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1.
Bull Exp Biol Med ; 176(4): 523-527, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38492101

RESUMO

We performed a comparative assessment of the immunohistochemical distribution of markers of mitochondrial fission (Drp-1), mitochondrial fusion (Mfn-2), and mitochondrial biogenesis (PGC-1α) in pyramidal neurons of different zones of the hippocampus in mice with intrahippocampal administration of ß-amyloid peptide 25-35. The most pronounced changes in the dynamics associated with a decrease in the amount of the fission marker and an increase in the amount of the fusion marker were observed in the CA3 field on day 38 after peptide administration. In the CA1 field, a significant decrease in the marker of mitochondrial biogenesis PGC-1α was found on day 38, which can indicate a decrease in the intensity of mitochondrial biogenesis. Early mitochondrial changes can play an important role in the pathogenesis of all types of memory impairment in Alzheimer's disease.


Assuntos
Doença de Alzheimer , Camundongos , Animais , Doença de Alzheimer/metabolismo , Dinâmica Mitocondrial , Hipocampo/metabolismo , Mitocôndrias/metabolismo , Peptídeos beta-Amiloides/metabolismo
2.
Bull Exp Biol Med ; 175(3): 315-320, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37561373

RESUMO

A comparative assessment of the expression of the mitochondrial fission marker Drp1 and the autophagy marker LC3 in neurons and endothelial cells in the hippocampus and entorhinal cortex during progression of cognitive deficit was performed in animals with intrahippocampal administration of ß-amyloid. In both brain regions, the expression of Drp1 and LC3 in neuronal and endothelial cells was enhanced. The peak of cognitive impairment corresponded to the maximum expression of Drp1 and LC3 in hippocampal neurons and was preceded by an increase in the number of Drp1+ and LC3+ endothelial cells in this brain region. These data attests to a possible role of aberrant mitochondrial dynamics and autophagy of endothelial cells in the impairment of brain plasticity in the Alzheimer's type neurodegeneration.


Assuntos
Doença de Alzheimer , Autofagia , Encéfalo , Mitocôndrias , Neurônios , Animais , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias/metabolismo , Modelos Animais de Doenças , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Encéfalo/metabolismo , Células Endoteliais/metabolismo , Neurônios/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo
3.
Cell Mol Neurobiol ; 42(5): 1355-1371, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33392919

RESUMO

A common feature of neurodegenerative disorders, in particular Alzheimer's disease (AD), is a chronic neuroinflammation associated with aberrant neuroplasticity. Development of neuroinflammation affects efficacy of stem and progenitor cells proliferation, differentiation, migration, and integration of newborn cells into neural circuitry. However, precise mechanisms of neurogenesis alterations in neuroinflammation are not clear yet. It is well established that expression of NLRP3 inflammasomes in glial cells marks neuroinflammatory events, but less is known about contribution of NLRP3 to deregulation of neurogenesis within neurogenic niches and whether neural stem cells (NSCs), neural progenitor cells (NPCs) or immature neuroblasts may express inflammasomes in (patho)physiological conditions. Thus, we studied alterations of neurogenesis in rats with the AD model (intra-hippocampal injection of Aß1-42). We found that in Aß-affected brain, number of CD133+ cells was elevated after spatial training in the Morris water maze. The number of PSA-NCAM+ neuroblasts diminished by Aß injection was completely restored by subsequent spatial learning. Spatial training leads to elevated expression of NLRP3 inflammasomes in the SGZ (subgranular zones): CD133+ and PSA-NCAM+ cells started to express NLRP3 in sham-operated, but not AD rats. Taken together, our data suggest that expression of NLRP3 inflammasomes in CD133+ and PSA-NCAM+ cells may contribute to stimulation of adult neurogenesis in physiological conditions, whereas Alzheimer's type neurodegeneration abolishes stimuli-induced overexpression of NLRP3 within the SGZ neurogenic niche.


Assuntos
Doença de Alzheimer , Inflamassomos , Doença de Alzheimer/metabolismo , Animais , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Neurogênese , Ratos , Aprendizagem Espacial
4.
Urologiia ; (6): 61-65, 2022 Dec.
Artigo em Russo | MEDLINE | ID: mdl-36625615

RESUMO

AIM: To analyze some effects of plasma acid in vitro on the bladder tissue obtained from laboratory animals and to evaluate the possibility of its application for in vitro modeling of IC/BPS. MATERIALS AND METHODS: The tissue samples of the bladder wall were obtained from female Wistar rats aged 3 months (n=16, weighing 180-200 g). The tissues were processed for 1 hour in the plasma acid prepared by spark discharge of water for injection in air. The immunohistochemical study of obtained samples was performed. RESULTS: The changes in the expression profile of bladder epithelial cells under the action of plasma acid in vitro were found indicating the development of oxidative, nitrosative and dicarbonyl stress, impaired expression of NADPH oxidase DUOX2 and VEGF, and a decrease in cell proliferative activity, which, in general, corresponds to the main mechanisms of urothelial alterations specific for the IC/BPS. CONCLUSION: The revealed effects of plasma acid on bladder epithelial cells confirm the possibility of using it as an inducer of urothelial cell damage typical for IC/BPS in the in vitro models.


Assuntos
Cistite Intersticial , Bexiga Urinária , Ratos , Animais , Feminino , Bexiga Urinária/metabolismo , Ratos Wistar , Estresse Oxidativo
5.
Bull Exp Biol Med ; 170(6): 693-698, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33893948

RESUMO

The protocol of optogenetic ChR2-mediated activation of astrocytes was used in a model of artificial neurogenic niche, neurospheres implanted into ex vivo organotypic cultures of mouse hippocampus. The electrophysiological characteristics of the hippocampus and expression of molecules involved in the mechanisms of activation of astrocytes and microglia (GFAP, CD38, C3/C3b, Cx43, CD11b, and CD18) were evaluated. Photoactivation of astrocytes led to activation of neurogenesis and changes in the expression of molecules (Cx43 and CD38) that determine bioavailability of NAD+ to ensure proliferative activity of cells in the neurogenic niche. Implantation of neurospheres into organotypic slices of the hippocampus caused an increase in C3/C3b expression and suppression of the synaptic plasticity of hippocampal neurons.


Assuntos
Astrócitos/metabolismo , Neurogênese/fisiologia , Células-Tronco/metabolismo , Animais , Imuno-Histoquímica , Camundongos , Camundongos Endogâmicos C57BL , Neurogênese/genética , Optogenética
6.
Genet Mol Res ; 16(1)2017 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-28363009

RESUMO

The aim of this study was to assess the association between the TNFR1 rs2234649 polymorphism and ankylosing spondylitis susceptibility in a Russian Caucasian population. A total of 41 ankylosing spondylitis patients and 43 healthy controls, matched according to age and sex, were enrolled, and polymerase chain reaction-restriction fragment length polymorphism analysis was used to genotype the rs2234649 variant. We evaluated genotype distributions in the patient and control groups with the chi-square test, and assessed the relationship between genotypes and ankylosing spondylitis using the odds ratio. Our analysis showed that the rs2234649 polymorphism does not increase ankylosing spondylitis risk. In conclusion, the TNFR1 gene polymorphism tested does not appear to be useful for assessing predisposition to this disease or for its diagnosis or prognosis.


Assuntos
Receptores Tipo I de Fatores de Necrose Tumoral/genética , Espondilite Anquilosante/genética , Adulto , Alelos , Estudos de Casos e Controles , Frequência do Gene , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Polimorfismo de Nucleotídeo Único , Receptores Tipo I de Fatores de Necrose Tumoral/metabolismo , Federação Russa , População Branca/genética
7.
Adv Gerontol ; 30(1): 49-55, 2017.
Artigo em Russo | MEDLINE | ID: mdl-28557390

RESUMO

The purpose of the study was to develop a battery of tests to study social and cognitive impairments for behavioral phenotyping of aging experimental animals with physiological neurodegeneration. Object of the study were outbred CD1 mice in the following groups: 1st group - 12-month old male mice (physiological aging); 2nd group - 2-month old male mice (control group). Social recognition test, elevated plus maze test (EPM), open field test, light-dark box test, and Fear conditioning protocol were used to estimate the neurological status of experimental animals. We found that aging male mice in a contrast to young ones have demonstrated lower social interest to female mice in the social recognition task. EPM and light-dark box tests showed increased level of anxiety in the group of aged mice comparing to the control group. Fear conditioning protocol revealed impairment of associative learning and memory in the group of aged mice, particularly, fear memory consolidation was dramatically suppressed. Analysis of behavioral factors, social interactions and anxiety level in the experimental mice has confirmed age-related neurodegeneration in the 1st group. We found that the most informative approach to identifying neurological impairments in aging mice (social interaction deficit, limitation of interests, increased level of anxiety) should be based on the open field test light-dark box test, and Fear conditioning protocol. Such combination allows obtaining new data on behavioral alterations in the age-associated of neurodegeneration and to develop novel therapeutic strategies for the treatment of age-related brain pathology.


Assuntos
Envelhecimento/psicologia , Comportamento Animal/fisiologia , Transtornos Cognitivos/diagnóstico , Transtornos do Comportamento Social/diagnóstico , Fatores Etários , Animais , Ansiedade/diagnóstico , Condicionamento Psicológico , Medo/psicologia , Feminino , Deficiências da Aprendizagem/diagnóstico , Masculino , Memória , Camundongos , Doenças do Sistema Nervoso/diagnóstico
8.
Bull Exp Biol Med ; 161(5): 666-669, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27709386

RESUMO

We compared the intensity of apoptosis in the peri-infarction area of the brain after isolated and combined exposure to hypoxia and hypercapnia prior to focal ischemic stroke modeling. Hypoxia and hypercapnia reduced the number of TUNEL-positive cells in the peri-infarction area, and their combination was most effective in comparison with effects of isolated exposures. The maximum neuroprotective effect of combined exposure to hypoxia and hypercapnia in comparison with isolated exposures was determined by inhibition of apoptosis in the peri-infarction zone.


Assuntos
Apoptose , Isquemia Encefálica/patologia , Hipercapnia/patologia , Hipóxia Encefálica/patologia , Animais , Córtex Cerebral/patologia , Precondicionamento Isquêmico , Masculino , Fatores de Proteção , Ratos Wistar
9.
Tsitologiia ; 58(5): 364-9, 2016.
Artigo em Inglês, Russo | MEDLINE | ID: mdl-30188631

RESUMO

Formation and functional plasticity of the blood-brain barrier is associated with the molecular events that occur in the brain neurovascular unit in the embryonic and early postnatal development. To study the characteristics of barriergenesis under physiological conditions, as well as recovering from perinatal hypoxia and early life stress, we examined the expression of proteins of cerebral endothelial tight junctions (JAM, ZO1, CLDN5) in rats aged 7, 28 and 70 days of postnatal development (P7­P70). Under physiological conditions, we have found that the number of endothelial cells expressing JAM, ZO1, CLDN5 slightly increases in the cortex, hippocampus and amygdala of the brain in the period from P7 to P70. Perinatal hypoxia significantly increased the number of cells expressing proteins of tight junction proteins (JAM, CLDN5) up to the age P28­P70, whereas the number of cells expressing ZO1 was reduced in the same period of time. Early life stress led to an imbalance between the number of cells expressing ZO1 proteins and that expressing tight junctions proteins, but these changes were in opposite direction to that observed in perinatal hypoxia


Assuntos
Cerebelo/metabolismo , Células Endoteliais/metabolismo , Regulação da Expressão Gênica , Proteínas de Junções Íntimas/biossíntese , Junções Íntimas/metabolismo , Animais , Cerebelo/citologia , Cerebelo/crescimento & desenvolvimento , Células Endoteliais/citologia , Feminino , Masculino , Ratos , Ratos Wistar
10.
Bull Exp Biol Med ; 161(6): 770-774, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27783302

RESUMO

The peculiarities in expression of transport proteins and the proteins implicated in the control of glycolysis by the cellular components of neurovascular units were examined in animals of different age under normal conditions and after modeled perinatal stress or hypoxic brain injury. In both cases, the specialties in expression of transport proteins in ontogenesis were revealed. The perinatal hypoxic brain injury resulted in up-regulation of MCT1, MCT4, and GLUT4 expression in endotheliocytes of hippocampal microvessels accompanied by transient elevation of HIF-1α and GSK3 expression.


Assuntos
Ansiedade de Separação/genética , Transportador de Glucose Tipo 4/genética , Quinase 3 da Glicogênio Sintase/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Hipóxia/genética , Estresse Psicológico/genética , Fatores Etários , Animais , Animais Recém-Nascidos , Ansiedade de Separação/complicações , Ansiedade de Separação/metabolismo , Ansiedade de Separação/patologia , Astrócitos/metabolismo , Astrócitos/patologia , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/patologia , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Feminino , Regulação da Expressão Gênica , Transportador de Glucose Tipo 4/metabolismo , Quinase 3 da Glicogênio Sintase/metabolismo , Hipocampo/irrigação sanguínea , Hipocampo/metabolismo , Hipocampo/patologia , Humanos , Hipóxia/complicações , Hipóxia/metabolismo , Hipóxia/patologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Masculino , Microvasos/metabolismo , Microvasos/patologia , Neurônios/metabolismo , Neurônios/patologia , Acoplamento Neurovascular , Ratos , Ratos Wistar , Estresse Psicológico/complicações , Estresse Psicológico/metabolismo , Estresse Psicológico/patologia
11.
Eksp Klin Farmakol ; 79(12): 7-12, 2016.
Artigo em Russo | MEDLINE | ID: mdl-29791096

RESUMO

Metabolic activity of cells within a neurovascular unit is among the factors determining structural and functional integritY of the blood-brain barrier and the an- giogenesis process. in order to verify the hypothesis about the role Of g1YcolYtic activity in the perivascula astroglialcells associated with lactate release in the development of functioning of cerebral microvessel endothelial cells, we have used a three-component model of the brain neurovascular unit in vitro. The cells o f n o n -en d o th elia l o rig in w ere in c u b a te d in th e p rese n ce o f m o d u la to rs o f la c ta te pro d u c n ago ni glu c ose ta a G ly c o s o) , bas t h e oe t a n t a at- blocker of monocarboxylate transporters MCTlprCT and recepltiors of3Ctate0produasan (2-donisyoflactate G e8 breceptor) Iasa estbishe vthat that te suppression of lactate production and transport, prdc o1,adrcpin(C-O-Aa n (2gdoxysgflucoase as a glycolysis inhibitor), transport (phloretin as a sukr of lacaroduto transport , aswellasastimultionof3lactate receptors in astroglial cells, lead to aberrant development of endothelial layer, ther by u g g e tin t h efor atio o f anti ngi gencmi roen ircm ent for cerebral endothelium due to inappropriate lactate-m ediated effects. KeYw.ords:-n-eur-ovascular unit; metabolism; glYcolysis; lactate.


Assuntos
Astrócitos/metabolismo , Barreira Hematoencefálica/metabolismo , Endotélio Vascular/metabolismo , Glicólise , Ácido Láctico/biossíntese , Modelos Biológicos , Animais , Transporte Biológico , Barreira Hematoencefálica/inervação , Células Cultivadas , Endotélio Vascular/inervação , Glicólise/efeitos dos fármacos , Ácido Láctico/metabolismo , Microvasos/inervação , Microvasos/metabolismo , Transportadores de Ácidos Monocarboxílicos/metabolismo , Ratos Wistar
12.
Klin Med (Mosk) ; 94(2): 113-20, 2016.
Artigo em Russo | MEDLINE | ID: mdl-27459760

RESUMO

The purpose of the study was to examine the relationship between functional parameters, arterial rigidity, lipid profile, markers of systemic inflammation and endothelial dysfunction in patients with COPD and COPD + coronary heart disease. We examined 110 subjects divided into 3 groups. G group 1 included 40 patients with severe and very severe COPD, group 2 consisted of 40 patients with severe and very severe COPD + coronary artery disease, the control group was comprised of 30 healthy volunteers. We studied parameters of respiratory function, the level of blood oxygenation, the main characteristics of arterial rigidity plasma lipid, TNF-α, CRP, fibrinogen, sPECAM-1 levels and the expression of CD38/ADP-ribosylcyclase in peripheral blood lymphocytes. The study revealed increased rigidity of the central arteries in the patients of groups 1and 2 regardless of the duration of observation and the presence of coronary artery disease, as evidenced by the increase of the pulse wave velocity in the aorta. Patients of both groups had elevated levels of TNF-α, CRP and fibrinogen indicating systemic inflammatory response. Taken together, the enhanced expression of CD38 in peripheral blood lymphocytes, elevated concentration of soluble CD31 (sPECAM-1) in both groups related to bronchial obstruction and neutrophil elastase activity as well as increased rigidity of the vascular bed gives evidence that the CD38 and sCD31 relationship plays a role in the formation of endothelial dysfunction, and dysregulation of vascular tone in COPD patients. Disorders of lipid metabolism combined with increased rigidity of the vascular wall, elevated levels of markers of systemic inflammation and endothelia dysfunction, suggest that patients with COPD are at risk of cardiovascular events.


Assuntos
Doença da Artéria Coronariana/sangue , Endotélio Vascular/patologia , Doença Pulmonar Obstrutiva Crônica/sangue , Adulto , Comorbidade , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/patologia
13.
Tsitologiia ; 57(10): 710-3, 2015.
Artigo em Russo | MEDLINE | ID: mdl-26863769

RESUMO

There are many ways to model blood brain barrier and neurovascular unit in vitro. All existing models have their disadvantages, advantages and some peculiarities of preparation and usage. We obtained the three-cells neurovascular unit model in vitro using progenitor cells isolated from the rat embryos brain (Wistar, 14-16 d). After withdrawal of the progenitor cells the neurospheres were cultured with subsequent differentiation into astrocytes and neurons. Endothelial cells were isolated from embryonic brain too. During the differentiation of progenitor cells the astrocytes monolayer formation occurs after 7-9 d, neurons monolayer--after 10-14 d, endothelial cells monolayer--after 7 d. Our protocol for simultaneous isolation and cultivation of neurons, astrocytes and endothelial cells reduces the time needed to obtain neurovascular unit model in vitro, consisting of three cells types and reduce the number of animals used. It is also important to note the cerebral origin of all cell types, which is also an advantage of our model in vitro.


Assuntos
Astrócitos/citologia , Barreira Hematoencefálica/citologia , Células Endoteliais/citologia , Neurônios/citologia , Animais , Encéfalo/citologia , Encéfalo/embriologia , Diferenciação Celular , Técnicas In Vitro , Ratos , Células-Tronco/citologia
14.
Bull Exp Biol Med ; 159(5): 614-6, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26459476

RESUMO

Glutamine transporter protein SLC1A5 and glutamate transporter protein EAAT2 responsible for cell-cell communication and energetic coupling were studied using in vitro model of multicellular neurovascular unit consisting of astrocytes, neurons, and endotheliocytes under standard conditions and during chemical hypoxia in vitro. Hypoxic damage to the neurovascular unit cells increased the number of SLC1A5-expressing cells and reduced the number of EAAT2-expressing astrocytes. Metabolic uncoupling in the neurovascular unit cells under hypoxic conditions resulted from abnormal expression of glutamine and glutamate transporter proteins, which is indicative of impaired glutamine and glutamate transport.


Assuntos
Sistema ASC de Transporte de Aminoácidos/genética , Astrócitos/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Transportador 2 de Aminoácido Excitatório/genética , Expressão Gênica/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Sistema ASC de Transporte de Aminoácidos/metabolismo , Animais , Astrócitos/citologia , Astrócitos/metabolismo , Transporte Biológico , Encéfalo , Comunicação Celular , Diferenciação Celular , Hipóxia Celular , Embrião de Mamíferos , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Transportador 2 de Aminoácido Excitatório/metabolismo , Ácido Glutâmico/metabolismo , Glutamina/metabolismo , Ácido Iodoacético/farmacologia , Antígenos de Histocompatibilidade Menor , Modelos Biológicos , Células-Tronco Neurais/citologia , Células-Tronco Neurais/efeitos dos fármacos , Células-Tronco Neurais/metabolismo , Neurônios/citologia , Neurônios/metabolismo , Cultura Primária de Células , Ratos
15.
Bull Exp Biol Med ; 159(4): 546-9, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26395632

RESUMO

We studied in vitro development of brain progenitor cells isolated from healthy 7-9-month-old Wistar rats and rats with experimental Alzheimer's disease kept under standard conditions and in enriched (multistimulus) environment in vivo. Progenitor cells from healthy animals more rapidly formed neurospheres. Considerable changes at the early stages of in vitro development of brain progenitor cells were observed in both groups kept in enriched environment.


Assuntos
Células-Tronco Neurais/fisiologia , Doença de Alzheimer/patologia , Animais , Encéfalo/patologia , Proliferação de Células , Células Cultivadas , Meio Ambiente , Planejamento Ambiental , Abrigo para Animais , Ratos Wistar
16.
Vestn Ross Akad Med Nauk ; (6): 694-703, 2015.
Artigo em Russo | MEDLINE | ID: mdl-27093797

RESUMO

The review contains data on the diversity of endogenous ligands of RAGE receptors (receptor for advanced glycation end products) that play an important role in the signal transduction in (patho) physiological conditions. RAGE takes part in various physiological processes like cell growth and survival, apoptosis and regeneration. They serve as regulators of inflammatory reactions due to their ability to induce secretion of cytokines and chemokines. In addition, they facilitate elimination of apoptotic cells and mediate innate immune response. We discuss mechanisms of soluble RAGE production as well as the role of membrane and soluble forms of the receptor in cell signaling. Several endogenous ligands of RA GE are well-known: advanced glycation end products (AGE), amyloid-beta (Aß), nuclear high mobility group box 1 proteins (HMGB1), and calcium-binding proteins S100A4, S100A8/A9, S100A12 u S100B. The review is focused on the mechanisms of the ligands production, their secretion from the cells of various origin, interaction with RAGE, and associated intracellular signal transduction pathways. Special attention is paid to the role of RAGE in pathogenesis of inflammation, particularly, in brain injury and neurodegeneration.


Assuntos
Comunicação Celular , Inflamação/metabolismo , Receptor para Produtos Finais de Glicação Avançada/fisiologia , Humanos , Ligantes , Transdução de Sinais
17.
Vestn Ross Akad Med Nauk ; (1): 17-25, 2015.
Artigo em Russo | MEDLINE | ID: mdl-26027267

RESUMO

The review covers current concepts on cell and molecular mechanisms of neuroinflammation and aging with the special focus on the regulation of cytokine-producing activity of astroglial cells and intercellular communication. The review reflects that a key component of the aging phenomenon as a result of ineffective implementation of anti-inflammatory response are processes of the dysregulated cytokine production, in particular, an increase in the secretion of proinflammatory cytokines and an imbalance in the expression of the receptors and receptor associated proteins. Interpretation of the molecular mechanisms of cell conjugating neuroinflammation and aging cells can give rise to new therapeutic strategies that are relevant to the treatment of a wide range of central nervous system diseases and the development of new experimental models of diseases of the central nervous system.


Assuntos
Encéfalo , Senescência Celular , Doenças do Sistema Nervoso Central , Inflamação/metabolismo , Neurônios/metabolismo , Encéfalo/fisiologia , Encéfalo/fisiopatologia , Comunicação Celular , Doenças do Sistema Nervoso Central/metabolismo , Doenças do Sistema Nervoso Central/fisiopatologia , Citocinas/metabolismo , Humanos , Modelos Neurológicos
18.
Eksp Klin Farmakol ; 78(12): 41-50, 2015.
Artigo em Russo | MEDLINE | ID: mdl-27051929

RESUMO

Review covers current achievements in the methodology of target discovery and validation for the development of drugs restoring structural and functional integrity of the blood-brain barrier (BBB) in cases of brain injury and neuroinflammation. Some new targets (in the context of BBB permeability) are discussed, which are involved in the regulation of signal transduction involving HIF-1, JNK, NF-κB, Rac, 1 etc., expression of tight-junction proteins, and activity of enzymes producing molecules with pro-inflammatory effects in the BBB cells.


Assuntos
Anti-Inflamatórios/uso terapêutico , Barreira Hematoencefálica/efeitos dos fármacos , Lesões Encefálicas/tratamento farmacológico , Encéfalo/efeitos dos fármacos , Fármacos Neuroprotetores/uso terapêutico , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/patologia , Encéfalo/metabolismo , Encéfalo/patologia , Lesões Encefálicas/genética , Lesões Encefálicas/metabolismo , Lesões Encefálicas/patologia , Permeabilidade Capilar/efeitos dos fármacos , Regulação da Expressão Gênica , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Inflamação/tratamento farmacológico , Inflamação/genética , Inflamação/metabolismo , Inflamação/patologia , MAP Quinase Quinase 4/genética , MAP Quinase Quinase 4/metabolismo , Terapia de Alvo Molecular , NF-kappa B/genética , NF-kappa B/metabolismo , Transdução de Sinais , Proteínas de Junções Íntimas/genética , Proteínas de Junções Íntimas/metabolismo , Proteínas rac1 de Ligação ao GTP/genética , Proteínas rac1 de Ligação ao GTP/metabolismo
19.
Khirurgiia (Mosk) ; (2): 63-69, 2015.
Artigo em Russo | MEDLINE | ID: mdl-26031822

RESUMO

Levels of interleukins-6, 8, 10, TNF-alpha and basic fibroblast growth factor (bFGF) were examined in peripheral blood of 60 patients with diabetes mellitus type II and soft tissues infections. It was revealed the elevated levels of proinflammatory (IL-6, 8), anti-inflammatory (IL-10) cytokines and basic fibroblast growth factor at the time of admission. Application of combined ozone therapy including ozonated autohemotherapy and superficial management of wounds with ozone-oxygen mixture resulted in significant decrease of IL-6, 8, 10 production and high level of bFGF on blood serum. Thus effective local bactericidal impact of ozone in combination with normalization of proinflammatory cytokines levels and preserved high level of bFGF in peripheral blood provide better results of wound healing process in patients with diabetes mellitus type II.


Assuntos
Transfusão de Sangue Autóloga/métodos , Diabetes Mellitus Tipo 2/complicações , Ozônio/uso terapêutico , Infecções dos Tecidos Moles/terapia , Idoso , Citocinas/sangue , Diabetes Mellitus Tipo 2/sangue , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Oxidantes Fotoquímicos/uso terapêutico , Infecções dos Tecidos Moles/sangue , Infecções dos Tecidos Moles/complicações , Resultado do Tratamento , Cicatrização
20.
Klin Med (Mosk) ; 92(11): 43-8, 2014.
Artigo em Russo | MEDLINE | ID: mdl-25796946

RESUMO

The aim of the work was to study clinical and pathophysiological features of endothelial dysfunction, structural and functional state of the left heart in patients with bronchial asthma (BA). The study included 290 patients. 250 of them presented with moderate or severe BA during exacerbation and within 12 months after the onset of observation, 40 healthy volunteers served as controls. The endothelial function was disturbed in 63 and 74% of the patients with moderate and severe BA respectively. They showed reduced endothelium-dependent vasodilation in combination with a significant increase of the plasma sDC31/ sPECAM-1 level. It is concluded that patients with BA develop structural and functional changes in the left ventricular myocardium proportional to the severity of BA which leads to diastolic dysfunction.


Assuntos
ADP-Ribosil Ciclase 1/sangue , Asma , Doenças Cardiovasculares , Endotélio Vascular , Molécula-1 de Adesão Celular Endotelial a Plaquetas/sangue , Adulto , Asma/complicações , Asma/diagnóstico , Asma/fisiopatologia , Biomarcadores/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Endotélio Vascular/imunologia , Endotélio Vascular/fisiopatologia , Feminino , Humanos , Inflamação/imunologia , Masculino , Pessoa de Meia-Idade , Testes de Função Respiratória/métodos , Fatores de Risco , Índice de Gravidade de Doença , Estatística como Assunto , Vasodilatação , Remodelação Ventricular
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