RESUMEN
Glucocorticoid therapy is widely used in the treatment of various pathologies. Sensitivity to glucocorticoids (GC) has a serious impact not only on the effectiveness of their action, but also on the severity of side effects, the formation of risk factors and the development of cardiovascular diseases (CVD). Variability of sensitivity to GC causes different phenotypes and severity of metabolic disorders underlying CVD. Among them, one can distinguish a decrease in muscle mass and strength, obesity, glucose and lipid metabolism impairment, and others. Glucocorticoids carry out their effects by binding to the glucocorticoid receptor (GR), and therefore this is considered a critical point in their action. This review presents data on the significance of the glucocorticoid receptor structure, examines the main single nucleotide polymorphisms (SNP) of the NR3C1 gene associated with hypersensitivity or relative resistance to glucocorticoids in the context of metabolic disorders and the development of CVD. The association of the four most studied SNP of the GR gene with metabolic risks is described in detail: BclI (rs41423247), N363S (rs56149945), ER22/23EK (rs6189/rs6190), GR-9ß (rs6198). Their determination can contribute to clarifying the prognosis of both the effectiveness of GC and the development of metabolic disorders, and subsequent early correction of CVD risk factors.
Asunto(s)
Enfermedades Cardiovasculares , Enfermedades Metabólicas , Humanos , Polimorfismo de Nucleótido Simple/genética , Receptores de Glucocorticoides/genética , Glucocorticoides/uso terapéutico , Enfermedades Metabólicas/genética , Enfermedades Cardiovasculares/genética , NucleótidosRESUMEN
Aim. This review article describes literature sources devoted to the investigation of mitochondrial dysfunction using cytoplasmic hybrids (cybrids). The presented studies were carried out on cultures of cybrid cell lines HL60, MOL T-4, A549, 143B, HeLa, Arpe-19, HEK-293, SH-SY5Y and NT2. According to the analysis of scientific world literature, some of the most promising models for studying mitochondrial dysfunction are cell cultures without mitochondria (rho0) and cytoplasmic hybrids containing one or several mutations of mitochondrial genome. In the review scientific researches on studying biochemical and molecular cellular pathological processes in cybrid cells in various human diseases such as Alzheimer's disease and mild cognitive impairment, MERRF and MELAS syndromes, Leber's optic atrophy and Parkinson's disease were considered. Material dedicated to cybrids as potential models for the study of treatment possibilities was presented separately. Conclusion. The analyzed in the review rho0-cell cultures and cybrid lines containing mtDNA mutations may be models for the study of mitochondrial genome dysfunctions, biochemical and molecular cellular pathological processes. It is worth noting that in various cell cultures, similar tendencies are observed in functional activity changes of rho0-cell and cybrids compared with native cell lines. For example, such tendencies as reduction of oxygen consumption level, morphological changes of mitochondrial structure, resistance to apoptosis, reduction of ATP consumption level, increase in glucose consumption, activity deterioration of some respiratory chain complexes.
Asunto(s)
Células Híbridas/metabolismo , Mitocondrias/metabolismo , Modelos Biológicos , Células A549 , Fusión Celular , Células HEK293 , Células HL-60 , Células HeLa , Humanos , Células Híbridas/patología , Mitocondrias/patología , Enfermedades MitocondrialesRESUMEN
In the present study, the frequencies of genotypes and alleles of candidate genes with respect to polymorphisms associated with increased pregnancy loss in the first trimester of pregnancy, including MMP11607insG, MMP9 A8202G, and TIMP1 С536T, were reported. The frequency of homozygotes for allele MMP9 A8202 was increased by a factor of two among women with miscarriage in the first trimester compared to the control. Significant models of interaction of genes MMPs and TIMP1 were revealed. The genotypes of genes MMP1 (rs1799750), MMP9 (rs11697325), and TIMP1 (rs11551797) increasing the risk of pregnancy loss in the first trimester were determined.
Asunto(s)
Aborto Espontáneo/genética , Alelos , Frecuencia de los Genes , Metaloproteinasa 1 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/genética , Polimorfismo Genético , Primer Trimestre del Embarazo/genética , Aborto Espontáneo/enzimología , Adulto , Femenino , Humanos , Metaloproteinasa 1 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Embarazo , Primer Trimestre del Embarazo/metabolismo , Inhibidor Tisular de Metaloproteinasa-1/genética , Inhibidor Tisular de Metaloproteinasa-1/metabolismoRESUMEN
The sample of women with physiologic pregnancy consisting of 40 females with fetus normosomia and 8 females with fetus macrosomia were examined. The examination covered the evaluation of changes in concentration of ghrelin, somatotropin, insulin-like growth factor-I, insulin, leptin and thyroid hormones in mother and umbilical blood. In females with fetus macrosomia the changes in concentration of hormones regulating trophism, energy balance and anabolic processes in organisms of mother and fetus were detected
Asunto(s)
Sangre Fetal/química , Macrosomía Fetal/sangre , Factor I del Crecimiento Similar a la Insulina/análisis , Hormonas Peptídicas/sangre , Embarazo/sangre , Hormonas Tiroideas/sangre , Biomarcadores/sangre , Estudios de Casos y Controles , Femenino , Ghrelina/sangre , Hormona de Crecimiento Humana/sangre , Humanos , Técnicas para Inmunoenzimas , Insulina/sangre , Leptina/sangreRESUMEN
Plastoquinone, a very effective electron carrier and antioxidant of chloroplasts, was conjugated with decyltriphenylphosphonium to obtain a cation easily penetrating through membranes. This cation, called SkQ1, is specifically targeted to mitochondria by electrophoresis in the electric field formed by the mitochondrial respiratory chain. The respiratory chain also regenerates reduced SkQ1H(2) from its oxidized form that appears as a result of the antioxidant activity of SkQ1H(2). SkQ1H(2) prevents oxidation of cardiolipin, a mitochondrial phospholipid that is especially sensitive to attack by reactive oxygen species (ROS). In cell cultures, SkQ1 and its analog plastoquinonyl decylrhodamine 19 (SkQR1) arrest H(2)O(2)-induced apoptosis. When tested in vivo, SkQs (i) prolong the lifespan of fungi, crustaceans, insects, fish, and mice, (ii) suppress appearance of a large number of traits typical for age-related senescence (cataract, retinopathies, achromotrichia, osteoporosis, lordokyphosis, decline of the immune system, myeloid shift of blood cells, activation of apoptosis, induction of ß-galactosidase, phosphorylation of H2AX histones, etc.) and (iii) lower tissue damage and save the lives of young animals after treatments resulting in kidney ischemia, rhabdomyolysis, heart attack, arrhythmia, and stroke. We suggest that the SkQs reduce mitochondrial ROS and, as a consequence, inhibit mitochondria-mediated apoptosis, an obligatory step of execution of programs responsible for both senescence and fast "biochemical suicide" of an organism after a severe metabolic crisis.
Asunto(s)
Sistemas de Liberación de Medicamentos , Mitocondrias/efectos de los fármacos , Plastoquinona/análogos & derivados , Factores de Edad , Envejecimiento , Animales , Antioxidantes/farmacología , Apoptosis/efectos de los fármacos , Electroforesis , Humanos , Mitocondrias/metabolismo , Plastoquinona/farmacología , Especies Reactivas de Oxígeno/metabolismoRESUMEN
The ability of cationic plastoquinone derivative 10-(6'-plastoquinonyl) decyltriphenylphosphonium (SkQ1) to modify processes of spontaneous and induced mutagenesis was studied. It is shown that daily introduction of this compound into male Wistar rats in doses of 25 and 250 nmol/kg during two weeks decreases spontaneous level of chromosome aberrations in anaphase in the eye cornea from 0.39 +/- 0.09 to 0.13 +/- 0.08 and 0.14 +/- 0.05, respectively. The level of 8-hydroxy-2'-deoxyguanosine in blood serum of the investigated animals decreases from 32.12 +/- 1.55 to 25.90 +/- 2.26 and 25.76 +/- 1.50 ng/ml, respectively. These facts indicate that the decrease in spontaneous clastogenesis is caused by decreased level of DNA damage by endogenous reactive oxygen species. A higher dose of SkQ1 also decreases to control level chromosome aberrations caused by oxygen under pressure of 0.5 MPa for 60 min. It is also shown in experiments with bacterial biosensors that SkQ1 is able to efficiently protect cells against genotoxic effect of UV radiation at 300-400 nm.
Asunto(s)
Antimutagênicos/farmacología , Mitocondrias/efectos de los fármacos , Plastoquinona/farmacología , Animales , Masculino , Ratas , Ratas WistarRESUMEN
Influence of infrared cold laser emission (IRCL) on the dynamic equilibrium between lipid peroxidation and tension of the antioxidant defense system in rat's tissues (blood, brain, retina, cornea) was evaluated in animals with circulatory cerebral hypoxia induced by occlusion of the left carotid artery. Tissues of white rats were examined for IRCL effects on hemiluminescence, malonic dialdehyde, SOD and catalase activities on the background of circulatory cerebral hypoxia. Data of the experiment evidenced an antioxidant effect of posthypoxic IRCL therapy as it reduces intensity of the free radical processes in plasma, cerebral tissues and retina. The experiment demonstrated the IRCL ability to modulate LPO, to stiffen the antioxidant defense system in the event of eye diseases originated from circulatory hypoxia of the ocular analyzer.
Asunto(s)
Encéfalo/metabolismo , Circulación Cerebrovascular/efectos de la radiación , Córnea/metabolismo , Depuradores de Radicales Libres/metabolismo , Hipoxia Encefálica/radioterapia , Terapia por Luz de Baja Intensidad/métodos , Retina/metabolismo , Animales , Encéfalo/efectos de la radiación , Córnea/efectos de la radiación , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Depuradores de Radicales Libres/efectos de la radiación , Hipoxia Encefálica/metabolismo , Masculino , Ratas , Retina/efectos de la radiaciónRESUMEN
Effects of infrared cold laser radiation (IRCLR) on mutagenesis and proliferation of the corneal epithelium were studied with laboratory white mice subjected to instigated circulatory hypoxia of the brain. The experiment was to reveal whether IRCLR influences the frequency of chromosomal rearrangements and to allow calculation of the corneal cells mitotic index for circulatory brain hypoxia. Laser radiation was shown to reconstitute the normal frequency of chromosomal aberrations as well as the mitotic cycle in epithelial cells of the mice cornea. Data of the experiment are promising from the standpoint of antihypoxic use of IRCLR in ophthalmology.
Asunto(s)
Isquemia Encefálica/genética , Aberraciones Cromosómicas/efectos de la radiación , Epitelio Corneal/efectos de la radiación , Terapia por Luz de Baja Intensidad/métodos , Mutagénesis/efectos de la radiación , Animales , Isquemia Encefálica/patología , Isquemia Encefálica/radioterapia , Epitelio Corneal/patología , Masculino , RatasRESUMEN
The paper deals with the impact of infrared low-intensity laser radiation (IRLILR) on a mutation process and the proliferative activity of the animal cornea during stimulation of circulatory brain hypoxia. During an experiment on laboratory albino rats, IRLILR was studied for its impact on the level of chromosomal rearrangements and the mitotic index in the corneal cells was calculated in circulatory brain hypoxia. Laser exposure during stimulation of circulatory brain hypoxia favors normalization of the level of chromosomal aberrations and a mitotic cycle in the rat corneal epithelial cells. The experimental findings suggest that IRLILR may be used in ophthalmological care for antihypoxic purposes.
Asunto(s)
Córnea/patología , Enfermedades de la Córnea/radioterapia , Hipoxia Encefálica/complicaciones , Terapia por Luz de Baja Intensidad/métodos , Mutación/efectos de la radiación , Estrés Oxidativo/genética , Animales , Proliferación Celular/efectos de la radiación , Aberraciones Cromosómicas/efectos de la radiación , Córnea/efectos de la radiación , Enfermedades de la Córnea/etiología , Enfermedades de la Córnea/genética , Modelos Animales de Enfermedad , Hipoxia Encefálica/genética , Hipoxia Encefálica/metabolismo , Masculino , Estrés Oxidativo/efectos de la radiación , Ratas , Resultado del TratamientoRESUMEN
Effects of 24-hr breathing air mixtures containing xenon (XBM) and krypton (KBM) were compared in terms of hormonal status, and blood biochemical indices and morphology in laboratory animals. Some changes observed in blood and hormone indices could be a nonspecific adaptive response. Hence, we should elicit whether these effects are quickly reversible or long. For several indices krypton was a more favorable factor than xenon. However, some of its effects invite to delve into effects of different krypton concentrations on organism.
Asunto(s)
Adaptación Fisiológica/efectos de los fármacos , Criptón/administración & dosificación , Linfocitos/citología , Monocitos/citología , Neutrófilos/citología , Xenón/administración & dosificación , Administración por Inhalación , Anestésicos por Inhalación/administración & dosificación , Animales , Pruebas Respiratorias , Relación Dosis-Respuesta a Droga , Linfocitos/efectos de los fármacos , Masculino , Monocitos/efectos de los fármacos , Neutrófilos/efectos de los fármacos , Ratas , Ratas WistarRESUMEN
A historical review of allantoin research is presented. An increased allantoin level in the trophoblast and serum of pregnant women has been demonstrated. Allantoin concentration decreased in placental tissues and increased in the serum in developing placental insufficiency.
Asunto(s)
Alantoína , Placenta/metabolismo , Insuficiencia Placentaria , Alantoína/sangre , Alantoína/metabolismo , Alantoína/fisiología , Femenino , Edad Gestacional , Humanos , Insuficiencia Placentaria/sangre , Insuficiencia Placentaria/metabolismo , EmbarazoRESUMEN
The purpose was to look into the effects of 24-hr. exposure in a normoxic air-argon environment (AAE) on the epitheliocyte proliferative system, i.e. chromosomal aberrations dynamics and cornea proliferative activity, in laboratory mice. Argon was found to significantly decrease the percentage of spontaneous mutations in cells and, probably, to induce reversible inhibition of cell division. Subsequent experiments may not only disclose the still unknown properties and advantages of argon but also shed light on cell mechanisms triggered by the noble gases in general.
Asunto(s)
Aire , Argón , Aberraciones Cromosómicas , Córnea/citología , Citogenética/métodos , Ambiente , Células Epitelioides/citología , Telofase/genética , Animales , Antimutagênicos/farmacología , Movimiento Celular/fisiología , Córnea/patología , Hipoxia/patología , Masculino , Ratones , Mitosis/efectos de los fármacos , Factores de TiempoAsunto(s)
Alantoína/química , Alantoína/farmacología , Ácido Ascórbico/química , Ácido Ascórbico/farmacología , Escherichia coli/efectos de los fármacos , Alantoína/metabolismo , Corion/metabolismo , Relación Dosis-Respuesta a Droga , Radicales Libres , Humanos , Peróxido de Hidrógeno/farmacología , Dosificación Letal Mediana , Pruebas de Mutagenicidad , Estrés Oxidativo/efectos de los fármacos , Placenta/metabolismo , Vitaminas/química , Vitaminas/metabolismo , Vitaminas/farmacologíaAsunto(s)
Alantoína/química , Escherichia coli/genética , Depuradores de Radicales Libres/química , Urea/análogos & derivados , Alantoína/farmacología , Escherichia coli/efectos de los fármacos , Depuradores de Radicales Libres/farmacología , Hipoxantina/química , Modelos Moleculares , Estructura Molecular , Respuesta SOS en Genética/efectos de los fármacos , Urea/química , Ácido Úrico/química , Xantina/químicaRESUMEN
Polymorphism of Shereshevsky-Turner syndrome (STS) was studied in 233 patients who were examined at medical genetic services of the Research Institute of Obstetrics and Pediatrics (Rostov-on-Don) and Rostov Regional Hospital from 1978 to 1998. The subjects examined were residents of the Rostov oblast (administrative region) (RO) and some settlements in the northern Caucasus (NC). The mean incidence rate of STS was 3.8 per 10,000 newborns in this region in the period studied. Most STS cases were accounted for by the X trisomy (60 and 66.6% in the RO and NC, respectively). The mosaic form of STS was found in 25% of cases in both RO and NC. Other cytogenetic forms were found in 13.5 and 8.33% of patients from the RO and NC, respectively. The clinical polymorphism of STS, dynamics of its manifestation during ontogeny, and anthropometric parameters of the patients were studied. The effects of the age of parents, the season and month of conception, occupational hazards at the parents' workplaces, and the place of residence on the risk of STS were analyzed. Factor analysis was used to determine the sets of the main clinical signs characteristic of different STS cytogenetic forms in the RO and NC populations.
Asunto(s)
Síndrome de Turner , Adulto , Femenino , Humanos , Recién Nacido , Masculino , Monosomía , Factores de Riesgo , Federación de Rusia/epidemiología , Síndrome de Turner/epidemiología , Síndrome de Turner/genética , Síndrome de Turner/fisiopatología , Cromosoma XRESUMEN
We studied the level of lipid peroxidation and the activity of antioxidant enzymes (superoxide dismutase and catalase) in various tissues of adult Xenopus laevis after an initial exposure to hyperbaric oxygenation at the developmental stage 38. We have found that irrespective to the mode of treatment, the level of lipid peroxidation and activity of antioxidant enzymes in the brain, lungs, and blood of these animals were higher as compared to control animals. We demonstrate that, after the exposure of adult animals to hyperoxia, if they were earlier subjected to hyperbaric oxygenation (0.2 MPa) at stage 38, there was no intensification of lipid peroxidation or changes in the activity of superoxide dismutase and catalase. In adult animals initially subjected to hyperbaric oxygenation at the same stage of development but at the pressure--0.7 MPa, the second exposure to hyperoxia led to a drastic intensification of lipid peroxidation in the brain; in some animals, an increased level of lipid peroxidation products in the lungs was observed.
Asunto(s)
Adaptación Fisiológica/efectos de los fármacos , Antioxidantes/metabolismo , Oxigenoterapia Hiperbárica , Oxígeno/farmacología , Xenopus laevis/fisiología , Animales , Encéfalo/metabolismo , Peroxidación de Lípido/fisiología , Hígado/metabolismo , Pulmón/metabolismo , Músculo Esquelético/metabolismo , Estrés Oxidativo/fisiología , Xenopus laevis/embriologíaRESUMEN
The levels of tissue antioxidant uric acid in relation to chromosomal aberrations and leaving erythrocytic chromatin were determined in the spleen, bone marrow and blood of rats exposed to toxic hyperoxia (0.7 MPa O2, convulsions). Considerable growth of the uric acid levels and the rate of chromosomal aberrations in all tissues was observed within the first hours after treatment. The article discusses mechanisms of uric acid formation, redistribution and disintegration in tissues under extreme conditions. Specificity of the uric acid metabolism in tissues was shown with the help of the correlation analysis of uric acid concentrations. Inverse relationship between uric levels and chromosomal impairments noted in some cases permits to make a supposition about genoprotective properties and adaptogenic role of uric acid during oxidative stress.
Asunto(s)
Médula Ósea/metabolismo , Oxigenoterapia Hiperbárica , Bazo/metabolismo , Ácido Úrico/metabolismo , Adaptación Fisiológica , Animales , Aberraciones Cromosómicas , Femenino , Masculino , Ratas , Ácido Úrico/sangreRESUMEN
The effect of different regimens of hyperbaric oxygenation (0.2 MPa and 0.4 MPa for 1 or 3 hour) has been investigated in the culture of diploid and triploid human fibroblasts, picked out from aborts. The quantity of marked thymidine in nuclei of cells depends on both the value of pressure and time of treatment. HBO causes stimulant effect under 3-hour treatment. Influence of different regimens of HBO on human fibroblasts reveals high resistance of triploid to oxidative stress in comparison with diploid fibroblasts.