Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 506
Filtrar
1.
Sci Total Environ ; 946: 174191, 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38945249

RESUMEN

East-Central Europe's largest shallow lake, Balaton, experienced strong eutrophication in the 1970-80s, followed by water quality improvement and oligotrophication by 2010 CE. Recently however, repeated cyanobacterial blooms occurred and warned that internal P-recycling can act similarly to external P load, therefore we need a better understanding of past water level (WL) and trophic changes in the lake. In this study we discuss the last 500-yr trophic, WL and habitat changes of the lake using paleoecological (chironomids, pollen) and geochemical (sediment chlorophyll, TOC, TS, TN, C/H ratio, major and trace element) methods. We demonstrate that the most intensive and irreversible change in the macroinvertebrate fauna occurred during the period of economic boom between the First and Second World War (∼1925-1940 CE), when large-scale built-in and leisure use of the lake has intensified. At that time, the Procladius-Microchironomus-Stempellina dominated community transformed to Procladius-Chironomus plumosus-type-Microchironomus community that coincided with land use changes, intensified erosion and water-level regulation in the lake with the maintenance of year-round high WL. This was followed by the impoverishment and population size decrease of the chironomid fauna and Procladius dominance since 1940 CE, without any recovery after 1994 CE despite the ongoing oligotrophication. Accelerated rate of change and turnover of the fauna was connected to an increase in the benthivorous fish biomass and eutrophication. The basin lost almost completely its once characteristic Stempellina species between 1927 and 1940 CE due to trophic level increase and seasonal anoxia in the Szemes Basin. Reference conditions for ecosystem improvement were assigned to 1740-1900 CE. We conclude that in spite of the ongoing oligotrophication, the re-establishment of the Procladius-Microchironomus-Stempellina assemblage is hampered, and requires fish population regulation.

2.
Semin Arthritis Rheum ; 63: 152285, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37944298

RESUMEN

BACKGROUND: Giant Cell Arteritis (GCA) is the commonest form of systemic vasculitis in people over the age of 50. Published research highlighted the lack of a disease-specific patient reported outcomes (PROMs) for GCA. OBJECTIVES: To assess the validity, reliability and responsiveness to change of a devised disease specific patient self-reported outcome measures questionnaire for Giant Cell Arteritis (GCA). METHODS: The GCA-PROMs was conceptualized based on frameworks outlined in the OMERACT developed core set of Outcome Measures for Large-Vessel Vasculitis and the guiding principles of the FDA guidance. Initially, cognitive interviews were conducted to identify item pool of questions. Item selection and reduction was achieved based on patients as well as an interdisciplinary group of specialists. Rasch and internal consistency reliability analyses were implemented. RESULTS: A total of 54 GCA patients completed the questionnaire. The GCA-PROMs questionnaire was reliable as demonstrated by a high standardized alpha (0.878-0.983). Content construct assessment of the GCA-PROMs functional disability and QoL revealed significant correlation (p< 0.01) with both HAQ and EQ-5D. Changes in functional disability, QoL showed significant (p< 0.01) variation with diseases activity status in response to therapy. CONCLUSIONS: The developed GCA-PROMs questionnaire is a reliable and valid instrument for assessment of GCA patients. A stratified treatment regimen depending on the individual patient's risk factors as well as preferences and associated comorbidities is the best approach to tailored patient management.


Asunto(s)
Arteritis de Células Gigantes , Humanos , Calidad de Vida , Reproducibilidad de los Resultados , Medición de Resultados Informados por el Paciente , Evaluación de Resultado en la Atención de Salud
3.
Pituitary ; 25(6): 982-987, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36260240

RESUMEN

Central Diabetes Insipidus (CDI) is mainly associated with structural pathologies of the hypothalamic-pituitary area. Etiologies underlying CDI are identified in most patients, however idiopathic CDI is reported in 13-17% of cases after excluding other etiologies. The Hypopituitarism ENEA Rare Observational Study (HEROS study) retrospectively collected data of patients with idiopathic CDI from 14 pituitary centers in 9 countries. The cohort included 92 patients (59 females 64%), mean age at diagnosis was 35.4 ± 20.7 years, and a mean follow up of 19.1 ± 13.5 years following CDI diagnosis. In 6 women, diagnosis was related to pregnancy. Of 83 patients with available data on pituitary imaging, 40(48%) had normal sellar imaging, and 43(52%) had pathology of the posterior pituitary or the stalk, including loss of the bright spot, posterior pituitary atrophy or stalk enlargement. Anterior pituitary hormone deficiencies at presentation included hypogonadism in 6 (6.5%) patients (5 females), and hypocortisolism in one; during follow-up new anterior pituitary deficiencies developed in 6 patients. Replacement treatment with desmopressin was given to all patients except one, usually with an oral preparation. During follow up, no underlying disease causing CDI was identified in any patient. Patients with idiopathic CDI following investigation at baseline are stable with no specific etiology depicted during long-term follow-up.


Asunto(s)
Diabetes Insípida Neurogénica , Diabetes Insípida , Diabetes Mellitus , Hipopituitarismo , Enfermedades de la Hipófisis , Humanos , Femenino , Diabetes Insípida Neurogénica/tratamiento farmacológico , Diabetes Insípida Neurogénica/diagnóstico , Estudios Retrospectivos , Imagen por Resonancia Magnética , Diabetes Insípida/etiología , Hipopituitarismo/complicaciones , Enfermedades de la Hipófisis/complicaciones , Hipófisis/patología
4.
J Endocrinol Invest ; 41(3): 315-323, 2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-28815484

RESUMEN

BACKGROUND: Late-night salivary cortisol level is one of the first-line tests recommended by the Endocrine Society for the diagnosis of endogenous hypercortisolism. Most routine laboratories measure cortisol levels using immunoassay tests which fail to determine low cortisol levels accurately due to the numerous interfering substances. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method with simple and rapid sample preparation was developed for the simultaneous measurement of cortisol and cortisone and its performance in the diagnosis of endogenous hypercortisolism was evaluated. METHODS: 324 late-night saliva samples were analyzed from which 272 samples were derived from patients with a suspected diagnosis of endogenous hypercortisolism. Salivary cortisol levels were assayed using an electrochemiluminescent immunoassay (ECLIA, Cortisol II, Roche), and simultaneous measurement of cortisol and cortisone was performed using an LC-MS/MS method. RESULTS: A strong correlation between cortisol results measured using ECLIA and LC-MS/MS (r 2 = 0.892) was demonstrated. Receiver operating characteristics (ROC) analysis showed good diagnostic performance of cortisol and cortisone levels assayed using LC-MS/MS method and for cortisol measured using ECLIA. CONCLUSIONS: Late-night salivary cortisol and cortisone are useful parameters for the diagnosis of hypercortisolism. Using samples obtained from patients where the diagnosis of hypercortisolism is extremely challenging cut-off values for midnight salivary cortisol and cortisone measured by LC-MS/MS method were established.


Asunto(s)
Bioensayo , Cromatografía Liquida/métodos , Cortisona/metabolismo , Síndrome de Cushing/diagnóstico , Hidrocortisona/metabolismo , Saliva/metabolismo , Espectrometría de Masas en Tándem/métodos , Biomarcadores/metabolismo , Estudios de Casos y Controles , Síndrome de Cushing/metabolismo , Humanos , Pronóstico , Curva ROC
5.
Cell Death Dis ; 7(9): e2367, 2016 09 08.
Artículo en Inglés | MEDLINE | ID: mdl-27607582

RESUMEN

Retinal pigment epithelial (RPE) cells can undergo different forms of cell death, including autophagy-associated cell death during age-related macular degeneration (AMD). Failure of macrophages or dendritic cells (DCs) to engulf the different dying cells in the retina may result in the accumulation of debris and progression of AMD. ARPE-19 and primary human RPE cells undergo autophagy-associated cell death upon serum depletion and oxidative stress induced by hydrogen peroxide (H2O2). Autophagy was revealed by elevated light-chain-3 II (LC3-II) expression and electron microscopy, while autophagic flux was confirmed by blocking the autophago-lysosomal fusion using chloroquine (CQ) in these cells. The autophagy-associated dying RPE cells were engulfed by human macrophages, DCs and living RPE cells in an increasing and time-dependent manner. Inhibition of autophagy by 3-methyladenine (3-MA) decreased the engulfment of the autophagy-associated dying cells by macrophages, whereas sorting out the GFP-LC3-positive/autophagic cell population or treatment by the glucocorticoid triamcinolone (TC) enhanced it. Increased amounts of IL-6 and IL-8 were released when autophagy-associated dying RPEs were engulfed by macrophages. Our data suggest that cells undergoing autophagy-associated cell death engage in clearance mechanisms guided by professional and non-professional phagocytes, which is accompanied by inflammation as part of an in vitro modeling of AMD pathogenesis.


Asunto(s)
Autofagia/efectos de los fármacos , Medio de Cultivo Libre de Suero/farmacología , Peróxido de Hidrógeno/farmacología , Macrófagos/efectos de los fármacos , Fagocitosis/efectos de los fármacos , Epitelio Pigmentado de la Retina/efectos de los fármacos , Adenina/análogos & derivados , Adenina/farmacología , Autofagia/genética , Biomarcadores/metabolismo , Línea Celular , Cloroquina/farmacología , Técnicas de Cocultivo , Expresión Génica , Genes Reporteros , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Humanos , Interleucina-6/biosíntesis , Interleucina-6/metabolismo , Interleucina-8/biosíntesis , Interleucina-8/metabolismo , Macrófagos/citología , Macrófagos/inmunología , Degeneración Macular/genética , Degeneración Macular/inmunología , Degeneración Macular/patología , Proteínas Asociadas a Microtúbulos/genética , Proteínas Asociadas a Microtúbulos/inmunología , Modelos Biológicos , Estrés Oxidativo , Cultivo Primario de Células , Epitelio Pigmentado de la Retina/inmunología , Epitelio Pigmentado de la Retina/patología , Triamcinolona/farmacología
6.
Genes Brain Behav ; 15(6): 578-87, 2016 07.
Artículo en Inglés | MEDLINE | ID: mdl-27198123

RESUMEN

The developing fetus and neonate are highly sensitive to maternal environment. Besides the well-documented effects of maternal stress, nutrition and infections, maternal mutations, by altering the fetal, perinatal and/or early postnatal environment, can impact the behavior of genetically normal offspring. Mutation/premutation in the X-linked FMR1 (encoding the translational regulator FMRP) in females, although primarily responsible for causing fragile X syndrome (FXS) in their children, may also elicit such maternal effects. We showed that a deficit in maternal FMRP in mice results in hyperactivity in the genetically normal offspring. To test if maternal FMRP has a broader intergenerational effect, we measured social behavior, a core dimension of neurodevelopmental disorders, in offspring of FMRP-deficient dams. We found that male offspring of Fmr1(+/-) mothers, independent of their own Fmr1 genotype, exhibit increased approach and reduced avoidance toward conspecific strangers, reminiscent of 'indiscriminate friendliness' or the lack of stranger anxiety, diagnosed in neglected children and in patients with Asperger's and Williams syndrome. Furthermore, social interaction failed to activate mesolimbic/amygdala regions, encoding social aversion, in these mice, providing a neurobiological basis for the behavioral abnormality. This work identifies a novel role for FMRP that extends its function beyond the well-established genetic function into intergenerational non-genetic inheritance/programming of social behavior and the corresponding neuronal circuit. As FXS premutation and some psychiatric conditions that can be associated with reduced FMRP expression are more prevalent in mothers than full FMR1 mutation, our findings potentially broaden the significance of FMRP-dependent programming of social behavior beyond the FXS population.


Asunto(s)
Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/genética , Conducta Social , Amígdala del Cerebelo/metabolismo , Amígdala del Cerebelo/fisiología , Animales , Epigénesis Genética , Femenino , Sistema Límbico/metabolismo , Sistema Límbico/fisiología , Masculino , Ratones
7.
Acta Physiol Hung ; 102(4): 451-8, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26690037

RESUMEN

The aim of the study was to determine the importance of two sport-associated gene polymorphisms, alpha-actinin-3 R577X (ACTN3) and angiotensin-converting enzyme I/D (ACE), among Hungarian athletes in different sports. The examination was carried out only on women (n = 100). Sport-specific groups were formed in order to guarantee the most homogeneous clusters. Human genomic DNA was isolated from blood, and genotyping was performed by polymerase chain reaction. To measure the differences between the participating groups, Chi-squared test was performed using Statistica 9.0 for Windows® (significance level: p < 0.05). In comparing the ACE I/D allele frequencies, significant difference was detected between water polo (I = 61.11%; D = 38.89%) and combat sports (I = 35.71%, D = 64.29%) athletes (p < 0.03). There was no statistical difference when ACE I/D alleles in combat sports and kayaking/rowing (p > 0.05) were compared. A similarity was detectable in the I allele frequencies of the water polo (61.11%) and kayaking/rowing (56.67%) groups. The ACTN3 R/X polymorphism showed no differences in comparison with the sport groups. R allele frequencies were higher in every group compared to the X allele. The potential significance of the ACE I allele in sports of an aerobic nature was not clearly confirmed among Hungarian athletes.


Asunto(s)
Actinina/genética , Rendimiento Atlético , Peptidil-Dipeptidasa A/genética , Polimorfismo Genético , Deportes , Adulto , Atletas , Femenino , Genotipo , Humanos , Hungría , Adulto Joven
8.
Transplant Proc ; 47(6): 1600-4, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26293020

RESUMEN

The low availability of donor organs requires long-term successful transplantation as an accepted therapy for patients with end-stage renal and liver diseases. The health benefits of regular physical activity are well known among healthy individuals as well as patients under rehabilitation programs. Our aim was to describe the cardiorespiratory capacity of the Hungarian National Transplant Team. Twenty-five kidney (n = 21) or liver (n = 4) transplant athletes participated in this study. Maximal cardiorespiratory capacity (VO2max) was measured on a treadmill with the use of gas analysis. After a resting pulmonary function test, subjects completed a vita maxima test until exhaustion. Aerobic capacity of transplant athletes was higher than the age- and sex-predicted cardiorespiratory fitness (VO2max, 109.9 ± 21.7% of the predicted values; P = .0101). Resting respiratory function indicators exceeded 80% of predicted age- and sex-matched normal values. There were positive correlations between VO2max and workload (r(2) = 0.40; P = .0463), metabolic equivalent (r(2) = 0.72; P < .0001), and oxygen pulse (r(2) = 0.30; P = .0039). However, age showed negative correlation with VO2max (r(2) = 0.32; P = .0031), and there was no significant correlation between graft age and maximal oxygen consumption (r(2) = 0.15; P = .4561). Although the small amount of participants can not represent the general kidney and liver transplant population, the excellent cardiorespiratory performance suggests that a normal level of physical capacity is available after transplantation and can be even higher with regular physical activity. This favorable physiologic background leads to a state that provides proper graft oxygenization, which is an important factor in long-term graft survival.


Asunto(s)
Tolerancia al Ejercicio/fisiología , Trasplante de Riñón , Trasplante de Hígado , Aptitud Física/fisiología , Adulto , Atletas , Presión Sanguínea/fisiología , Prueba de Esfuerzo , Femenino , Rechazo de Injerto/prevención & control , Frecuencia Cardíaca , Humanos , Hungría , Masculino , Persona de Mediana Edad , Consumo de Oxígeno/fisiología , Pruebas de Función Respiratoria , Estudios Retrospectivos
10.
Acta Physiol Hung ; 101(3): 321-8, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25183506

RESUMEN

Cardiovascular disease (CVD) is responsible for more than half of all deaths in the European region. The aim of the study was to compare body composition, blood pressure, total cholesterol (TC) and high density lipoprotein cholesterol (HDL-C), family history, activity behaviors, and the 10-year risk of having a heart attack between 166 university students (21.62 ± 2.59 yrs) from Utah (USA) and 198 students (22.11 ± 2.51 yrs) from Hungary. Ninety-two percent of the Hungarian students and 100% of the Utah students had an estimated 10-year Framingham risk score of 1% or less. The high prevalence of low risk was primarily due to the young age of study participants, healthy body composition and non-smoking behavior. Hungarians who had higher 10-year risk of heart attack had significantly higher waist hip ratio (WHR), TC, diastolic blood pressure (DBP) and were smokers compared to those Hungarians with lower risk. The self-reported physical activity levels between the two groups of students were not different. In conclusion the young men and women who participated in this study were, for the most part healthy; however the smoking habits and the lower physical activity of the Hungarian students likely elevated their risk of CVD.


Asunto(s)
Enfermedades Cardiovasculares/epidemiología , Estudiantes , Universidades , Adiposidad , Adolescente , Adulto , Factores de Edad , Biomarcadores/sangre , Presión Sanguínea , Índice de Masa Corporal , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/fisiopatología , Colesterol/sangre , HDL-Colesterol/sangre , Femenino , Conductas Relacionadas con la Salud , Estado de Salud , Humanos , Hungría/epidemiología , Estilo de Vida , Masculino , Actividad Motora , Prevalencia , Factores de Riesgo , Fumar/efectos adversos , Fumar/epidemiología , Estudiantes/psicología , Factores de Tiempo , Utah/epidemiología , Relación Cintura-Cadera , Adulto Joven
11.
Bioorg Med Chem ; 21(21): 6634-41, 2013 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-24012376

RESUMEN

The objective of this study was to synthesize and evaluate a novel fluorine-18 labeled deuterium substituted analogue of rasagiline (9, [(18)F]fluororasagiline-D2) as a potential PET radioligand for studies of monoamine oxidase B (MAO-B). The precursor compound (6) and reference standard (7) were synthesized in multi-step syntheses. Radiolabeling of 9 was accomplished by a two-step synthesis, compromising a nucleophilic substitution followed by hydrolysis of the sulfamidate group. The incorporation radiochemical yield from fluorine-18 fluoride was higher than 30%, the radiochemical purity was >99% and the specific radioactivity was >160GBq/µmol at the time of administration. In vitro compound 7 inhibited the MAO-B activity with an IC50 of 173.0±13.6nM. The MAO-A activity was inhibited with an IC50 of 9.9±1.1µM. The fluorine-18 version 9 was characterized in the cynomolgus monkey brain where a high brain uptake was found (275% SUV at 4min). There was a higher uptake in the striatum and thalamus compared to the cortex and cerebellum. A pronounced blocking effect (50% decrease) was observed in the specific brain regions after administration of l-deprenyl (0.5mg/kg) 30min prior to the administration of 9. Radiometabolite studies demonstrated 40% of unchanged radioligand at 90min post injection. An efficient radiolabeling of 9 was successfully established and in the monkey brain 9 binds to MAO-B rich regions and its binding is blocked by the selective MAO-B compound l-deprenyl. The radioligand 9 is a potential candidate for human PET studies.


Asunto(s)
Indanos/química , Inhibidores de la Monoaminooxidasa/química , Monoaminooxidasa/química , Radiofármacos/química , Animales , Encéfalo/diagnóstico por imagen , Corteza Cerebral/metabolismo , Deuterio/química , Radioisótopos de Flúor/química , Humanos , Indanos/metabolismo , Macaca fascicularis/metabolismo , Monoaminooxidasa/metabolismo , Inhibidores de la Monoaminooxidasa/metabolismo , Tomografía de Emisión de Positrones , Unión Proteica , Radiofármacos/metabolismo , Tálamo/metabolismo
12.
Psychopharmacology (Berl) ; 229(4): 579-89, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23722830

RESUMEN

RATIONALE: Hypersignaling of corticotropin releasing factor (CRF) has been implicated in stress disorders; however, many of its downstream mechanisms of action remain unclear. In vitro, CRF1 receptor activation initiates multiple cell signaling cascades, including protein kinase A (PKA), protein kinase C (PKC), and mitogen-activated protein kinase kinase MEK1/2 signaling. It is unclear, however, which of these signaling cascades mediate CRF-induced behaviors during stress. OBJECTIVES: We examined the role of PKA, PKC, and MEK1/2 signaling pathways in CRF-induced anxiety as measured by startle hyperreactivity. METHODS: Mice treated with intracerbroventricular (ICV) ovine CRF (oCRF) were pretreated with the PKA inhibitor Rp-cAMPS, PKC inhibitor bisindolylmaleimide (BIM), or MEK1/2 inhibitor PD98059 (ICV) and assessed for acoustic startle reactivity. RESULTS: The PKC inhibitor BIM significantly attenuated CRF-induced increases in startle. BIM was also able to block startle increases induced by oCRF when both compounds were infused directly into the bed nucleus of stria terminalis (BNST). PKA and MEK1/2 inhibition had no significant effects on CRF-induced changes in startle at the dose ranges tested. CRF-induced disruption of prepulse inhibition was not significantly reversed by any of the three pretreatments at the dose ranges tested. CONCLUSIONS: PKC signaling is required for CRF-induced increases in startle, and this effect is mediated at least in part at the BNST. These findings suggest that PKC signaling cascades (1) may be important for the acute effects of CRF to induce startle hyperreactivity and (2) support further research of the role of PKC signaling in startle abnormalities relevant to disorders such as posttraumatic stress disorder.


Asunto(s)
Hormona Liberadora de Corticotropina/metabolismo , Proteína Quinasa C/metabolismo , Reflejo de Sobresalto/fisiología , Estrés Psicológico/fisiopatología , Animales , Ansiedad/fisiopatología , Hormona Liberadora de Corticotropina/administración & dosificación , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , MAP Quinasa Quinasa 1/metabolismo , MAP Quinasa Quinasa 2/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Inhibidores de Proteínas Quinasas/farmacología , Reflejo de Sobresalto/efectos de los fármacos , Núcleos Septales/metabolismo , Ovinos , Transducción de Señal , Trastornos por Estrés Postraumático/fisiopatología
13.
Transl Psychiatry ; 3: e218, 2013 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-23340501

RESUMEN

Early life adversity, including adverse gestational and postpartum maternal environment, is a contributing factor in the development of autism, attention deficit hyperactivity disorder (ADHD), anxiety and depression but little is known about the underlying molecular mechanism. In a model of gestational maternal adversity that leads to innate anxiety, increased stress reactivity and impaired vocal communication in the offspring, we asked if a specific DNA methylation signature is associated with the emergence of the behavioral phenotype. Genome-wide DNA methylation analyses identified 2.3% of CpGs as differentially methylated (that is, differentially methylated sites, DMSs) by the adverse environment in ventral-hippocampal granule cells, neurons that can be linked to the anxiety phenotype. DMSs were typically clustered and these clusters were preferentially located at gene bodies. Although CpGs are typically either highly methylated or unmethylated, DMSs had an intermediate (20-80%) methylation level that may contribute to their sensitivity to environmental adversity. The adverse maternal environment resulted in either hyper or hypomethylation at DMSs. Clusters of DMSs were enriched in genes that encode cell adhesion molecules and neurotransmitter receptors; some of which were also downregulated, indicating multiple functional deficits at the synapse in adversity. Pharmacological and genetic evidence links many of these genes to anxiety.


Asunto(s)
Ansiedad/genética , Islas de CpG/genética , Metilación de ADN/genética , Giro Dentado/metabolismo , Receptor de Serotonina 5-HT1A/genética , Animales , Adhesión Celular/genética , Modelos Animales de Enfermedad , Epigénesis Genética , Femenino , Masculino , Ratones , Ratones Transgénicos , Embarazo , Efectos Tardíos de la Exposición Prenatal/genética , Vocalización Animal/fisiología
14.
Nanotechnology ; 24(3): 035301, 2013 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-23263276

RESUMEN

Direct-write three-dimensional nanolithography is demonstrated using cryogenic electron beam-induced deposition (EBID). Cryogenic cooling and an electron beam were used to condense and expose the precursor methylcyclopentadienyl(trimethyl)platinum (MeCpPtMe(3)). The exposure process was modeled by Monte Carlo simulations of electron-condensate interactions, which were used to develop two approaches for the fabrication of three-dimensional self-supporting structures with incorporated gaps. Vertical and lateral resolutions of approximately 150 and 22 nm are demonstrated, and underlying mechanisms that limit resolution and throughput are identified. Resolution can be traded off for condensate exposure efficiency, which is shown to be up to four orders of magnitude greater than that of conventional, room temperature EBID.

15.
Rozhl Chir ; 92(12): 715-21, 2013 Dec.
Artículo en Checo | MEDLINE | ID: mdl-24479517

RESUMEN

INTRODUCTION: Endovascular abdominal aortic aneurysm repair (EVAR) is a modern and, compared to conventional open surgery, less invasive therapeutic strategy with short-term lower morbidity and mortality. The aim of our retrospective analysis was the assessment of safety, technical success, short-term and mid-term results of elective patients scheduled for total percutaneous EVAR implantation (PEVAR). MATERIAL AND METHODS: One hundred and sixteen consecutive patients (M:F 104:12, age 71±9 years, maximum AAA diameter 60±14mm) underwent elective PEVAR between January 2009 and August 2012. All the patients were treated under local anaesthesia by total percutaneous approach via femoral access. The immediate technical success of stentgraft implantation as well as the presence of 30-day and 1-year complications and the need of reintervention rate were assessed. RESULTS: In 115/116 patients (99.1%),immediate technical success of the procedure was recorded, with no need of conversion to open surgery; in 1 patient (0.9%) the performance technically failed due to unfavourable arterial anatomy. The mortality in 30-day follow-up was 2.6% (3 patients), during 1-year follow-up it amounted to 8.6% (10 patients), without causal relationship with stentgraft implantation. Overall event-free survival was 85% (98/116) without serious complications (mortality, MI, stroke, reintervention, severe ischemic complication) in the one-year follow-up period. CONCLUSION: Endovascular AAA repair is a safe and feasible method with low mortality and acceptable complication rate in patients scheduled for EVAR implantation. Percutaneous approach allows for the extension of indications also for the highest-risk group of polymorbid patients. Technical feasibility and adequate periprocedural management are essential for further reduction in adverse events after PEVAR.


Asunto(s)
Aneurisma de la Aorta Abdominal/cirugía , Procedimientos Endovasculares/métodos , Complicaciones Posoperatorias/etiología , Stents , Anciano , Aneurisma de la Aorta Abdominal/mortalidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/mortalidad , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del Tratamiento
17.
Mol Psychiatry ; 17(6): 612-23, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-21808255

RESUMEN

Depression is a major health problem worldwide. Most prescribed anti-depressants, the selective serotonin reuptake inhibitors (SSRI) show limited efficacy and delayed onset of action, partly due to the activation of somatodendritic 5-HT(1A)-autoreceptors by the excess extracellular serotonin (5-HT) produced by SSRI in the raphe nuclei. Likewise, 5-HT(1A) receptor (5-HT(1A)R) gene polymorphisms leading to high 5-HT(1A)-autoreceptor expression increase depression susceptibility and decrease treatment response. In this study, we report on a new treatment strategy based on the administration of small-interfering RNA (siRNA) to acutely suppress 5-HT(1A)-autoreceptor-mediated negative feedback mechanisms. We developed a conjugated siRNA (C-1A-siRNA) by covalently binding siRNA targeting 5-HT(1A) receptor mRNA with the SSRI sertraline in order to concentrate it in serotonin axons, rich in serotonin transporter (SERT) sites. The intracerebroventricular (i.c.v.) infusion of C-1A-siRNA to mice resulted in its selective accumulation in serotonin neurons. This evoked marked anti-depressant-like effects in the forced swim and tail suspension tests, but did not affect anxiety-like behaviors in the elevated plus-maze. In parallel, C-1A-siRNA administration markedly decreased 5-HT(1A)-autoreceptor expression and suppressed 8-OH-DPAT-induced hypothermia (a pre-synaptic 5-HT(1A)R effect in mice) without affecting post-synaptic 5-HT(1A)R expression in hippocampus and prefrontal cortex. Moreover, i.c.v. C-1A-siRNA infusion augmented the increase in extracellular serotonin evoked by fluoxetine in prefrontal cortex to the level seen in 5-HT(1A)R knockout mice. Interestingly, intranasal C-1A-siRNA administration produced the same effects, thus opening the way to the therapeutic use of C-1A-siRNA. Hence, C-1A-siRNA represents a new approach to treat mood disorders as monotherapy or in combination with SSRI.


Asunto(s)
Antidepresivos/uso terapéutico , Autorreceptores/antagonistas & inhibidores , Depresión/tratamiento farmacológico , Combinación de Medicamentos , ARN Interferente Pequeño/uso terapéutico , Receptor de Serotonina 5-HT1A/genética , 8-Hidroxi-2-(di-n-propilamino)tetralin/antagonistas & inhibidores , 8-Hidroxi-2-(di-n-propilamino)tetralin/farmacología , Administración Intranasal , Animales , Autorreceptores/biosíntesis , Modelos Animales de Enfermedad , Diseño de Fármacos , Fluoxetina/farmacología , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Hipotermia/inducido químicamente , Hipotermia/tratamiento farmacológico , Infusiones Intraventriculares , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Corteza Prefrontal/efectos de los fármacos , Corteza Prefrontal/metabolismo , Receptor de Serotonina 5-HT1A/biosíntesis , Receptor de Serotonina 5-HT1A/química , Neuronas Serotoninérgicas/efectos de los fármacos , Neuronas Serotoninérgicas/metabolismo , Sertralina/administración & dosificación , Sertralina/química
18.
Acta Physiol Hung ; 98(3): 284-93, 2011 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-21893467

RESUMEN

UNLABELLED: To clarify whether the higher E/A quotient of male athletes is a favourable change in the intrinsic relaxation properties of the left ventricle. METHODS: Peak early (E) and atrial blood flow velocities (A) were assessed by Doppler echocardiography at rest in 1237 males (939 athletes) in Hungary. Data were collected between 1993 ­ 2009. Relationship between E/A and resting heart rate (HR), was determined by linear regression analysis. RESULTS: The E/A decreased with age, the rate of decrease was slower in the physically trained subjects, except in children. In children, adolescent-young and young adult subjects E/A against HR equations of the athletic and nonathletic groups were similar, differences between the means were only due to the differences of the HR. In the 31 ­ 44 yr old males, the intercepts of the athletes' regression lines were higher. The oldest (>44 yr) active subjects showed a significant regression while sedentary males did not. CONCLUSIONS: The HR-independent beneficial effect of regular physical training on the diastolic function manifests itself at the older ages. The impact of resting HR should always be taken into consideration when assessing intergroup differences in the E/A ratio, especially when studying the effect of exercise training upon cardiac function.


Asunto(s)
Función Atrial , Frecuencia Cardíaca , Esfuerzo Físico , Conducta Sedentaria , Función Ventricular Izquierda , Adaptación Fisiológica , Adolescente , Adulto , Factores de Edad , Envejecimiento , Diástole , Ecocardiografía Doppler , Atrios Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/diagnóstico por imagen , Humanos , Hungría , Modelos Lineales , Masculino , Adulto Joven
19.
Acta Physiol Hung ; 98(3): 313-20, 2011 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-21893470

RESUMEN

Information about children's daily physical activity in Eastern-Europe is essential because of the increasing prevalence in overweight and obesity. Sixty-three children (age=11.16 ± 1.10 years; 33 boys and 30 girls) from two public elementary schools had their physical activity objectively measured using uni-axial accelerometer every 5 seconds for five consecutive days (3 weekdays, 2 weekend days). After data cleaning, 10 children were excluded from database. There were no significant differences in boys' and girls' BMI (17.6 ± 2.2 vs. 17.1 ± 2.4) and BF% (18.0 ± 5.2 vs. 19.4 ± 5.0). Children engaged in more sedentary, light, moderate, and vigorous physical activity and had higher counts per minute during weekdays compared to weekend days. There were no sex differences in moderate to vigorous physical activity (87.6 ± 22.4 vs. 93.5 ± 20.6 min and 53.6 ± 21.3 vs. 59.4 ± 22.0 min) during weekday and weekend days. Data indicated that 96% of the girls and 92% of the boys met the international physical activity guideline for children of 60 minutes of MVPA, on weekdays.


Asunto(s)
Conducta Infantil , Conductas Relacionadas con la Salud , Actividad Motora , Conducta Sedentaria , Actigrafía/instrumentación , Análisis de Varianza , Niño , Femenino , Humanos , Hungría , Masculino , Factores Sexuales , Factores de Tiempo
20.
J Dent Res ; 90(10): 1228-33, 2011 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-21828354

RESUMEN

Two main proteases cleave enamel extracellular matrix proteins during amelogenesis. Matrix metalloprotease-20 (Mmp20) is the predominant enzyme expressed during the secretory stage, while kallikrein-related peptidase-4 (Klk4) is predominantly expressed during maturation. Mutations to both Mmp20 and Klk4 result in abnormal enamel phenotypes. During a recent whole-genome microarray analysis of rat incisor enamel organ cells derived from the secretory and maturation stages of amelogenesis, the serine protease chymotrypsin C (caldecrin, Ctrc) was identified as significantly up-regulated (> 11-fold) during enamel maturation. Prior reports indicate that Ctrc expression is pancreas-specific, albeit low levels were also noted in brain. We here report on the expression of Ctrc in the enamel organ. Quantitative PCR (qPCR) and Western blot analysis were used to confirm the expression of Ctrc in the developing enamel organ. The expression profile of Ctrc is similar to that of Klk4, increasing markedly during the maturation stage relative to the secretory stage, although levels of Ctrc mRNA are lower than for Klk4. The discovery of a new serine protease possibly involved in enamel development has important implications for our understanding of the factors that regulate enamel biomineralization.


Asunto(s)
Amelogénesis/genética , Quimotripsina/biosíntesis , Quimotripsina/genética , Proteínas del Esmalte Dental/biosíntesis , Órgano del Esmalte/metabolismo , Animales , Western Blotting , Proteínas del Esmalte Dental/genética , Regulación del Desarrollo de la Expresión Génica , Calicreínas/biosíntesis , Calicreínas/genética , Masculino , Metaloproteinasa 20 de la Matriz/biosíntesis , Metaloproteinasa 20 de la Matriz/genética , Reacción en Cadena de la Polimerasa , ARN Mensajero/biosíntesis , Ratas , Ratas Wistar , Regulación hacia Arriba
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...