RESUMO
The relationship between dietary sodium, hypertension, and cardiovascular injury is far from clear. One of the important links in this process can be microRNAs that have the ability to modulate gene expression at the post-transcriptional level. However, their role in this process has not been fully studied. In addition, further studies require the identification of structural changes in the myocardium in conditions of long-term consumption of a high-salt diet. The aim of the study was to evaluate the expression levels of nuclear transcription factor κB (NFκB), microRNA (miRNA)-21 and structural changes in the myocardium during long-term consumption of a diet containing 8% (high) sodium chloride in Wistar rats. Material and methods. 20 Wistar rats with initial body weight 280.5±42.7 g were divided into two equal groups. The high salt (HS) group received 8% NaCl in the diet, the control (NS) group received the standard diet (0.34% NaCl). After 4 months, systolic blood pressure was measured in rats using the cuff method on the tail; the myocardial mass index was assessed after dissection; histological and electron microscopic examination of the myocardium was performed, and the expression levels of miRNA-21 and NFκB in the myocardium were determined. Results and discussion. Consumption of a diet high in sodium chloride for 4 months did not significantly affect the level of systolic blood pressure in normotensive Wistar rats, but led to an increase in myocardial mass index by 25.0% (p<0.05). In the HS group, hypertrophy of cardiomyocytes and an increase in the wall thickness of arterial vessels were revealed. The area of perivascular fibrosis in rats of the HS-group was almost 1.8 fold higher than in the NS-group. In animals of HS-group, the relative levels of expression of NFκB (more than 2 times) and miRNA-21 (almost 6 times) increased compared with the control. It can be assumed that the negative impact on the cardiovascular system of high-salt diets is partially realized through NFκB-associated signaling pathways and miRNA-21 activation. Conclusion. In Wistar rats, long-term use of a high-salt diet results in myocardial remodeling that is not associated with changes in blood pressure. At the same time, the adverse effects of high salt intake on the myocardium are mediated, in particular, by postgenomic mechanisms, namely an increase in the expression levels of NFκB and microRNA-21.
Assuntos
MicroRNAs , Cloreto de Sódio , Ratos , Animais , Cloreto de Sódio na Dieta/efeitos adversos , Ratos Wistar , Dieta , Miocárdio , MicroRNAs/genéticaRESUMO
Morphological properties and the size of microvesicles were assessed using atomic force microscopy, electron microscopy, and granulometric analysis. As these methods require significant numbers of microvesicles, we chose microvesicles derived from cell lines for our research.
Assuntos
Membrana Celular/ultraestrutura , Micropartículas Derivadas de Células/ultraestrutura , Células Endoteliais/ultraestrutura , Células Matadoras Naturais/ultraestrutura , Trofoblastos/ultraestrutura , Linhagem Celular , Humanos , Microscopia de Força Atômica , Microscopia Eletrônica de Transmissão , Células THP-1RESUMO
Extracellular vesicles are subspherical membranous structures secreted by cells and enriched with different types of biological molecules. The number and the molecular content of these structures depend on pathological conditions and the physiological state of the organism. Extracellular vesicles play an important role in intercellular communication and represent potential disease biomarkers. However, mechanisms of formation, functions and morphological characteristics of extracellular vesicles are still studied insufficiently. Low voltage scanning electron microscopy is a promising method to investigate extracellular vesicles, since it does not require conductive coating and therefore enables a high-resolution visualization of morphological details of nanosized objects. This paper presents the results of low voltage scanning electron microscopy study of morphology and size of objects from blood plasma fractions.
Assuntos
Micropartículas Derivadas de Células/ultraestrutura , Vesículas Extracelulares/ultraestrutura , Microscopia Eletrônica de Varredura , Plasma , Animais , Micropartículas Derivadas de Células/metabolismo , Vesículas Extracelulares/metabolismo , Humanos , Masculino , Ratos , Ratos WistarRESUMO
We studied the effect of two pectic polysaccharides PS-B1-AG and PS-B2-RG that were contained in total polysaccharides extracted from Betula pendula leaves on NO production by mouse macrophages and the contribution of signaling molecules to macrophage activation by the test substances. Unlike the total sample, pectins produced a NO-stimulating effect on macrophages. The effect of PS-B2-RG (10 µg/ml) did not differ from the effect of LPS, while PS-B1-AG produced this effect only in a concentration of 20 µg/ml, which was probably due to differences in the chemical structure of the test substances. The studied pectin polysaccharides activated transcription factor NF-κB, kinases p38 and PI3, and cAMP as a negative regulator. These results indicate that Betula pendula polysaccharides are promising substances for creation of immunomodulating drugs.
Assuntos
Betula/química , Fatores Imunológicos/farmacologia , Ativação de Macrófagos/efeitos dos fármacos , Polissacarídeos/farmacologia , Animais , Células Cultivadas , AMP Cíclico/metabolismo , Feminino , Lipopolissacarídeos/farmacologia , Macrófagos/imunologia , Macrófagos/metabolismo , Masculino , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Óxido Nítrico/biossíntese , Fosfatidilinositol 3-Quinases/metabolismo , Folhas de Planta/química , Transdução de Sinais , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
We studied the capacity of IKK-2 inhibitor ([5-(p-fluorophenyl)-2-ureido] thiophene-3-carboxamide) and non-steroidal anti-inflammatory drug voltaren to reduce the severity of local inflammation in Th1- and Th2-type immune response. The test substances (inhibitor in concentrations from 2×10(-13)to 2×10(-16)M and 9.8×10(-4)M voltaren) were shown to reduce edema caused by sheep erythrocytes (Th1-type immune response) and local immediate-type hypersensitivity response (Th2-type immune response). The anti-inflammatory effects of IKK-2 inhibitor in Th1-type immune response were similar to those of voltaren.
Assuntos
Diclofenaco/farmacologia , Hipersensibilidade Tardia/tratamento farmacológico , Hipersensibilidade Imediata/tratamento farmacológico , Quinase I-kappa B/antagonistas & inibidores , Compostos de Fenilureia/farmacologia , Células Th1/imunologia , Células Th2/imunologia , Tiofenos/farmacologia , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Edema/tratamento farmacológico , Feminino , Hipersensibilidade Tardia/imunologia , Hipersensibilidade Imediata/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Células Th1/efeitos dos fármacos , Células Th2/efeitos dos fármacosRESUMO
Pronounced regenerative effects of alkaloid napelline extracted from Aconitum baicalense on granulocytic hemopoiesis were revealed in the model of cytostatic myelosuppression. Activation of functions of hemopoietic progenitor cells along with increased feeder capacity of the stromal elements in the hemopoiesis inducing microenvironment with decreased levels mesenchymal progenitor cells in the bone marrow are the mechanisms underlying the hemostimulating action of this substance.
Assuntos
Hematopoese/efeitos dos fármacos , Aconitina/farmacologia , Animais , Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/fisiologia , Células Cultivadas , Citostáticos/farmacologia , Fluoruracila/farmacologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Camundongos Endogâmicos CBA , Células Progenitoras Mieloides/efeitos dos fármacos , Células Progenitoras Mieloides/fisiologia , Medicina RegenerativaRESUMO
We compared the effect of NF-κB inhibitor aurothiomalate and voltaren on local inflammation in different types of immune response. Both substances reduced edema caused by sheep erythrocytes (Th1-type immune response) and local immediate-type hypersensitivity response induced with ovalbumin (Th2-dependent response). The anti-inflammatory effects of aurothiomalate were similar to those of voltaren during Th1-type immune response.
Assuntos
Tiomalato Sódico de Ouro/farmacologia , Hipersensibilidade Tardia/tratamento farmacológico , Hipersensibilidade Imediata/tratamento farmacológico , Imunidade Celular/imunologia , NF-kappa B/antagonistas & inibidores , Células Th1/imunologia , Células Th2/imunologia , Análise de Variância , Animais , Citocinas/imunologia , Diclofenaco/farmacologia , Diclofenaco/uso terapêutico , Eritrócitos , Feminino , Tiomalato Sódico de Ouro/uso terapêutico , Hipersensibilidade Tardia/induzido quimicamente , Hipersensibilidade Imediata/induzido quimicamente , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Ovalbumina/toxicidadeRESUMO
We compared the effects of NF-κB inhibitor aurothiomalate and voltaren on NO production by mouse macrophages in vitro, their ability to cause local edema at the site of injection, and their effect on carrageenan-induced inflammation. High concentrations of aurothiomalate reduced NO production, while in low concentrations both aurothiomalate and voltaren stimulated this process. When injected into mouse footpad, aurothiomalate in a dose >1 mM and voltaren in a dose >1.6 µM induce paw edema. Both compounds suppressed carrageenan-induced inflammation, but the efficacy of aurothiomalate 2-fold exceeded that of voltaren.
Assuntos
Anti-Inflamatórios/farmacologia , Tiomalato Sódico de Ouro/farmacologia , Inflamação/tratamento farmacológico , NF-kappa B/antagonistas & inibidores , Animais , Anti-Inflamatórios/uso terapêutico , Diclofenaco/farmacologia , Diclofenaco/uso terapêutico , Feminino , Tiomalato Sódico de Ouro/uso terapêutico , Inflamação/induzido quimicamente , Inflamação/patologia , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Óxido Nítrico/metabolismoRESUMO
Macrophage activity was studied after treatment with hybrid molecules obtained by condensation of terpenic acid residues (betulinic and betulonic acids) and α-tocopherol analogues (α-tocopherol hemisuccinate and Trolox acid). As distinct from betulinic acid and α-tocopherol hemisuccinate, hybrid molecules did not exhibit cytotoxicity in relation to mouse peritoneal macrophages in the MTT test. Test substances inhibited the production of NO by mouse peritoneal macrophages. However, hybrid molecules had no effect on activity of macrophage arginase. Our results indicate that new molecules have anti-inflammatory activity. It can be hypothesized that these substances have immunomodulatory properties.
Assuntos
Triterpenos/farmacologia , Vitamina E/análogos & derivados , Vitamina E/farmacologia , Animais , Arginase/metabolismo , Cromanos/farmacologia , Feminino , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Óxido Nítrico/metabolismo , Triterpenos Pentacíclicos , alfa-Tocoferol/farmacologia , Ácido BetulínicoRESUMO
Male generative buds of the Siberian larch have no organic quiescence during the autumn-winter period and are capable of completing the development of male generative structures under favorable conditions. When microsporophylls of the Siberian larch were cultivated on medium MS with 0.2 mg/l 2,4-D, embryoids of two types were obtained: directly from the microspore body and via formation of organogenic callus. This means that in the Siberian larch, direct and indirect androgenesis in vitro is possible. The Siberian larch pollen was first germinated in vitro, which was enhanced by pretreatment with hydrogen peroxide.
Assuntos
Larix/fisiologia , Fenômenos Fisiológicos Vegetais , Pólen/fisiologia , Larix/citologia , Pólen/citologia , Reprodução/fisiologiaRESUMO
The article covers clinical and ophthalmologic characteristics of oculomotor disturbances in myastenic patients with endocrine ophtalmopathy, and differential diagnostic signs and peculiarities of endocrine ophtalmopathy in patients with a combination of the two diseases.
Assuntos
Diplopia/epidemiologia , Diplopia/metabolismo , Doenças do Sistema Endócrino/epidemiologia , Doenças do Sistema Endócrino/metabolismo , Miastenia Gravis/diagnóstico , Miastenia Gravis/epidemiologia , Miastenia Gravis/fisiopatologia , Doenças do Nervo Oculomotor/epidemiologia , Doenças do Nervo Oculomotor/metabolismo , Adulto , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
A graphical method to reveal the so-called 'critical fragments' in schemes of biochemical systems is considered. These fragments produce multiple steady states or self-oscillations in systems. As an example, the bifunctional enzyme, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase, regulated by glucagon through enzyme phosphorylation, is discussed. It is shown that this enzyme may act as a metabolic switching mechanism in discontinuous or oscillatory regimes, depending on the specific structure of its kinetic scheme. The boundaries of concentrational and parameter domains for these critical phenomena are also predicted.
Assuntos
Glucagon/fisiologia , Modelos Biológicos , Monoéster Fosfórico Hidrolases/metabolismo , Fosfotransferases/metabolismo , Cinética , Modelos Químicos , Fosfofrutoquinase-2 , FosforilaçãoRESUMO
In a series of experiments the alpha-glycerophosphate dehydrogenase and succinate dehydrogenase (SDH) activities were daily determined simultaneously by the cytochemical method in peripheral blood lymphocytes of normal rats and those with the Walker carcinosarcoma. Using an original algorithm a hierarchy of biorhythms was singled out by a computer according to individual changes in the dehydrogenase activity for each rat. The mean level of succinate dehydrogenase activity was higher than that of alpha-glycerophosphate dehydrogenase. A set of discovered biorhythms and their representation were identical in the both enzymes. The tumor transplantation caused changes in the phase coordination of investigated dehydrogenases in all rhythms and promoted an increase of the succinate dehydrogenase amplitude as compared with the alpha-glycerophosphate dehydrogenase amplitude in certain rhythms. It is concluded that biorhythmological parameters of these enzymes may be used for characterization of the tumor-bearing host.
Assuntos
Carcinoma 256 de Walker/enzimologia , Fenômenos Cronobiológicos/fisiologia , Linfócitos/enzimologia , Oxirredutases/sangue , Animais , Glicerolfosfato Desidrogenase/sangue , Masculino , Ratos , Succinato Desidrogenase/sangue , Fatores de TempoRESUMO
Kinetic models for enzyme reactions are considered which take into account enzyme and substrate isomerization. Application of graph-theoretic methods allows to reveal fragments in schemes which may induce multiple stead-states or concentrational selfoscillations. The role of substrate isomers in the inhibition of enzyme isomers to produce critical phenomena is considered. The boundaries of parameter domains for critical phenomena are estimated. It is shown that the controlled change in concentrations of substrate and enzyme isomers may be important in regulation of enzyme systems, if different enzyme isomers are inhibited mainly by different substrate isomers. The models are used for interpretation of possible critical phenomena in the open reaction catalyzed by lactate dehydrogenase. It is shown that lactate dehydrogenase may act as a trigger in carbohydrate metabolism by changing "critically" its activity in relation to changes in pH and pyruvate fluxes. Slow enzyme inhibition by enolpyruvate is suggested as a possible reason for glycolytic oscillations.
Assuntos
Enzimas/metabolismo , Modelos Biológicos , Isomerismo , Cinética , L-Lactato Desidrogenase/metabolismo , Matemática , Conformação Proteica , Especificidade por SubstratoRESUMO
The kinetic model for K+, H+, Ca2+ concentrational self-oscillations in erythrocytes induced by A23187 and FCCP ionophores are considered. The model is based on the experimental data available and contains the minimal number of essential variables. The model was analysed by the method based on the graph representation of kinetic equations. The critical graph fragments provoking self-oscillatory trajectories in the system were revealed. It is shown that self-oscillatory behaviour is basically induced by conjugated processes produced by A23187. The parameter domain for self-oscillations is estimated including parameters of Ca2+-induced (through K+-channels) proton transport with FCCP participation. Numerical integration of kinetic equations was performed. The results obtained are in a good qualitative agreement with experimental data.
Assuntos
Eritrócitos/metabolismo , Canais Iônicos/efeitos dos fármacos , Ionóforos/farmacologia , Transporte Biológico/efeitos dos fármacos , Calcimicina/farmacologia , Carbonil Cianeto p-Trifluormetoxifenil Hidrazona/farmacologia , Eritrócitos/efeitos dos fármacos , Humanos , Técnicas In Vitro , Cinética , Modelos BiológicosRESUMO
The reliability theory model of aging (Kol'tover 1981, 1982) was used for analysis of life-tables of Swedish males and females for 1951-1955, 1962-1973 and 1971-1975 calendar years. In terms of the model it has been possible 1) to explain the Gompertz "law" of mortality; 2) to describe quantitatively statistical life-table data including Gompertz's and geriatric ages; 3) to predict the behavior of mortality rate function depending on the extent of population heterogeneity, among them the existence, at respective degrees of heterogeneity, of a maximum in geriatric age range and 4) to estimate the species-specific maximum life-span potential of animals.
Assuntos
Modelos Estatísticos , Mortalidade , Taxa de Sobrevida , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento , Feminino , Humanos , Tábuas de Vida , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Fatores Sexuais , SuéciaRESUMO
Contusions of the eyeball involve reactive or secondary changes in intraocular pressure. Clinical examinations of 151 patients with contusion disorders in ophthalmic tone revealed reactive hypertension in 6.62%, reactive hypotone in 31.79%, secondary hypertension in 48.34%, and stable hypotone of the injured eye in 15.89% cases. Secondary changes in intraocular pressure were caused by massive intraocular hemorrhages and structural injuries to the eyeball. The main cause of reactive hypotone resulting from blunt injury to the eye was exfusion, detachment of the vascular membrane diagnosed at that period by ultrasonic examination in 76.92% cases. The main factors responsible for the postcontusion reactive syndrome are changes occurring within a very short period of time, intraocular pressure differences, and "loss" of the threshold volume of the anterior chamber humor because of its discharge during the shock, and activation of the kallikrein-kinin system with release of kinins causing capillary dilatation and increasing capillary wall permeability in the presence of low activity of angiotensin-converting enzyme which destroys bradykinin.
Assuntos
Contusões/fisiopatologia , Traumatismos Oculares/fisiopatologia , Pressão Intraocular/fisiologia , Humor Aquoso/fisiologia , Bradicinina/metabolismo , Permeabilidade Capilar , Contusões/complicações , Contusões/metabolismo , Traumatismos Oculares/complicações , Traumatismos Oculares/metabolismo , Humanos , Sistema Calicreína-Cinina/fisiologia , Hipertensão Ocular/etiologia , Hipertensão Ocular/metabolismo , Hipertensão Ocular/fisiopatologia , Hipotensão Ocular/etiologia , Hipotensão Ocular/metabolismo , Hipotensão Ocular/fisiopatologia , Peptidil Dipeptidase A/metabolismo , VasodilataçãoRESUMO
The results of the overtime combined clinico-laboratory investigations have evidenced a high medical effectiveness of red blood cell pack transfusions in the treatment of anemia in patients with varying diseases of internal organs.