The therapeutic effect of multipotent mesenchymal stem cells has been proven on various disease models. One of the mechanisms is the paracrine effect of the cells on the surrounding tissues.The aim. To investigate the secretome effectiveness of the multipotent mesenchymal stem cells in the treatment of adjuvant arthritis and contact-allergic dermatitis in Wistar rats.Materials and methods. Adjuvant arthritis was simulated in 26 female rats by the administration of Freund's complete adjuvant and then treated with the administration of 100 µl of multipotent mesenchymal stem cell secretome or saline. Contact-allergic dermatitis was modeled on 30 female rats by applying 200 μl of an oil solution of dinitrofluorobenzene to the skin on days 1, 5 and 6. Then the rats were treated with fluocinolone ointment (a positive control), baby cream (a negative control), baby cream with a secretome of native multipotent mesenchymal stem cells or from the cells processed with dexamethasone.Results. Judging by the indicators of the longitudinal and transverse dimensions of the paws in rats and a histological examination, the secretome did not have any anti-inflammatory effect on adjuvant arthritis. A cream with a secret from multipotent mesenchymal stem cells processed with dexamethasone, was the most effective on the model of contact-allergic dermatitis: the clinical improvement occurred on the 2nd day. The secretome from native multipotent mesenchymal stem cells and fluocinolone had a therapeutic effect on the 3rd day of application, the negative control - on the 4th day. The lymphocytic infiltration coefficient was significantly lower (p <0.05) in all the cases compared to the negative control (2.8 ± 0.1). However, the lowest infiltration was observed when the cream with secretome from native (1.75 ± 0,1) and dexamethasone-stimulated (1.76 ± 0.1) multipotent mesenchymal stem cells was being used.Conclusion. The cream with the secretome of multipotent mesenchymal stem cells suppresses lymphocytic infiltration more strongly than the highly active topical glucocorticosteroid - fluocinolone - on the model of contact-allergic dermatitis, which is a classic local delayed-type hypersensitivity reaction. However, a further study of the therapeutic effect of the secretome on models of systemic inflammatory diseases is required after its preliminary purification from large-molecular proteins.
Исследовано нейропротективное действие агониста имидазолиновых рецепторов типов I и II, 3-(1H-бензимидазол-2-ил)-1,2,2-триметилциклопентанкарбоновой кислоты, в дозе 50 мг/кг в сравнении с пикамилоном в дозе 30 мг/кг на модели ишемической нейропатии зрительного нерва у крыс-самцов линии Wistar. В эксперименте выявлено, что 3-(1H-бензимидазол-2-ил)-1,2,2-триметилциклопентанкарбоновая кислота предотвращает развитие ишемической нейропатии зрительного нерва, вызванной введением неселективного ингибитора NO-синтазы N-нитро-L-аргинин-метилового эфира (L-NAME) в дозе 12,5 мг/кг в течение 28 сут, и однократным повышением внутриглазного давления (ВГД) до 110 мм рт. ст., в большей степени, чем пикамилон. У крыс в группе с коррекцией 3-(1H-бензимидазол-2-ил)-1,2,2-триметилциклопентанкарбоновой кислотой удельное количество ядер нейронов в наружном ядерном слое достоверно выше на 15,0 % (p < 0,05), в сравнении с группой животных с введением пикамилона; на 33,3 % (p < 0,05), в сравнении с группой с моделированием патологии, что свидетельствует о сохранении их жизнеспособности. Обнаруженные протективные эффекты подтверждены результатами офтальмоскопии и гистологических исследований на 29 сут эксперимента.
Соразмерность является ключевым элементом концепции правовой государственности и в таком качестве основывается на либеральной идеологии. Исходя из взаимосвязи формальных и материальных аспектов правового государства, принцип соразмерность служит средством антиформализма и означае т недопустимость произвола властей при вмешательстве в конституционные права. С процессуальной точки зрения соразмерность представляет собой основание конституционного судебного нормоконтроля. Ключевые слова: принцип соразмерности, основы конституционного строя, правовое государство.
General aspects of glaucoma: Glaucoma is a heterogeneous multi-factorial disease that is one of the main causes of blindness, along with degeneration of retinal ganglion cells and optic nerve atrophy. Theories of pathogenesis: There are three theories of glaucoma pathogenesis: biomechanical, vascular, and biochemical. Basic theory of the glymphatic system: The classical knowledge of cerebrospinal fluid circulation has been revised, and in 2012 a new concept of glial-perivascular – glymphatic perfusion of the brain parenchyma was introduced. Due to experimental and clinical studies, it is approved by many scientists, especially in relation to Alzheimer’s disease (AD), in which amyloid pathology is the result of dysfunction of the para-/perivascular transport/cleansing pathways. Features of the optic nerve and the cribriform plate: The cribriform plate forms a barrier at the border of intraocular (IOP) and intracranial (ICP) pressures, thus affecting the para-/periarterial flow of cerebrospinal fluid to the optic nerve and retina, as well as the para-/perivenous cleansing outflow. Morphofunctional evidence of an ocular glymphatic system: The presence of an ocular glymphatic system is confirmed by in vivo experiments with the transfer of labeled substances through para-/perivascular structures from the ventricular or subarachnoid space to the optic nerve and by postmortem morphology. Clinical evidence for the glymphatic system hypothesis: There is some clinical, including case-based, and epidemiological evidence for similarities between glaucomatous optic nerve/retinal injuries and AD, since both occur in the form of improper secretion of neurotoxic metabolites, and both are often diagnosed together.
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