RÉSUMÉ
Investigation of multiple sclerosis (MS) pathogenesis requires sophisticated analytical tools of precision medicine, such as omics research, which include genomics, microbiomics and metabolomics (proteomics, lipidomics and glycomics). Such sensitive methods are based on careful preanalytical work with biomaterials to maintain quality and obtain objective results. Implementation of biobanking as a universal method for working with biomaterials will help to standardize the stages of research, compare different scientific team's results. Collaboration of MS researchers with large biobanks can also help to conduct multicenter and long-term prospective studies, to include a wide number of patients. In this article, we analyze the experience of biobanking practice technologies in studies of MS patients and share the experience of partnership between the Center for MS of the Tomsk Region and the Bank of Biological Material of the Siberian State Medical University.
Sujet(s)
Biobanques , Sclérose en plaques , Médecine de précision , Humains , Essais cliniques comme sujet , Métabolomique , Sclérose en plaques/anatomopathologie , Médecine de précision/méthodes , SibérieRÉSUMÉ
Phenotypic characteristics of alveolar macrophages in the bronchoalveolar lavage fluid as well as their ability to acquire the M1 and M2 phenotypes during in vitro culturing with reprogramming factors were studied in rats with modeled diet-induced metabolic syndrome. A decrease in the number of alveolar macrophages with the M1 phenotype was found in animals with metabolic syndrome. The factors of metabolic syndrome do not affect phenotypic plasticity of cells in culture, but under the action of M2 reprogramming factors, the cells demonstrate a wide range of phenotypic plasticity by the CD80 and CD206 markers. The consistently high level of production of IL-6 and IL-10 by macrophages during culturing under different conditions indicates functional rigidity of the cells, which is probably a consequence of in vivo predetermined functional phenotype of these cells against the background of metabolic disorders.
Sujet(s)
Macrophages alvéolaires , Syndrome métabolique X , Rats , Animaux , Syndrome métabolique X/métabolisme , Macrophages/métabolisme , Phénotype , Liquide de lavage bronchoalvéolaireRÉSUMÉ
We studied antihypertensive activity of an indolinone derivative (compound GRS), a soluble guanylate cyclase stimulator and a drug with previously proven antiaggregant effects. Contraction activity of isolated aorta segments of Wistar-Kyoto (WKY) rats was assessed in vitro using a mechanographic method. Addition of GRS (0.1-100 µÐ) resulted in dose-dependent relaxation of endothelium-denuded aorta segments. Pretreatment of aorta smooth muscle segments with a specific inhibitor of soluble guanylate cyclase (ODQ, 1 µM) weakened the vasodilatory effect of GRS. Antihypertensive activity of the indolinone derivative GRS was studied in spontaneously hypertensive SHR rats. Single oral administration of 5 and 10 mg/kg GRS was followed by a significant dose-dependent reduction of systolic and diastolic BP in SHR rats. Antihypertensive effect of GRS in a dose of 5 mg/kg was more potent than that of the reference drug isosorbide dinitrate. GRS in a dose of 10 mg/kg did not affect systolic and diastolic BP in normotensive WKY rats.
Sujet(s)
Antihypertenseurs , Pression sanguine , Oxindoles , Soluble guanylyl cyclase , Vasodilatateurs , Animaux , Rats , Antihypertenseurs/pharmacologie , Oxindoles/pharmacologie , Rats de lignée SHR , Rats de lignée WKY , Soluble guanylyl cyclase/métabolisme , Vasodilatateurs/pharmacologie , Vasodilatation , Pression sanguine/effets des médicaments et des substances chimiquesRÉSUMÉ
We studied contractile responses of isolated airway smooth muscle segments from rats with metabolic syndrome. Metabolic syndrome was induced in rats by high-fat and high-carbohydrate diet. It was shown that metabolic syndrome was associated with an increase of bronchoconstrictor action of cholinergic receptor activator carbacholine (0.1-100 µM) and a decrease of the dilatory effect of ß2-adrenoreceptor activator salbutamol (0.1-100 µM). The observed effects of agonists are epithelium-dependent. Disorders in contractile activity in the airway smooth muscles were accompanied by bronchial epithelium destruction, immune inflammation in the bronchial wall, muscular and peribronchial adipose tissue hypertrophy.
Sujet(s)
Bronchoconstricteurs , Syndrome métabolique X , Salbutamol/pharmacologie , Animaux , Bronches , Bronchoconstricteurs/métabolisme , Bronchoconstricteurs/pharmacologie , Carbachol/métabolisme , Carbachol/pharmacologie , Glucides/pharmacologie , Syndrome métabolique X/métabolisme , Contraction musculaire , Muscles lisses , Rats , Récepteurs cholinergiques/métabolismeRÉSUMÉ
We studied the effect of the H2S donor (NaHS, 1-500 µM) on the contractile responses of isolated aortic smooth muscle segments from rats with metabolic syndrome induced by high-fat, high-carbohydrate diet. It was found that the vasorelaxing effect of NaHS (5-100 µM) decreased in under conditions of MS. The endothelial NO synthase inhibitor L-NAME (100 µM) suppressed the effect of NaHS, while cystathionine-gamma-lyase inhibitor PAG (100 µM) decreased the vasodilating effects of acetylcholine (0.1-100 µM). Application of endogenous NO precursor L-arginine (1 mM) potentiated in the effects of H2S donor NaHS. Thus, the contractile activity of vascular smooth muscles in metabolic syndrome is determined by not only the effect of H2S, but also the influence of NO.
Sujet(s)
Sulfure d'hydrogène/pharmacologie , Maladies métaboliques/physiopathologie , Contraction musculaire/effets des médicaments et des substances chimiques , Muscles lisses vasculaires/effets des médicaments et des substances chimiques , Animaux , Phénomènes biomécaniques/effets des médicaments et des substances chimiques , Mâle , Maladies métaboliques/anatomopathologie , Syndrome métabolique X/anatomopathologie , Syndrome métabolique X/physiopathologie , Muscles lisses vasculaires/physiologie , L-NAME/pharmacologie , Rats , Rat WistarRÉSUMÉ
Reduced glucose tolerance, hyperglycemia, and imbalance in lipid levels were found in rats with metabolic syndrome induced by a high-fat, high-carbohydrate diet. The contractile responses of intact and endothelium-denuded aortic smooth muscle segments from rats with metabolic syndrome to application of acetylcholine, phenylephrine, sodium nitroprusside, and forskolin were studied by mechanographic method. It was found that endothelial dysfunction develops against the background of metabolic and hemodynamic disorders in metabolic syndrome. It was shown that the regulation of vasoconstrictor reactions of vascular smooth muscles in metabolic syndrome is due to a decrease in Ca2+ entry, mainly voltage-independent, as well as changes in the function of cGMP- and cAMP-activated K+-channels.
Sujet(s)
Syndrome métabolique X/physiopathologie , Contraction musculaire/effets des médicaments et des substances chimiques , Muscles lisses vasculaires/effets des médicaments et des substances chimiques , Vasoconstriction/effets des médicaments et des substances chimiques , Acétylcholine/pharmacologie , Animaux , Aorte/physiopathologie , Poids , Calcium/métabolisme , Glucides , Colforsine/pharmacologie , Modèles animaux de maladie humaine , Endothélium vasculaire/métabolisme , Glucose/métabolisme , Hémodynamique , Lipides/sang , Mâle , Syndrome métabolique X/métabolisme , Muscles lisses/physiopathologie , Nitroprussiate/pharmacologie , Phényléphrine/pharmacologie , Canaux potassiques , Rats , Rat Wistar , Contrainte mécanique , Triglycéride/sangRÉSUMÉ
The effect of H2S on changes in erythrocyte volume was studied by spectrophotometrical and potentiometric methods. It was found that H2S donor NaHS (2.5, 10, and 100 µM) induced an increase in erythrocyte volume in heterosmotic media. Activation of Gardos channels with A23187 or ascorbate-phenazine methosulfate system causes erythrocyte shrinkage and hyperpolarization of their membrane, while addition of NaHS restored erythrocyte volume. The decrease in erythrocyte volume upon blockade of Na+,K+,2Cl- cotransporter (bumetanide) or anion exchanger (SITS) was abolished by H2S donor NaHS, which attested to an important role of these transporters and chlorine conductivity of the membrane in the maintenance of the homeostasis of blood cells.
Sujet(s)
Bumétanide/pharmacologie , Membrane érythrocytaire/effets des médicaments et des substances chimiques , Membrane érythrocytaire/métabolisme , Érythrocytes/effets des médicaments et des substances chimiques , Érythrocytes/métabolisme , Sulfure d'hydrogène/pharmacologie , Symporteurs des ions sodium-potassium-chlorure/métabolisme , Adulte , Femelle , Humains , Canaux potassiques calcium-dépendants de conductance intermédiaire , Mâle , Jeune adulteRÉSUMÉ
We studied the role of carbon monoxide (CO) in the effect of P2X and P2Y receptor agonist ATP on the tone of rat aorta segments with intact endothelium. ATP (1-1000 µM) and P2X receptor agonist α,ß-MeATP (100 µM) relaxed segments precontracted with phenylephrine (10 µM), while UTP (100-1000 µM) increased the amplitude of phenylephrine-induced contraction. The relaxing effect of ATP was enhanced by CORM II (100 µM), NO synthase inhibitor L-NAME, and guanylate cyclase inhibitor ODQ and attenuated by ZnPP IX (100 µM). The constrictive effect of UTP was weakened by CORM II (100 µM), but was not changed by ZnPP IX (100 µM). ZnPP IX (100 µM) weakened the relaxation response to α,ß-MeATP. Thus, ATP involves the CO-dependent signaling cascade through P2X receptors.
Sujet(s)
Aorte/physiologie , Monoxyde de carbone/pharmacologie , Endothélium/physiologie , Contraction musculaire/effets des médicaments et des substances chimiques , Muscles lisses vasculaires/effets des médicaments et des substances chimiques , Adénosine triphosphate/métabolisme , Animaux , Aorte/cytologie , Cellules cultivées , Endothélium/cytologie , Endothélium/effets des médicaments et des substances chimiques , L-NAME/pharmacologie , Composés organométalliques/pharmacologie , Oxadiazoles/pharmacologie , Phényléphrine/pharmacologie , Protoporphyrines/pharmacologie , Agonistes des récepteurs purinergiques P2X/pharmacologie , Agonistes des récepteurs purinergiques P2Y/pharmacologie , Quinoxalines/pharmacologie , Rats , Rat Wistar , Récepteurs purinergiques P2X/métabolisme , Récepteurs purinergiques P2Y/métabolismeRÉSUMÉ
We analyzed the effects of hypoxia and reoxygenation on changes in contractile activity in rat aortic smooth muscles. Both hypoxia and reoxygenation induced relaxation of smooth muscle cells precontracted with high-potassium Krebs solution (30 mM KCl) or α1-adrenoceptor agonist phenylephrine. Vasodilation resulted from enhancement of potassium permeability of smooth muscle cell membranes caused by activation of voltage-gated potassium channels (triggered by both precontracting agents) or by opening of ATP-sensitive potassium channels (phenylephrine). In isolated smooth muscle cells, both hypoxia and inhibition of Na+,K+-ATPase with ouabain led to depletion of intracellular store of macroergic substances, reduced potassium concentration, and elevated the content of sodium ions.
Sujet(s)
Hypoxie/métabolisme , Contraction isométrique/effets des médicaments et des substances chimiques , Muscles lisses vasculaires/effets des médicaments et des substances chimiques , Oxygène/pharmacologie , Potassium/métabolisme , Sodium/métabolisme , Adénosine triphosphate/métabolisme , Agonistes des récepteurs alpha-1 adrénergiques/pharmacologie , Animaux , Aorte/cytologie , Aorte/effets des médicaments et des substances chimiques , Aorte/métabolisme , Antienzymes/pharmacologie , Canaux KATP/métabolisme , Mâle , Muscles lisses vasculaires/cytologie , Muscles lisses vasculaires/métabolisme , Myocytes du muscle lisse/cytologie , Myocytes du muscle lisse/effets des médicaments et des substances chimiques , Myocytes du muscle lisse/métabolisme , Ouabaïne/pharmacologie , Phényléphrine/pharmacologie , Canaux potassiques voltage-dépendants/métabolisme , Culture de cellules primaires , Rats , Rat Wistar , Sodium-Potassium-Exchanging ATPase/métabolisme , Techniques de culture de tissus , Vasodilatation/effets des médicaments et des substances chimiquesRÉSUMÉ
The hydrogen sulfide (H2S) influence on the contractile activity of vascular smooth muscle cells (SMC) was studied on endothelium-denuded aortic ring segments of male Wistar rats with method of mechanography. Contractions of SMS were induced by incubation in high potassium solution as well as in hyper-, hypo- and isosmotic solutions. 5-100 LM of H2S donor--sodium hydrosulfide (NaHS) increased mechanical tension of SMC precontracted with high potassium solution that was abolished by bumetanide--the inhibitor of Na+, K+, 2Cl(-) -cotransporter (NKCC), but 100-1000 microM of NaHS relaxed SMS. NaHS (10 microM) increased the amplitude of hyper- and isosmotic contraction, but not of hyposmotic contraction. NaHS (ImM) decreased the amplitude of hyper-, iso-, and hyposmotic contractions. The direct measurements of NKCC activity with radionuclide method showed an increase in NKCC activity under the action of 5-100 microM of NaHS. These findings suggest that low concentrations of H2S participate in the NKCC activation. This mechanism underlines constrictive action of H2S on smooth muscle cells.