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1.
BMC Sports Sci Med Rehabil ; 16(1): 47, 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38360814

RESUMEN

BACKGROUND: The COVID-19 pandemic was associated with limited physical activity (PA) of most of the world's population. This cross-sectional prospective study aimed to assess the levels of PA of university students in Poland, Czech Republic and Slovakia after COVID-19 using the International Physical Activity Questionnaire Short Form (IPAQ-SF). METHODS: A total of 2635 students completed questionnaires regarding their PA levels using the IPAQ-SF between September and December 2022. RESULTS: PA measured by metabolic equivalent of task (MET) scores, varied between the three countries: Slovakia median MET-minutes/week score 4459.9; Czech Republic 3838.8 Poland 3567.1. The results of the post hoc analysis revealed there were significant differences in MET-minutes/week values between the Czech Republic and Poland (p < 0.035) as well as between the Czech Republic and Slovakia (p < 0.037). The analysis of energetic expenditure during walking revealed that students from the Czech Republic and Slovakia had higher median MET-min/weeks values (Czech 2284.1; Slovak 2467.1) compared to their Polish (1536.1) peers (p < 0.001). Polish cohort presented with significantly higher body mass index (BMI) (p < 0.001) than Czech and Slovak groups (BMI Czech: 22.3; Slovak 22.8; Polish 23.8). CONCLUSIONS: Significant differences in PA levels between the Czech Republic, Poland, and Slovakia university students were identified. Slovakia showed the highest median PA measured as a MET score, and Poland showed the lowest. Compared to available pre-COVID studies it seems the total level of PA in the observed cohorts has not returned to the pre-COVID levels and students remain less active.

2.
Eur J Pediatr ; 183(2): 515-522, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37947925

RESUMEN

We would like to provide an updated comprehensive perspective and identify the components linked to chronic spontaneous urticaria (CSU) without specific triggers in autoimmune atrophic gastritis (AAG). AAG is an organ-specific autoimmune disease that affects the corpus-fundus gastric mucosa. Although we lack a unified explanation of the underlying pathways, when considering all paediatric patients reported in the literature, alterations result in gastric neuroendocrine enterochromaffin-like (ECL) cell proliferation and paracrine release of histamine. Several mechanisms have been proposed for the pathogenesis of CSU, with much evidence pointing towards AAG and ECL cell responses, which may be implicated as potential factors contributing to CSU. The excessive production/release of histamine into the bloodstream could cause or trigger exacerbations of CSU in AAG, independent of Helicobacter pylori; thus, the release of histamine from ECL cells may be the primary modulator. CONCLUSION: Considering the understanding of these interactions, recognising the respective roles of AAG in the pathogenesis of CSU may strongly impact the diagnostic workup and management of unexplained/refractory CSU and may inform future research and interventions in the paediatric population. WHAT IS KNOWN: • Autoimmune atrophic gastritis is a chronic immune-mediated inflammatory disease characterised by the destruction of the oxyntic mucosa in the gastric body and fundus, mucosal atrophy, and metaplastic changes. • Autoimmune atrophic gastritis in paediatric patients is important because of the poor outcome and risk of malignancy and possibly underestimated entities primarily reported in single-case reports. WHAT IS NEW: • Upper gastrointestinal inflammatory disorders, independent of H. pylori, have been implicated as potential inducing factors in the development of chronic spontaneous urticaria. • If a paediatric patient presents with symptoms such as anaemia, reduced vitamin B12 levels, recurrent urticaria with no other detectable aetiology, positive anti-parietal cell antibodies, and elevated gastrin levels, autoimmune atrophic gastritis should be considered a possible cause of chronic urticaria.


Asunto(s)
Enfermedades Autoinmunes , Urticaria Crónica , Gastritis Atrófica , Gastritis , Infecciones por Helicobacter , Helicobacter pylori , Humanos , Niño , Gastritis Atrófica/complicaciones , Gastritis Atrófica/patología , Histamina , Gastritis/complicaciones , Gastritis/diagnóstico , Mucosa Gástrica/patología , Urticaria Crónica/etiología , Urticaria Crónica/patología , Enfermedades Autoinmunes/complicaciones , Enfermedades Autoinmunes/diagnóstico , Enfermedad Crónica , Infecciones por Helicobacter/complicaciones
3.
Rozhl Chir ; 101(6): 278-283, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35973823

RESUMEN

INTRODUCTION: Total knee replacement is one of the most common surgical methods in diagnosis of end staged osteoarthritis. In this retrospective analysis, we focus on comparison of functional and clinical outcome in patients undergoing unilateral and bilateral replacement within a single surgical procedure. METHODS: 54 patients (bilateral 19, unilateral 35) underwent total knee replacement in our clinic participated in the current study. The length of hospital stay was monitored in all patients. Assessment of functional results was based on the WOMAC score, KSS 1, KSS2, range of motion and presence of complications in both groups. RESULTS: Both groups of patients were homogeneous with age, body mass index and sex. The length of hospital stay in the unilateral group was 4.7±1.3 and 5.6±2.0 in the bilateral group. Patients operated on unilaterally achieved flexion of 114.9±9.3 after one year, bilateral group 112.6±8.6, the difference was insignificant. In both groups, there is a significant improvement one year postoperatively at WOMAC, KSS1 and KSS2. Comparing WOMAC, KSS1 and KSS2 between the unilateral and bilateral groups 3, 6, 12 months postoperatively, the differences are insignificant. The revision of implants in two-year follow-up reached 1.5% in unilateral group and 1.4% in bilateral group. CONCLUSION: Unilateral and bilateral knee joint endoprosthesis implantation is a successful surgical method in orthopedic practice. With conscious selection of patients, bilateral implantation may be more advantageous alternative, as the patient undergoes one operation and the associated risks.


Asunto(s)
Artroplastia de Reemplazo de Rodilla , Osteoartritis de la Rodilla , Artroplastia de Reemplazo de Rodilla/métodos , Estudios de Seguimiento , Humanos , Osteoartritis de la Rodilla/cirugía , Rango del Movimiento Articular , Estudios Retrospectivos , Resultado del Tratamiento
4.
Physiol Res ; 70(6): 893-903, 2021 Dec 30.
Artículo en Inglés | MEDLINE | ID: mdl-34717066

RESUMEN

There are concerns about altered vascular functions that could play an important role in the pathogenesis and influence the severity of chronic disease, however, increased cardiovascular risk in paediatric cystic fibrosis (CF) has not been yet fully understood. Aim was to analyse vascular disease risk and investigate changes over times in CF and controls. We prospectively enrolled 22 CF subjects (a median age of 16.07 years), and 22 healthy demographically matched controls (a median age of 17.28 years) and determined endothelial function. We utilised a combined diagnostic approach by measuring the plethysmographic Reactive Hyperemia Index (RHI) as the post-to preocclusive endothelium-dependent changes of vascular tone, and biomarkers that are known to be related to endothelial dysfunction (ED): asymmetric dimethyl arginine (ADMA), high-sensitive CRP (hsCRP), VCAM-1 and E-selectin. RHI values were significantly lower in CF young adults (p<0.005). HsCRP (p<0.005), E-selectin (p<0.001) and VCAM-1 (p<0.001) were significantly increased in CF patients since childhood. The findings have provided a detailed account of the ongoing process of microvascular dysfunction with gradual progression with the age of CF patients, making them further at risk of advanced vascular disease. Elevations of biomarkers in CF children with not yet demonstrated RHI changes but with significantly reduced RHI in adulthood and lipid profile changes indicate the possible occurrence of ED with CF-related specific risk factors over time and will enable us to provide the best possible support.


Asunto(s)
Fibrosis Quística/fisiopatología , Endotelio Vascular/fisiopatología , Hiperemia , Adolescente , Adulto , Factores de Edad , Biomarcadores/sangre , Estudios de Casos y Controles , Niño , Fibrosis Quística/sangre , Fibrosis Quística/diagnóstico , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Estudios Prospectivos , Adulto Joven
5.
Physiol Res ; 70(5): 799-808, 2021 11 29.
Artículo en Inglés | MEDLINE | ID: mdl-34505533

RESUMEN

Fatty acid (FA) profiles as potentially relevant components of Crohn's disease (CD) have been insufficiently analysed. We sought to explore the plasma profiles of n-3 and n-6 polyunsa-turated fatty acids (PUFAs) in newly diagnosed untreated active CD. We included 26 consecutive CD pediatric patients (<19 years) and 14 healthy controls (HCs). Disease characteristics, including inflammatory markers, dietary histories, and the Pediatric Crohn's Disease Activity Index (PCDAI), were obtained. The profiles of plasma FAs in plasma lipid classes were analysed by gas chromatography with FID detection of methyl esters. The erythrocyte sedimentation rate, C-reactive protein level and fecal calprotectin level (all p<0.001) were significantly higher in CD patients than in HCs. Most changes were observed in plasma phospholipids (PLs), such as a higher content of n-3 and changes in n-6 long-chain PUFAs in the CD group. The CD group had a lower ratio of n-6/n-3 PUFAs in PLs (p<0.001) and triacylglycerols (TAGs) (p<0.01). Correlations of the FA content in plasma PLs with disease activity scores of CD were also observed, which were positive for the sum of monounsaturated fatty acids (MUFAs) as well as oleic acid (18:1n-9) (both p<0.05). The metabolism of PUFAs is significantly altered even in treatment-naive newly diagnosed active pediatric CD, and the content of major FAs in PLs correlates with disease activity and inflammatory markers, thus probably contributing to the still unclear early disease pathogenesis.


Asunto(s)
Enfermedad de Crohn/sangre , Ácidos Grasos/sangre , Adolescente , Estudios de Casos y Controles , Dieta/estadística & datos numéricos , Femenino , Humanos , Masculino , Estudios Prospectivos , Índice de Severidad de la Enfermedad
6.
Physiol Res ; 70(1): 27-32, 2021 03 17.
Artículo en Inglés | MEDLINE | ID: mdl-33453718

RESUMEN

Cardiac troponin T determination plays a dominant role in diagnosis of myocardial pathologies. Despite generally accepted use of high-sensitive cardiac troponin T assays (hscTnT) and clearly defined cut-off limit in adults, the uncertainty persists in infants. The aim of this study was to assess plasmatic concentrations of hscTnT and describe sequential age-related dynamic changes of hscTnT in healthy infants and toddlers. Seventy-eight children (52 males/26 females) from Czech Republic aged 44 to 872 days (median, interquartile range 271; 126 to 486 days) were consecutively enrolled in the single-center, prospective observational study. Plasma concentrations of hscTnT were analyzed by the electrochemiluminescent method, age-related reference intervals were calculated using the polynominal regression model. Amongst the study population (n=78), the upper limit of hscTnT concentration defined as the 99th percentile was calculated. The 99th percentile with 95 % confidence interval at the end of 2nd, 3rd, 4th, 5th, 6th and 7th month of postnatal life were: 81 (40.6 to 63.6), 61 (36.0 to 55.3), 47 (31.9 to 48.3), 37 (28.1 to 42.3), 30 (24.7 to 37.2) and 25 (21.5 to 32.7) ng/l, respectively. Concentration of adults 99th percentile (14 ng/l) was achieved approximately at 1 year of postnatal life. Statistically significant negative correlation of hscTnT concentration with age (r=-0.81, p<0.001) was found. Significant gender differences were not found (p>0.07). The study revealed substantially increased reference intervals of hscTnT levels in infants when compared with adult population. Based on our preliminary results, the age-related interpretation of hscTnT plasmatic concentration is recommended.


Asunto(s)
Biomarcadores/sangre , Infarto del Miocardio/diagnóstico , Troponina T/sangre , Factores de Edad , Preescolar , República Checa/epidemiología , Femenino , Humanos , Lactante , Masculino , Infarto del Miocardio/sangre , Infarto del Miocardio/epidemiología , Estudios Prospectivos , Valores de Referencia , Factores Sexuales
7.
Rev Sci Instrum ; 91(12): 123903, 2020 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-33379987

RESUMEN

Interphase precipitation occurring during solid-state phase transformations in micro-alloyed steels is generally studied through transmission electron microscopy, atom probe tomography, and ex situ measurements of Small-Angle Neutron Scattering (SANS). The advantage of SANS over the other two characterization techniques is that SANS allows for the quantitative determination of size distribution, volume fraction, and number density of a statistically significant number of precipitates within the resulting matrix at room temperature. However, the performance of ex situ SANS measurements alone does not provide information regarding the probable correlation between interphase precipitation and phase transformations. This limitation makes it necessary to perform in situ and simultaneous studies on precipitation and phase transformations in order to gain an in-depth understanding of the nucleation and growth of precipitates in relation to the evolution of austenite decomposition at high temperatures. A furnace is, thus, designed and developed for such in situ studies in which SANS measurements can be simultaneously performed with neutron diffraction measurements during the application of high-temperature thermal treatments. The furnace is capable of carrying out thermal treatments involving fast heating and cooling as well as high operation temperatures (up to 1200 °C) for a long period of time with accurate temperature control in a protective atmosphere and in a magnetic field of up to 1.5 T. The characteristics of this furnace give the possibility of developing new research studies for better insight of the relationship between phase transformations and precipitation kinetics in steels and also in other types of materials containing nano-scale microstructural features.

8.
Physiol Res ; 67(6): 903-909, 2018 12 18.
Artículo en Inglés | MEDLINE | ID: mdl-30204466

RESUMEN

Acute lymphoblastic leukemia (ALL) and its treatment are associated with endothelial dysfunction (ED) and increased cardiovascular risk in adulthood. There are no data on ED in children after successful treatment of ALL. We aimed to assess new ED in these children using the plethysmographic reactive hyperemia index (RHI) and biomarkers that are known to be related to ED. In all, 22 children (mean 15.6 years), after successful treatment of ALL, and 18 healthy subjects were included in this prospective study. RHI, plasma concentrations of asymmetric dimethyl arginine (ADMA), high-sensitive CRP (hsCRP) and E-selectin were measured in all children. RHI values were significantly lower in ALL patients when compared with healthy controls (p<0.05). hsCRP was significantly increased in ALL patients compared with the control group (p<0.001). E-selectin plasma levels were higher in ALL patients as compared to healthy controls (p=0.05). This is the first study that combines both plethysmographic and biochemical methods to assess ED in ALL survivors. Significantly decreased RHI with elevated plasma concentrations of biochemical markers imply a possible association with premature ED in ALL patients. The combined diagnostic approach seems to be a valuable tool for more accurate detection of ED and preventive cardiovascular management in these patients.


Asunto(s)
Endotelio Vascular/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangre , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Enfermedades Vasculares/sangre , Enfermedades Vasculares/diagnóstico , Adolescente , Arginina/análogos & derivados , Arginina/sangre , Biomarcadores/sangre , Proteína C-Reactiva/metabolismo , Niño , Selectina E/sangre , Endotelio Vascular/fisiopatología , Femenino , Humanos , Masculino , Pletismografía/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/fisiopatología , Estudios Prospectivos , Factores de Riesgo , Enfermedades Vasculares/fisiopatología
9.
Science ; 356(6344): 1269-1272, 2017 06 23.
Artículo en Inglés | MEDLINE | ID: mdl-28642434

RESUMEN

In the lower solar atmosphere, the chromosphere is permeated by jets known as spicules, in which plasma is propelled at speeds of 50 to 150 kilometers per second into the corona. The origin of the spicules is poorly understood, although they are expected to play a role in heating the million-degree corona and are associated with Alfvénic waves that help drive the solar wind. We compare magnetohydrodynamic simulations of spicules with observations from the Interface Region Imaging Spectrograph and the Swedish 1-m Solar Telescope. Spicules are shown to occur when magnetic tension is amplified and transported upward through interactions between ions and neutrals or ambipolar diffusion. The tension is impulsively released to drive flows, heat plasma (through ambipolar diffusion), and generate Alfvénic waves.

11.
Cell Death Dis ; 7: e2209, 2016 04 28.
Artículo en Inglés | MEDLINE | ID: mdl-27124583

RESUMEN

Glioblastoma (GBM) is one of the most aggressive types of cancer with limited therapeutic options and unfavorable prognosis. Stemness and non-classical epithelial-to-mesenchymal transition (ncEMT) features underlie the switch from normal to neoplastic states as well as resistance of tumor clones to current therapies. Therefore, identification of ligand/receptor systems maintaining this privileged state is needed to devise efficient cancer therapies. In this study, we show that the expression of CD95 associates with stemness and EMT features in GBM tumors and cells and serves as a prognostic biomarker. CD95 expression increases in tumors and with tumor relapse as compared with non-tumor tissue. Recruitment of the activating PI3K subunit, p85, to CD95 death domain is required for maintenance of EMT-related transcripts. A combination of the current GBM therapy, temozolomide, with a CD95 inhibitor dramatically abrogates tumor sphere formation. This study molecularly dissects the role of CD95 in GBM cells and contributes the rational for CD95 inhibition as a GBM therapy.


Asunto(s)
Neoplasias Encefálicas/genética , Transición Epitelial-Mesenquimal/genética , Regulación Neoplásica de la Expresión Génica , Glioblastoma/genética , Recurrencia Local de Neoplasia/genética , Receptor fas/genética , Antineoplásicos Alquilantes/farmacología , Neoplasias Encefálicas/clasificación , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/patología , Fosfatidilinositol 3-Quinasa Clase Ia/genética , Fosfatidilinositol 3-Quinasa Clase Ia/metabolismo , Dacarbazina/análogos & derivados , Dacarbazina/farmacología , Combinación de Medicamentos , Sinergismo Farmacológico , Glioblastoma/clasificación , Glioblastoma/mortalidad , Glioblastoma/patología , Humanos , Inmunoglobulina G/farmacología , Recurrencia Local de Neoplasia/clasificación , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/patología , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Cultivo Primario de Células , Pronóstico , ARN Mensajero/genética , ARN Mensajero/metabolismo , Proteínas Recombinantes de Fusión/farmacología , Transducción de Señal , Esferoides Celulares/efectos de los fármacos , Esferoides Celulares/metabolismo , Esferoides Celulares/patología , Análisis de Supervivencia , Temozolomida , Receptor fas/metabolismo , Receptor fas/farmacología
12.
Cell Death Differ ; 22(7): 1192-202, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25613377

RESUMEN

Cancer stem cells (CSCs) have been implicated in the initiation and maintenance of tumour growth as well as metastasis. Recent reports link stemness to epithelial-mesenchymal transition (EMT) in cancer. However, there is still little knowledge about the molecular markers of those events. In silico analysis of RNA profiles of 36 pancreatic ductal adenocarcinomas (PDAC) reveals an association of the expression of CD95 with EMT and stemness that was validated in CSCs isolated from PDAC surgical specimens. CD95 expression was also higher in metastatic pancreatic cells than in primary PDAC. Pharmacological inhibition of CD95 activity reduced PDAC growth and metastasis in CSC-derived xenografts and in a murine syngeneic model. On the mechanistic level, Sck was identified as a novel molecule indispensable for CD95's induction of cell cycle progression. This study uncovers CD95 as a marker of EMT and stemness in PDAC. It also addresses the molecular mechanism by which CD95 drives tumour growth and opens tantalizing therapeutic possibilities in PDAC.


Asunto(s)
Carcinoma Ductal Pancreático/fisiopatología , Metástasis de la Neoplasia , Neoplasias Pancreáticas/fisiopatología , Proteínas Adaptadoras de la Señalización Shc/fisiología , Receptor fas/fisiología , Animales , Biomarcadores de Tumor , Carcinoma Ductal Pancreático/metabolismo , Transición Epitelial-Mesenquimal , Femenino , Humanos , Ratones , Neoplasias Pancreáticas/metabolismo , Transducción de Señal , Proteína Transformadora 2 que Contiene Dominios de Homología 2 de Src , Ensayos Antitumor por Modelo de Xenoinjerto
13.
Science ; 346(6207): 1255724, 2014 Oct 17.
Artículo en Inglés | MEDLINE | ID: mdl-25324396

RESUMEN

The physical processes causing energy exchange between the Sun's hot corona and its cool lower atmosphere remain poorly understood. The chromosphere and transition region (TR) form an interface region between the surface and the corona that is highly sensitive to the coronal heating mechanism. High-resolution observations with the Interface Region Imaging Spectrograph (IRIS) reveal rapid variability (~20 to 60 seconds) of intensity and velocity on small spatial scales (≲500 kilometers) at the footpoints of hot and dynamic coronal loops. The observations are consistent with numerical simulations of heating by beams of nonthermal electrons, which are generated in small impulsive (≲30 seconds) heating events called "coronal nanoflares." The accelerated electrons deposit a sizable fraction of their energy (≲10(25) erg) in the chromosphere and TR. Our analysis provides tight constraints on the properties of such electron beams and new diagnostics for their presence in the nonflaring corona.

14.
Science ; 346(6207): 1255711, 2014 Oct 17.
Artículo en Inglés | MEDLINE | ID: mdl-25324395

RESUMEN

As the interface between the Sun's photosphere and corona, the chromosphere and transition region play a key role in the formation and acceleration of the solar wind. Observations from the Interface Region Imaging Spectrograph reveal the prevalence of intermittent small-scale jets with speeds of 80 to 250 kilometers per second from the narrow bright network lanes of this interface region. These jets have lifetimes of 20 to 80 seconds and widths of ≤300 kilometers. They originate from small-scale bright regions, often preceded by footpoint brightenings and accompanied by transverse waves with amplitudes of ~20 kilometers per second. Many jets reach temperatures of at least ~10(5) kelvin and constitute an important element of the transition region structures. They are likely an intermittent but persistent source of mass and energy for the solar wind.

15.
Science ; 346(6207): 1255757, 2014 Oct 17.
Artículo en Inglés | MEDLINE | ID: mdl-25324399

RESUMEN

The heating of the outer solar atmospheric layers, i.e., the transition region and corona, to high temperatures is a long-standing problem in solar (and stellar) physics. Solutions have been hampered by an incomplete understanding of the magnetically controlled structure of these regions. The high spatial and temporal resolution observations with the Interface Region Imaging Spectrograph (IRIS) at the solar limb reveal a plethora of short, low-lying loops or loop segments at transition-region temperatures that vary rapidly, on the time scales of minutes. We argue that the existence of these loops solves a long-standing observational mystery. At the same time, based on comparison with numerical models, this detection sheds light on a critical piece of the coronal heating puzzle.

16.
Science ; 346(6207): 1255732, 2014 Oct 17.
Artículo en Inglés | MEDLINE | ID: mdl-25324398

RESUMEN

The solar chromosphere and transition region (TR) form an interface between the Sun's surface and its hot outer atmosphere. There, most of the nonthermal energy that powers the solar atmosphere is transformed into heat, although the detailed mechanism remains elusive. High-resolution (0.33-arc second) observations with NASA's Interface Region Imaging Spectrograph (IRIS) reveal a chromosphere and TR that are replete with twist or torsional motions on sub-arc second scales, occurring in active regions, quiet Sun regions, and coronal holes alike. We coordinated observations with the Swedish 1-meter Solar Telescope (SST) to quantify these twisting motions and their association with rapid heating to at least TR temperatures. This view of the interface region provides insight into what heats the low solar atmosphere.

17.
Physiol Res ; 63(Suppl 1): S165-76, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24564656

RESUMEN

Large number of extracellular signals is received by plasma membrane receptors which, upon activation, transduce information into the target cell interior via trimeric G-proteins (GPCRs) and induce activation or inhibition of adenylyl cyclase enzyme activity (AC). Receptors for opioid drugs such as morphine (micro-OR, delta-OR and kappa-OR) belong to rhodopsin family of GPCRs. Our recent results indicated a specific up-regulation of AC I (8-fold) and AC II (2.5-fold) in plasma membranes (PM) isolated from rat brain cortex exposed to increasing doses of morphine (10-50 mg/kg) for 10 days. Increase of ACI and ACII represented the specific effect as the amount of ACIII-ACIX, prototypical PM marker Na, K-ATPase and trimeric G-protein alpha and beta subunits was unchanged. The up-regulation of ACI and ACII faded away after 20 days since the last dose of morphine. Proteomic analysis of these PM indicated that the brain cortex of morphine-treated animals cannot be regarded as being adapted to this drug because significant up-regulation of proteins functionally related to oxidative stress and alteration of brain energy metabolism occurred. The number of delta-OR was increased 2-fold and their sensitivity to monovalent cations was altered. Characterization of delta-OR-G-protein coupling in model HEK293 cell line indicated high ability of lithium to support affinity of delta-OR response to agonist stimulation. Our studies of PM structure and function in context with desensitization of GPCRs action were extended by data indicating participation of cholesterol-enriched membrane domains in agonist-specific internalization of delta-OR. In HEK293 cells stably expressing delta-OR-G(i)1alpha fusion protein, depletion of PM cholesterol was associated with the decrease in affinity of G-protein response to agonist stimulation, whereas maximum response was unchanged. Hydrophobic interior of isolated PM became more "fluid", chaotically organized and accessible to water molecules. Validity of this conclusion was supported by the analysis of an immediate PM environment of cholesterol molecules in living delta-OR-G(i)1alpha-HEK293 cells by fluorescent probes 22- and 25-NBD-cholesterol. The alteration of plasma membrane structure by cholesterol depletion made the membrane more hydrated. Understanding of the positive and negative feedback regulatory loops among different OR-initiated signaling cascades (micro-, delta-, and kappa-OR) is crucial for understanding of the long-term mechanisms of drug addiction as the decrease in functional activity of micro-OR may be compensated by increase of delta-OR and/or kappa-OR signaling.


Asunto(s)
Analgésicos Opioides/metabolismo , Membrana Celular/metabolismo , Membrana Celular/ultraestructura , Corteza Cerebral/metabolismo , Corteza Cerebral/ultraestructura , Lípidos de la Membrana/metabolismo , Receptores Opioides/metabolismo , Animales , Células HEK293 , Humanos , Fluidez de la Membrana/fisiología , Ratas , Transducción de Señal/fisiología , Relación Estructura-Actividad
18.
Klin Onkol ; 25(1): 26-35, 2012.
Artículo en Eslovaco | MEDLINE | ID: mdl-22348217

RESUMEN

BACKGROUNDS: AML is an aggressive, phenotypically and genetically heterogenous clonal disease of hematopoietic progenitor cells with a great molecular variability. New WHO classification 2008 divides de novo AML according to cytogenetic and molecular prognostic and predictive markers. Recently, it is increasingly possible to identify a subgroup of poorer prognosis patients among those with normal karyotype AML. The aim of our study was to identify prognostically important molecular markers in children with AML, to stratify patients with normal karyotype and to monitor the disease according the genetic findings. MATERIAL AND METHODS: In 2008-2010, we analyzed bone marrow and peripheral blood samples of 20 children with de novo AML by conventional cytogenetic analysis, fluorescence in situ hybridisation and molecular diagnostics. The molecular analysis was performed on the cDNA level, with the restriction analysis of PCR products (FLT3-TKD), conventional PCR (MLL-PTD, NPM1mut, FLT3-ITD) and quantification RT-PCR method (expression of fusion transcripts, BAALC, WT1). RESULTS: Samples from 20 children with AML were analyzed using the conventional cytogenetics, FISH and molecular methods. Abnormal karyotype was identified in 13 patients (65%). Further analysis revealed FLT3-ITD in 5/20 (25%), FLT3-TKD in 3/20 (15%), NPM1mut in 2/20 (10%) and MLL-PTD in 1/20 (5%), overexpression of WT1 gene in 15/20 (75%) and overexpression of BAALC in 13/20 (65%) patients. CONCLUSION: Wide cytogenetic and molecular screening helped to find at least one genetic marker in all 20 patients for later follow-up and risk stratification. 4/20 (20%) patients died of the disease progression.


Asunto(s)
Leucemia Mieloide Aguda/genética , Adolescente , Niño , Preescolar , Análisis Citogenético , Femenino , Genes del Tumor de Wilms , Humanos , Hibridación Fluorescente in Situ , Lactante , Cariotipificación , Masculino , Proteína de la Leucemia Mieloide-Linfoide/genética , Proteínas de Neoplasias/genética , Proteínas Nucleares/genética , Nucleofosmina , Reacción en Cadena de la Polimerasa , Pronóstico , Tirosina Quinasa 3 Similar a fms/genética
19.
Inorg Chem ; 50(13): 6122-34, 2011 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-21650203

RESUMEN

Re(I) carbonyl-diimine complexes [Re(L-AA)(CO)(3)(N,N)](+) (N,N = bpy, phen) containing an aromatic amino acid (AA), phenylalanine (Phe), tyrosine (Tyr), or tryptophan (Trp), linked to Re by a pyridine-amido or imidazole-amido ligand L have been synthesized and their excited-state properties investigated by nanosecond time-resolved IR (TRIR) and emission spectroscopy. Near-UV optical excitation populates a Re(I)(CO)(3)→N,N (3)MLCT excited state *[Re(II)(L-AA)(CO)(3)(N,N(•-))](+). Decay to the ground state (50-300 ns lifetime) is the only excited-state deactivation process observed in the case of Phe and Tyr complexes, whereas the Trp-containing species undergo a Trp(indole)→*Re(II) electron transfer (ET) producing a charge-separated (CS) state, [Re(I)(L-Trp(•+))(CO)(3)(N,N(•-))](+). The ET occurs with a 8-40 ns lifetime depending on L, N,N, and the solvent. The CS state is characterized by ν(CO) IR bands shifted to lower wavenumbers from their respective ground-state positions and two bands at 1278 and 1497 cm(-1) tentatively attributed to Trp(•+). The amido bridge is affected by both the MLCT excitation and the subsequent ET, manifested by the shifts and intensity changes of the amide-I IR band at about 1680 cm(-1). The CS state decays to the ground state by a N,N(•-)→Trp(•+) back-ET the rates of which are comparable to those of the forward ET, 30-60 ns. This study independently demonstrates that Trp can act as an electron-hopping intermediate in photodriven ET systems based on Re-labeled proteins and supramolecules. Photoinduced ET in Trp-containing Re complexes also can be used to generate Trp(•+) and investigate its spectral properties and reactivity.


Asunto(s)
Compuestos Organometálicos/química , Triptófano/química , Monóxido de Carbono/química , Imidazoles/química , Iminas/química , Estructura Molecular , Compuestos Organometálicos/síntesis química , Oxidación-Reducción , Fenilalanina/química , Procesos Fotoquímicos , Piridinas/química , Teoría Cuántica , Renio/química , Estereoisomerismo , Tirosina/química
20.
Physiol Res ; 60(4): 647-58, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21574763

RESUMEN

The aims of our study were to evaluate plasma levels of gut hormones in children with Type 1 diabetes mellitus (T1DM) in comparison with healthy controls and to correlate plasma concentrations of gut hormones with blood biochemistry, markers of metabolic control and with anthropometric parameters. We measured postprandial levels of specific gut peptide hormones in T1DM children. Amylin, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide 1 (GLP-1), ghrelin, leptin, pancreatic polypeptide (PP), and polypeptide YY (PYY) were assessed in 19 T1DM children and 21 healthy reference controls. Multiplex assay kit (LINCOplex(®)) was used for determination of the defined plasma hormone levels. T1DM subjects had significantly reduced amylin (p<0.001) and ghrelin (p<0.05) levels, whereas GIP (p<0.05) was elevated when compared with healthy controls. Plasma levels of other measured hormones did not differ statistically between the studied groups. Further analysis of T1DM patients demonstrated an association between body mass index and GLP-1 (r=0.4642; p<0.05), leptin (r=0.5151; p<0.05), and amylin (r=0.5193; p<0.05). Ghrelin levels positively correlated with serum HDL cholesterol (r=0.4760; p<0.05). An inverse correlation was demonstrated with triglycerides (TG) (r= -0.5674; p<0.01), insulin dosage (r= -0.5366; p<0.05), and HbA1c% (r= -0.6864; p<0.01). Leptin was inversely correlated with TG (r= -0.6351; p<0.01). Stepwise regression analysis was performed to enlighten the predictive variables. Our study demonstrated an altered secretion pattern of gut peptide hormones in T1DM children. A close correlation was revealed between these peptides as well as with blood biochemistry, markers of metabolic control and with anthropometric parameters. Further studies are essential to explore this issue in T1DM children.


Asunto(s)
Diabetes Mellitus Tipo 1/sangre , Hormonas Gastrointestinales/sangre , Hormonas Peptídicas/sangre , Adolescente , Factores de Edad , Biomarcadores/sangre , Niño , Diabetes Mellitus Tipo 1/diagnóstico , Femenino , Humanos , Masculino , Valor Predictivo de las Pruebas
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