RESUMEN
The influence of adiponectin, a protein secreted by adipocytes, on the activation of transendothelial LDL transport, the initial event of atherogenesis, was studied. The addition of adiponectin to the cultured endothelial hybridoma EA.hy926 cells did not affect both basal and TNF-stimulated transendothelial transport of LDL. In addition, adiponectin affects neither expression levels of CAV1, SCARB1, and ACVRL1 genes encoding proteins involved in transendothelial LDL transport, nor the MMP secretion by the EA.hy926cells. At the same time, adiponectin suppressed the TNF-stimulated IL-8 production and expression of the adhesion molecule gene ICAM1 in these cells. Thus, adiponectin reduces proinflammatory activation of EA.hy926 cells, which is not accompanied by changes in the transendothelial LDL transport. We speculate that anti-inflammatory action of adiponectin is the base for the influence of this adipokine on atherogenesis.
Asunto(s)
Adiponectina , Aterosclerosis , Humanos , Receptores de Activinas Tipo II/metabolismo , Adiponectina/genética , Adiponectina/farmacología , Adiponectina/metabolismo , Aterosclerosis/genética , Aterosclerosis/metabolismo , Células Endoteliales/metabolismo , Endotelio/metabolismo , Lipoproteínas LDL/farmacologíaRESUMEN
The mechanism of valve calcification that is the main cause of aortic stenosis formation and progression is not yet clear. In recent years, the role of the OPG/RANKL/RANK system is considered as one of possible variants of pathogenesis of valve calcification. In presented work the differences in OPG and sRANKL levels involved in the calcification processes in tissues of patients with severe aortic stenosis have been examined. The study was performed using three groups of patients: group 1 - patients with aortic stenosis, group 2 - patients with aortic aneurysm, and group 3 - patients with aortic stenosis and aortic dilatation. In patients with aortic stenosis, the level of RANKL was significantly higher, and the level of RANKL was higher in valve than in tissue. The negative correlation between aortic dilatation and RANKL level indicated the lack of RANKL influence on pathogenesis of aortic dilatation. The obtained data confirm the increased expression of RANKL in patients with aortic valve calcification. The results of this study confirm importance of the OPG/RANKL/RANK system in calcification in patients with aortic stenosis. Athough patients of all groups had comparable values of OPG (including patients with aortic dilatation), the RANKL level increased only in patients with aortic stenosis. This suggest involvement of some additional mechanisms influencing the increase of RANKL expression.
Asunto(s)
Estenosis de la Válvula Aórtica , Calcinosis/metabolismo , Osteoprotegerina/metabolismo , Ligando RANK/metabolismo , Válvula Aórtica/patología , Humanos , Receptor Activador del Factor Nuclear kappa-B/metabolismoRESUMEN
Collagen I gels with protein concentrations of 1, 2, and 3.5 mg/ml were prepared and embedded in a porous polylactide scaffold to reduce their contraction. Concentration of the gel did not affect its degradation. Collagen gels promoted the formation of cell networks. The cells in the collagen gel with a concentration of 1 mg/ml embedded in polylactide scaffold had elongated spindle-like shape, in contrast to flattened cells in collagen gel of the same concentration not embedded in the scaffold. Stabilization of the collagen gel in the polylactide scaffold promoted active synthesis of laminin and fibronectin by cells as soon as on day 5 of culturing in comparison with that in free collagen substrate.
Asunto(s)
Colágeno/química , Colágeno/farmacología , Células Madre Mesenquimatosas/efectos de los fármacos , Animales , Materiales Biocompatibles/farmacología , Células de la Médula Ósea/efectos de los fármacos , Técnicas de Cultivo de Célula , Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Poliésteres/química , Conejos , Ingeniería de Tejidos , Andamios del Tejido/químicaRESUMEN
The highly organized contractile apparatus of cardiomyocytes in heart tissue allows for their continuous contractility, whereas extracellular matrix components are synthesized and spatially organized by fibroblasts and endothelial cells. However, reorganization of the cardiomyocyte contractile apparatus occurs upon their 2D cultivation, which is accompanied by transient loss of their contractility and acquired capability of extracellular matrix synthesis (Bildyug, N. B., and Pinaev, G. P. (2013) Tsitologiya, 55, 713-724). In this study, matrix metalloproteinases were investigated at different times of cardiomyocyte 2D cultivation and 3D cultivation in collagen gels. It was found that cardiomyocytes in 2D culture synthesize matrix metalloproteinases MMP-2 and MMP-9, wherein their amount varies with the cultivation time. The peak MMP-9 amount is at early cultivation time, when the reorganization of cardiomyocyte contractile apparatus occurs, and the MMP-2 peak precedes the recovery of the initial organization of their contractile apparatus. Upon cardiomyocyte cultivation in 3D collagen gels, in which case their contractile apparatus does not rearrange, a steady small amount of MMP-2 and MMP-9 is observed. These data indicate that the cardiomyocyte contractile apparatus reorganization in culture is associated with synthesis and spatial organization of their own extracellular matrix.
Asunto(s)
Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Miocitos Cardíacos/enzimología , Animales , Células Cultivadas , Colágeno/farmacología , Metaloproteinasa 2 de la Matriz/biosíntesis , Metaloproteinasa 9 de la Matriz/biosíntesis , Contracción Miocárdica/efectos de los fármacos , Miocitos Cardíacos/citología , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/fisiología , Ratas , Factores de TiempoRESUMEN
We have shown that antioxidant N-acetylcysteine (NAC, 2-10 mM) quickly (for 2 hours) and completely inactivates the activity of matrix metalloproteinases (gelatinases MMP-2 and MMP-9, and collagenases MMP-1 and MMP-8) secreted by transformed mouse fibroblasts 3T3-SV40 into the medium. The same MMP inhibition took place in the cell-free conditioned medium of HT-1080 fibroblasts, which suggests a direct chemical interaction between NAC and MMP resulting in the loss of MMP activity. Besides inhibitory effect, NAC decreased MMP-1 and MMP-9 (but not MMP-2) production in the cell medium. However, the level of MMP-1 and MMP-9 inhibitor (TIMP-1) remained normal, indicating a shift in the balance between the enzyme and inhibitor. The correlation between MMP-2 level and tissue enzyme inhibitor TIMP-2 was similar in control and NAC treated cells. At the same time, reorganization of type I collagen at the cell surface occurred. All together permits the conclusion that NAC action results in the extracellular matrix remodeling and changing in cellular functions.
Asunto(s)
Acetilcisteína/farmacología , Antioxidantes/farmacología , Matriz Extracelular/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Animales , Línea Celular Transformada , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Matriz Extracelular/enzimología , Matriz Extracelular/ultraestructura , Metaloproteinasa 1 de la Matriz/genética , Metaloproteinasa 1 de la Matriz/metabolismo , Metaloproteinasa 2 de la Matriz/genética , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 8 de la Matriz/genética , Metaloproteinasa 8 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/metabolismo , Ratones , Células 3T3 NIH , Inhibidor Tisular de Metaloproteinasa-1/genética , Inhibidor Tisular de Metaloproteinasa-1/metabolismo , Inhibidor Tisular de Metaloproteinasa-2/genética , Inhibidor Tisular de Metaloproteinasa-2/metabolismoRESUMEN
This paper presents the results of the study of rabbit bone marrow stromal cells (BMSC) and rabbit dermal fibroblasts (DF) migration rates to collagen type I and fibrin gels. It has been shown that DF exhibit greater migration activity in collagen gel, whereas BMSC show a higher migration activity in fibrin gels. By studying the activity of matrix metalloproteinases (MMPs) synthesized by cells during cultivation in gels, it has been found for both cell types that the activity of MMP-9 is increased in fibrin gels and activity of MMP-2 is increased in collagen gels. Different speed of the migration of cells may be due to the properties of the cells, the activity of MMP synthesized by the cells and the influence of the microenvironment (collagen or fibrin) on the process of synthesis.
Asunto(s)
Células de la Médula Ósea/efectos de los fármacos , Colágeno Tipo I/farmacología , Dermis/efectos de los fármacos , Fibrina/farmacología , Fibroblastos/efectos de los fármacos , Células del Estroma/efectos de los fármacos , Animales , Animales Recién Nacidos , Células de la Médula Ósea/citología , Células de la Médula Ósea/fisiología , Movimiento Celular/efectos de los fármacos , Colágeno Tipo I/química , Dermis/citología , Dermis/fisiología , Fibrina/química , Fibroblastos/citología , Fibroblastos/fisiología , Geles , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Especificidad de Órganos , Cultivo Primario de Células , Conejos , Células del Estroma/citología , Células del Estroma/fisiologíaRESUMEN
Thoracic aortic aneurism (TAA) develops as a result of complex series of events that dynamically alter the structure and composition of the aortic vascular extracellular matrix (ECM). The main elements that alter the composition of aortic wall are smooth muscle cells (SMC). The purpose of the present work was to study alteration of smooth muscle cell functions derived from the patients with TAA and from healthy donors. As it is supposed that TAA associated with bicuspid aortic valve (BAV) and with tricuspid aortic valve (TAV) differ in their pathogenesis, we compared the SMC and tissues samples from BAV-, TAV-patients and healthy donors. We compared TAA patients' derived tissues and SMC to healthy donors' ones in several parameters: SMC growth, migration and apoptotic dynamics; metalloproteinase MMP2 and MMP9 activity (zymography) and elastin, collagen and fibrillin content (Western blot) in both tissue samples and cultured SMC. Proliferation ability of both BAV and TAV SMC was decreased comparing to donors cells; migration ability in scratch tests was increased in TAV-derived SMC comparing to donor cells. BAV-cells migration ability was not changed comparing to donor-SMC. Elastin content was decreased in TAA SMC comparing to donor cells whereas the content of fibrillin and collagen was not altered. At the same time elastin and collagen protein level was significantly higher in tissue samples of TAA patients comparing to donor-derived samples. SMS proliferation and migration ability is differently affected in TAV and BAV-associated TAA that supports the idea of different nature of these two groups of TAA. Also our data show that SMC functional properties are altered in TAA patients and these alterations could play a significant role in the disease pathogenesis.
Asunto(s)
Aorta/fisiopatología , Aneurisma de la Aorta Torácica/fisiopatología , Válvula Aórtica/anomalías , Enfermedades de las Válvulas Cardíacas/fisiopatología , Miocitos del Músculo Liso/patología , Atresia Tricúspide/fisiopatología , Aorta/metabolismo , Aorta/patología , Aneurisma de la Aorta Torácica/complicaciones , Aneurisma de la Aorta Torácica/metabolismo , Aneurisma de la Aorta Torácica/patología , Válvula Aórtica/metabolismo , Válvula Aórtica/patología , Válvula Aórtica/fisiopatología , Apoptosis , Enfermedad de la Válvula Aórtica Bicúspide , Biomarcadores/metabolismo , Estudios de Casos y Controles , Movimiento Celular , Proliferación Celular , Colágeno/metabolismo , Elastina/metabolismo , Fibrilinas , Enfermedades de las Válvulas Cardíacas/complicaciones , Enfermedades de las Válvulas Cardíacas/metabolismo , Enfermedades de las Válvulas Cardíacas/patología , Humanos , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Proteínas de Microfilamentos/metabolismo , Miocitos del Músculo Liso/metabolismo , Atresia Tricúspide/complicaciones , Atresia Tricúspide/metabolismo , Atresia Tricúspide/patologíaRESUMEN
A new feeder-free culture system for human embryonic stem cells (hESC) was developed. It consist of extracellular matrix proteins synthesized by feeder cells--mesenchymal stem cell line SC5-MSC, which was derived from initial hESC line SC5. The major ECM proteins--fibronectin and laminin--that maintain hESC growth in feeder-free system were identified. An essential component of this system is a SC5-MSC-conditioned medium. Two hESC sublines were derived. The subline SC5-FF was cultured in autogenic and subline SC7-FF in allogenic system. Sublines SC5-FF and SC7-FF passed through more than 300 and 115 cell population doublings, retained normal diploid karyotype and an ability of in vitro differentiation into derivates of three germ layers. These sublines express markers of undifferentiated hESC: alkaline phosphatase, Oct-4, SSEA-4, TRA-1-81 and multidrug resistance transporter--ABCG2. The RT-PCR analysis revealed that undifferentiated cells SC5-FF subline, like cells of initial feeder-maintained hESC line SC5, expressed genes OCT4 and NANOG, and germ line specific genes such as DPPA3/STELLA and DAZL. An expression of OCT4, NANOG, DPPA3/STELLA ans DAZL was down-regulated during embryonic bodies differentiation, whereas expression of somatic lineages specific genes like GATA4 and AFP (extra embryonic and embryonic endoderm), PAX6 (neuroectoderm) and BRY (mesoderm) was up-regulated. The comparative analysis of some typical features (karyotype structure, the average population doubling time and the number of undifferentiated cells in populations) did not reveal essential differences between initial SC5 and SC7 lines and their sublines SC5-FF and SC7-FF. This shows that feeder-free culture systems, which are much more stable than any feeder systems, do not break main hESC features during long cultivation and can be recommended for fundamental, biomedicine and pharmacological investigations, using hESCs.
Asunto(s)
Técnicas de Cultivo de Célula , Medios de Cultivo Condicionados , Células Madre Embrionarias/citología , Células Madre Mesenquimatosas/citología , Biomarcadores , Diferenciación Celular , Células Madre Embrionarias/metabolismo , Células Nutrientes , Expresión Génica , Humanos , Cariotipo , Células Madre Mesenquimatosas/metabolismoRESUMEN
Embryonic cells regulate the expression of matrix metalloproteinases (MMP) providing remodulation of extracellular matrix, which in turn provides the changes in cell adhesion and migration during the cell development and differentiation. In present work we studied the changes of gelatinases (MMP-2 and MMP-9) and collagenases (MMP-1 and MMP-8) activities in the process of cultivating the primary murine embryonic fibroblasts (MEF). Cultivation was continued for 6 passages, after that the culture died in time. According to gelatin and collagen zymography results, drastic changes of all MMPs activities occurred during the third passage of cell cultivation. The MMP-1 and MMP-9 activity appears in the middle of cultivation and then disappeared at the end. The most important event MEF cultivation is appearance and subsequent reservation of collagenase MMP-8 and active form of gelatinase MMP-2.
Asunto(s)
Embrión de Mamíferos/enzimología , Matriz Extracelular/enzimología , Fibroblastos/enzimología , Animales , Caseínas/metabolismo , Técnicas de Cultivo de Célula , Proliferación Celular , Colágeno/metabolismo , Cruzamientos Genéticos , Electroforesis en Gel de Poliacrilamida , Embrión de Mamíferos/citología , Femenino , Fibroblastos/citología , Gelatina/metabolismo , Masculino , Metaloproteinasa 1 de la Matriz/metabolismo , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 8 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos CBARESUMEN
We analyzed the effectiveness of wound healing in rats after application of the dermal equivalent (DE) based on fibrin with dermal fibroblasts. Histological studies of newly formed dermis biopsy samples selected during its recovery in the model wound in laboratory animals have shown a positive effect of DE on wound healing. It was found a significant increase in the area of collagen fibers, in the number of prekapillaries, capillaries and postcapillaries in the granulation tissue after application of DE compared with the control group, suggesting a more intense repair.
Asunto(s)
Dermis/trasplante , Fibrina/administración & dosificación , Fibroblastos/trasplante , Trasplante de Piel/métodos , Cicatrización de Heridas , Animales , Colágeno Tipo I/administración & dosificación , Dermis/citología , Humanos , Ratas , Ratas WistarRESUMEN
The engraftment of a skin sheet together with transplantation of dermal equivalent was studied on rats. The skin sheet was taken as a source of epithelization material in unhealing wound. The process of wound healing was evaluated by changes of matrix metalloproteinases (MMP) activity levels in wound fluid. It was shown that results of skin sheet transplantation could be predicted by monitoring of wound fluid MMP-2 and MMP-9 activity levels. It was determined that skin sheet engraftment appeared at medium values of wound fluid MMP-2 and MMP-9, and transplanted skin sheet was lysed at high and low values.
Asunto(s)
Exudados y Transudados/enzimología , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Trasplante de Piel , Cicatrización de Heridas/fisiología , Animales , Biomarcadores/análisis , Biomarcadores/metabolismo , Electroforesis en Gel de Poliacrilamida , Exudados y Transudados/metabolismo , Rechazo de Injerto/diagnóstico , Rechazo de Injerto/metabolismo , Masculino , Metaloproteinasa 2 de la Matriz/análisis , Metaloproteinasa 9 de la Matriz/análisis , RatasRESUMEN
The effect of two antioxidants on the activities of matrix metalloproteinases (MMP) secreted by normal (3T3) and transformed (3T3-SV40) mouse fibroblasts was examined. We compared the effect of N-acetylcystein (NAC) and alpha-lipoic acid (ALA) on two gelatinases, MMP-2 and MMP-9. Gel zymography demonstrated that activity of MMP-2 was higher in normal 3T3 cells, and MMP-9 activity was higher in transformed 3T3-SV40 cells. NAC action for 2-6 hours completely inhibited MMP-2 and MMP-9 activity in both cell lines. The inhibitory effect almost did not depend on NAC concentration at the range of 1-10 mM. ALA (1.2 mM) affected the cells not so dramatically. ALA decreased the MMP-2 activity in both cellular types. As to MMP-9 activity, it decreased in 3T3 cells and slightly increased in 3T3-SV40 cells in the presence of ALA. The activity of membrane bound and intracellular MMP was not changed under the same conditions. In conclusion, an altered activity of MMP in the presence of an antioxidant may influence the intracellular signalling and cell functions.
Asunto(s)
Acetilcisteína/farmacología , Antioxidantes/farmacología , Inhibidores Enzimáticos/farmacología , Inhibidores de la Metaloproteinasa de la Matriz , Ácido Tióctico/farmacología , Células 3T3 , Animales , Línea Celular Transformada , Transformación Celular Viral/efectos de los fármacos , Fibroblastos/efectos de los fármacos , Fibroblastos/enzimología , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , RatonesRESUMEN
One of the problems in wound treatment optimization is the necessity of an effective and objective method of laboratory wound process monitoring. In present study the current wound process was estimated by changes in MMP-2 and MMP-9 activities in the wound fluid. An original model was used in this work to study correlation of morphological structure of the wound with the activities of MMP-2 and MMP-9 in wound fluid at various types of wound process. Protein fractions of the coelomic liquid from regenerating sea star Asterias rubens were used as the substances changing the wound process. The correlation of wound process with MMP-2 and MMP-9 activities in wound fluid was revealed on the basis of correlation analysis.
Asunto(s)
Exudados y Transudados/enzimología , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Regeneración , Cicatrización de Heridas/fisiología , Heridas y Lesiones/enzimología , Animales , Asterias/química , Masculino , Metaloproteinasa 2 de la Matriz/análisis , Metaloproteinasa 9 de la Matriz/análisis , Proteínas/farmacología , Ratas , Factores de Tiempo , Cicatrización de Heridas/efectos de los fármacosRESUMEN
The aim of the study was to evaluate the functional condition of the endothelium in patients with type II diabetes and arterial hypertension, depending on various metabolic factors. 85 patients aged 54.69 +/- 7.08 years were under dynamic observation. The patients had had diabetes and arterial hypertension (AH) for 5.99 +/- 4.37 and 8.65 +/- 5.52 years, respectively. The average HbAlc level was 7.91 +/- 1.73 mmol/ 1, total cholesterol level--6.35 +/- 1.81 mmol/l, body weight index--32.98 +/- 5.14 kg/m2. The average systolic and diastolic blood pressure levels were 162 +/- 7.6 and 97 +/- 3.4 mmHg, respectively. Carbohydrate and lipid exchange parameters, the extent of hyperinsulinemia and insulin resistance, and lipid peroxidation activity were evaluated. The functional condition of the endothelium was evaluated by D. Celermajer non-invasive measurement of flow-induced endothelium-dependent vasodilatation (EDVD) of the brachial artery (BA) using high-resolution ultrasound. 87% of the patients with type II diabetes and AH had endothelial dysfunction (ED), revealed by reactive hyperemia test; 30% of the patients had significant disorder of vasoreactivity (no BA artery diameter increase, but paradoxical vasoconstriction in response to reactive hyperemia). The presence and length of endothelial dysfunction (ED) in the patients with type II diabetes and AH depended on the length of diabetes, the length and extent of AH, and presence of long-term macro- and microvascular complications (coronary heart disease, diabetic retino- and nephropathy). The study did not found any dependence of the vasorelaxing endothelial function on glycosylated hemoglobin level, atherogenic blood lipid spectrum fractions, or lipid peroxidation activity. EDVD positively correlated with ApoA-1 protein level, reflecting the antiatherogenic potential of blood lipid spectrum.
Asunto(s)
Diabetes Mellitus Tipo 2/fisiopatología , Endotelio Vascular/fisiopatología , Hipertensión/fisiopatología , Adulto , Factores de Edad , Anciano , Índice de Masa Corporal , Metabolismo de los Hidratos de Carbono , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/metabolismo , Femenino , Hemoglobina Glucada/análisis , Humanos , Hipertensión/sangre , Hipertensión/complicaciones , Hipertensión/metabolismo , Resistencia a la Insulina , Metabolismo de los Lípidos , Peroxidación de Lípido , Masculino , Persona de Mediana Edad , Factores de Riesgo , Factores de Tiempo , VasodilataciónRESUMEN
The study was undertaken to evaluate the antihypertensive effectiveness and metabolic safety of the selective imidazoline receptor agonist moxonidine. Thirty patients with mild and moderate arterial hypertension associated with type 2 diabetes mellitus were ex-amined. The patients' mean age was S2.43±4.65 years. The history of diabetes mellitus and arterial hypetension averaged 4.77±2.69 and 6.93±2.98 years, respectively. The duration of the study was 16 weeks. The drug was found to have a positive effect on the 24-hour blood pressure (BP) profile: a long-term significant optimal lowering of DP during 12 hours, a significant reduction in the pressure load index, a decrease of the baseline greater variability, and normalization of a two-phase BP profile. There was a significant improvement of carbohydrate metabolism: a reduction in the level of glycolysated hemoglobin and fasting glycemia, a decrease in the fasting and postprandial immunoreactive insulin levels, which suggests the positive effect of the drug on tissue insulin sensitivity at the level of peripheral tissues and the liver. There was a significant tendency for changing the qualitative composition of blood lipids by lowering the atherogenic fractions of lipoproteins and by elevating the level of high-density lipoproteins. Physiotens is a highly effective antihypertensive drug that may be recommended for the treatment of mild and moderate arterial hypertension in patients with impairments considered within the metabolic syndrome.
RESUMEN
AIM: To assess hypotensive efficacy and metabolic neutrality of moxonidine (physiotenz)--a selective agonist of imidasoline receptors--in patients with mild and moderate arterial hypertension (AH) associated with diabetes mellitus (DM) type 2. MATERIAL AND METHODS: Follow-up and treatment were conducted in 30 hypertensive diabetics (mean age 52.43 +/- 4.65 years). Mean duration of DM and AH was 4.77 +/- 2.69 and 6.93 +/- 2.98 years, respectively. The study was made of lipid exchange, glycemia, levels of glycosylated hemoglobin (GH), fasting and postprandial immunoreactive insulin. Hypotensive efficacy was examined by 24-h monitoring of arterial pressure after 16 weeks of therapy. RESULTS: Mean 24-h systolic arterial pressure fell by 8.02%, diastolic arterial pressure--by 6.47%. The drug had a good effect on a 24-h profile of arterial pressure: a significant decrease of day and night pressure load index, lowering of initially high 24-h variability of systolic and diastolic arterial pressure, normalization of two-phase profile of arterial pressure. Carbohydrate metabolism improved also: GH, glycemia, immunoreactive insulin decreased. There was a significant trend to a change in qualitative composition of blood lipid--a decrease in lipoproteins atherogenic fractions and a rise in HDLP. CONCLUSION: Physiotens is a highly effective hypotensive drug for use in mild and moderate AH in DM of type 2.
Asunto(s)
Antihipertensivos/administración & dosificación , Diabetes Mellitus Tipo 2 , Hipertensión/tratamiento farmacológico , Imidazoles/administración & dosificación , Diabetes Mellitus Tipo 2/complicaciones , Femenino , Humanos , Hipertensión/etiología , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Intrachromosomal homologous recombination has been revealed in the DNA from transgenic mice of three pedigrees. The recombination DNA of aminoglycosid phosphoribosiltransferase (neo) gene was observed in liver, kidney, spleen, heart, skeletal muscle, germinal glands and tail. It is concluded that the constructed model can be used for studying recombinations in cells of various organs and tissues both in the course of embryogenesis and during their malignant transformation and tumor progression.
Asunto(s)
Cromosomas/genética , ADN/genética , Regulación Enzimológica de la Expresión Génica/genética , Pentosiltransferasa/genética , Recombinación Genética/genética , Homología de Secuencia de Ácido Nucleico , Animales , Secuencia de Bases , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos CBA , Ratones Transgénicos , Datos de Secuencia Molecular , Reacción en Cadena de la PolimerasaRESUMEN
For determination of the extrachromosomal homologous DNA recombination efficiency, somatic cells of various lines have been transformed with plasmid DNAs which contain copies of neo-gene with non-overlapping deletions. Reconstruction of the neo-gene functional activity, which imparts a geneticin-resistant phenotype to cells, indicates that recombination has occurred. If dP1 and dR copies of the neo-gene are used, a single (reciprocal) exchange is necessary for reconstruction of the neo-gene by homologous DNA recombination, but a double exchange (gene conversion) is needed in the case of dP1 and dS copies. It is shown that in human cells of line HeLa and in mouse cells of line LMtk-, in contrast to the Chinese hamster cells of line A238, the frequency of double exchanges is comparable to that of the single DNA exchanges which is an evidence of participation in DNA recombination of gene conversion in addition to a single exchange mechanism. The treatment of cells with sodium butyrate and luminol exerts different influences on the rate of the single DNA exchanges and on that of gene conversion (double exchanges) in cells of lines LMtk- and HeLa, respectively. Essential distinctions in correlation of the single DNA exchange frequency and the gene conversion frequency in cells of the studied lines, and the possibility to distinguish between these mechanisms of recombination, under the treatment by sodium butyrate and luminol, may suggest the existence of two mechanisms of homologous DNA recombination in cultured animal cells, which function independently of one another, to a considerable extent.