Bulletin of RSMU

ISSN Print 2500–1094 ISSN Online 2542–1204

Bulletin of RSMU

BIOMEDICAL JOURNAL OF PIROGOV UNIVERSITY (MOSCOW, RUSSIA)

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Gavisova AA, Stenyaeva NN, Gardanova ZR, Nazarenko TA, Dolgushina NV

Androgens play a key role in the physiology of the female body and the reproductive system. Androgen receptor expression in the various tissues points to the importance of androgens in the regulation of the female sexual and social functioning. The study aimed to evaluate sexual functioning in women with infertility and diminished ovarian reserve (DOR) using the Female Sexual Functioning Index questionnaire (FSFI). A cross-sectional study of 496 patients with infertility and DOR assessed the degree of sexual dysfunction in conjunction with the changes in the androgenic profiles as indicated by the androstenedione levels in the blood serum. Women with infertility and DOR were significantly more likely to report changes in sexual functioning, including a decrease in libido and in the quality and frequency of sexual relations. Furthermore, patients with normal androstenedione levels generally significantly outscored patients with decreased androstenedione levels (average questionnaire scores 21.2 ± 7.2 and 15.17 ± 3.0 respectively), indicating a lesser degree of sexual dysfunction in the former group; on the other hand, the latter group reported increased pain and decreased attraction, arousal, lubrication, orgasm, and satisfaction. Hormonal profile changes in patients with DOR, including decreased androstenedione levels, significantly impact sexual functioning, and their detection in clinical practice will allow to objectify complaints at an earlier state in order to assess the severity of sexual dysfunction and determine further personalized management tactics.

Received: 2022-08-26

Published online: 2022-09-23

DOI: 10.24075/brsmu.2022.045

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VIEWS 18

Birulina JG, Voronkova OV, Ivanov VV, Buyko EE, Shcherbakova MM, Chernyshov NA, Motlokhova EA

Chronic systemic inflammation is essential in many chronic non-infectious diseases, including type 2 diabetes, obesity and metabolic syndrome (MS). This study aimed at characterization of systemic inflammatory reaction as a component of diet-induced MS in rat model. Thirty-three male Wistar rats were distributed into two groups designated 'control' (n = 15) and 'experimental (MS)' (n = 18). The groups were fed, respectively, regular and high-fat/high-carbohydrate diets for 12 weeks. The intensity of systemic inflammatory process against the background of metabolic impairments was assessed by total and differential counts of white blood cells and serum levels of total protein, C-reactive protein, cytokines (IL6, IL10 and TNFα), insulin and leptin. We also assessed the production of reactive oxygen species in adipose tissue samples. The experiment revealed signs of systemic inflammation in MS as compared to control, including reactive leukocytosis, hyperproteinemia and increased serum levels of C-reactive protein (2.6-fold; р = 0.001), IL10 (3.7-fold; р = 0.029) and TNFα (4.2-fold; р = 0.035). The observed changes were accompanied by elevated metabolic activity of visceral adipose tissue, indicated by hyperleptinemia and increased free radical oxidation intensity. Pairwise positive correlations of serum levels were revealed for leptin and insulin (r = 0.701; р = 0.001) and leptin and IL10 (r = 0.523; р = 0.012). Thus, high-fat/ high-carbohydrate diet promoted metabolic impairments concomitantly with early signs of systemic inflammation characteristic of MS and obesity.

Received: 2022-08-11

Published online: 2022-08-30

DOI: 10.24075/brsmu.2022.043

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VIEWS 91

Poydasheva AG, Bakulin IS, Sinitsyn DO, Zabirova AH, Suponeva NA, Maslenikov NV, Tsukarzi EE, Mosolov SN, Piradov MA

Stanford neuromodulation therapy (SNT) is the state-of-the-art magnetic stimulation protocol that has been developed for management of treatment-resistant depression (TRD). The study was aimed to assess the possibility of SNT implementation in clinical practice and to define the protocol safety and efficacy in patients with TRD being an episode of the recurrent depressive disorder or bipolar disorder at the independent center. The study involved six patients (among them three women aged 21–66) with TRD associated with recurrent depression and type 1 or 2 bipolar disorder. The patients received intermittent theta-burst stimulation in accordance with the SNT protocol for five days: applying 10 triple blocks of stimulation daily at intervals of 1 hr between the blocks to the selected stimulation site showing maximum negative functional connectivity with subgenual cingulate cortex within the left dorsolateral prefrontal cortex. The Montgomery–Asberg Depression Rating Scale (MADRS) was used for clinical assessment of the effects, the follow-up period was three months. The improvement of depressive symptoms to the levels characteristic of remission immediately after the SNT completion was observed in five patients (MADRS score ≤10). After three months, two patients still had remission, the condition of three patients met the criteria of mild depressive episode, and one female patient withdrew from the study due to logistical difficulties. No serious adverse events were reported. The findings confirm safety and potentially high efficacy of SNT, including in patients with type 1 and 2 bipolar disorders.

Received: 2022-08-08

Published online: 2022-08-30

DOI: 10.24075/brsmu.2022.044

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VIEWS 88

Vagner VD, Sarf EA, Belskaya LV, Korshunov AS, Kuryatnikov KN, Bondar AA, Meloyan AD, Maksimenko KA, Kasiy MN

Oral fluid is a valuable substrate for assessing dental health and other aspects of physical status. New methods for early diagnosis and prognosis of dental diseases on the basis of oral fluid composition are in constant demand. Excessive fluoride concentrations, often oversighted by dental therapists, negatively affect organs and tissues of the oral cavity. This study aimed at development and approbation of a method for reliable measurement of fluoride ions in oral fluid by capillary electrophoresis to be used in patients with dental diseases. The fluoride ion concentrations were measured in health (2.16 ± 0.48 mg/L), in isolated acute pericoronitis (15.2 ± 2.7 mg/L) and in acute pericoronitis combined to multiple caries (18.9 ± 4.2 mg/L). By post-operative day 3, fluoride levels in the group with isolated acute pericoronitis dropped to normal values (2.28 ± 0.52 mg/L), whereas in the group with acute pericoronitis combined to multiple caries fluoride levels remained high (8.7 ± 1.9 mg/L; р < 0.0001). The developed protocol is efficient for studying fluoride ion concentrations in isolated and combined dental diseases.

Received: 2022-08-12

Published online: 2022-08-29

DOI: 10.24075/brsmu.2022.042

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VIEWS 90

Gavisova AA, Shevtsova MA, Kindysheva SV, Starodubtseva NL, Frankevich VE, Nazarenko TA, Dolgushina NV

Androgen concentrations in follicular fluid samples collected from patients undergoing in vitro fertilization (IVF) may provide useful clinical indicators. This study aimed to analyze possible associations of the androgen levels in follicular fluid and blood plasma in patients with diminished ovarian reserve (POR) in IVF programs. Cross-sectional study with a parallel group design, conducted in 2019–2021, enrolled 300 patients with infertility, aged 18–42 years, applying for assisted reproduction involving IVF/intracytoplasmic sperm injection and embryo transfer. The androgen profiles of blood plasma and follicular fluid were determined by liquid chromatography with tandem mass spectrometry (LC-MS/MS). Androgen concentrations in blood plasma and follicular fluid, particularly those of dehydroepiandrosterone (DHEA-S), androstenedione and total testosterone, significantly correlated. The results implicate androgen levels in blood plasma and follicular fluid as early markers of POR in patients with infertility.

Received: 2022-07-29

Published online: 2022-08-19

DOI: 10.24075/brsmu.2022.041

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VIEWS 137

Soldatov VO, Pokrovskiy MV, Puchenkova OA, Zhunusov NS, Krayushkina AM, Grechina AV, Soldatova MO, Lapin KN, Bushueva OYu

Mitochondrial dysfunction is a key driver of neurodegeneration. This study aimed to evaluate the protective potential of EPOR/CD131 (heterodimeric erythropoietin receptor) stimulation in the neurodegeneration caused by rotenone-induced mitochondrial dysfunction. The effects of erythropoietin (EPO) and an EPO mimetic peptide pHBSP were assessed using in vivo and in vitro models. Single injections of 10 µg/kg EPO or 5 µg/kg pHBSP significantly alleviated the degeneration of ganglion cells of the retina in a rotenone-induced retinopathy in rats (p < 0.05). Consistently, in vitro exposure of rotenone-treated murine primary neuroglial cultures to 500 nM EPO or pHBSP significantly rescued the survival of the cells (p < 0.005). The observed enhancement of LC3A, ATG7, Beclin-1, Parkin and BNIP3 mRNA expression by EPOR/CD131 agonists implicates the autophagy and mitophagy activation as a plausible mitoprotective mechanism.

Received: 2022-07-11

Published online: 2022-08-12

DOI: 10.24075/brsmu.2022.040

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VIEWS 130

Radygina TV, Petrichuk SV, Kuptsova DG, Potapov AS, Illarionov AS, Anushenko AO, Kurbatova OV, Semikina EL

The regulation of TNF inhibitor therapy-associated immune responses in inflammatory bowel diseases (IBD) in children remains an urgent problem. The study aimed at analyzing the expression of CD39/CD73 endonucleotidases by different subsets of peripheral blood T cells in children with IBD including Crohn's disease (n = 34) and ulcerative colitis (n = 33) having received TNF inhibitors in comparison with conditionally healthy children (n = 45). Lymphocyte subsets including regulatory T cells (Treg, CD4+CD127lowCD25high), activated T cells (Tact, CD4+CD25+CD127high) and Th17 cells (CD4+CD161+CD3+) were studied by flow cytometry. The results are presented as medians (Me) and quartiles (Q25–Q75). In children with IBD the highest and the lowest relative counts of CD39+ cells were found in Treg and Tact subsets — 31% (15–38) and 4% (1–7), respectively. The highest relative counts of CD73+ cells were found in Tact — 13% (8–21). The CD39 and CD73 expression ratio in patients with IBD, and in the control group as well, depended on particular subset. CD39 expression in Treg, Tact and Th17 of patients with IBD was not age-dependent. Patients with acute Crohn's disease revealed decreased expression of CD39 in Treg compared with the control group (12% (9–23) vs 35% (28–39), respectively; р = 10–6). Patients with Crohn's disease in remission revealed increased expression of CD39 in Treg compared with the acute of the disease (31% (27–40) vs 12% (9–23); р = 9.4 × 10–5). Patients with Crohn's disease in remission revealed no significant differences with the control group apart from reduced expression of CD73 by Treg in Crohn's disease. The results indicate significant association of CD39 and CD73 expression levels in particular subsets of CD4+ cells with the phase of the disease (acute vs remission) and, accordingly, with the anti-TNF regimen efficacy.

Received: 2022-06-22

Published online: 2022-07-31

DOI: 10.24075/brsmu.2022.039

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VIEWS 158

Starodubtseva NL, Eldarov ChM, Kirtbaya AR, Balashova EN, Gryzunova AS, Ionov OV, Zubkov VV, Silachev DN

The prognosis in neonatal hypoxic ischemic encephalopathy (HIE) depends on early differential diagnosis for justified administration of emergency therapeutic hypothermia. The moment of therapy initiation directly affects the long-term neurological outcome: the earlier the commencement, the better the prognosis. This review analyzes recent advances in systems biology that facilitate early differential diagnosis of HIE as a pivotal complement to clinical indicators. We discuss the possibilities of clinical translation for proteomic, metabolomic and extracellular vesicle patterns characteristic of HIE and correlations with severity and prognosis. Identification and use of selective biomarkers of brain damage in neonates during the first hours of life is hindered by systemic effects of hypoxia. Chromatography– mass spectrometry blood tests allow analyzing hundreds and thousands of metabolites in a small biological sample to identify characteristic signatures of brain damage. Clinical use of advanced analytical techniques will facilitate the accurate and timely diagnosis of HIE for enhanced management.

Received: 2022-07-06

Published online: 2022-07-29

DOI: 10.24075/brsmu.2022.038

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VIEWS 155