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1.
Bull Exp Biol Med ; 177(1): 169-175, 2024 May.
Article in English | MEDLINE | ID: mdl-38960964

ABSTRACT

In order to obtain models of gliomas of varying degrees of malignancy, we performed morphological and molecular genetic study of a tissue strain of glioma 10-17-2 (Astrid-17) obtained by intracranial passaging of tumor fragments of chemically induced rat brain tumor, and a cell strain isolated from it. More or less pronounced changes in the expression levels of Mki67, Trp53, Vegfa, and Gfap genes in the tissue and cell strain of glioma 10-17-2 (Astrid-17) compared with intact brain tissue were shown. The tissue model of glioma 10-17-2 (Astrid-17) according to the studied characteristics shows features of grade 3-4 astrocytoma and the cellular model - grade 2-3 astrocytoma.


Subject(s)
Brain Neoplasms , Glial Fibrillary Acidic Protein , Glioma , Vascular Endothelial Growth Factor A , Animals , Rats , Brain Neoplasms/genetics , Brain Neoplasms/pathology , Brain Neoplasms/metabolism , Glioma/genetics , Glioma/pathology , Glioma/metabolism , Glial Fibrillary Acidic Protein/genetics , Glial Fibrillary Acidic Protein/metabolism , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor A/metabolism , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolism , Ki-67 Antigen/metabolism , Ki-67 Antigen/genetics , Male , Astrocytoma/genetics , Astrocytoma/pathology , Astrocytoma/metabolism , Gene Expression Regulation, Neoplastic , Cell Line, Tumor , Brain/pathology , Brain/metabolism
2.
Bull Exp Biol Med ; 177(1): 147-154, 2024 May.
Article in English | MEDLINE | ID: mdl-38963598

ABSTRACT

Hyaluronidase increases tissue permeability and diffusion of the extracellular fluid by cleaving hyaluronan, the primary component of the extracellular matrix. Hyaluronidase pegylation (Hyal-PEG) decreases its clearance and enhances biodistribution. The pro- and anticancer activity of Hyal-PEG and a combination of Hyal-PEG with doxorubicin were studied in vitro (morphological analysis of rat glioblastoma 101.8 spheroids) and in vivo (by the survival time of rats after intracerebral transplantation of the tumor and morphological analysis). In the presence of doxorubicin and Hyal-PEG in the culture medium in vitro, spheroids lost their ability to adhere to the substrate and disintegrate into individual cells. Intracerebral transplantation of the tumor tissue with Hyal-PEG did not accelerate glioblastoma growth. The mean survival time for animals receiving transplantation of the tumor alone and in combination with Hyal-PEG was 13 and 20 days, respectively. In one rat with transplanted tumor and Hyal-PEG, this parameter increased by 53%. The survival time of rats receiving systemic therapy with doxorubicin and Hyal-PEG significantly increased (p=0.003). Antitumor effect of therapeutic doses of doxorubicin combined with Hyal-PEG was demonstrated on the model of rat glioblastoma 101.8 in vitro. Hyal-PEG inhibited adhesion of tumor cells, but did not cause their death. Transplantation of Hyal-PEG-treated tumor did not reduce animal survival time. Systemic administration of therapeutic doses of doxorubicin with Hyal-PEG increased survival time of rats with glioblastoma 101.8.


Subject(s)
Brain Neoplasms , Doxorubicin , Glioblastoma , Hyaluronoglucosaminidase , Polyethylene Glycols , Animals , Doxorubicin/pharmacology , Hyaluronoglucosaminidase/metabolism , Rats , Brain Neoplasms/drug therapy , Brain Neoplasms/pathology , Polyethylene Glycols/chemistry , Polyethylene Glycols/pharmacology , Glioblastoma/drug therapy , Glioblastoma/pathology , Male , Cell Line, Tumor , Spheroids, Cellular/drug effects
3.
Sci Rep ; 14(1): 10722, 2024 05 10.
Article in English | MEDLINE | ID: mdl-38729956

ABSTRACT

Application of optical coherence tomography (OCT) in neurosurgery mostly includes the discrimination between intact and malignant tissues aimed at the detection of brain tumor margins. For particular tissue types, the existing approaches demonstrate low performance, which stimulates the further research for their improvement. The analysis of speckle patterns of brain OCT images is proposed to be taken into account for the discrimination between human brain glioma tissue and intact cortex and white matter. The speckle properties provide additional information of tissue structure, which could help to increase the efficiency of tissue differentiation. The wavelet analysis of OCT speckle patterns was applied to extract the power of local brightness fluctuations in speckle and its standard deviation. The speckle properties are analysed together with attenuation ones using a set of ex vivo brain tissue samples, including glioma of different grades. Various combinations of these features are considered to perform linear discriminant analysis for tissue differentiation. The results reveal that it is reasonable to include the local brightness fluctuations at first two wavelet decomposition levels in the analysis of OCT brain images aimed at neurosurgical diagnosis.


Subject(s)
Brain Neoplasms , Glioma , Tomography, Optical Coherence , Humans , Tomography, Optical Coherence/methods , Glioma/diagnostic imaging , Glioma/pathology , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/pathology , Wavelet Analysis
4.
Bull Exp Biol Med ; 176(5): 697-702, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38724814

ABSTRACT

One of the key problems of glioblastoma treatment is the low effectiveness of chemotherapeutic drugs. Incorporation of doxorubicin into PLGA nanoparticles allows increasing the antitumor effect of the cytostatics against experimental rat glioblastoma 101.8. Animal survival, tumor volume, and oncogene expression in tumor cells were compared after early (days 2, 5, and 8 after tumor implantation) and late (days 8, 11, and 14) start of the therapy. At late start, a significant increase in the expression of oncogenes Gdnf, Pdgfra, and Melk and genes determining the development of multidrug resistance Abcb1b and Mgmt was revealed. At early start of therapy, only the expression of oncogenes Gdnf, Pdgfra, and Melk was enhanced. Early start of treatment prolonged the survival time and increased tumor growth inhibition by 141.4 and 95.7%, respectively, in comparison with the untreated group; these differences were not observed in the group with late start of therapy. The results indicate that the time of initiation of therapy is a critical parameter affecting the antitumor efficacy of DOX-PLGA.


Subject(s)
Doxorubicin , Glioblastoma , Nanoparticles , Animals , Glioblastoma/drug therapy , Glioblastoma/pathology , Doxorubicin/pharmacology , Doxorubicin/therapeutic use , Rats , Nanoparticles/chemistry , Polylactic Acid-Polyglycolic Acid Copolymer/chemistry , Antibiotics, Antineoplastic/pharmacology , Antibiotics, Antineoplastic/therapeutic use , Male , Cell Line, Tumor , Brain Neoplasms/drug therapy , Brain Neoplasms/pathology , Polyglycolic Acid/chemistry , Gene Expression Regulation, Neoplastic/drug effects
5.
Article in Russian | MEDLINE | ID: mdl-38334730

ABSTRACT

Targeted delivery of chemotherapeutic agents with aptamers is a very effective method increasing therapeutic index compared to non-targeted drugs. OBJECTIVE: To study the effectiveness of in vitro therapeutic effect of covalently conjugated GR20 DNA aptamer with doxorubicin on glioblastoma cells compared to reference culture of human fibroblasts. MATERIAL AND METHODS: A Sus/fP2 cell culture was obtained from glioblastoma tissue sample to analyze the effectiveness of conjugate. A linear culture of human dermal fibroblasts (mesenchymal stem cells) DF1 was used as a control. To assess antiproliferative activity of covalently conjugated GR20 aptamer with doxorubicin, we used the MTS test. The Cell Index was measured using the xCelligence S16 cell analyzer assessing viability of cell cultures by recording changes in real time. RESULTS: Human glioblastoma Sus/fP2 cells reduce own proliferative potential by 80% when exposed to doxorubicin (0.5 µM, 72 hours, MTS test), by 9% when exposed to GR20 aptamer (10 µM, 72 hours, MTS test) and by 26% when exposed to covalently conjugated DOX-GR20 (0.5 µM, 72 hours, MTS test). A long-term study of proliferative potential of Sus/fP2 cells on the xCelligence S16 analyzer revealed a significant decrease in the number of cells under the effect of doxorubicin and covalently conjugated DOX-GR20. Effectiveness of covalently conjugated DOX-GR20 is halved. GR20 aptamer at a concentration of 10 µM and its conjugate with doxorubicin DOX-GR20 at a concentration of 1 µM have no negative effect on cells of the control culture of DF1 fibroblasts, while doxorubicin is toxic for these cells. MTS test and xCelligence S16 cell analyzer found no decrease in metabolic activity of DF1 cells and their ability to proliferate. CONCLUSION: We established obvious antiproliferative effect of covalent conjugate DOX-GR20 on continuous human glioblastoma cell culture Sus/fP2 without toxic effect on the reference culture (dermal fibroblasts DF1).


Subject(s)
Aptamers, Nucleotide , Glioblastoma , Humans , Aptamers, Nucleotide/metabolism , Aptamers, Nucleotide/pharmacology , Glioblastoma/drug therapy , Cell Line, Tumor , Doxorubicin/pharmacology , Doxorubicin/metabolism , Doxorubicin/therapeutic use , Drug Delivery Systems/methods
6.
Zh Nevrol Psikhiatr Im S S Korsakova ; 123(11. Vyp. 2): 62-67, 2023.
Article in Russian | MEDLINE | ID: mdl-38127702

ABSTRACT

OBJECTIVE: To determine the clinical and psychopathological features of existential depression in youth. MATERIAL AND METHODS: 53 male patients (16-25 years old) with diagnosis F31.3, F31.4, F32, F33 with existential themes of depressive experiences were studied by clinical and psychopathological method. RESULTS: The axial symptom of existential was over-value ideas about the meaninglessness of their own and human life with ideas of self-abasement, insolvency, low value, imperfection of society, which in most of the studied cases (79.2%) was accompanied by various degrees of severity suicidal thoughts and intentions. Three varieties were identified: with the prevalence of reflections on the meaninglessness of life (39.6%); with the prevalence of neurotic religiosity (28.3%); with an existential philosophical interpretation (32.1%). CONCLUSION: As a result of the study, the heterogeneity of existential depressions, a significant role of psychogenic factors in their formation were revealed, as a high suicidal risk. Existential depressive states differed in duration, severity of depressive symptoms, high frequency of non-suicidal self-neglect and suicidal risk.


Subject(s)
Depression , Suicidal Ideation , Humans , Male , Adolescent , Young Adult , Adult , Depression/epidemiology , Depression/psychology , Psychopathology
7.
Zh Nevrol Psikhiatr Im S S Korsakova ; 123(11. Vyp. 2): 101-107, 2023.
Article in Russian | MEDLINE | ID: mdl-38127709

ABSTRACT

OBJECTIVE: Identification of psychopathological characteristics of depressive-delusional states with religious content, development of a typology, determination of formation features, nosological assessment. MATERIAL AND METHODS: A total of 79 patients (47 female, 32 male, mean age 27±6.5 years) with depressive-delusional states with religious content within the affective and schizophrenia spectrum disorders were studied. Clinical-psychopathological, psychometric (PANSS, HDRS, S. Huber CRS) and statistical methods were used. RESULTS: Based on the psychopathological structure, specific mechanisms of development of delusions and themes of the religious experiences, three types of depressive-delusional states were identified: type 1 - with a predominance of depressive delusions congruent with affect and delusional ideas of guilt, sinfulness, abandonment of God (14 patients, 17.7%; 6 women, 8 men; mean age 28±4.5 years; HDRS score 33±5.6, the total PANSS score 71±5.3, the PANSS positive subscale score 15.8±3.7); type 2 - with the addition of incongruent delusional constructs, persecutory disorders and acute sensory delusions to the existing depressive religious delusion, with the phenomenon of confessional ambivalence (27 patients, 34.2%; 16 women, 11 men; mean age at attack manifestation 25±9 years; HDRS score 29.6±4.4, the total PANSS score 87±6.2, the PANSS positive subscale score 23.5±4.2); type 3 - depressive-paranoid states with a predominance of Kandinsky-Clerambault syndrome of religious content (38 cases, 48.1%; 20 women, 18 men; mean age at attack manifestation 23.4±2.5 years; HDRS score 32.7±3.7, the total PANSS score 102±7.3, the PANSS positive subscale score 32.5±4.5). CONCLUSION: The study of depressive-delusional states with religious content has shown their clinical-psychopathological heterogeneity. The religious experiences served as a pathoplastic factor, which essentially modified the clinical-psychopathological picture of the disease due to presence of the specific religious phenomena. The identified types of depressive-delusional disorders with religious content had different diagnostic value.


Subject(s)
Delusions , Schizophrenia , Humans , Male , Female , Young Adult , Adult , Adolescent , Delusions/diagnosis , Schizophrenia/diagnosis , Psychopathology , Religion , Neurocognitive Disorders
8.
Sci Rep ; 13(1): 16596, 2023 10 03.
Article in English | MEDLINE | ID: mdl-37789192

ABSTRACT

Terahertz (THz) technology offers a variety of applications in label-free medical diagnosis and therapy, majority of which rely on the effective medium theory that assumes biological tissues to be optically isotropic and homogeneous at the scale posed by the THz wavelengths. Meanwhile, most recent research discovered mesoscale ([Formula: see text]) heterogeneities of tissues; [Formula: see text] is a wavelength. This posed a problem of studying the related scattering and polarization effects of THz-wave-tissue interactions, while there is still a lack of appropriate tools and instruments for such studies. To address this challenge, in this paper, quantitative polarization-sensitive reflection-mode THz solid immersion (SI) microscope is developed, that comprises a silicon hemisphere-based SI lens, metal-wire-grid polarizer and analyzer, a continuous-wave 0.6 THz ([Formula: see text] µm) backward-wave oscillator (BWO), and a Golay detector. It makes possible the study of local polarization-dependent THz response of mesoscale tissue elements with the resolution as high as [Formula: see text]. It is applied to retrieve the refractive index distributions over the freshly-excised rat brain for the two orthogonal linear polarizations of the THz beam, aimed at uncovering the THz birefringence (structural optical anisotropy) of tissues. The most pronounced birefringence is observed for the Corpus callosum, formed by well-oriented and densely-packed axons bridging the cerebral hemispheres. The observed results are verified by the THz pulsed spectroscopy of the porcine brain, which confirms higher refractive index of the Corpus callosum when the THz beam is polarized along axons. Our findings highlight a potential of the quantitative polarization THz microscopy in biophotonics and medical imaging.


Subject(s)
Immersion , Refractometry , Animals , Swine , Birefringence , Microscopy, Polarization , Brain/diagnostic imaging
9.
Bull Exp Biol Med ; 175(4): 576-584, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37770789

ABSTRACT

The use of relevant, accessible, and easily reproducible preclinical models of diffuse gliomas is a prerequisite for the development of successful therapeutic approaches to their treatment. Here we studied the gene expression profile of 3D spheroids in a comparison with 2D cell cultures and tissue strains of diffuse high-grade gliomas. Using real time PCR, we evaluated the expression of Gfap, Cd44, Pten, S100b, Vegfa, Hif1a, Sox2, Melk, Gdnf, and Mgmt genes playing an important role in the progression of gliomas and regulating tumor cell proliferation, adhesion, invasion, plasticity, apoptosis, DNA repair, and recruitment of tumor-associated cells. Gene expression analysis showed that 3D spheroids are more similar to tumor tissue strains by the expression levels of Gfap, Cd44, and Pten, while the expression levels of Hif1a and Sox2 in 3D spheroids did not differ from those of 2D cell cultures, the expression levels S100b and Vegfa in 3D spheroids was higher than in other models, and the expression levels of Melk, Gdnf, and Mgmt genes changed diversely. Thus, 3D spheroid model more closely mimics the tumor tissue than 2D cell culture, but still is not the most relevant, probably due to too small size of spheroids, which does not allow reproducing hypoxia and apoptotic and necrotic processes in the tumor tissue.

10.
Sci Rep ; 13(1): 12694, 2023 08 04.
Article in English | MEDLINE | ID: mdl-37542119

ABSTRACT

Hypoxia is a major pathogenetic factor in many cancers. Individual resistance to suboptimal oxygen availability is subject to broad variation and its possible role in tumorigenesis remains underexplored. This study aimed at specific characterization of glioblastoma progression in male tolerant and susceptible to hypoxia Wistar rats. Hypoxia resistance was assessed by gasping time measurement in an 11,500 m altitude-equivalent hypobaric decompression chamber. Based on the outcome, the animals were assigned to three groups termed 'tolerant to hypoxia' (n = 13), 'normal', and 'susceptible to hypoxia' (n = 24). The 'normal' group was excluded from subsequent experiments. One month later, the animals underwent inoculation with rat glioblastoma 101.8 followed by monitoring of survival, body weight dynamics and neurological symptoms. The animals were sacrificed on post-inoculation days 11 (subgroup 1) and 15 (subgroup 2). Relative vessels number, necrosis areas and Ki-67 index were assessed microscopically; tumor volumes were determined by 3D reconstruction from histological images; serum levels of HIF-1α, IL-1ß, and TNFα were determined by ELISA. None of the tolerant to hypoxia animals died of the disease during observation period, cf. 85% survival on day 11 and 55% survival on day 15 in the susceptible group. On day 11, proliferative activity of the tumors in the tolerant animals was higher compared with the susceptible group. On day 15, proliferative activity, necrosis area and volume of the tumors in the tolerant to hypoxia animals were higher compared with the susceptible group. ELISA revealed no dynamics in TNFα levels, elevated levels of IL-1ß in the susceptible animals on day 15 in comparison with day 11 and tolerant ones. Moreover, there were elevated levels of HIF-1α in the tolerant animals on day 15 in comparison with day 11. Thus, the proliferative activity of glioblastoma cells and the content of HIF-1α were higher in tolerant to hypoxia rats, but the mortality associated with the tumor process and IL-1ß level in them were lower than in susceptible animals. Specific features of glioblastoma 101.8 progression in tolerant and susceptible to hypoxia rats, including survival, tumor growth rates and IL-1ß level, can become the basis of new personalized approaches for cancer diseases treatment in accordance to individual hypoxia resistance.


Subject(s)
Glioblastoma , Tumor Necrosis Factor-alpha , Rats , Male , Animals , Rats, Wistar , Glioblastoma/complications , Hypoxia/pathology , Disease Susceptibility , Necrosis/complications , Hypoxia-Inducible Factor 1, alpha Subunit
11.
Bull Exp Biol Med ; 174(4): 518-522, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36899203

ABSTRACT

We compared the expression of the main glioblastoma oncogenes during therapy with doxorubicin (Dox) and Dox in nanoparticles based on a copolymer of lactic and glycolic acids (Dox-PLGA) at a delayed start of treatment. Late initiation of Dox-PLGA therapy of glioblastoma showed an increase in the expression of multiple drug resistance genes, such as Abcb1b and Mgmt, and a decrease in Sox2 expression. Increased expression of other oncogenes (Melk, Wnt3, Gdnf, and Pdgfra) were observed during both Dox and Dox-PLGA therapy. These changes indicate increased tumor aggressiveness and its resistance to cytostatics at the late start of therapy.


Subject(s)
Doxorubicin , Glioblastoma , Nanoparticles , Animals , Rats , Cell Line, Tumor , Doxorubicin/therapeutic use , Drug Carriers , Glioblastoma/drug therapy , Glioblastoma/genetics , Nanoparticles/therapeutic use , Oncogenes , Polylactic Acid-Polyglycolic Acid Copolymer , Disease Models, Animal , Pharmacogenomic Testing
12.
Klin Lab Diagn ; 67(11): 647-651, 2022 Nov 14.
Article in English | MEDLINE | ID: mdl-36398773

ABSTRACT

Due to the steady increase in the number of children with autism and the high heterogeneity of clinical groups, the diagnosis of these disorders and their severity is an urgent problem in modern medicine. In the course of the work, 126 children from 3 to 13 years old with typical neurodevelopment and with severe and mild autism spectrum disorders (ASD) were examined. Disease severity was determined according to the Childhood Autism Rating Scale (CARS). The levels of pro-/anti-inflammatory cytokines and neurotrophic factors (nerve growth factor beta and brain-derived neurotrophic factor) in blood plasma were assessed by enzyme immunoassay. Associations between indicators in each group of patients were assessed using the Spearman test and visualized as a heatmap of correlations. Statistical data processing was carried out in the R software. Significantly high levels of IL-4 in blood plasma and a decrease in the number of significant correlations within/between systems were revealed in children with mild autism compared with children with typical neurodevelopment. Such data can probably reflect the theory that some children with ASD are characterized by slow brain development, as a variant of the evolutionary norm. On the contrary, in children with severe ASD, high systemic levels of IL-6 and IFNg are shown against the background of low values of IL-10, IL-1ß, TNFα and NGFß, supported by the almost complete absence of intra/ and intersystem interactions. This may act as an indicator of maladaptation of the immune and nervous systems in severe autism, which contributes to the pathogenesis of the disease. Thus, a set of indicators: high levels of key pro-inflammatory cytokines - IL-6 and IFNg, low levels of IL-10, NGFß and disintegration of the cytokine and nervous systems in the periphery can be proposed as an approach to indicate the severity of the condition in children with ASD.


Subject(s)
Autism Spectrum Disorder , Autistic Disorder , Child , Humans , Child, Preschool , Adolescent , Autistic Disorder/diagnosis , Cytokines , Interleukin-10 , Interleukin-6 , Autism Spectrum Disorder/diagnosis , Interferon-gamma
13.
Klin Lab Diagn ; 67(3): 186-192, 2022 Mar 25.
Article in English | MEDLINE | ID: mdl-35320636

ABSTRACT

The characteristics of resistome and virulome structure of four carbapenem-resistant Klebsiella pneumoniae clinical strains are present in the work. Two strains belonged to the sequence-type ST395, one strain - ST2262, one strain - to the new sequence-type 5816. The genes of fimbriae, enterobactin, beta-lactamase SHV type, resistance to fosfomycin fosA and transport of fluoroquinolones oqxAB in all Klebsiella strains chromosome structure were identified. The determinants of yersineobactin and aerobactin are enriched the virulome of ST395 NNKP315 and NNKP343 strains. The aerobactin genes are located on IncHI1B plasmids (IncHI1B/FIB) which highly homologous to the virulence pLVPK and pK2044 plasmids. IncR, IncL, IncQ plasmids carrying blaOXA-48, blaCTX-M-15, blaOXA-1, blaTEM-1, qnrS1, tetA, sul1, dfrA1, aac(6 ')-Ib-cr, catA1, catB3 etc. were identified in these strains. As a result of in silico analysis, an assumption about the localization of the blaOXA-48 in the structure of the IncHI1B plasmid of NNKP315 strain was made. This plasmid also contains the aminoglycosidases genes inserted into a class 1 integron In822. The mutations were found in the porin proteins OmpK35, OmpK36 and OmpK37 genes, which increases the carbapenem resistance. The virulome of NNKP16 (ST2262) strain additionally includes of the iron utilization system kfuABC chromosomal genes, and the virulome of NNKP15 (ST5816) strain contains of the capsular polysaccharide kvgAS and microcin E492 genes. Additional determinants of resistance were not identified in the resistome structure of K. pneumoniae NNKP16 and only the blaCTX-M-15 gene was found in the NNKP15 strain. The absence of acquired resistance genes seems to be due to the presence of the type I-E CRISPR-Cas system. Multiple drug resistance of the studied strains is associated with mutations identified in the gene structure of porin proteins OmpK36 and OmpK37, as well as the activity of efflux systems. It was showed the stop codon formation in the nucleotide sequence of the regulatory gene ramR to both strains, which can potentially provide overexpression of AcrAB efflux proteins.


Subject(s)
Klebsiella Infections , Klebsiella pneumoniae , Anti-Bacterial Agents/pharmacology , Carbapenems/pharmacology , Humans , Klebsiella Infections/drug therapy , Klebsiella Infections/genetics , Klebsiella pneumoniae/genetics , Microbial Sensitivity Tests , Molecular Biology
14.
Article in Russian | MEDLINE | ID: mdl-35170278

ABSTRACT

BACKGROUND: Doxorubicin is a well-known antitumor drug that is not employed for chemotherapy of brain tumors. Indeed, doxorubicin does not penetrate across the blood-brain barrier in therapeutic concentrations. OBJECTIVE: To study the antitumor effect of doxorubicin combined with nitrosorbide on intracranial experimental glioblastoma 101/8 in rats. MATERIAL AND METHODS: Male Wistar rats (n=86) with intracranial implanted glioblastoma 101/8 received doxorubicin (i.v. 1.5 mg/kg thrice) alone or in combination with nitrosorbide (i.v or orally, 0.5 mg/kg thrice) in 2, 5 and 8 days after implantation. Efficacy was assessed considering survival and brain tumor volume in 14 days after tumor implantation. RESULTS: Combination of doxorubicin and nitrosorbide significantly increased survival (57% and 155%, respectively) and slowed down tumor growth (16±12 and 8±6 mm3, respectively) compared to doxorubicin alone. Effectiveness of nitrosorbide alone was trivial. CONCLUSION: Nitric oxide donor nitrosorbide considerably potentiated the antitumor effect of doxorubicin against intracranial 101/8 glioblastoma in rats.


Subject(s)
Brain Neoplasms , Glioblastoma , Animals , Brain Neoplasms/drug therapy , Doxorubicin/pharmacology , Glioblastoma/drug therapy , Isosorbide Dinitrate/pharmacology , Male , Nitric Oxide Donors/pharmacology , Rats , Rats, Wistar
15.
Biomed Opt Express ; 12(8): 5272-5289, 2021 Aug 01.
Article in English | MEDLINE | ID: mdl-34513256

ABSTRACT

Terahertz (THz) technology holds strong potential for the intraoperative label-free diagnosis of brain gliomas, aimed at ensuring their gross-total resection. Nevertheless, it is still far from clinical applications due to the limited knowledge about the THz-wave-brain tissue interactions. In this work, rat glioma model 101.8 was studied ex vivo using both the THz pulsed spectroscopy and the 0.15λ-resolution THz solid immersion microscopy (λ is a free-space wavelength). The considered homograft model mimics glioblastoma, possesses heterogeneous character, unclear margins, and microvascularity. Using the THz spectroscopy, effective THz optical properties of brain tissues were studied, as averaged within the diffraction-limited beam spot. Thus measured THz optical properties revealed a persistent difference between intact tissues and a tumor, along with fluctuations of the tissue response over the rat brain. The observed THz microscopic images showed heterogeneous character of brain tissues at the scale posed by the THz wavelengths, which is due to the distinct response of white and gray matters, the presence of different neurovascular structures, as well as due to the necrotic debris and hemorrhage in a tumor. Such heterogeneities might significantly complicate delineation of tumor margins during the intraoperative THz neurodiagnosis. The presented results for the first time pose the problem of studying the inhomogeneity of brain tissues that causes scattering of THz waves, as well as the urgent need to use the radiation transfer theory for describing the THz-wave - tissue interactions.

16.
Biomed Opt Express ; 11(11): 6780-6798, 2020 Nov 01.
Article in English | MEDLINE | ID: mdl-33282523

ABSTRACT

Optical coherence tomography (OCT) of the ex vivo rat and human brain tissue samples is performed. The set of samples comprises intact white and gray matter, as well as human brain gliomas of the World Health Organization (WHO) Grades I-IV and glioma model 101.8 from rats. Analysis of OCT signals is aimed at comparing the physically reasonable properties of tissues, and determining the attenuation coefficient, parameter related to effective refractive index, and their standard deviations. Data analysis is based on the linear discriminant analysis and estimation of their dispersion in a four-dimensional principal component space. The results demonstrate the distinct contrast between intact tissues and low-grade gliomas and moderate contrast between intact tissues and high-grade gliomas. Particularly, the mean values of attenuation coefficient are 7.56±0.91, 3.96±0.98, and 5.71±1.49 mm-1 for human white matter, glioma Grade I, and glioblastoma, respectively. The significant variability of optical properties of high Grades and essential differences between rat and human brain tissues are observed. The dispersion of properties enlarges with increase of the glioma WHO Grade, which can be attributed to the growing heterogeneity of pathological brain tissues. The results of this study reveal the advantages and drawbacks of OCT for the intraoperative diagnosis of brain gliomas and compare its abilities separately for different grades of malignancy. The perspective of OCT to differentiate low-grade gliomas is highlighted by the low performance of the existing intraoperational methods and instruments.

17.
Kardiologiia ; 60(7): 125-135, 2020 Aug 11.
Article in Russian | MEDLINE | ID: mdl-33155951

ABSTRACT

Extensive use of antithrombotic drugs (ATD) in patients with ischemic heart disease (IHD), on the one hand, provides a considerable decrease in the risk for development of life-threatening cardiovascular complications but on the other hand, is associated with a risk of gastrointestinal bleedings (GIB), which may develop in 0.5-1.0 % of patients. In such cases, the major measures for prevention of GIB are strict adherence to indications for the ATD treatment, detection and analysis of risk factors for GIB and their elimination as far as feasible. For evaluation of GIB risk in patients with IHD, the PRECISE-DAPT and DAPT, HAS-BLED scales should be used. If the risk factors are non-modifiable the therapeutic tactics for further management of these patients should be strictly individual with determining the nature of damage, degree of a risk for present and possible complications, and the range of required therapeutic and diagnostic measures. The use of ATD requires monitoring of the patient's condition to timely detect and treat GI complications.


Subject(s)
Coronary Disease , Platelet Aggregation Inhibitors , Gastrointestinal Hemorrhage/chemically induced , Gastrointestinal Hemorrhage/prevention & control , Humans , Platelet Aggregation Inhibitors/adverse effects , Retrospective Studies , Risk Factors
18.
J Headache Pain ; 21(1): 65, 2020 Jun 05.
Article in English | MEDLINE | ID: mdl-32503421

ABSTRACT

The fifth cranial nerve is the common denominator for many headaches and facial pain pathologies currently known. Projecting from the trigeminal ganglion, in a bipolar manner, it connects to the brainstem and supplies various parts of the head and face with sensory innervation. In this review, we describe the neuroanatomical structures and pathways implicated in the sensation of the trigeminal system. Furthermore, we present the current understanding of several primary headaches, painful neuropathies and their pharmacological treatments. We hope that this overview can elucidate the complex field of headache pathologies, and their link to the trigeminal nerve, to a broader field of young scientists.


Subject(s)
Facial Pain/pathology , Headache/pathology , Trigeminal Ganglion/pathology , Trigeminal Nerve/pathology , Animals , Brain Stem/metabolism , Brain Stem/pathology , Brain Stem/physiopathology , Facial Pain/metabolism , Facial Pain/physiopathology , Headache/metabolism , Headache/physiopathology , Humans , Trigeminal Ganglion/metabolism , Trigeminal Ganglion/physiopathology , Trigeminal Nerve/metabolism , Trigeminal Nerve/physiopathology
19.
Acta Naturae ; 12(1): 56-62, 2020.
Article in English | MEDLINE | ID: mdl-32477599

ABSTRACT

The genome structure of three ciprofloxacin-resistant Mycoplasma hominis clinical isolates was studied using next-generation sequencing on the Illumina platform. The protein sequences of the studied Mycoplasma strains were found to have a high degree of homology. Mycoplasma hominis (M45, M57, MH1866) was shown to have limited biosynthetic capabilities, associated with the predominance of the genes encoding the proteins involved in catabolic processes. Multiple single-nucleotide substitutions causing intraspecific polymorphism of Mycoplasma hominis were found. The genes encoding the efflux systems - ABC transporters (the ATP-binding cassette superfamily) and proteins of the MATE (multidrug and toxic compound extrusion) family - were identified. The molecular mechanism of ciprofloxacin resistance of the Mycoplasma hominis M45 and M57 isolates was found to be associated with the Ser83Leu substitution in DNA gyrase subunit A. In the Mycoplasma hominis MH1866 isolate it was related to the Lys144Arg substitution in topoisomerase IV subunit A.

20.
Phys Rev Lett ; 123(23): 236801, 2019 Dec 06.
Article in English | MEDLINE | ID: mdl-31868465

ABSTRACT

In high-mobility materials, conduction electrons can form a viscous fluid at low temperatures. We demonstrate that in a high-frequency flow of a two-dimensional electron fluid in a magnetic field the two types of excitations can coexist: those of the shear stress (previously unknown transverse magnetosound) and those associated with the charge density (conventional magnetoplasmons). The dispersion law and the damping coefficient of transverse magnetosound originate from the time dispersion of the viscosity of the fluid. Both the viscoelastic and the plasmonic components of the flow exhibit the recently proposed viscoelastic resonance that is related to the own dynamics of shear stress of charged fluids in a magnetic field. We argue that the generation of transverse magnetosound, manifesting itself by the viscoelastic resonance, is apparently responsible for the peak in photoresistance and peculiarities in photovoltage observed in ultrahigh-mobility GaAs quantum wells.

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