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1.
Bull Exp Biol Med ; 173(3): 293-297, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35844021

RESUMO

Reduced daylight duration causes the development of seasonal affective disorder (SAD; depression-like disorders characterized by depressed mood, apathy, bulimia, and weight gain) in sensitive individuals. Neurotransmitter serotonin (5-HT) is involved in the mechanism of SAD. Zebrafish (D. rerio) is a promising model for translational studies. We studied changes in the behavior, content of 5-HT and its major metabolite 5-hydroxyindoleacetic acid (5-HIAA), and the expression of genes encoding the key enzymes of 5-HT metabolism, tryptophan hydroxylases TPH1A, TPH1B, TPH2, monoamine oxidase (MAO), 5-HT transporter, and 5-HT1A and 5-HT2A receptors in the brain of zebrafish reared for 60 days under short (04:20 h) compared to those reared at normal (12:12 h) photoperiod. Exposure to short photoperiod decreased locomotor activity in the novel tank diving test, increased the level 5-HIAA, and reduced the level of Mao gene mRNA, but did not affect the level of 5-HT and expression of Tph1a, Tph1b, Tph2, Slc6a4a (transporter), Htr1aa, and Htr2aa (receptors) genes. Thus, zebrafish can be used as a promising model to study the involvement of 5-HT in the SAD mechanism.


Assuntos
Serotonina , Peixe-Zebra , Animais , Encéfalo/metabolismo , Ácido Hidroxi-Indolacético/metabolismo , Monoaminoxidase/genética , Monoaminoxidase/metabolismo , Fotoperíodo , Serotonina/metabolismo , Peixe-Zebra/genética , Peixe-Zebra/metabolismo
2.
Nitric Oxide ; 117: 46-52, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34678508

RESUMO

Nitric oxide (NO) mediates diverse physiological processes in living organisms. Small molecular NO donors usually lack stability and have a short half-life in human tissues, limiting the therapeutic application. The anionic tetranitrosyl iron complex with thiosulfate ligands (TNIC) is one of the most promising NO donors. This study shows that bovine serum albumin (BSA) can effectively stabilize the TNIC complex under aerobic (physiological) conditions, which contributes to its prolonged action as NO donor. Our results demonstrated that TNIC-BSA inhibits formation of TBARS - standard biomarker for the lipid peroxidation induced oxidative stress. Also, it was found that TNIC-BSA inhibits the catalytic activity of mitochondrial membrane-bound enzymes: cytochrome c oxidase and monoamine oxidase A. Together, these results demonstrate that, stabilization of TNIC with BSA opens up the possibility of its practical application in chemotherapy of socially significant diseases.


Assuntos
Ferro , Peroxidação de Lipídeos/efeitos dos fármacos , Mitocôndrias , Óxidos de Nitrogênio , Soroalbumina Bovina , Tiossulfatos , Animais , Encéfalo/citologia , Ferro/química , Ferro/farmacologia , Camundongos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/enzimologia , Mitocôndrias/metabolismo , Monoaminoxidase/metabolismo , Óxidos de Nitrogênio/química , Óxidos de Nitrogênio/farmacologia , Soroalbumina Bovina/química , Soroalbumina Bovina/farmacologia , Tiossulfatos/química , Tiossulfatos/farmacologia
3.
Mol Biol (Mosk) ; 55(4): 660-666, 2021.
Artigo em Russo | MEDLINE | ID: mdl-34432783

RESUMO

Fundamental neurophysiological processes are often studied using Danio rerio fish as a model. A selective inhibitor of striatal-enriched protein tyrosine phosphatase (STEP) reduces serotonin metabolism in the D. rerio brain. Both STEP and serotonin are involved in the development of neurodegenerative behavioral disorders. Reduction or elevation of the serotonin level in the brain of mice caused by the administration of p-chlorophenylalanine or pargyline, respectively, results in a decrease in the level of ptpn5 mRNA in the striatum, ptpn5 being the gene encoding STEP. However, it has not been established whether this occurs in other organisms. We studied the effect of inhibitors of synthesis (p-chlorophenylalanine) and degradation (pargyline) of serotonin on the expression of the ptpn5 gene and the activity of STEP in the brain of D. rerio. The fish were placed in water containing p-chlorophenylalanine (2 mg/L) or pargyline (0.5 mg/L) for 72 hours, and control subjects were kept in aquarium water. The p-chlorophenylalanine treatment decreased the serotonin level in the brain fourfold, whereas pargyline increased the level of this transmitter sixfold. Both p-chlorophenylalanine and pargyline decrease STEP activity in the D. rerio brain, without affecting the level of the ptpn5 mRNA gene. Thus, interaction between STEP and the serotonin system is observed in both mammals and fish, which indicates the similarity of the regulation processes in vertebrates.


Assuntos
Pargilina , Peixe-Zebra , Animais , Encéfalo , Fenclonina/farmacologia , Camundongos , Proteínas Tirosina Fosfatases , Peixe-Zebra/genética
4.
Artigo em Russo | MEDLINE | ID: mdl-34283524

RESUMO

OBJECTIVE: To develop clinical and social models and management routes for patients with autism spectrum disorders (ASD). MATERIAL AND METHODS: A clinical follow-up study was performed for 254 patients, aged 4-17 years (average age 7.3 years), who represented the main forms of ASD. Psychopathological, clinical-follow-up, psychological and statistical methods were used. RESULTS AND CONCLUSION: Five management models for patients with different forms of ASD are described; differentiation of routes for interagency monitoring of patients is proposed. The effectiveness of the integrated use of drug and non-drug therapeutic approaches for the management of patients with ASD in the clinical-age aspect is shown. Timely diagnosis of ASD makes it possible to develop differentiated routes of patient management within the framework of interdepartmental interaction and achieve positive results in the clinical and age aspect.


Assuntos
Transtorno do Espectro Autista , Transtorno do Espectro Autista/diagnóstico , Transtorno do Espectro Autista/terapia , Criança , Seguimentos , Humanos
5.
Mol Biol (Mosk) ; 55(3): 422-430, 2021.
Artigo em Russo | MEDLINE | ID: mdl-34097677

RESUMO

The transcription factor KAISO is important for proper development of animal embryos. In the cell, KAISO regulates cell division and apoptosis. KAISO is abundant in the central nervous system. Here we describe the effects of Zbtb33 gene knockout on the transcription of several genes that regulate the development of the central nervous system, including Fgf9, Fgfr3, Sox9, Sox2, c-Myc, NeuroD1 and FoxG1. These genes are related to the Wnt/ß-catenin signaling pathway, which is closely connected to KAISO. Hippocampal, frontal cortical, and striatal tissue from C57BL/6j mice with a knockout in the Zbtb33 gene encoding KAISO (ZBTB33-) and wild-type mice (ZBTB33+) were collected and profiled at different stages of development. Age-dependent and region-specific differences in the mRNA levels of the Fgf9, Fgfr3, c-Myc, FoxG1 genes in the developing brain of ZBTB33- and ZBTB33+ mice were described and discussed.


Assuntos
Encéfalo , Fatores de Transcrição , Animais , Fator 9 de Crescimento de Fibroblastos , Fatores de Transcrição Forkhead/genética , Técnicas de Inativação de Genes , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas do Tecido Nervoso , Proteínas Proto-Oncogênicas c-myc , Fatores de Transcrição/genética
6.
Bull Exp Biol Med ; 170(5): 627-630, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33788115

RESUMO

Effects of acute treatment with antidepressant drugs, imipramine and citalopram, on behavior and activity of striatal-enriched tyrosine protein phosphatase (STEP) in the whole brain of zebrafish Danio rerio were studied. Mature zebrafish were exposed for 3 h to water (control) or to solutions of 0.25, 0.5, or 1 mg/liter of imipramine or citalopram, and then their behavior was studied in novel tank test. STEP activity was assayed in the brain of animals by the difference between the rates of transformation of p-nitrophenyl phosphate to 4-nitrophenol in the absence or presence of a selective STEP inhibitor. In novel tank test, imipramine and citalopram reduced locomotor activity and increased freezing time; at this, imipramine increased the total time spent in top of the tank. Citalopram (all concentrations) and imipramine (0.5 and 1 mg/liter) increased STEP activity in zebrafish brain.


Assuntos
Encéfalo/metabolismo , Citalopram/farmacologia , Imipramina/farmacologia , Proteínas Tirosina Fosfatases/metabolismo , Animais , Antidepressivos/farmacologia , Encéfalo/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Feminino , Masculino , Peixe-Zebra
7.
Clin Hemorheol Microcirc ; 78(3): 247-257, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33682698

RESUMO

BACKGROUND: The role of microcirculatory disorders is progressively being accepted in the pathogenesis of cardiovascular diseases. OBJECTIVE: The purpose of current study is to assess whether we can consider skin microcirculation disorders as a biomarker of cardiovascular events. METHODS: Group 1 consisted of healthy volunteers (n = 31); group 2 (n = 42) consisted of patients with diseases that increase the risk of cardiovascular events; group 3 (n = 39) included patients with the history of cardiovascular events. Skin microcirculation measurement was performed using laser Doppler flowmetry during the heating test. RESULTS: LDF parameters reflecting the rapid response of microcirculation to heating ("Slope 120 s" and "Slope 180 s") significantly differed in three groups (p <  0.05). A decrease in the "Slope 180 s" parameter less than 0.5 PU/s is associated with cardiovascular events (sensitivity 69.2%, specificity 66.7%; the area under the ROC curve, 0.667; 95% confidence interval [CI], 0.545-0.788, p = 0.01). Multivariable logistic regression analysis revealed that "Slope 180 s≤0.5 PU/s" was significantly related to cardiovascular events (adjusted odds ratio = 3.9, p = 0.019, CI 95% 1.2-12). CONCLUSIONS: Reduced reactivity of the skin microcirculation may be useful as a biomarker of severe damage to the cardiovascular system and is promising as a risk factor for cardiovascular events.


Assuntos
Doenças Cardiovasculares , Pele , Biomarcadores , Humanos , Fluxometria por Laser-Doppler , Microcirculação , Projetos Piloto
8.
Adv Gerontol ; 34(6): 863-869, 2021.
Artigo em Russo | MEDLINE | ID: mdl-35152602

RESUMO

It has been established that the age together with the number of chronic diseases cause the decrease of the reactivity of the microcirculatory bed. This study aims to evaluate the relationship between cutaneous microcirculation parameters and biological and chronological age of patients with diabetes mellitus. 11 diabetic patients (median age 57 (51; 64) years) were examined in course of this study; biological age was figured by Aging.AI3.0 calculator. Cutaneous microcirculation parameters were measured by laser Doppler flowmetry with an occlusion-heating test. Spearman's rank correlation coefficients were calculated to analyze the relationships between quantitative parameters. Significant multiple negative correlations of biological age and microvascular reactivity indices on exposure to both heat and occlusion (correlation strength from -0,618, to -0,97, p<0,05) were found. Diabetic patients have decreased microvascular reactivity that is more associated with biological age than with chronological age.


Assuntos
Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Envelhecimento , Humanos , Fluxometria por Laser-Doppler , Microcirculação , Pele
9.
Mol Biol (Mosk) ; 54(2): 313-320, 2020.
Artigo em Russo | MEDLINE | ID: mdl-32392202

RESUMO

Striatal-enriched protein tyrosine phosphatase (STEP), which was initially identified in the striatum, is encoded by the Ptpn5 gene and is expressed in neurons of various structures of the brain. STEP is involved in regulating neuroplasticity, and its expression abnormalities are associated with human neurodegenerative disorders. The STEP inhibitor 8-trifluoromethyl-1,2,3,4,5-benzopentathiepin-6-amine hydrochloride (TC-2153) has been shown to affect the serotoninergic system of the brain. However, the influence of the serotoninergic system on the STEP regulation has not been studied yet. The aim of the study was to investigate how pharmacologically induced changes in the brain serotonin (5-HT) level affect Ptpn5 expression and STEP activity in adult male C57BL/6J mice. To modulate the 5-HT level in the brain, the 5-HT synthesis inhibitor p-chlorophenylalanine or 5-HT degradation inhibitor pargyline was administered intraperitoneally for three successive days. Changes in 5-HT concentration in the brain were assayed using high-performance liquid chromatography. The STEP activity was determined spectrophotometrically in the supernatant by the rate of p-nitrophenyl phosphate dephosphorylation in the absence and presence of the selective STEP inhibitor TC-2153. The Ptpn5 mRNA level was determined using quantitative RT-PCR. The Ptpn5 expression level in the striatum was three times higher than in the cortex and hippocampus. Both increases and decreases in brain 5-HT were for the first time associated with a decrease in Ptpn5 mRNA in the striatum. STEP activity in the striatum and cortex was significantly higher than in the hippocampus. However, p-chlorophenylalanine and pargyline did not affect the STEP activity in the brain structures tested. Thus, a new method was proposed to study the STEP activity in the brain and p-chlorophenylalanine and pargyline were shown to decrease Ptpn5 expression in the striatum in mice.


Assuntos
Alanina/análogos & derivados , Cloraminas/farmacologia , Corpo Estriado/metabolismo , Pargilina/farmacologia , Proteínas Tirosina Fosfatases não Receptoras/metabolismo , Alanina/farmacologia , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neurônios , Serotonina
10.
Mol Biol (Mosk) ; 54(1): 60-68, 2020.
Artigo em Russo | MEDLINE | ID: mdl-32163389

RESUMO

A decrease in the light in autumn and winter causes depression like seasonal affective disorders (SAD) in sensitive patients, in which the serotonin (5-HT) and dopamine (DA) brain mediator systems are involved. We studied the interaction of the 5-HT and DA brain systems in an experimental SAD model in sexually mature male mice of the congenic B6-1473C and B6-1473G lines with high and low activity of tryptophan hydroxylase 2, a key enzyme of 5-HT synthesis in the brain. Mice of each line (divided into two groups of eight individuals) were kept for 30 days in standard (14 h light/10 h dark) and short (4 h light/20 h dark) daylight. The presence of the C1473G variant in the tryptophan hydroxylase 2 gene did not affect the expression of key genes of DA system: Drd1, Drd2, Scl6a3, Th, and Comt, that encode the D1 and D2 receptors, dopamine transporter, tyrosine hydroxylase, and catechol-o-methyltransferase, respectively. A decrease in the level of DA in the midbrain, as well as of its metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) in the striatum, was detected in B6-1473G mice. Keeping mice in short daylight did not affect expression of the Drd1 gene in all brain structures nor the expression of the Slc6a3 and Th genes in the midbrain. Drd2 expression increased in the midbrain and decreased in the hippocampus, where Comt expression increased. An increase in DA level in the midbrain and DOPAC in the striatum was detected in mice kept in short daylight. This indicates the involvement of the brain's DA system in the reaction to a decrease in daylight duration. No statistically significant effect of the interaction between the presence of the C1473G variant and daylight length on indicators of the activity of DA system was detected. No reasons were found to assert that this polymorphism determines the observed reaction of the brain DA system in keeping of animals under short daylight conditions.


Assuntos
Encéfalo/metabolismo , Dopamina/metabolismo , Fotoperíodo , Polimorfismo Genético , Triptofano Hidroxilase/genética , Animais , Encéfalo/enzimologia , Masculino , Camundongos , Triptofano Hidroxilase/metabolismo
11.
Bull Exp Biol Med ; 168(1): 95-98, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31758379

RESUMO

The effects of composite fibroin-gelatin microparticles (100-250 µ) on the rate of wound healing and regeneration under conditions of contraction prevention were studied on the model of splinted full-thickness skin wound in a mouse. Subcutaneous injection of these particles into the defect area accelerated wound healing and promoted re-epithelialization and recovery of normal structure of the epidermis. In addition, the composite microparticles promoted the formation of connective tissue of characteristic structure, replacing the derma over the entire defect, and stimulated regeneration of subcutaneous muscle (panniculus carnosus) and skin appendages (sebaceous glands and hair follicles).


Assuntos
Fibroínas/química , Fibroínas/farmacologia , Gelatina/química , Gelatina/farmacologia , Dermatopatias/tratamento farmacológico , Pele/metabolismo , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Regeneração/efeitos dos fármacos , Pele/efeitos dos fármacos , Cicatrização/efeitos dos fármacos
12.
Bull Exp Biol Med ; 167(1): 100-103, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31177455

RESUMO

We studied the influence of obesity caused by lethal yellow (AY) mutation in the agouti gene, short photoperiod (4/20 h light/darkness), and combination of these factors on depressive-like behavior in the forced swimming test and expression of genes encoding proinflammatory cytokines in the hypothalamus of heterozygous male C57Bl/6-AY/a mice and their wild-type littermate controls (C57Bl/6-a/a). It was shown that AY mutation as well as short photoperiod increased depressive-like behavior in mice. No effect of the interaction of AY mutation and photoperiod on immobility in the forced swimming test was revealed. In wild-type mice, increased depressive-like behavior caused by short photoperiod was accompanied by enhanced expression of Tnf gene. Exposure to short daylight increased the expression of Nos2.


Assuntos
Citocinas/metabolismo , Depressão/genética , Transtorno Depressivo/metabolismo , Hipotálamo/metabolismo , Fotoperíodo , Animais , Locomoção/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mutação/genética , Natação/fisiologia
13.
Adv Gerontol ; 31(3): 316-322, 2018.
Artigo em Russo | MEDLINE | ID: mdl-30584868

RESUMO

A statistically significant difference in the cumulative survival of Wistar rats born in different seasons has been shown: animals born in late November - early December had an average lifespan by 24,8% longer, a minimum lifespan by 14,3% longer, and a maximum lifespan by 20,7% longer in comparison with animals born in April. The geroprotective effect of the technique of thymus tissue transplantation into the immune privileged anterior chamber of the eye in animals born both in November and April has been shown.


Assuntos
Animais de Laboratório , Longevidade , Animais , Câmara Anterior , Ratos , Ratos Wistar , Estações do Ano
14.
Neuroscience ; 394: 220-231, 2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-30367948

RESUMO

The serotoninergic 5-HT2A receptor is involved in the mechanism of depression and antidepressant drugs action. Earlier we showed that striatal-enriched protein tyrosine phosphatase (STEP) inhibitor - 8-(trifluoromethyl)-1,2,3,4,5-benzopentathiepin-6-amine hydrochloride (TC-2153) affects both the brain serotoninergic system and the brain-derived neurotropic factor that are known to be involved in the psychopathology of depression. In the present study we investigated the effects of chronic TC-2153 administration on behavior in the standard battery of tests as well as the effects of acute and chronic TC-2153 treatment on the brain 5-HT2A receptors in mice. We obtained a prominent antidepressant-like effect of chronic TC-2153 treatment in the forced swim test without any adverse side effects on locomotor activity, anxiety, exploration, motor skill and obsessive-compulsive-like behavior. Moreover, both acute and chronic TC-2153 administration inhibited the functional activity of 5-HT2A receptors estimated by the number of 2,5-dimethoxy-4-iodoamphetamine (DOI, agonist of 5-HT2A receptors)-induced head-twitches. TC-2153 treatment also attenuated the DOI-induced c-fos expression in cortical and hippocampal neurons and reduced the 5-HT2A receptor protein level in the hippocampus and frontal cortex, but not in the striatum. Taken together, our combined data demonstrate that the antidepressant effect of STEP inhibitor TC-2153 could be mediated by its inhibitory properties towards the 5-HT2A receptor-mediated signaling.


Assuntos
Antidepressivos/administração & dosagem , Benzotiepinas/administração & dosagem , Encéfalo/efeitos dos fármacos , Depressão/tratamento farmacológico , Proteínas Tirosina Fosfatases não Receptoras/antagonistas & inibidores , Receptor 5-HT2A de Serotonina/metabolismo , Animais , Comportamento Animal/efeitos dos fármacos , Encéfalo/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Atividade Motora/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo
15.
Bull Exp Biol Med ; 164(5): 620-623, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29577201

RESUMO

We compared the effect of a new potential antidepressant 8-trifluoromethyl 1,2,3,4,5-benzopentathiepine-6-amine hydrochloride (TC-2153) and classical antidepressant fluoxetine in a dose of 0.25 mg/liter on the behavior of Danio rerio in the "novel tank" test and content of biogenic amines and their metabolites in the brain. Fluoxetine alone and TC-2153 alone significantly increased the time spent in the upper part of the tank and insignificantly reduced motor activity. Combined exposure of fishes in the solution containing potential and classical antidepressants potentiated their effects on both parameters. The compounds did not affect brain contents of serotonin, dopamine, and norepinephrine. At the same time, fluoxetine, but not TC-2153, reduced brain content of the main serotonin metabolite 5-hydroxyindole acetic acid.


Assuntos
Antidepressivos/farmacologia , Benzotiepinas/farmacologia , Aminas Biogênicas/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Fluoxetina/farmacologia , Animais , Comportamento Animal/efeitos dos fármacos , Dopamina/metabolismo , Norepinefrina/metabolismo , Serotonina/metabolismo , Peixe-Zebra
16.
Zh Nevrol Psikhiatr Im S S Korsakova ; 117(9. Vyp. 2): 80-87, 2017.
Artigo em Russo | MEDLINE | ID: mdl-29213044

RESUMO

AIM: To study the anamnesis, clinical state, electro-encephalographic and brain MRI characteristics in patients with Rett syndrome (МЕСР2) and epilepsy. MATERIAL AND METHODS: Eleven female patients, aged from 3 to 23 years, with Rett syndrome and MeCP2 mutations were studied. The study continued for 10 years (2006-2015). Assessment of neurological and mental status, night sleep video-EEG monitoring, MRI were performed. RESULTS AND CONCLUSION: Epilepsy was diagnosed in six cases (54.5%). Mean age at onset of epileptic seizures was 3 years 9 month. The following types of seizures were described: generalized, myoclonic, myotonic, tonic, versive, focal motor, atypical absences. Status epilepticus developed in one patient. Generalized seizures were identified in 56.25%, focal seizures in 43.75%. EEG changes were found in 9 patients (81.8%): slowing of the activity, episodes of periodic regional slowing, regional epileptiform activity and diffuse epileptiform activity, benign focal epileptiform discharges (BFED) of childhood, multiregional epileptiform activity. Five patients were treated with antiepileptic drugs. All of them had improved during treatment: a reduction of frequency of seizures was up to 50% in 4 cases (80%). One patient with resistant epilepsy was treated with the combination of drugs (levetiracetam, topiramate, zonisamide, benzodiazepine) that led to stopping of seizures during night sleep and decrease in the frequency of daytime seizures by 50%. Further research of epilepsy and efficacy of antiepileptic drugs in Rett syndrome is required.


Assuntos
Epilepsia , Síndrome de Rett , Adolescente , Adulto , Criança , Pré-Escolar , Eletroencefalografia , Epilepsia/complicações , Epilepsia/diagnóstico por imagem , Epilepsia/tratamento farmacológico , Epilepsia/genética , Feminino , Humanos , Imageamento por Ressonância Magnética , Mutação , Síndrome de Rett/complicações , Síndrome de Rett/diagnóstico por imagem , Síndrome de Rett/genética , Convulsões , Adulto Jovem
17.
Dokl Biochem Biophys ; 472(1): 12-14, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28421432

RESUMO

Regenerative properties of fibroin implant vitalized with allogeneic bone marrow cells were assessed. The study was performed using the experimental model of rat jejunum wall damage. Three weeks after surgery, we observed recovery of all layers of the jejunum wall at the site of injury and complete degradation of the implant material.


Assuntos
Fibroínas/química , Regeneração Tecidual Guiada/métodos , Jejuno/cirurgia , Regeneração , Animais , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/fisiologia , Fibroínas/efeitos adversos , Implantes Experimentais , Jejuno/fisiologia , Masculino , Ratos , Ratos Wistar , Tecidos Suporte/efeitos adversos , Tecidos Suporte/química
18.
Dokl Biochem Biophys ; 472(1): 27-30, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28421447

RESUMO

The most common drug resistance mechanism in tumor cells is expression on their surface of the energy-dependent pump like P-glycoprotein (P-gp) that expels chemotherapeutic agents from the interior. An imitation of the hypoxic condition by the iron chelator deferoxamine caused Hypoxia-inducible factor 1-alpha (HIF-1α) stabilization and inhibition of doxorubicin-induced apoptosis in colon cancer НСТ116 cells. P-gp blocker verapamil suppressed doxorubicin accumulation leading to cell death induction. Considering these results, P-gp may be used as a potential target to stimulate chemotherapeutic drugs activity that will contribute to more efficient tumor cells elimination.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/antagonistas & inibidores , Apoptose/efeitos dos fármacos , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Hipóxia Celular , Desferroxamina/toxicidade , Doxorrubicina/toxicidade , Células HCT116 , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Sideróforos/toxicidade , Verapamil/farmacologia
19.
Neurosci Lett ; 640: 88-92, 2017 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-28088578

RESUMO

The study of spaceflight effects on the brain is technically complex concern; complicated by the problem of applying an adequate ground model. The most-widely used experimental model to study the effect of microgravity is the tail-suspension hindlimb unloading model; however, its compliance with the effect of actual spaceflight on the brain is still unclear. We evaluated the effect of one month hindlimb unloading on the expression of genes related to the brain neuroplasticity-brain neutotrophic factors (Gdnf, Cdnf), apoptotic factors (Bcl-xl, Bax), serotonin- and dopaminergic systems (5-HT2A, Maoa, Maob, Th, D1r, Comt), and compared the results with the data obtained on mice that spent one month in spaceflight on Russian biosatellite Bion-M1. No effect of hindlimb unloading was observed on the expression of most genes, which were considered as risk neurogenes for long-term actual spaceflight. The opposite effect of hindlimb unloading and spaceflight was found on the level of mRNA of D1 dopamine receptor and catechol-O-methyltransferase in the striatum. At the same time, the expression of Maob in the midbrain decreased, and the expression of Bcl-xl genes increased in the hippocampus, which corresponds to the effect of spaceflight. However, the hindlimb unloading model failed to reproduce the majority of effects of long-term spaceflight on serotonin-, dopaminergic systems and some apoptotic factors.


Assuntos
Apoptose , Encéfalo/metabolismo , Dopamina/metabolismo , Serotonina/metabolismo , Ausência de Peso , Animais , Dopamina/genética , Elevação dos Membros Posteriores , Masculino , Camundongos Endogâmicos C57BL , Monoaminoxidase/metabolismo , Receptor 5-HT2A de Serotonina/metabolismo , Serotonina/genética , Voo Espacial , Fatores de Tempo
20.
Anesteziol Reanimatol ; 61: 209-215, 2017 Sep.
Artigo em Russo | MEDLINE | ID: mdl-29465206

RESUMO

OBJECTIVE: The study focuses on identifying predictors of treatment outcome in abdominal sepsis (AS) in humans. SUBJECTS AND METHODS: 70 patients underwent determination of blood pressure, heart rate, SpO , the content of leu- kocytes, albumin, C-reactive protein, fibrinogen and TNF-a in arterial (femoral artery) and venous (subclavian vein) blood. Automatic biochemical analyzer Cobas-Integra 400 ('Roche", Switzerland), the test system Microlab STAR ELISA kit reagents "alpha TNF - ELISA - best" were used during the research. System statistical analysis included paired comparison of patients with favorable (n=27) and lethal (n=43) outcome, correlation, cluster; discriminating analysis, multidimensional scaling and plotting ROC curves with sensitivity and specificity indicators predictive value. RESULTS: Identfied predictors of outcome inpatients,from which to form a predictive model of CRP fibrinogen, albumin, and TNF-a arterial blood. It is established that if the basic treatment of the patient CRP <9,8 g/l,fibrinogen >3,43 g/l, albumin <28,9 gl and TNF-a <499,3 ng/ml, the probability of death was statistically significantly higher thanfavorable. CONCLUSION: It is assumed that therapeutic measures should be aimed at correction of the above mentioned indicators.


Assuntos
Mediadores da Inflamação/sangue , Infecções Intra-Abdominais/sangue , Modelos Biológicos , Sepse/sangue , Adulto , Idoso , Biomarcadores/sangue , Pressão Sanguínea/fisiologia , Intervalo Livre de Doença , Feminino , Frequência Cardíaca/fisiologia , Humanos , Infecções Intra-Abdominais/imunologia , Infecções Intra-Abdominais/fisiopatologia , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Curva ROC , Sepse/imunologia , Sepse/fisiopatologia , Adulto Jovem
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