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BSTS epitaxial thin film topological insulators were grown using the MBE technique on two different types of substrates i.e., Si (111) and SiC/graphene with Bi0.7Sb1.6Te1.8Se0.9 and Bi0.9Sb1.5Te1.8Se1.1, respectively. The crystallographic properties of BSTS films were investigated via X-ray diffraction, which showed the strongest reflections from the (0 0 l) facets corresponding to the rhombohedral phase. Superior epitaxial growth, homogeneous thickness, smooth surfaces, and larger unit cell parameters were observed for the films grown on the Si substrate. Polarization dependent Raman spectroscopy showed a weak appearance of the Ag mode in cross--polarized geometry. In contrast, a strong Eg mode was observed in both parallel and cross-polarized geometries which correspond to the rhombohedral crystal symmetry of BSTS films. A redshift of Ag and Eg modes was observed in the Raman spectra of BSTS films grown on the Si substrate, compared to those on SiC/graphene, which was directly associated with the unit cell parameter and composition of the films. Raman spectra showed four fundamental modes with asymmetric line shape, and deconvolution of the peaks resulted in additional modes in both the BSTS thin films. The sum of relative ratios of linewidths of fundamental modes (Ag and Eg) of BSTS films grown on Si substrate was lower, indicating a more ordered structure with lower contribution of defects as compared to BSTS film grown on SiC/graphene substrate.
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High X-ray absorption combined with photothermal properties make bismuth nanoparticles (Bi NP) a promising agent for multimodal cancer theranostics. However, the synthesis of Bi NP by the "classical" chemical methods has numerous limitations, including potential toxicity of the produced nanomaterials. Here we studied in vitro toxicity of laser-synthesized Bi NP coated with Pluronic F-127 on mouse fibroblast cell line L929. The survival of L929 cells decreased linearly with increasing the concentration of Bi NP in a concentration range of 3-500 µg/ml; the LC50 value was 57 µg/ml. The unique combination of functional properties and moderate toxicity of the laser-synthesized Bi NP makes them a new promising platform for sensitization of multimodal cancer theranostics.
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Nanopartículas del Metal , Animales , Ratones , Bismuto/toxicidad , Bismuto/química , Línea Celular Tumoral , Nanopartículas del Metal/toxicidad , Nanopartículas del Metal/química , Nanopartículas/toxicidad , Nanopartículas/química , Nanoestructuras , Neoplasias/metabolismo , Fototerapia/métodosRESUMEN
The best way to understand the environmental status of a certain region involves thorough non-target analysis, which will result in a list of pollutants under concern. Arkhangelsk (64° 32' N 40° 32' E, pop. ~ 344,000) is the largest city in the world to the north of the 60th parallel. Several industrial enterprises and the "cold finger" effect represent the major sources of air contamination in the city. Analysis of snow with comprehensive two-dimensional gas chromatography-high-resolution mass spectrometry allows detecting and quantifying the most hazardous volatile and semivolatile anthropogenic pollutants and estimating long-term air pollution. Target analysis, suspect screening, and non-target analysis of snow samples collected from ten sites within the city revealed the presence of several hundreds of organic compounds including 18 species from the US EPA list of priority pollutants. Fortunately, the levels of these compounds appeared to be much lower than the safe levels established in Russia. Phenol and dioctylphthalate could be considered as the pollutants of concern because their levels were about 20% of the safe thresholds. ChromaTOF® Tile, MetaboAnalyst software platform, and open-source software protocols were applied to process the obtained data. The obtained clusterization results of the samples were generally similar for various tools; however, each of them had certain peculiarities. Bis(2-ethylhexyl) hexanedioate, benzyl alcohol, phthalates, aniline, dinitrotoluenes, and fluoranthene showed the strongest influence on the clusterization of the studied samples. Possible sources of the major pollutants were proposed: car traffic and pulp and paper mills.
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BACKGROUND: Epidemiological studies have reported associations of anti-androgenic phthalate metabolite concentrations with later onset of male puberty, but few have assessed associations with progression. OBJECTIVES: We examined the association of prepubertal urinary phthalate metabolite concentrations with trajectories of pubertal progression among Russian boys. METHODS: At enrollment (ages 8-9 years), medical history, dietary, and demographic information were collected. At entry and annually to age 19 years, physical examinations including testicular volume (TV) were performed and spot urines collected. Each boy's prepubertal urine samples were pooled, and 15 phthalate metabolites were quantified by isotope dilution LC-MS/MS at Moscow State University. Metabolites of anti-androgenic parent phthalates were included: butylbenzyl (BBzP), di-n-butyl (DnBP), diisobutyl (DiBP), di(2-ethylhexyl) (DEHP) and diisononyl (DiNP) phthalates. We calculated the molar sums of DEHP, DiNP, and all AAP metabolites. We used group-based trajectory models (GBTMs) to identify subgroups of boys who followed similar pubertal trajectories from ages 8-19 years based on annual TV. We used multinomial and ordinal regression models to evaluate whether prepubertal log-transformed phthalate metabolite concentrations were associated with slower or faster pubertal progression trajectories, adjusting for covariates. RESULTS: 304 boys contributed a total of 752 prepubertal urine samples (median 2, range: 1-6) for creation of individual pools. The median length of follow-up was 10.0 years; 79% of boys were followed beyond age 15. We identified three pubertal progression groups: slower (34%), moderate (43%), and faster (23%) progression. A standard deviation increase in urinary log-monobenzyl phthalate (MBzP) concentrations was associated with higher adjusted odds of being in the slow versus faster pubertal progression trajectory (aOR 1.47, 95% CI 1.06-2.04). None of the other phthalate metabolites were associated with pubertal progression. CONCLUSIONS: On average, boys with higher concentrations of prepubertal urinary MBzP had a slower tempo of pubertal progression, perhaps attributable to the disruption of androgen-dependent biological pathways.
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Dietilhexil Ftalato , Contaminantes Ambientales , Ácidos Ftálicos , Humanos , Masculino , Adulto Joven , Adulto , Adolescente , Contaminantes Ambientales/metabolismo , Cromatografía Liquida , Espectrometría de Masas en Tándem , Ácidos Ftálicos/orina , Antagonistas de Andrógenos , Exposición a Riesgos Ambientales/análisisRESUMEN
The study of the role of cytokines in various pathological conditions of the body is a topical area in modern biomedicine. Understanding the physiological roles played by cytokines will aid in finding applications for them as pharmacological agents in clinical practice. Interleukin 11 (IL-11) was discovered in 1990 in fibrocyte-like bone marrow stromal cells, but there has been increased interest in this cytokine in recent years. IL-11 has been shown to correct inflammatory pathways in the epithelial tissues of the respiratory system, where the main events occur during SARS-CoV-2 infection. Further research in this direction will probably support the use of this cytokine in clinical practice. The cytokine plays a significant role in the central nervous system; local expression by nerve cells has been shown. Studies show the involvement of IL-11 in the mechanisms of development of a number of pathologies of the nervous system, and therefore it seems relevant to generalize and analyze the experimental data obtained in this direction. This review summarizes information that shows the involvement of IL-11 in the mechanisms of development of brain pathologies. In the near future this cytokine will likely find clinical application for the correction of mechanisms that are involved in the formation of pathological conditions of the nervous system.
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COVID-19 , Interleucina-11 , Humanos , Antígenos CD/metabolismo , COVID-19/genética , Receptor gp130 de Citocinas , Citocinas/farmacología , Interleucina-11/genética , Sistema Nervioso/metabolismo , SARS-CoV-2/metabolismoRESUMEN
Vitamin D deficiency, like cardiovascular disease, is widespread throughout the world. Researches indicate a number of potential mechanisms for the relationship between vitamin D deficiency and cardiometabolic risk factors. The results of studying the relationship between 25-hydroxyvitamin D [25(OH)D] in blood serum and lipid profile indicators are contradictory, studies were mainly carried out among the adult and elderly population. The aim of the research was to study the relationship between the level of 25(OH)D and lipid spectrum indicators in young people. Material and methods. The cross-sectional study included 278 young adults (aged from 18 to 24 years), of which 64 (23%) were boys, 214 (77%) were girls. The assessment of lipid spectrum indicators included total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, calculation of the atherogenic index; vitamin D status was evaluated by 25(OH)D blood serum level determination. Results. The levels of 25(OH)D below the criterion of insufficiency (30 ng/ml) were found in 81% of participants. A weak positive correlation was found between the level of triglycerides and 25(OH)D concentration (ρ=0.181, p=0.003). Gender differences were found in the association of 25(OH)D level with lipid profile parameters. In young men, a negative correlation was found between 25(OH)D level and indicators of total cholesterol (ρ=-0.316, p=0.014) and LDL cholesterol (ρ=-0.348, p=0.007), as well as significantly lower concentrations of 25(OH)D in the group with elevated LDL cholesterol levels. Conclusion. The results of the study indicate the existence of the relationships between 25(OH)D concentration and various parameters of the lipid spectrum of blood serum. Vitamin D deficiency may be associated with an increased risk of dyslipidemia, especially in males. The relationship between 25(OH)D level and lipid profile scores may differ depending on gender.
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Deficiencia de Vitamina D , Adolescente , Anciano , Colesterol , HDL-Colesterol , LDL-Colesterol , Estudios Transversales , Femenino , Humanos , Masculino , Triglicéridos , Vitamina D , Deficiencia de Vitamina D/epidemiología , Adulto JovenRESUMEN
The article is devoted to the problem of diagnosing subclinical keratoconus (KK). The need to identify early signs of KK is primarily associated with the potential for the development of iatrogenic keratoectasia in cases of underdiagnosis of the disease when determining the conditions for laser keratorefractive surgery involving a decrease in the thickness of the cornea. Today generally accepted algorithms for early computer-assisted diagnosis of KK are mainly based on the analysis of various morphometric parameters of the cornea, reflecting changes in its shape and thickness induced by structural abnormalities. Direct detection of structural changes in the cornea characteristic of early KK requires the use of high-tech imaging methods that are not always applicable in everyday clinical practice. The promising approach proposed in this study is based on the fact that a digital image of a corneal «slice¼ obtained using serial analyzers such as the Scheimpflug camera widely used in clinical practice provides indirect information about the structure of the epithelial layer, the local thickening of which takes place in the initial stages KK. It is this criterion that underlies the proposed system of computer-assisted diagnosis of KK. The carried out studies have shown the high sensitivity of this algorithm, and its specificity can be increased by involving the known diagnostic indicators of KK.
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Queratocono , Computadores , Córnea/diagnóstico por imagen , Topografía de la Córnea/métodos , Diagnóstico por Computador , Humanos , Queratocono/diagnóstico , Curva ROCRESUMEN
Multicenter studies of the last decade have confirmed the direct relationship between the spatial structure of drug compounds and their biological activity. Aim - the relevance of this topic, on the one hand, is explained by the rapid development of new technologies, on the other hand, by a large number of researches works devoted to the study of the influence of stereoisomeric factors on the therapeutic effect and side effects of drugs. In recent decades, computational approaches have been used to reveal the relationship between the biological properties of substances and their structure and to quantitatively describe this relationship. Quantitative Structure - Activity Relationships (QSAR) is widely used in modern drug chemistry. In combination with molecular modeling techniques, this trend has been commonly referred to as in silico methods, which implies a preliminary search for drugs by computer only, prior to experimental screening. Hundreds of QSAR and molecular modeling programs have been developed around the world: dozens of specialized scientific journals are published dedicated to computer-based methods of searching for biologically active substances. Thousands of articles have been published demonstrating the results of successful application of QSAR methods in the search for new biologically active substances. There are currently more than 101 million known organic compounds in the world, and the known number of biological activities exceeds 25,000, so global experimental testing of all substances is impossible. Thus, the use of in silico methods to search for drugs, in particular, for the preliminary selection of unpromising compounds is super relevant.
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Desarrollo de Medicamentos , Relación Estructura-Actividad Cuantitativa , Modelos Moleculares , Simulación por ComputadorRESUMEN
Among the most significant challenges presented to modern medicine is the problem of cognitive disorders. The relevance of her research is determined by the wide spread of disorders of the higher cortical functions, their significant negative impact on the quality of life of patients, as well as high economic costs on the part of the state and the patient's relatives aimed at organizing medical, diagnostic and rehabilitation processes. The main cause of cognitive impairment in the elderly is Alzheimer's disease. Currently, the criteria for the diagnosis of this nosological form have been developed and are widely used in practice. However, it should be noted that their use is most effective if the patient has a detailed clinical picture, at the stage of dementia. In addition, they provide for the study of biomarkers in a number of cases in the cerebrospinal fluid or using positron emission tomography, which presents certain technical difficulties. Especially significant problems arise in the pre-dement stages. This situation dictates the need to search for new promising diagnostic methods that will have high sensitivity and specificity, as well as the possibility of application in the early stages of Alzheimer's disease, including in outpatient settings. The article provides information about modern methods of computer neuroimaging, discusses the research directions of individual biomarkers, and also shows the prospects for using diagnostic test panels developed on the basis of graphene biosensors, taking into account the latest achievements of nanotechnology and their integration into medical science.
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Enfermedad de Alzheimer , Grafito , Anciano , Enfermedad de Alzheimer/diagnóstico , Biomarcadores , Pruebas Diagnósticas de Rutina , Progresión de la Enfermedad , Diagnóstico Precoz , Femenino , Humanos , Calidad de VidaRESUMEN
Skin secretion represents the only means of defense for the majority of frog species. That phenomenon is based on the fact that the main components of the secretion are peptides demonstrating greatly varying types of bioactivity. They fulfill regulatory functions, fight microorganisms and may be even helpful against predators. These peptides are considered to be rather promising pharmaceuticals of future generation as according to the present knowledge microorganisms are unlikely to develop resistance to them. Mass spectrometry sequencing of these peptides is the most efficient first step of their study providing reliably their primary structures, i.e., amino acids sequence and S-S bond motif. Besides discovering new bioactive peptides, mass spectrometry appears to be an efficient tool of taxonomy studies, allowing for distinguishing not only between closely related species, but also between populations of the same species. Application of several tandem mass spectrometry tools (CID, HCD, ETD, EThcD) available with Orbitrap mass analyzer allowed us to obtain full sequence of about 60 peptides in the secretion of Slovenian population of brown ranid frog Rana temporaria. The problem of sequence inside C-terminal cycle formed by two Cys and differentiation of isomeric Leu and Ile residues was done in top-down mode without any derivatization steps. Besides general biomarkers of Rana temporaria species, Central Slovenian population of Rana temporaria demonstrates six novel temporins and one brevinin 1, which may be treated as biomarkers of that population.
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Proteínas Anfibias/análisis , Péptidos Catiónicos Antimicrobianos/análisis , Rana temporaria , Secuencia de Aminoácidos , Animales , Moscú , Rana temporaria/metabolismo , Análisis de Secuencia de Proteína , Piel/química , Eslovenia , Especificidad de la Especie , Espectrometría de Masas en TándemRESUMEN
The review presents data on the expression of ghrelin receptor GHS-R1a in the brain in model animals (Danio rerio, rodents, primates), and in the human brain. Studies show widespread localization of GHS-R1a in the brain, which indicates the involvement of the receptor in many physiological processes. Using various models, information has been obtained regarding the participation of the receptor in the regulation of the pro- and anti-inflammatory response, apoptosis and proliferation. It is known that the ghrelin receptor plays an important role in eating behavior and is also involved in the pathogenetic mechanisms of obesity, drug addiction, and alcoholism. With this in mind, research is underway with the use of various therapeutic agents (receptor agonists and antagonists) that can be used for the pharmacological correction of these pathological conditions. This review also presents hypothetical mechanisms of intracellular signaling, in which GHS-R1a may participate; however, a complete understanding of these mechanisms has not yet been reached. The ghrelin intracellular pathways seem to be specific to brain region and, probably, also depend on the metabolic or stress status of the organism.
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Alcoholismo , Receptores de Ghrelina , Animales , Encéfalo/metabolismo , Ghrelina/genética , Humanos , Receptores de Ghrelina/genética , Receptores de Ghrelina/metabolismo , Transducción de SeñalRESUMEN
Obesity in childhood and adolescence is an important clinical and social problem in all countries, due to its extremely adverse long-term health effects. Vitamin D deficiency is extremely widespread in the world. Obesity and metabolic syndrome are often associated with vitamin D deficit. The role of vitamin D deficiency in obesity and metabolic syndrome in childhood is not well understood. Aims - to study the relationship of vitamin D deficiency and carbohydrate metabolism parameters in school children with obesity. Material and methods. The cross-sectional study included 71 patients of the Arkhangelsk Children's Clinical Hospital named after P.G. Vyhletsova (32 boys, 39 girls, aged 10 to 15 years, all children live in Arkhangelsk) with abdominal obesity. An anthropometric study was conducted: height (cm), body weight (kg), waist circumference (cm), body mass index (BMI). Serum 25(ÐÐ)D level, fasting glycemia, insulin level and HOMA-IR index were assessed. Results. It has been revealed that 98,6% of children have vitamin D deficiency of varying severity. 25(OH)D level in severely obese children (BMI>3SDS) was significantly lower than in other obese children (BMI<3SDS): 12.8 [7.3-14.9] vs 13.5 [8.9-18.2] ng/ml, (p=0.039). In children with hyperglycemia and insulin resistance, 25(OH)D levels were significantly lower compared with those who had normal glycemic parameters and HOMA-IR index. Conclusions. The high prevalence of vitamin D deficiency in children and adolescents with overweight and obesity, progressing with increasing obesity severity, has been demonstrated. The association of glucose metabolism disorders with vitamin D deficiency has been shown.
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Obesidad Infantil , Deficiencia de Vitamina D , Adolescente , Metabolismo de los Hidratos de Carbono , Niño , Estudios Transversales , Femenino , Humanos , Masculino , Obesidad Infantil/epidemiología , Vitamina D , Deficiencia de Vitamina D/complicaciones , Deficiencia de Vitamina D/epidemiologíaRESUMEN
Living cells interact with their immediate environment by exerting mechanical forces, which regulate important cell functions. Elucidation of such force patterns yields deep insights into the physics of life. Here we present a top-down nanostructured, ultraflexible nanowire array biosensor capable of probing cell-induced forces. Its universal building block, an inverted conical semiconductor nanowire, greatly enhances both the functionality and the sensitivity of the device. In contrast to existing cellular force sensing architectures, microscopy is performed on the nanowire heads while cells deflecting the nanowires are confined within the array. This separation between the optical path and the cells under investigation excludes optical distortions caused by cell-induced refraction, which can give rise to feigned displacements on the 100 nm scale. The undistorted nanowire displacements are converted into cellular forces via the nanowire spring constant. The resulting distortion-free cellular force transducer realizes a high-resolution and label-free biosenor based on optical microscopy. Its performance is demonstrated in a proof-of-principle experiment with living Dictyostelium discoideum cells migrating through the nanowire array. Cell-induced forces are probed with a resolution of 50 piconewton, while the most flexible nanowires promise to enter the 100 femtonewton realm.
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Técnicas Biosensibles , Rastreo Celular/métodos , Nanoestructuras/química , Nanocables/química , Microscopía/métodos , Nanotecnología/métodos , Óptica y Fotónica/tendencias , Semiconductores , TransductoresRESUMEN
A 93-year-old patient underwent endoscopic treatment of perforated duodenal ulcer after previous laparoscopic suturing complicated by failure of sutured defect. A self-expanding nitinol stent with partial polyurethane coating was used. Positive effect of the treatment was noted. Further study of this method and its clinical introduction in case of favorable results can significantly reduce the incidence of complications and mortality in patients with perforated gastroduodenal ulcers.
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Úlcera Duodenal/cirugía , Úlcera Péptica Perforada/cirugía , Anciano de 80 o más Años , Aleaciones , Materiales Biocompatibles Revestidos , Duodenoscopía , Gastroscopía , Humanos , Laparoscopía/efectos adversos , Poliuretanos , Implantación de Prótesis , Reoperación , Stents Metálicos Autoexpandibles , Técnicas de Sutura/efectos adversosRESUMEN
The aim of this study was to evaluate changes in the content of sphingoid bases - sphingosine (SPH), sphinganine, and sphingosine-1-phosphate (SPH-1-P) - and in expression of genes encoding enzymes involved in their metabolism in the brain structures (hippocampus, cortex, and cerebellum) and spinal cord of transgenic FUS(1-359) mice. FUS(1-359) mice are characterized by motor impairments and can be used as a model of amyotrophic lateral sclerosis (ALS). Lipids from the mouse brain structures and spinal cord after 2, 3, and 4 months of disease development were analyzed by chromatography/mass spectrometry, while changes in the expression of the SPHK1, SPHK2, SGPP2, SGPL1, ASAH1, and ASAH2 genes were assayed using RNA sequencing. The levels of SPH and sphinganine (i.e., sphingoid bases with pronounced pro-apoptotic properties) were dramatically increased in the spinal cord at the terminal stage of the disease. The ratio of the anti-apoptotic SPH-1-P to SPH and sphinganine sharply reduced, indicating massive apoptosis of spinal cord cells. Significant changes in the content of SPH and SPH-1-P and in the expression of genes related to their metabolism were found at the terminal ALS stage in the spinal cord. Expression of the SGPL gene (SPH-1-P lyase) was strongly activated, while expression of the SGPP2 (SPH-1-P phosphatase) gene was reduced. Elucidation of mechanisms for the regulation of sphingolipid metabolism in ALS will help to identify molecular targets for the new-generation drugs.
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Esclerosis Amiotrófica Lateral/metabolismo , Encéfalo/metabolismo , Modelos Animales de Enfermedad , Proteína FUS de Unión a ARN/metabolismo , Esfingolípidos/metabolismo , Médula Espinal/metabolismo , Animales , Ratones , Ratones Transgénicos , Esfingolípidos/químicaRESUMEN
Lipid metabolism disorders are the most significant risk factor of development of cardiovascular diseases (CVD). In the process of diagnosing ischemic heart disease and other cardiovascular pathologies, levels of total cholesterol, low- and high- density lipoprotein cholesterol, triglycerides are determined. However, in recent years, close attention has been paid to the intersection of the metabolic pathways of the biosynthesis of cholesterol and sphingolipids. Sphingolipids - a group of lipids, which include a molecule of aliphatic alcohol sphingosine. This group includes sphingomyelins, cerebrosides, gangliosides and ceramides, sphingosines and sphingosine-1-phosphate (S-1-P). Ceramides and sphingosines have pro-apoptotic properties, and S-1-P protects cells from apoptosis. Particular attention as inducer CVD attracts ceramide. It has been established that aggregated lipoproteins isolated from atherosclerotic zones are enriched with ceramides. The level of ceramide and sphingosine increases with ischemia/reperfusion of the heart, in the infarction zone and in the blood, and also in hypertensive disease. S-1-P has a pronounced cardioprotective properties. Its content sharply decreases with ischemia and myocardial infarction. S-1-P performs a special function in the structure of high-density lipoproteins (HDL), being one of the main lipid components of these lipoproteins, which determines their multiple functions. Recently, work has been underway to create drugs that can correct the metabolism of S-1-P. The most successful drugs are those that use the S-1-P receptor as a target, since all of its actions are carried out through receptors. Increasing ceramide and sphingosine and reducing blood plasma level of S-1-P can be an important factor in the development of atherosclerosis. It is proposed to use the determination of the level of sphingolipids in blood plasma for early diagnosis of cardiac ischemia and in arterial hypertension. Chromatography-mass spectrometry has been suggested as the main method for testing these lipids.
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Aterosclerosis , Ceramidas , HDL-Colesterol , Humanos , Esfingolípidos , TriglicéridosRESUMEN
The last decades are characterized by advanced incidence of injuries with the share of abdominal injuries 1.5-18%. Blunt abdominal trauma is characterized by high incidence of complications and mortality due to severity of injury of internal organs and difficult diagnosis. The article presents 3 case reports of isolated and combined abdominal trauma followed by intestinal injury. Patients were treated at the department of emergency surgical gastroenterology of Sklifosovsky Research Institute for Emergency Care in for the period from August 2017 to February 2018.
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Traumatismos Abdominales/complicaciones , Intestinos/lesiones , Intestinos/cirugía , Heridas no Penetrantes/complicaciones , Urgencias Médicas , HumanosRESUMEN
Corticoliberin (CRF) isn't only regulates hypothalamic-pituitary-adrenal axis activity, but also functions as a neurotransmitter in extrahypothalamic brain regions like amygdala, implicated in the emotional responses to stress. The CRF system provides an input to orexin neurons and can modulate the activity of orexinergic neurons in stress response. Some data showed the role of orexin-A in extinction of aversive memory. The orexin system was shown to participate in stress-induced behavior connected with the extended amygdala structures, like central nucleus of the amygdala. The objective was to study the effects of orexin-A antagonist SB-408124 in rats after predator-induced stress using behavioral tests and its effects on CRF level in amygdala. In this study 30 male Wistar rats were used. The animals received an intranasally selective antagonist of Orexin receptor 1 type SB-408124. Posttraumatic stress disorder was modelled by single predator exposure. A group of 10-12 rats were placed in a terrarium with an indian python. 7 days after exposure to the predator, the behavior of animals was tested in the Open Field and Elevated Cross-Maze tests. Free motor activity of animals was studied in the "open field" test. To assess stress, we used the "elevated cross-maze " test. CRF concentrations in brain structures were measured by solid-phase ELISA using the Corticotropin Releasing Factor (CRF) test system. In the group of stressed rats receiving intranasally SB-408124, the time of stay in the light arm was restored, but did not reach the control values, the number of runs was restored to the control level, and the number of grooming acts increased in comparison with both the control group and the stressed animals. In the "open field" in the group of stressed rats receiving saline solution, the number of sniffs and rearing were decreased, but the number of peeks into holes was increased. In the group of stressed rats receiving SB-408124 20 µg intranasally, the number of sniffs was increased and the number of hole peeking decreased in comparison with the stressed rats receiving saline solution. The CRF level in the homogenates of amygdala in stressed rats was lower (0.44±0.07 ng/mg protein vs. 0.61±0.01 ng/mg in the control group). In the intranasal administration of SB408124 group this decrease was not recorded and the CRF level in the amygdala was 0.57±0.01 pg/mg protein. Orexin A antagonist SB-408124 reduced anxiety after psychotraumatic exposure. Predator induced acute psychotraumatic exposure decrease CRF level in the rat's amygdala. Intranasal administration of selective orexin 1 receptor antagonist SB408124 restored it closely to normal and has an anxiolytic effect on animal behaviour.
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Amígdala del Cerebelo/efectos de los fármacos , Conducta Animal/efectos de los fármacos , Hormona Liberadora de Corticotropina/farmacología , Sistema Hipotálamo-Hipofisario/efectos de los fármacos , Receptores de Orexina , Compuestos de Fenilurea , Trastornos por Estrés Postraumático/fisiopatología , Amígdala del Cerebelo/fisiología , Animales , Sistema Hipotálamo-Hipofisario/fisiología , Masculino , Sistema Hipófiso-Suprarrenal/efectos de los fármacos , Sistema Hipófiso-Suprarrenal/fisiología , Ratas , Ratas Wistar , Trastornos por Estrés Postraumático/inducido químicamenteRESUMEN
Thyroid hormones can exert responses in various immune cells affecting several inflammation-related processes. The interactions between the endocrine and immune systems have been shown to contribute to pathophysiological conditions. Aim of study - to answer the question if hyper- or/and hypothyroid state can be as provoking factor for inflammation in colon. The study was performed on 60 mature male mice of the inbred line C3H-A. On male mice was reproduced a model of experimental hyperthyroidism and hypothyroidism by oral intake of L-thyroxin and propylthyouracil, accordingly. By the 22nd week of the experiment all animals were sacrificed. The rectum was removed for histo- and immunocytochemical examination. In histological examination in hyperthyroid group the hypertrophy of the mucous membrane of the colon is detected. Simultaneously the frequency of cell mitosis is increased. Among the epithelium glands of the colon can clearly be seen apoptotic bodies. Moderate or expressed infiltration by lymphocytes and plasma cells is elucidated in mucous membrane of colon relatively to mucous membrane of colon of euthyroid group i.e. control one. In hyporthyroid group the hyportrophy of the mucous membrane of the colon was detected. The lymphocytic infiltration is not found. In immunocytochemical examination the frequency of CD20 and CD56 positive cells was significantly higher (>23%) in cytological preparation of membrane mucous of colon from hyperthyroid mice (p<0.01). Meanwhile CD20 and CD56 positive cells were detected in single cases in cytological preparation of membrane mucous of colon from hypothyroid mice. The same observation was done for healthy membrane mucous from control (euthyroid) group. It is possible that the thyroid status is one of the factors modulating the inflammation. This discussion is far from over, because it is unclear whether prolonged hyperthyroidism can actually activate pro-inflammatory reactions, which subsequently, in turn, activate carcinogenesis.
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Colon/fisiopatología , Hipertiroidismo , Hipotiroidismo , Animales , Masculino , Ratones , Ratones Endogámicos C3H , TiroxinaRESUMEN
The effect of a cerebroprotective agent magnesium bis-aminoethanesulfonate (laboratory code FS-LKhT-317) on intracellular calcium concentration was studied by the fluorescent imaging technique on neuroglial cell culture from Spraque-Dawley rat hippocampus. The substance produced a pronounced inhibitory effect and suppressed NMDA receptor activity in concentrations of ≥50 µM. The observed effects were reversible or partially reversible and were detected by a decrease in Ca2+ signal amplitude in neurons in response to NMDA applications in a Mg2+-free medium and by inhibition of Ca2+ pulses in magnesium-free medium (elimination of magnesium block).