8.45%) patients of the control group. The duration of hospitalisation after childbirth did not differ significantly between the groups.

Conclusion. An integrated approach to the prevention of PPH, which employs a double-sided compression suture on the lower uterine segment, uterine balloon tamponade using a double-balloon Zhukovsky system, and intravenous administration of a uterotonic drug, is more effective in preventing PPH in high-risk patients as compared with routine practice. Further multicenter extended studies in this direction are needed.

66-71 233
Abstract

Aim. Previously, low-density lipoprotein-containing circulating immune complexes (LDL-CIC) were found in the blood of atherosclerotic patients. High diagnostic and prognostic significance of cholesterol level in LDL-CIC (Chol-CIC) in relation to the development of asymptomatic atherosclerosis suggested its clinical utility. Here we attempted to improve the prognostic value of CholCIC by combining this marker with other features.

Materials and Methods. The study included 101 male patients with asymptomatic carotid atherosclerosis. During 1 year, we carried out quarterly measurements of clinical and biochemical features including Chol-CIC and intima-media thickness (IMT).

Results. Combination with age increased the prognostic significance of Chol-CIC from 63.5% to 78.3% that exceeded those of low-density lipoprotein cholesterol (LDL-C) and Chol-CIC alone. Age did not improve prognostic significance of other lipid parameters. Therefore, Chol-CIC had higher prognostic significance in comparison to other lipid profile parameters.

Conclusion. Combination of Chol-CIC and patient age may be used for the prognosis of increasing intima-media thickness.

REVIEW ARTICLES

72-85 266
Abstract

About 120 chemical compounds are registered in Russia as anticancer drugs, and screening and investigation of novel therapies remain an urgent task for specialists in pathophysiology, pharmacology and oncology. Among them, treatments targeting neovascularisation and regulated cell death of atypical cells within the malignant tumours are of utmost importance. Hence, development of novel anti-cancer drugs must include testing of their pro-apoptotic and anti-angiogenic activity. Here we review the markers of angiogenesis and regulated cell death during the tumor development and the respective immunohistochemical applications for preclinical trials. Here we discuss relevant molecular markers for studying primary cell death subroutines which can be targeted by anticancer agents. The most sensitive and specific immunohistochemical markers of programmed cell death are tumor necrosis factor alpha (TNF-α) for necrosis and anti-cellular apoptosis susceptibility/CSE1L, Bcl-2, and apoptotic protease activating factor-1 (APAF1) for apoptosis. Primary markers of angiogenesis include vascular endothelial growth factor A (VEGF-A), hypoxia-inducible factor 1-alpha (HIF-1α), and platelet-derived growth factor (PDGF). Analysis of tumour blood supply, metastasis and apoptosis has both theoretical and practical significance with direct implications for the pharmaceutical industry.

86-93 248
Abstract

The placenta is a functional link between mother and fetus during pregnancy and the most important factor determining newborn and infant health. Postpartum hemorrhage is a leading cause of maternal morbidity and mortality worldwide and is affected by numerous factors including placental size. Here we analysed the role of placental disorders as a risk factor for the development of postpartum hemorrhage. We screened the available literature via PubMed, PubMed Central, Scopus, MEDLINE, ScienceDirect, Cochrane Library, and eLibrary from 2001 to October 2023. Placental insufficiency may cause either hyperplasia (i.e., placental expansion to meet the nutritional needs of the growing fetus) or hypoplasia, which cause deficiency in nutrients and oxygen and slows down fetal growth and development. Both of these conditions significantly affect the probability and volume of postpartum haemorrhage.

94-102 245
Abstract

Type 1 diabetes mellitus is a chronic autoimmune disease with a onset in childhood and adolescence. Neurological disorders are among the most frequent complications of type 1 diabetes mellitus and might lead to cognitive impairment termed as diabetic encephalopathy. Besides regulating blood glucose, insulin have neuroprotective and pro-cognitive effects through its action on insulin receptors in the brain, promoting the production of neurotransmitters, long-term potentiation, synaptic plasticity, and neuronal differentiation. By enhancing abovementioned processes responsible for learning and memory, insulin improves cognitive functioning. Insulin deficiency triggers cognitive dysfunction and diabetic encephalopathy via mitochondrial dysfunction, oxidative stress, and disorganisation of glucose metabolism which alter functioning of glucose transporter proteins and induce pericyte loss, ultimately compromising integrity of the blood-brain barrier. Intranasal delivery of exogenous insulin, which bypasses the bloodbrain barrier, may serve as an efficient therapeutic strategy for correcting cognitive impairment in patients with diabetic encephalopathy. Further research is needed to uncover and understand the effects of exogenous insulin on cognitive functions in patients with type 1 diabetes mellitus.

103-111 408
Abstract

In this paper, we aimed to: 1) discuss the approaches for increasing the effectiveness of organ-preserving surgical treatment of uterine fibroids; 2) analyse pre-operative preparation options for the formation of a restitutive scar during myomectomy. The article addresses the epidemiology of uterine fibroids in women, particularly in the reproductive age, and discussed the role of inflammation, disrupted nutrition, and proteolysis in the development of myomatous nodules. We also consider the terminology, classification, primary clinical symptoms of uterine fibroids, and discuss the causes of uterine scar incompetence. Various growth factors and collagen types have a differential impact on myometrial and on the formation of a restitutive scar. Finally, we talk about the histological and immunohistochemical methods in the diagnosis of uterine scar incompetence.

CASE REPORTS

112-117 282
Abstract

The Brooke-Spiegler syndrome is a rare autosomal dominant disorder characterized by development of multiple skin tumours including multiple cylindromas and trichoepitheliomas. Here we describe a case of 68-year-old man admitted at a consultative appointment into the surgical department of Siberian State Medical University with numerous asymptomatic, skin-coloured, dense smooth papulonodular lesions from 2 to 5 mm diameter over the face and with multiple pinkish dense smooth dome-shaped nodules from 1 to 5 cm over the scalp. The patient has noted their appearance since childhood. Earlier, similar lesions have been observed in his father and grandmother. Histopathological examination classified facial lesions as trichoepitheliomas and defined scalp lesions as cylindromas, thereby confirming the diagnosis of Brooke-Spiegler syndrome.



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ISSN 2500-0764 (Print)
ISSN 2542-0941 (Online)