RESUMEN
About 7% of all cancer deaths are caused by pancreatic cancer (PCa). PCa is known for its lowest survival rates among all oncological diseases and heterogenic molecular profile. Enormous amount of genetic changes, including somatic mutations, exceeds the limits of routine clinical genetic laboratory tests and further stagnates the development of personalized treatments. We aimed to build a mutational landscape of PCa in the Russian population based on full exome next-generation sequencing (NGS) of the limited group of patients. Applying a machine learning model on full exome individual data we received personalized recommendations for targeted treatment options for each clinical case and summarized them in the unique therapeutic landscape.
Asunto(s)
Adenocarcinoma , Neoplasias Pancreáticas , Humanos , Adenocarcinoma/genética , Adenocarcinoma/terapia , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/terapia , Exoma/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Aprendizaje AutomáticoRESUMEN
Hepatic artery aneurysms (HAA) are rare (20% of all visceral arteries). Most often, HAAs are asymptomatic and detected at autopsy. However, their ruptures and/or bleeding following pressure ulcers in visceral gastrointestinal organs are a significant clinical and diagnostic problem. We present 2 patients with obstructive jaundice and hemobilia. Diagnostics revealed aneurysm of the right hepatic artery with arterio-biliary fistula. Life-threatening hemobilia is a consequence of HAA rupture into biliary system. Endovascular approach is preferable for HAA without clinical manifestations. Awareness of this disease is important for early detection and active surgical intervention before possible complications.
Asunto(s)
Aneurisma , Fístula Biliar , Hemobilia , Ictericia Obstructiva , Humanos , Fístula Biliar/diagnóstico , Fístula Biliar/etiología , Fístula Biliar/cirugía , Hemobilia/etiología , Hemobilia/complicaciones , Aneurisma/cirugía , Arteria Hepática/diagnóstico por imagen , Arteria Hepática/cirugía , Ictericia Obstructiva/diagnóstico , Ictericia Obstructiva/etiología , Ictericia Obstructiva/cirugíaRESUMEN
Study of cervical cancer patients with I-III stage was performed with biomarker determination of the blood DNA radiosensitivity ex vivo. The biochemical index was measured before treatment start during 4 hours by use fluorescent dye. The relationship between changes of these index levels and volume tumor reductions after radiochemical treatment evidenced that blood DNA radiosensitivity was enabled to predict an outcome of the cervical cancer patient treatment earlier than the assessment of therapy efficacy by help of ultrasound measurements.
Asunto(s)
Biomarcadores de Tumor/sangre , ADN de Neoplasias/sangre , Tolerancia a Radiación/genética , Neoplasias del Cuello Uterino/sangre , Adulto , Biomarcadores de Tumor/genética , Proliferación Celular/genética , Proliferación Celular/efectos de la radiación , ADN de Neoplasias/efectos de la radiación , Femenino , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Tolerancia a Radiación/efectos de la radiación , Radiofármacos/administración & dosificación , Procedimientos de Cirugía Plástica , Resultado del Tratamiento , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/radioterapiaRESUMEN
Clinical characteristics of some diseases are defined by the phenotype of metabolic reactions, for example N-acetylation. Genetic polymorphism due to the activity of N-acetyltransferase (N-AT) is common in the majority of human populations. Consequently, persons with "slow" or "fast" acetylation phenotype should be identified. N-AT catalyzes acetylation of a number of medical products. Efficiency of pharmacotherapy is mostly associated with the specific features of medical products biotransformation. The processes of biotransformation with participation of acetyltransferase, monooxygenase or other ferment systems are under the gene control. The aim of the study was to characterize the features of the clinical course of acute respiratory infection complicated by pneumonia as dependent on the acetylation phenotype to predict the character of the disease and optimize the used antibiotic therapy among the native population (Yakut) and the arrived (Russian) in the Far North Regions (Sakha, Yakutia). 112 children with acute respiratory infections complicated by pneumonia and 49 practically healthy ones were examined. For the children with low N-AT activity (less than 30%) it was recommended to be treated with gentamicin which directly takes part in the acetylation and provides the antibiotic therapy efficiency in 80% of the cases. The use of cephalosporin antibiotics (beta-lactams), the metabolism of which is not directly connected with acetylation reactions provided the efficiency in 20% of the cases.
Asunto(s)
Acetiltransferasas/metabolismo , Antibacterianos/uso terapéutico , Gentamicinas/uso terapéutico , Neumonía Bacteriana/tratamiento farmacológico , Infecciones del Sistema Respiratorio/tratamiento farmacológico , beta-Lactamas/uso terapéutico , Acetilación , Acetiltransferasas/genética , Antibacterianos/metabolismo , Biotransformación , Niño , Preescolar , Clima Frío , Etnicidad , Femenino , Gentamicinas/metabolismo , Humanos , Masculino , Neumonía Bacteriana/complicaciones , Neumonía Bacteriana/enzimología , Neumonía Bacteriana/etnología , Polimorfismo Genético , Infecciones del Sistema Respiratorio/complicaciones , Infecciones del Sistema Respiratorio/enzimología , Infecciones del Sistema Respiratorio/etnología , Federación de Rusia , Resultado del Tratamiento , beta-Lactamas/metabolismoRESUMEN
Recently, the share of children with verified neonatal hepatitis induced by genetic predisposition, malformations of biliary tracts, inborn infections with affection of hepatobiliary system increased. The comprehensive biochemical examination of 62 children aged from 1.5 months to 2 years old with diagnosis of neonatal hepatitis. The changes of standard indicators of cytolysis, cholestasis and protein metabolism were on average moderate in group with reliable increase of protein concentration of acute phase of inflammation. The peak changes of biochemical indicators during primary examination are revealed in group of children with malformations of hepatobiliary system conditioned by viruses of herpetic group and in the process of development of expressed fibrosis of liver up to first year of life. The detection of proteins of acute phase makes it possible to objectively evaluate the presence of prolonged inflammatory process in liver and to promote prognosis of course of neonatal hepatitis in children of early age and timely correction of therapy and improvement of outcomes of disease. The detection of C-reactive protein, alpha2-macroglobulin and alpha1-antitripsin is recommended to be included into algorithm of examination of children with neonatal hepatitis.
Asunto(s)
Proteína C-Reactiva/aislamiento & purificación , Hepatitis/sangre , Pronóstico , alfa-Macroglobulinas/aislamiento & purificación , Fosfatasa Alcalina/sangre , Bilirrubina/sangre , Proteína C-Reactiva/metabolismo , Preescolar , Hepatitis/etiología , Hepatitis/patología , Humanos , Lactante , Hígado/patología , Nitritos/sangre , alfa-Macroglobulinas/metabolismoRESUMEN
On Wistar rats in view of electrophysiological parameters after sleep deprivation (SD; awake by gentle handling method) and the subsequent postdeprivative sleep (PDS) immunohistochemical investigation of Bcl-2 and p53 peptides optical density levels in neurons of paraventricular (PVN), supraoptic (SON) and median (MnPN) hypothalamus nuclei was carried out. The Bcl-2 was increased in all nuclei both after SD and PDS. The level of p53 was increased in PVN and SON after SD and PDS, but in MnPN only on PDS. Any morphological attributes of apoptosis in the nuclei was not revealed. Obtained data testify an active role of p53 and Bcl-2 peptides in regulation of neuronal activity in hypothalamus at change of a cycle wakefulness-sleep.
Asunto(s)
Núcleo Hipotalámico Paraventricular/fisiopatología , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Privación de Sueño/fisiopatología , Núcleo Supraóptico/fisiopatología , Proteína p53 Supresora de Tumor/metabolismo , Animales , Inmunohistoquímica , Masculino , Neuronas/metabolismo , Neuronas/fisiología , Núcleo Hipotalámico Paraventricular/metabolismo , Ratas , Ratas Wistar , Sueño/fisiología , Privación de Sueño/metabolismo , Núcleo Supraóptico/metabolismo , Vigilia/fisiologíaRESUMEN
The aim of the present work was to study the involvement of the dopaminergic system of the telencephalic and diencephalic areas of the vertebrate brain in the organization of the sleep-waking cycle in cold-blooded and warm-blooded vertebrates. Immunohistochemical studies of tyrosine hydroxylase content, this being the key enzyme in dopamine synthesis, in the striatum, supraoptic and arcuate nuclei, and zona incerta of the hypothalamus of sturgeon and mammals (rats) of three age groups (14 and 30 days and adults), in conditions of tactile and sleep-deprivation stressors. In fish, transient stress was followed by the detection of tyrosine hydroxylase-immunoreactive cells in all parts of the brain. In prolonged stress, tyrosine hydroxylase-immunoreactive cells and fibers were not found in the forebrain, though they were well represented in the hypothalamic nuclei. In 14-day-old rat pups, 2-h sleep deprivation increased the tyrosine hydroxylase content of fibers in the caudate nucleus and cells in the zona incerta of the hypothalamus, while 30-day-old animals subjected to 6-h sleep deprivation showed increases in tyrosine hydroxylaseimmunoreactive material contents in cells in the paraventricular nucleus and decreases in the quantity in fibers. In adult rats, the arcuate nucleus and zona incerta showed decreases in the content of tyrosine hydroxylase-immunoreactive material on the background of sleep deprivation, with increases during postdeprivation sleep. These data are discussed in the light of the phylo- and ontogenetic development of the neurosecretory and neurotransmitter functions of the dopaminergic system in the evolutionarily ancient diencephalic and evolutionarily young telencephalic areas of the vertebrate brain as major systems triggering and maintaining the functional states of the body during the sleep-waking cycle.
Asunto(s)
Diencéfalo/metabolismo , Dopamina/metabolismo , Sueño , Telencéfalo/metabolismo , Vigilia , Animales , Diencéfalo/enzimología , Diencéfalo/crecimiento & desarrollo , Peces , Inmunohistoquímica , Ratas , Privación de Sueño/enzimología , Estrés Psicológico/enzimología , Telencéfalo/enzimología , Telencéfalo/crecimiento & desarrollo , Tacto , Tirosina 3-Monooxigenasa/metabolismoRESUMEN
The aim of our study was to investigate the role of dopaminergic system in telencephalic and diencephalic brain regions of vertebrates in sleep-wakefulness cycle. The level of thyrosine-hydroxylase--the main enzyme in dopamine synthesis--was measured in striatum, zona inserta supraoptic and arcuate nuclea of hypothalamus in fish (Acipenceridae) and in mammals (rats) in ontogenesis (14-, 30-day old rats and adult animals) under tactile and sleep deprivation stresses. The thyrosine-hydroxylase-immunoreactive cells were revealed in all brain regions of fishes after a short-term stress. In the group after longtime stress, the thyrosine-hydroxylase-immunoreactive cells and fibers were almost absent in anterior brain but were found in hypothalamic nuclea. At 14-day old rats, 2-hour sleep deprivation caused increasing of thyrosine-hydroxylase-immunoreactivity both in fibers of caudate nucleus as well as in cells of the zona inserta. A 6-hour deprivation caused increasing of thyrosine-hydroxylase-immunoreactive material level in cells of zona inserta and decreasing it in fibers of 30-day old rats. In adult rats, the level of thyrosine-hydroxylase-immunoreactive material decreased in nucleus arcuatus and zona inserta after sleep deprivation and increased after sleep. Data obtained are discussed in terms ofphylo- and ontogenetic development of neurosecretory and neurotransmitter functions of dopaminergic system in evolutionary old diencephalic and evolutionary young telencephalic brain regions of vertebrates, which are the important systems of starting and maintenance of some functional conditions of the organism in sleep-wakefulness cycle.
Asunto(s)
Diencéfalo/metabolismo , Dopamina/metabolismo , Sueño , Telencéfalo/metabolismo , Vigilia , Animales , Diencéfalo/enzimología , Diencéfalo/crecimiento & desarrollo , Peces , Inmunohistoquímica , Ratas , Privación de Sueño/enzimología , Estrés Psicológico/enzimología , Telencéfalo/enzimología , Telencéfalo/crecimiento & desarrollo , Tacto , Tirosina 3-Monooxigenasa/metabolismoRESUMEN
The dynamics of changes in electrophysiological measures of the sleep-waking cycle were analyzed in Wistar rats after 6 h of sleep deprivation by gentle waking and subsequent 9-h post-deprivation sleep. A delayed sleep "overshoot" reaction was observed 2.5-3 h after sleep deprivation, as a moderate increase in the proportions of slow-wave and fast-wave sleep in the sleep-waking cycle. Immunohistochemical studies were performed in relation to changes in the sleep-waking cycle, with the aim of identifying changes in the quantities of immunoreactive dopamine D1 and D2 receptor material and tyrosine hydroxylase, the key enzyme in dopamine synthesis in the nigrostriatal system. In conditions of sleep deprivation, the caudate nucleus showed increases in the quantities of dopamine D1 and D2 receptor material, while there was a simultaneous decrease in the amount of immunoreactive material in the substantia nigra. Post-deprivation sleep was accompanied by decreases in the quantities of immunoreactive D1 receptor material and increases in D2 receptor material in the caudate nucleus, with an increase in the quantity of immunoreactive tyrosine hydroxylase in the substantia nigra. These data provide evidence of the active role of the dopaminergic nigrostriatal system which, along with other CNS transmitter systems, supports telencephalic-diencephalic interactions, in the sleep-waking cycle.
Asunto(s)
Dopamina/fisiología , Neostriado/fisiopatología , Privación de Sueño/fisiopatología , Sustancia Negra/fisiopatología , Animales , Gatos , Corteza Cerebral/fisiopatología , Sistema Hipotálamo-Hipofisario/fisiopatología , Inmunohistoquímica , Actividad Motora/fisiología , Sistemas Neurosecretores/fisiología , Ratas , Ratas Wistar , Receptores de Dopamina D1/fisiología , Receptores de Dopamina D2/fisiología , Tirosina 3-Monooxigenasa/metabolismo , Vigilia/fisiologíaRESUMEN
Based on sleep deprivation-produced changes of electrographic parameters of the wakefulness--sleep cycle (WSC) in rats and common frogs, dynamics of activity of tyrosine hydroxylase, the key enzyme of dopamine synthesis, was studied immunohistochemically in substantia nigra and nigrostriatal pathway in rats and in striatum, paraventricular organ, and extrahypothalamic pathways in frogs. There are revealed changes in dynamics of tyrosine hydroxylase in rats and in common frogs after the 6-h sleep deprivation and after 2 h of postdeprivation sleep. This allows determining the degree of participation of corticostriatal neuroregulatory and hypothalamo-pituitary neurosecretory systems and their role in regulation of WSC. Possible evolutionary peculiarities of morphofunctional differences in homoiothermal and poikilothermal animals are discussed.
Asunto(s)
Sistema Hipotálamo-Hipofisario/enzimología , Proteínas del Tejido Nervioso/metabolismo , Privación de Sueño/enzimología , Telencéfalo/enzimología , Tirosina 3-Monooxigenasa/metabolismo , Animales , Química Encefálica , Masculino , Rana temporaria , Ratas , Ratas Wistar , Sueño , VigiliaRESUMEN
The analysis of the electrophysiological features of sleep-wakefulness cycle in Wistar rats for 9h after a 6h sleep deprivation was carried out. The delay of sleep rebound (since 2.5-3 h after deprivation) was found in the form of moderate increasing of slow-wave sleep and fast-wave sleep phases. According to these sleep-wakefulness cycle changes, a quantitative immunohistochemical study of tyrosine hydroxylase: a key enzyme of dopamine synthesis--and D1 and D2 receptors in nigro-striatal projections has been performed. After sleep, an elevation of D1 receptors immunoreactivity in caudate nucleus and reduction of tyrosine hydroxylase immunoreactivity in compact part of substancia nigra was found. After postdeprivation sleep, a decrease of D1 receptors immunoreactivity and increase of D2 receptors immunoreactivity in caudate nucleus together some increase of tyrosine hydroxilase immunoreactivity in substancia nigra compacta has been observed. These data can testify about active role of dopaminergic nigrostriatal system which provide at the same time with another neurotransmitters of the central nervous system the telencephalo-diencephalic interaction in sleep-wakefulness-sleep cycle.
Asunto(s)
Cuerpo Estriado/fisiopatología , Receptores de Dopamina D1/metabolismo , Receptores de Dopamina D2/metabolismo , Privación de Sueño/fisiopatología , Sustancia Negra/fisiopatología , Vigilia , Animales , Cuerpo Estriado/química , Electrofisiología , Inmunohistoquímica , Masculino , Ratas , Ratas Wistar , Receptores de Dopamina D1/análisis , Receptores de Dopamina D2/análisis , Sustancia Negra/química , Tirosina 3-Monooxigenasa/análisis , Tirosina 3-Monooxigenasa/metabolismoRESUMEN
Two hundred forty-three isolates of alfalfa nodule bacteria (Sinorhizobium meliloti) were obtained from legume nodules and soils sampled in the northern Aral region, experiencing secondary salinization. Isolates obtained from nodules (N isolates) were significantly more salt-tolerant than those from soils (S isolates) when grown in a liquid medium with 3.5% NaCl. It was found that wild species of alfalfa, melilot, and trigonella preferably formed symbioses with salt-tolerant nodule bacteria in both salinized and nonsalinized soils. Only two alfalfa species, Medicago falcata and M. trautvetteri, formed efficient symbioses in soils contrasting in salinity. The formation of efficient symbiosis with alfalfa in the presence of 0.6% NaCl was studied in 36 isolates (N and S) differing in salt tolerance and symbiotic efficiency. Fifteen isolates formed efficient symbioses in the presence of salt. The increase in the dry weight of the plants was 25-68% higher than in the control group. The efficiency of symbiotic interaction under salinization conditions depended on the efficiency of the isolates under standard conditions but did not correlate with the source of nodule bacteria (soil or nodule) or their salt tolerance. The results indicate that nodule bacterium strains forming efficient symbioses under salinization conditions can be found.
Asunto(s)
Medicago sativa/crecimiento & desarrollo , Sinorhizobium meliloti/crecimiento & desarrollo , Cloruro de Sodio/farmacología , Microbiología del Suelo , Simbiosis/fisiología , Adaptación Fisiológica/efectos de los fármacos , Adaptación Fisiológica/fisiología , Especificidad de la Especie , Simbiosis/efectos de los fármacosRESUMEN
The role of radiotherapy in multiple modality treatment of Wilms' tumor is evaluated in 225 children aged 3 months to 11.5 years (mean age 3.5 years) with stage III-IV. 184 (81.8%) patients presented with stage III, 93.7% with typical nephroblastoma. Intervention was combined with drug and radiotherapy in 99.6% patients. Exposure of the abdominal cavity in total focal doses of 10.5-50.2 Gy (mean dose 28 Gy) was carried out in 219 (97.3%) of 225 patients. Special attention is paid to the incidence of relapses, remote metastases, and survival of patients in relation to prognostic factors (sex, age, stage of tumor process, terms of exposure, and total focal doses). All patients were followed up for 2-203 months (median 32 months). During this period relapses and/or metastases were observed in 34.2% patients; 30.2% died because of disease progress. 35.1% children live without signs of disease for more than 5 years, 14.7% for more than 10 years. Relapses were more incident during the first year of treatment (in 65% children) and outside the exposed field (72.5% cases). 33.2% patients with stage III developed metastases after 1-49 months; the lungs were involved most often. Prolongation of the period between surgery and exposure of the abdominal cavity led to increase in the incidence of relapses in the abdominal cavity from 6.7% (up to 2 weeks) to 21.9% (more than 1 month), p = 0.02. Relapses were the most frequent in children aged over 4 years. This parameter virtually did not depend on the total focal dose. The absence of relationship between the incidence of local relapses and life span after exposure to a total focal dose of up to 21.6 Gy in comparison with higher doses recommends reduced doses for therapy without notable deterioration of the survival of patients with nephroblastoma.
Asunto(s)
Neoplasias Renales/radioterapia , Neoplasias Renales/cirugía , Tumor de Wilms/radioterapia , Tumor de Wilms/cirugía , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Estadificación de NeoplasiasRESUMEN
Cardiovascular abnormalities developed in 7.3% among physically and mentally healthy males aged 20-29 years after 10 years of practical activities that made it necessary to take crucial decisions under conditions of time shortage and information gap, to show determination and courage. The incidence rate for cardiovascular diseases was 38.8% among males with asthenic personality traits and 6.9% in those with sthenic traits (p less than 0.001). In persons with well-balanced personality traits, cardiovascular diseases were ascertained not to develop. The disparity between the psychological traits and those demanded by occupational activities is the major pathogenic factor as considered by the authors.
Asunto(s)
Enfermedades Cardiovasculares/etiología , Personalidad , Adulto , Estudios de Seguimiento , Humanos , Masculino , Ocupaciones , Pruebas de Personalidad , Estudios Prospectivos , Factores de Riesgo , Factores de TiempoRESUMEN
Electrical response of electro-active points (EAP) in reflexogenic areas of body surface that are communicated with the uterus was examined in 146 patients, admitted to hospital for surgical treatment of benign or malignant genital tumors. Thirty normal females were taken as controls. Specific time needed for EAP potential to become close to constant or the bend point to emerge was shown to be the most certain indicator of proliferation. There was a correlation between temporal parameters of EAP response and the presence and activity of uterine proliferation.
Asunto(s)
Terapia por Acupuntura , Adenocarcinoma/fisiopatología , Respuesta Galvánica de la Piel/fisiología , Leiomioma/fisiopatología , Neoplasias Uterinas/fisiopatología , Abdomen , Adenocarcinoma/diagnóstico , Electrodiagnóstico/métodos , Femenino , Humanos , Leiomioma/diagnóstico , Neoplasias Uterinas/diagnósticoRESUMEN
PIP: Data from sample surveys conducted between 1978 and 1981 are used to examine the fertility of women in second and subsequent marriages in the USSR. The results indicate that women up to age 25 who have been married more than once have higher fertility than women in a first marriage. However, total fertility is higher for women in uninterrupted marriages. The analysis is presented separately for various cohorts and for socioeconomic characteristics such as educational status and rural or urban residence.^ieng