864 resultados para Precondition event
Resumo:
Questo elaborato ha analizzato le Event Related Spectral Perturbation (ERSP), cioè le variazioni nella potenza del segnale in corrispondenza di una frequenza o una banda di frequenze, suddivisi in Event Related Synchronization (ERS) nel caso di incremento di potenza e Event Related Desynchronization (ERD) nel caso di decremento di potenza, relative a movimenti di reaching eseguiti con l’arto superiore. In particolare, sono state prese in considerazione le potenze nel ritmo alpha (8-12 Hz) e ritmo beta (12-30 Hz), in quanto ritmi associati alla preparazione ed esecuzione del movimento. I segnali EEG analizzati (60 canali) sono relativi a 14 soggetti a cui è stato chiesto di compiere movimenti di reaching verso una posizione target, secondo una tempistica definita dall’accensione di uno stimolo visivo informativo (CUE, corrispondente al led nella posizione target) e un secondo stimolo visivo imperativo (GO) che dà il via libera all’esecuzione del movimento verso il target. Sono codificate 5 posizioni discrete, a 0°, 45°, 90°, 135° e 180°, su una semicirconferenza il cui centro rappresenta il punto di partenza e ritorno, chiamato base. I segnali preventivamente preprocessati, sono stati decomposti tramite trasformata wavelet ed elaborati con la tecnica dell’averaging, con lo scopo di evidenziare ERS e ERD in banda alpha e beta associati a eventi visivi e motori. È stata presentata l’evoluzione nel tempo della distribuzione topologica delle ERSP a livello dello scalpo e sono state svolte analisi suddividendo i dati secondo la direzione (destra, centro, sinistra) del target e secondo la profondità (vicino, medio, lontano) del target. I risultati mostrano una desincronizzazione (ERD) nella fase di preparazione del movimento (immediatamente prima dello stimolo GO), sia in banda alpha che beta e suggeriscono una modulazione dell’ERD in funzione della direzione/profondità del target.
Resumo:
Reversible phosphorylation of proteins, performed by kinases and phosphatases, is the major post translational protein modification in eukaryotic cells. This intracellular event represents a critical regulatory mechanism of several signaling pathways and can be related to a vast array of diseases, including cancer. Cancer research has produced increasing evidence that kinase and phosphatase activity can be compromised by mutations and also by miRNA silencing, performed by small non-coding and endogenously produced RNA molecules that lead to translational repression. miRNAs are believed to target about one-third of human mRNAs while a single miRNA may target about 200 transcripts simultaneously. Regulation of the phosphorylation balance by miRNAs has been a topic of intense research over the last years, spanning topics going as far as cancer aggressiveness and chemotherapy resistance. By addressing recent studies that have shown miRNA expression patterns as phenotypic signatures of cancers and how miRNA influence cellular processes such as apoptosis, cell cycle control, angiogenesis, inflammation and DNA repair, we discuss how kinases, phosphatases and miRNAs cooperatively act in cancer biology.
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Cyclosporine, a drug used in immunosuppression protocols for hematopoietic stem cell transplantation that has a narrow therapeutic index, may cause various adverse reactions, including nephrotoxicity. This has a direct clinical impact on the patient. This study aims to summarize available evidence in the scientific literature on the use of cyclosporine in respect to its risk factor for the development of nephrotoxicity in patients submitted to hematopoietic stem cell transplantation. A systematic review was made with the following electronic databases: PubMed, Web of Science, Embase, Scopus, CINAHL, LILACS, SciELO and Cochrane BVS. The keywords used were: bone marrow transplantation OR stem cell transplantation OR grafting, bone marrow AND cyclosporine OR cyclosporin OR risk factors AND acute kidney injury OR acute kidney injuries OR acute renal failure OR acute renal failures OR nephrotoxicity. The level of scientific evidence of the studies was classified according to the Oxford Centre for Evidence Based Medicine. The final sample was composed of 19 studies, most of which (89.5%) had an observational design, evidence level 2B and pointed to an incidence of nephrotoxicity above 30%. The available evidence, considered as good quality and appropriate for the analyzed event, indicates that cyclosporine represents a risk factor for the occurrence of nephrotoxicity, particularly when combined with amphotericin B or aminoglycosides, agents commonly used in hematopoietic stem cell transplantation recipients.
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The present study evaluated the role of N-methyl-D-aspartate receptors (NMDARs) expressed in the dorsal root ganglia (DRG) in the inflammatory sensitization of peripheral nociceptor terminals to mechanical stimulation. Injection of NMDA into the fifth lumbar (L5)-DRG induced hyperalgesia in the rat hind paw with a profile similar to that of intraplantar injection of prostaglandin E2 (PGE2), which was significantly attenuated by injection of the NMDAR antagonist D(-)-2-amino-5-phosphonopentanoic acid (D-AP-5) in the L5-DRG. Moreover, blockade of DRG AMPA receptors by the antagonist 6,7-dinitroquinoxaline-2,3-dione had no effect in the PGE2-induced hyperalgesia in the paw, showing specific involvement of NMDARs in this modulatory effect and suggesting that activation of NMDAR in the DRG plays an important role in the peripheral inflammatory hyperalgesia. In following experiments we observed attenuation of PGE2-induced hyperalgesia in the paw by the knockdown of NMDAR subunits NR1, NR2B, NR2D, and NR3A with antisense-oligodeoxynucleotide treatment in the DRG. Also, in vitro experiments showed that the NMDA-induced sensitization of cultured DRG neurons depends on satellite cell activation and on those same NMDAR subunits, suggesting their importance for the PGE2-induced hyperalgesia. In addition, fluorescent calcium imaging experiments in cultures of DRG cells showed induction of calcium transients by glutamate or NMDA only in satellite cells, but not in neurons. Together, the present results suggest that the mechanical inflammatory nociceptor sensitization is dependent on glutamate release at the DRG and subsequent NMDAR activation in satellite glial cells, supporting the idea that the peripheral hyperalgesia is an event modulated by a glutamatergic system in the DRG.
Resumo:
Maxillofacial trauma resulting from falls in elderly patients is a major social and health care concern. Most of these traumatic events involve mandibular fractures. The aim of this study was to analyze stress distributions from traumatic loads applied on the symphyseal, parasymphyseal, and mandibular body regions in the elderly edentulous mandible using finite-element analysis (FEA). Computerized tomographic analysis of an edentulous macerated human mandible of a patient approximately 65 years old was performed. The bone structure was converted into a 3-dimensional stereolithographic model, which was used to construct the computer-aided design (CAD) geometry for FEA. The mechanical properties of cortical and cancellous bone were characterized as isotropic and elastic structures, respectively, in the CAD model. The condyles were constrained to prevent free movement in the x-, y-, and z-axes during simulation. This enabled the simulation to include the presence of masticatory muscles during trauma. Three different simulations were performed. Loads of 700 N were applied perpendicular to the surface of the cortical bone in the symphyseal, parasymphyseal, and mandibular body regions. The simulation results were evaluated according to equivalent von Mises stress distributions. Traumatic load at the symphyseal region generated low stress levels in the mental region and high stress levels in the mandibular neck. Traumatic load at the parasymphyseal region concentrated the resulting stress close to the mental foramen. Traumatic load in the mandibular body generated extensive stress in the mandibular body, angle, and ramus. FEA enabled precise mapping of the stress distribution in a human elderly edentulous mandible (neck and mandibular angle) in response to 3 different traumatic load conditions. This knowledge can help guide emergency responders as they evaluate patients after a traumatic event.
Resumo:
one hundred (n=100) elderly outpatients with diabetic retinopathy taking antihypertensives and/or oral antidiabetics/insulin were interviewed. Adherence was evaluated by the adherence proportion and its association with the care taken in administrating medications and by the Morisky Scale. The National Eye Institute Visual Functioning Questionnaire (NEI VFQ-25) was used to evaluate HRQoL. most (58%) reported the use of 80% or more of the prescribed dose and care in utilizing the medication. The item stopping the drug when experiencing an adverse event, from the Morisky Scale, explained 12.8% and 13.5% of the variability of adherence proportion to antihypertensives and oral antidiabetics/insulin, respectively. there was better HRQoL in the Color Vision, Driving and Social Functioning domains of the NEI VFQ-25. Individuals with lower scores on the NEI VFQ-25 and higher scores on the Morisky Scale presented greater chance to be nonadherent to the pharmacological treatment of diabetes and hypertension.
Resumo:
The human mitochondrial Hsp70, also called mortalin, is of considerable importance for mitochondria biogenesis and the correct functioning of the cell machinery. In the mitochondrial matrix, mortalin acts in the importing and folding process of nucleus-encoded proteins. The in vivo deregulation of mortalin expression and/or function has been correlated with age-related diseases and certain cancers due to its interaction with the p53 protein. In spite of its critical biological roles, structural and functional studies on mortalin are limited by its insoluble recombinant production. This study provides the first report of the production of folded and soluble recombinant mortalin when co-expressed with the human Hsp70-escort protein 1, but it is still likely prone to self-association. The monomeric fraction of mortalin presented a slightly elongated shape and basal ATPase activity that is higher than that of its cytoplasmic counterpart Hsp70-1A, suggesting that it was obtained in the functional state. Through small angle X-ray scattering, we assessed the low-resolution structural model of monomeric mortalin that is characterized by an elongated shape. This model adequately accommodated high resolution structures of Hsp70 domains indicating its quality. We also observed that mortalin interacts with adenosine nucleotides with high affinity. Thermally induced unfolding experiments indicated that mortalin is formed by at least two domains and that the transition is sensitive to the presence of adenosine nucleotides and that this process is dependent on the presence of Mg2+ ions. Interestingly, the thermal-induced unfolding assays of mortalin suggested the presence of an aggregation/association event, which was not observed for human Hsp70-1A, and this finding may explain its natural tendency for in vivo aggregation. Our study may contribute to the structural understanding of mortalin as well as to contribute for its recombinant production for antitumor compound screenings.
Resumo:
Calcium dynamics is central in cardiac physiology, as the key event leading to the excitation-contraction coupling (ECC) and relaxation processes. The primary function of Ca(2+) in the heart is the control of mechanical activity developed by the myofibril contractile apparatus. This key role of Ca(2+) signaling explains the subtle and critical control of important events of ECC and relaxation, such Ca(2+) influx and SR Ca(2+) release and uptake. The multifunctional Ca(2+)-calmodulin-dependent protein kinase II (CaMKII) is a signaling molecule that regulates a diverse array of proteins involved not only in ECC and relaxation, but also in cell death, transcriptional activation of hypertrophy, inflammation and arrhythmias. CaMKII activity is triggered by an increase in intracellular Ca(2+) levels. This activity can be sustained, creating molecular memory after the decline in Ca(2+) concentration, by autophosphorylation of the enzyme, as well as by oxidation, glycosylation and nitrosylation at different sites of the regulatory domain of the kinase. CaMKII activity is enhanced in several cardiac diseases, altering the signaling pathways by which CaMKII regulates the different fundamental proteins involved in functional and transcriptional cardiac processes. Dysregulation of these pathways constitutes a central mechanism of various cardiac disease phenomena, like apoptosis and necrosis during ischemia/reperfusion injury, digitalis exposure, post-acidosis and heart failure arrhythmias, or cardiac hypertrophy. Here we summarize significant aspects of the molecular physiology of CaMKII and provide a conceptual framework for understanding the role of the CaMKII cascade on Ca(2+) regulation and dysregulation in cardiac health and disease.
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Genetically modified foods are a major concern around the world due to the lack of information concerning their safety and health effects. This work evaluates differences, at the proteomic level, between two types of crop samples: transgenic (MON810 event with the Cry1Ab gene, which confers resistance to insects) and non-transgenic maize flour commercialized in Brazil. The 2-D DIGE technique revealed 99 differentially expressed spots, which were collected in 2-D PAGE gels and identified via mass spectrometry (nESI-QTOF MS/MS). The abundance of protein differences between the transgenic and non-transgenic samples could arise from genetic modification or as a result of an environmental influence pertaining to the commercial sample. The major functional category of proteins identified was related to disease/defense and, although differences were observed between samples, no toxins or allergenic proteins were found.
Resumo:
Herein, we provide new contribution to the mechanisms involved in keratinocytes response to hyperosmotic shock showing, for the first time, the participation of Low Molecular Weight Protein Tyrosine Phosphatase (LMWPTP) activity in this event. We reported that sorbitol-induced osmotic stress mediates alterations in the phosphorylation of pivotal cytoskeletal proteins, particularly Src and cofilin. Furthermore, an increase in the expression of the phosphorylated form of LMWPTP, which was followed by an augment in its catalytic activity, was observed. Of particular importance, these responses occurred in an intracellular milieu characterized by elevated levels of reduced glutathione (GSH) and increased expression of the antioxidant enzymes glutathione peroxidase and glutathione reductase. Altogether, our results suggest that hyperosmostic stress provides a favorable cellular environment to the activation of LMWPTP, which is associated with increased expression of antioxidant enzymes, high levels of GSH and inhibition of Src kinase. Finally, the real contribution of LMWPTP in the hyperosmotic stress response of keratinocytes was demonstrated through analysis of the effects of ACP1 gene knockdown in stressed and non-stressed cells. LMWPTP knockdown attenuates the effects of sorbitol induced-stress in HaCaT cells, mainly in the status of Src kinase, Rac and STAT5 phosphorylation and activity. These results describe for the first time the participation of LMWPTP in the dynamics of cytoskeleton rearrangement during exposure of human keratinocytes to hyperosmotic shock, which may contribute to cell death.
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Use of cisplatin can induce type I hypersensitivity reactions that may also be linked to the quality of the drug utilized. We observed cases of hypersensitivity that appeared to be associated with the brand of cisplatin used. The aim of this study was to compare two different brands of cisplatin in relation to type I hypersensitivity reactions. Brand A was used in a tertiary care teaching hospital until 2012, and use of brand B started from January 2013, when the first hypersensitivity cases were observed. Patients were categorized based on symptom. Cisplatin of both brands was analysed by high-performance liquid chromatography (HPLC) and high-resolution electrospray ionization mass spectrometry (ESI-(+)-MS) and characterized according to US Pharmacopeia. There were no cases of hypersensitivity associated with the use of cisplatin brand A, whereas four of 127 outpatients that used cisplatin brand B were affected. The two brands were in accordance with the US Pharmacopeia parameters, and there was no significant difference in the total platinum levels between the two brands when analysed by HPLC. However, high-resolution ESI-(+)-MS analyses show that brand B contains approximately 2.7 times more hydrolysed cisplatin than brand A. The increase in the hydrolysed form of cisplatin found in brand B may be the cause of the hypersensitivity reaction observed in a subset of patients. We present the first study of the quality of drugs by high-resolution ESI-(+)-MS. Drug regulatory agencies and manufacturers should consider including measurement of hydrolysed cisplatin as a quality criterion for cisplatin formulations.
Resumo:
Cancer is a multistep process that begins with the transformation of normal epithelial cells and continues with tumor growth, stromal invasion and metastasis. The remodeling of the peritumoral environment is decisive for the onset of tumor invasiveness. This event is dependent on epithelial-stromal interactions, degradation of extracellular matrix components and reorganization of fibrillar components. Our research group has studied in a new proposed rodent model the participation of cellular and molecular components in the prostate microenvironment that contributes to cancer progression. Our group adopted the gerbil Meriones unguiculatus as an alternative experimental model for prostate cancer study. This model has presented significant responses to hormonal treatments and to development of spontaneous and induced neoplasias. The data obtained indicate reorganization of type I collagen fibers and reticular fibers, synthesis of new components such as tenascin and proteoglycans, degradation of basement membrane components and elastic fibers and increased expression of metalloproteinases. Fibroblasts that border the region, apparently participate in the stromal reaction. The roles of each of these events, as well as some signaling molecules, participants of neoplastic progression and factors that promote genetic reprogramming during epithelial-stromal transition are also discussed.
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Nowadays the consumer market demands a gradually increase in the products' quality control. The manual control that exits, used in animal production, shows ineficiency in warrating an increasing percentual of the desirable quality, so this can only be reached when an effective animal tracebility system is applied, from birth to slaughter. Individual electronic identification presents high importance in this focus, providing information recorded directly from the animal. Electronic traceability uses electronic devices that emit a signal activated by a fixed reader placed where it is needed to record a certain event, or uses a manual reader which allows a higher independence of the operator. Knowing the importance of the electronic identification as a tool for applying traceability in animal production, this research had as objective to evaluate the use of transponders in order to garantee the manual reading as well as the fixed antenna reading. The following implant places were analized in piglet, just after their birth: 1) forehead, 2) external ear lobule, 3) the posterior auricular base, and 4) a transponder inserted in a earing implanted in the ear lobule. The factors of skin damage and migration were analized, as well as the reading efficiency. It was found that the best implant place was the posterior ear base.
Resumo:
This study is a reflection about the similarities between uptake and trace, and translation taken as an event - at once possible and impossible - which deflagrates and constitutes meaning through the language game played by the subjects of communication: text-translator. Both Austin and Derrida, each one on his own way, show that meaning is part of the human language process. The uptake, in Austin s point of view, guarantees the existence of human language, assured by a process of recognition between the subjects of communication, process through which the production of meaning takes place. The trace, according to Derrida, deflagrates, through the human language, the crashing of meaning and destroys the possibility of someone reaching the origin. In this study, taking into consideration the similarities between uptake and trace, I try to disclose translation taken as an event which at once contaminates the languages and is contaminated by them.
Resumo:
Universidade Estadual de Campinas . Faculdade de Educação Física