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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Maksimova MYu, Ivanov AV, Nikiforova KA, Virus ED, Suanova ET, Ochtova FR, Piradov MA, Kubatiev AA

It was found that ischemic stroke (IS) results in decreased levels of a number of reduced forms of low molecular weight aminothiols (LMWTs). The study was aimed to assess the impact of type 2 diabetes mellitus (Т2D) on the total content, reduced forms and redox status of LMWTs in patients with IS. A total of 175 patients with IS in the internal carotid artery basin (the average age was 62 (55–69)) years) were assessed, who were admitted to the Center within the first 10–24 h since the onset of neurological disorder. The index group included 68 patients with IS and T2D (males made up 41.2%). The comparison group consisted of 107 patients with IS and stress hyperglycemia (males made up 57%), and the control group included 31 non-diabetic patients with chronic cerebrovascular disease (CCVD) (males made up 54.8%). The admission plasma levels of LMWTs were assessed by liquid chromatography in all patients. It was found, that IS in patients with T2D was associated with the rapid decrease in total cysteine (tCys), total glutathione (tGSH), total homocysteine (tHcy), reduced glutathione (rGSH), and glutathione redox status (GSH RS), along with the increase in cysteine redox status (Cys RS) and homocysteine redox status (Hcy RS). In contrast to patients with stress hyperglycemia developing during the acute period of IS, patients with T2D had lower tCys, tGSH, and tHcy levels. Thus, GSH RS of 4.06% or lower in the first 24 hours after the IS in patients with T2D was a predictor of poor functional outcome (mRS score was 3 or more 3 weeks after IS).

Received: 2021-10-25

Published online: 2021-12-09

DOI: 10.24075/brsmu.2021.057

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VIEWS 2646

Vorvul AO, Bobyntsev II, Medvedeva OA, Azarova YuE, Belykh AE, Andreeva LA

Studying the effects of regulatory peptides on the stress-induced shifts in the bodily processes is of great fundamental and applied significance. Currently, a wide range of peptide neurotropic drugs, affecting the stress response development, are used in medicine, and new promising molecules are being studied. The study was aimed to assess the effects of the adrenocorticotropic hormone (ACTH) synthetic analog, ACTH(6-9)-Pro-Gly-Pro, administered at a dose of 5, 50 and 500 μg/kg, on the free-radical oxidation processes in Wistar rats, subjected to chronic restraint stress (CRS) during two weeks. Serum levels of 8-oxo-2'-deoxyguanosine (8-OHdG) and superoxide dismutase 3 (SOD3) were assessed by enzyme immunoassay, and the levels of thiobarbituric acid reactive substances (TBARS) were assessed by fluorimetric method. CRS lead to the significant increase in the 8-OHdG levels by 18.4% (p = 0.01) and the decrease in the SOD3 levels by 14.3% (p = 0.01), however, it had no effect on the levels of TBARS. ACTH(6-9)-Pro-Gly-Pro, administered at a dose of 5 and 50 μg/kg, significantly decreased the levels of 8-OHdG by 19.8% (p = 0.03) and 30% (p = 0.001), respectively. Thus, it was found that CRS resulted in oxidative stress in animals. ACTH(6-9)-Pro-Gly-Pro administration at a dose of 5 and 50 μg/kg inhibits the stress-induced free-radical oxidation processes.

Received: 2021-10-28

Published online: 2021-11-28

DOI: 10.24075/brsmu.2021.056

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VIEWS 3288

Fokin VF, Ponomareva NV, Medvedev RB, Konovalov RN, Krotenkova MV, Lagoda OV, Tanashyan MM

Quantitative assessment of cerebral hemodynamics is important for patients with chronic cerebral ischemia (CCI), as it helps to reveal the pathogenesis of the disease and set the course for effective prevention and treatment. The study was aimed to assess the correlation of the left carotid artery (ICA) resistive index (RI) with cognitive functions and brain network organization based on fMRI data in patients with CCI (51 males and 105 females). The listed above indicators were studied in patients with the left ICA RI values below and above the average (0.54 ± 0.013). The lower, normal physiological ICA resistance levels corresponded to the more successful realization of verbal cognitive functions. In the first group, RI was within normal range (RI = 0.42 ± 0.007), and in the second group RI exceeded normal levels (RI = 0.61 ± 0.01). Variation of the right ICA RI did not correlate with the characteristics of verbal cognitive functions. FMRI data analysis was used to assess the differences in connectivity between various brain regions in the groups with low and high RI. The normal physiological and elevated RI values of the left ICA correlated with differences in the organization of brain networks: normal physiological RI values corresponded to a better organization of hemispheric connections in the basal ganglia and brainstem, and high RI values corresponded to a better organization of connections between the frontal regions and the cerebellum as well as occipital areas of the cerebral cortex. The left ICA RI can be considered as a biomarker of cognitive decline and brain networks reorganization in patients with CCI.

Received: 2021-10-27

Published online: 2021-11-27

DOI: 10.24075/brsmu.2021.055

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VIEWS 2976

Chechetkin AO, Moskalenko AN, Fedotova EYu, Illarioshkin SN

Parkinson’s disease (PD) is a neurodegenerative multisystem disorder characterized by pathologic α-synuclein aggregation affecting, among other things, vagal fibers. The aim of this study was to investigate the cross-sectional area (CSA) of the vagus nerve (VN) in patients with PD using ultrasound imaging. The study was conducted in 32 patients with PD (15 men and 17 women; mean age 58 ± 10 years) and 32 healthy controls comparable with the main group in terms of sex and age. All study participants underwent ultrasound examination of the VN using a high-resolution transducer. Left VN CSA was significantly smaller in patients with PD than in the control group (1.78 ± 0.52 mm2 vs 2.11 ± 0.41 mm2; р = 0.007). A similar result was obtained for right VN CSA at the trend level. ROC analysis demonstrated that the threshold CSA value of < 2.10 mm2 for the left VN has low diagnostic sensivity (59%) for VN atrophy in patients with PD. Right VN CSA was significantly larger than left VN CSA in both groups (p < 0.001). The analysis of the PD group did not reveal any associations between VN CSA and age, duration and stage of the disease, motor (UPDRS III) and non-motor (NMSQ) scores. Patients with akinetic-rigid form of PD had smaller left VN CSA than patients with the mixed form of the disease (р < 0.05). A moderate inverse correlation was established between left VN CSA and the area of substantia nigra hyperechogenicity on both sides (р < 0.04); for the right VN a similar correlation was established at the trend level. High-resolution ultrasound of patients with PD demonstrated atrophy of the VN and the association of VN CSA with the clinical form of the disease and the ultrasound features of the substantia nigra.

Received: 2021-10-25

Published online: 2021-11-24

DOI: 10.24075/brsmu.2021.054

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VIEWS 3606

Tokareva AO, Chagovets VV, Rodionov VV, Kometova VV, Rodionova MV, Starodubtseva NL, Frankevich VE

Early diagnosis of metastasis makes it possible to select the optimal treatment protocol and improve patient survival. Noninvasive and minimally invasive diagnostic techniques help to make a diagnosis with minimal damage to the body. The study was aimed to find biomarkers, being the hallmarks of the metastatic process initiation, and to develop a diagnostic model based on the plasma lipid profile using liquid chromatography-mass spectrometry. We studied blood plasma of 55 patients, 28 of them were diagnosed with the regional lymph node metastasis; the control group comprised 27 patients. The levels of lipids, belonging to the groups, such as oxidized lipids and sphingomyelins, in patients with metastases were significantly higher and significantly lower, respectively. The lipid panels were created by multivariate analysis, and the models based on these panels showed sensitivity and specificity of 79 and 74% (positive ion mode), and of 50 and 85% (negative ion mode) in leave-one-out cross-validation.

Received: 2021-10-26

Published online: 2021-11-10

DOI: 10.24075/brsmu.2021.053

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VIEWS 2825

Usman NYu, Rebrikov DV

Viral mechanisms for the delivery of genetic material are widely used in molecular medicine. Recombinant adeno-associated viruses (rAAV) represent a promising tool for in vivo gene delivery. The review considers nosological spectrum, molecular mechanisms, the choice of drug administration route depending on target structures, the choice of serotype, and the methods of active ingredient manufacturing for rAAV-mediated gene therapy.

Received: 2021-10-19

Published online: 2021-10-31

DOI: 10.24075/brsmu.2021.051

Comments 0

VIEWS 2918

Vishnyakova AYu, Rostovtseva TM, Kovrazhkina EA, Golovin DA, Gubsky IL, Lelyuk SE, Lelyuk VG

Moyamoya disease (MMD) is a rare progressive idiopathic arteriopathy that usually leads to ischemic stroke (IS) in young children, especially of East Asian origin. MMD can cause IS in the Caucasian race, too, but often remains unverified. The diagnosis of MMD relies on diagnostic radiology findings. Magnetic resonance imaging (MRI) is widely used in Japan to identify asymptomatic individuals with hereditary predisposition to MMD. There are no official statistics on MMD in Russia. A patient experiencing an acute cerebrovascular accident (CVA) is hospitalized to a stroke unit, where they undergo a multislice computed tomography (MSCT) scan of the brain. Below, we report the results of a complex radiological examination, which included MRI (T2, FLAIR, SWI, 3D-TOF), cerebral MSCT perfusion imaging, CT angiography of intracranial arteries, duplex ultrasonography of brachiocephalic arteries and was conducted in 4 adult Caucasian patients (3 men and 1 woman aged 38, 39, 51, and 57 years, respectively) with a past IS caused by MMD. We hope that the findings of different imaging techniques may be helpful in establishing the timely diagnosis of MMD and optimizing the treatment strategies.

Received: 2021-09-29

Published online: 2021-10-31

DOI: 10.24075/brsmu.2021.052

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VIEWS 2967

Voronkov DN, Stavrovskaya AV, Gushchina AS, Olshansky AS

It is assumed that dysfunction of tanycytes could be one of the components of pathogenesis of both Alzheimer disease and type 2 diabetes mellitus. The study was aimed to assess alterations in the tanycyte morphology in the Alzheimer disease model. The 3 mg/kg streptozotocin dose was injected in the lateral ventricles of Wistar rats in order to model the Alzheimer disease. Alterations in hypothalamic tanycytes were assessed 2 weeks, 4 weeks, 3 months and 6 months after administration of the toxin. Immunohistochemistry was used to identify the protein markers of tanycytes (vimentin, nestin), astrocytes (GFAP, glutamine synthetase) and neurons (HuC/D), as well as to assess cell proliferation (with the use of Ki67 protein) and mitochondrial alterations (mitochondrial complex IV, PGC1a). Administration of streptozotocin lead to β-amyloid accumulation in hypothalamus and ventricular enlargement (p < 0.001). Streptozotocin damaged both α1/α2 tanycytes and β1 tanycytes. The intensity of vimentin staining in α1/α2 tanycytes decreased by week 4 (p = 0.003), and in β1 tanycytes it decreased in three months (p < 0.001). The same trend was observed for nestin. The number of Ki67+ nuclei decreased (p < 0.05), and the expression of proteins associated with mitochondria changed. The density of hypothalamic tanycytes decreased by week 4 after administration of the toxin. Moreover, astrocyte activation was revealed. However, no prominent damage to both astrocytes and neurons was observed within four weeks after administration of streptozotocin. The revealed high tanycyte vulnerability to streptozotocin is in line with the hypothesis of the role of damage to hypothalamic structures in both local and systemic metabolic disorders occurring in the Alzheimer disease models.

Received: 2021-10-07

Published online: 2021-10-29

DOI: 10.24075/brsmu.2021.050

Comments 0

VIEWS 2957