911 resultados para heavy ion cancer therapy
Resumo:
Introducción: La utilización de catéteres venosos centrales (CVC) en la unidad de cuidado intensivo tiene gran importancia y amplio uso, son fuente de apoyo para la realización de varia actividades, pero con un gran potencial de complicaciones, por lo cual es fundamental conocer todos los aspectos relacionados con su uso, para así poder controlarlas. Métodos: Realizamos un estudio descriptivo de corte transversal con el objetivo de caracterizar los pacientes que requirieron CVC en el Hospital Universitario Fundación Santa Fe de Bogotá durante junio de 2011 y mayo de 2013, describimos sus complicaciones asociadas tanto mecánicas como infecciosas, determinamos la tasa de bacteriemia, gérmenes causales y sus patrones de resistencia. Resultados: Se colocaron 2.286 CVC, el 52,9% en hombres, la media de edad fue 58,9 años. El total de las complicaciones ascienden al 4,5%, infecciosas 4,0% y mecánicas 0,6%. Dentro de las mecánicas solo encontramos inmediatas, no tardías. Con respecto a las infecciosas encontramos infección del sitio de inserción y bacteriemia. Se documentó una tasa de bacteriemia de 3,4 por 1000-días catéter en 2013, en disminución con respecto a 2012 (3,9) y 2011 (4,4). El microorganismo mas frecuentemente aislado fue el Staphylococcus Coagulasa Negativo con patrón usual de resistencia. Conclusión: Las complicaciones asociadas al uso de CVC en el HUFSFB, se presentan en menor frecuencia a las descritas internacionalmente; la tasa de bacteriemia asociada al CVC ha disminuido año tras año, posiblemente asociado al cuidado mas estricto posterior a la implementación de protocolos de manejo.
Resumo:
Esta revisión de la literatura tuvo como objetivo describir las actitudes hacia el VIH/SIDA, el cáncer y la Enfermedad de Alzheimer desde el modelo tripartito. Se revisaron 109 artículos publicados entre 2005 y 2015 en algunas bases de datos especializadas y herramientas de análisis de impacto. También se incluyeron fuentes secundarias ampliándose la búsqueda a los últimos 20 años (1995-2015). Los resultados mostraron que la mayoría de los estudios realizados sobre las actitudes hacia estas tres enfermedades son de tipo cuantitativo y la información se analizó con base en los componentes del modelo tripartito. Algunos aspectos sociodemográficos como el sexo y la edad están asociados con las actitudes hacia las tres enfermedades y predominan las creencias erróneas sobre ellas respecto a sus causas, curso y tratamiento. También predominan actitudes negativas hacia las tres enfermedades y las conductas e intenciones conductuales son diversas hacia cada una de ellas. No se hallaron antecedentes empíricos del estudio de la estructura de las actitudes propuesta por el modelo tripartito hacia las tres enfermedades. La Salud Pública ha liderado la investigación con base en el modelo de conocimientos, actitudes y prácticas propuesto por la OMS.
Resumo:
A nanotecnologia, e a sua aplicação na área da biomedicina, em particular na terapêutica e diagnóstico oncológico, tem sido alvo de um desenvolvimento exponencial, com impacto profundo no que respeita a cuidados de saúde. O cancro é uma das doenças que afecta mais pessoas a nível mundial, com elevados índices de mortalidade, níveis de sofrimento físico e emocional e, encargos para o doente, família e sociedade. É uma doença complexa, e a prática clínica convencional constitui um paradigma, na medida em que se revela insuficiente e extremamente agressiva, expondo o doente a medicamentos citotóxicos, não específicos, com elevada toxicidade sistémica e efeitos adversos. A Nanomedicina, e a exploração das propriedades únicas das nanopartículas, apresenta a potencialidade de melhorar a capacidade de detecção e diagnóstico do cancro e, aumentar a especificidade e efectividade no tratamento das células tumorais. No entanto, o recurso a nanotecnologias continua a ser alvo de alguma controvérsia e cepticismo por parte de alguns elementos das comunidades científicas e académica. Com nanoprodutos já aprovados e utilizados em prática clínica e muitos outros em desenvolvimento e investigação em ensaios clínicos, a realização deste trabalho tem como objectivo compreender os conceitos de nanotecnologia e Nanomedicina, perceber o estado da arte, ponderando as vantagens e desvantagens da abordagem “nano” e a sua real aplicação à terapêutica oncológica.
Resumo:
The DNA G-qadruplexes are one of the targets being actively explored for anti-cancer therapy by inhibiting them through small molecules. This computational study was conducted to predict the binding strengths and orientations of a set of novel dimethyl-amino-ethyl-acridine (DACA) analogues that are designed and synthesized in our laboratory, but did not diffract in Synchrotron light.Thecrystal structure of DNA G-Quadruplex(TGGGGT)4(PDB: 1O0K) was used as target for their binding properties in our studies.We used both the force field (FF) and QM/MM derived atomic charge schemes simultaneously for comparing the predictions of drug binding modes and their energetics. This study evaluates the comparative performance of fixed point charge based Glide XP docking and the quantum polarized ligand docking schemes. These results will provide insights on the effects of including or ignoring the drug-receptor interfacial polarization events in molecular docking simulations, which in turn, will aid the rational selection of computational methods at different levels of theory in future drug design programs. Plenty of molecular modelling tools and methods currently exist for modelling drug-receptor or protein-protein, or DNA-protein interactionssat different levels of complexities.Yet, the capasity of such tools to describevarious physico-chemical propertiesmore accuratelyis the next step ahead in currentresearch.Especially, the usage of most accurate methods in quantum mechanics(QM) is severely restricted by theirtedious nature. Though the usage of massively parallel super computing environments resulted in a tremendous improvement in molecular mechanics (MM) calculations like molecular dynamics,they are still capable of dealing with only a couple of tens to hundreds of atoms for QM methods. One such efficient strategy that utilizes thepowers of both MM and QM are the QM/MM hybrid methods. Lately, attempts have been directed towards the goal of deploying several different QM methods for betterment of force field based simulations, but with practical restrictions in place. One of such methods utilizes the inclusion of charge polarization events at the drug-receptor interface, that is not explicitly present in the MM FF.
Resumo:
A new dayside source of O+ ions for the polar magnetosphere is described, and a statistical survey presented of upward flows of O+ ions using 2 years of data from the retarding ion mass spectrometer (RIMS) experiment on board DE 1, at geocentric distances below 3 RE and invariant latitudes above 40°. The flows are classified according to their spin angle distributions. It is believed that the spacecraft potential near perigee is generally less than +2 V, in which case the entire O+ population at energies below about 60 eV is sampled. Examples are given of field-aligned flow and of transversely accelerated “core” O+ ions; in the latter events a large fraction of the total O+ ion population has been transversely accelerated, and in some extreme cases all the observed ions (of all ion species) have been accelerated, and no residual cold population is observed (“toroidal” distributions). However, by far the most common type of O+ upflow seen by DE RIMS lies near the dayside polar cap boundary (particularly in the prenoon sector) and displays an asymmetric spin angle distribution. In such events the ions carry an upward heat flux, and strong upflow of all species is present (H+, He+, O+, O++, and N+ have all been observed with energies up to about 30 eV, but with the majority of ions below about 2 eV); hence, these have been termed upwelling ion events. The upwelling ions are embedded in larger regions of classical light ion polar wind and are persistently found under the following conditions: at geocentric distances greater than 1.4 RE; at all Kp in summer, but only at high Kp in winter. Low-energy conical ions (<30 eV) are only found near the equatorial edge of the events, the latitude of which moves equatorward with increasing Kp and is highly correlated with the location of field-aligned currents. The RIMS data are fully consistent with a “mass spectrometer effect,” whereby light ions and the more energetic O+ ions flow into the lobes and mantle and hence the far-tail plasma sheet, but lower-energy O+ is swept across the polar cap by the convection electric field, potentially acting as a source for the nightside auroral acceleration regions. The occurrence probability of upwelling ion events, as compared to those of low-altitude transversely accelerated core ions and of field-aligned flow, suggests this could be the dominant mechanism for supplying the nightside auroral acceleration region, and subsequently the ring current and near-earth plasma sheet, with ionospheric O+ ions. It is shown that the total rate of O+ outflow in upwelling ion events (greater than 10^25 s^{−1}) is sufficient for the region near the dayside polar cap boundary to be an important ionospheric heavy ion source.
Resumo:
Introduction Facing the challenging treatment of neurodegenerative diseases as well as complex craniofacial injuries such as those common after cancer therapy, the field of regenerative medicine increasingly relies on stem cell transplantation strategies. Here, neural crest-derived stem cells (NCSCs) offer many promising applications, although scale up of clinical-grade processes prior to potential transplantations is currently limiting. In this study, we aimed to establish a clinical-grade, cost-reducing cultivation system for NCSCs isolated from the adult human nose using cGMP-grade Afc-FEP bags. Methods We cultivated human neural crest-derived stem cells from inferior turbinate (ITSCs) in a cell culture bag system using Afc-FEP bags in human blood plasma-supplemented medium. Investigations of viability, proliferation and expression profile of bag-cultured ITSCs were followed by DNA-content and telomerase activity determination. Cultivated ITSCs were introduced to directed in vitro differentiation assays to assess their potential for mesodermal and ectodermal differentiation. Mesodermal differentiation was determined using an enzyme activity assay (alkaline phosphatase, ALP), respective stainings (Alizarin Red S, Von Kossa and Oil Red O), and RT-PCR, while immunocytochemistry and synaptic vesicle recycling were applied to assay neuroectodermal differentiation of ITSCs. Results When cultivated within Afc-FEP bags, ITSCs grew three-dimensionally in a human blood plasma-derived matrix, thereby showing unchanged morphology, proliferation capability, viability and expression profile in comparison to three dimensionally-cultured ITSCs growing in standard cell culture plastics. Genetic stability of bag-cultured ITSCs was further accompanied by unchanged telomerase activity. Importantly, ITSCs retained their potential to differentiate into mesodermal cell types, particularly including ALP-active, Alizarin Red S-, and Von Kossa-positive osteogenic cell types, as well as adipocytes positive in Oil Red O assays. Bag culture further did not affect the potential of ITSCs to undergo differentiation into neuroectodermal cell types coexpressing β-III-tubulin and MAP2 and exhibiting the capability for synaptic vesicle recycling. Conclusions Here, we report for the first time the successful cultivation of human NCSCs within cGMP-grade Afc-FEP bags using a human blood plasma-supplemented medium. Our findings particularly demonstrate the unchanged differentiation capability and genetic stability of the cultivated NCSCs, suggesting the great potential of this culture system for future medical applications in the field of regenerative medicine.
Resumo:
We calculate the spectra of produced thermal photons in Au + Au collisions taking into account the nonequilibrium contribution to photon production due to finite shear viscosity. The evolution of the fireball is modeled by second-order as well as by divergence-type 2 + 1 dissipative hydrodynamics, both with an ideal equation of state and with one based on Lattice QCD that includes an analytical crossover. The spectrum calculated in the divergence-type theory is considerably enhanced with respect to the one calculated in the second-order theory, the difference being entirely due to differences in the viscous corrections to photon production. Our results show that the differences in hydrodynamic formalisms are an important source of uncertainty in the extraction of the value of eta/s from measured photon spectra. The uncertainty in the value of eta/s associated with different hydrodynamic models used to compute thermal photon spectra is larger than the one occurring in matching hadron elliptic flow to RHIC data. (C) 2010 Elsevier B.V. All rights reserved.
Resumo:
Melanoma is the most aggressive form of skin cancer, and its incidence has increased dramatically over the years. The murine B16F10 melanoma in syngeneic C57Bl/6 mice has been used as a highly aggressive model to investigate tumor development. Presently, we demonstrate in the B16F10-Nex2 subclone that silencing of SOCS-1, a negative regulator of Jak/Stat pathway, leads to reversal of the tumorigenic phenotype and inhibition of melanoma cell metastasis. SOCS-1 silencing with short hairpin RNA affected tumor growth and cell cycle regulation with arrest at the S phase with large-sized nuclei, reduced cell motility, and decreased melanoma cell invasion through Matrigel. A clonogenic assay showed that SOCS-1 acted as a modulator of resistance to anoikis. In addition, down-regulation of SOCS-1 decreased the expression of epidermal growth factor receptor ( mainly the phosphorylated-R), Ins-R alpha, and fibroblast growth factor receptor. In vivo, silencing of SOCS-1 inhibited subcutaneous tumor growth and metastatic development in the lungs. Because SOCS-1 is expressed in most melanoma cell lines and bears a relation with tumor invasion, thickness, and stage of disease, the present results on the effects of SOCS-1 silencing in melanoma suggest that this regulating protein can be a target of cancer therapy.
Resumo:
The biological activity of the proline rich decapeptde Bj PRO 10c a processing product of the C type natriuretic peptide precursor protein, expressed in the brain and the venom gland of the pit viper Bothrops jararaca, was originally attributed to the inhibition of the somatic angiotensm converting enzyme activity with subsequent ant hypertensive effect However recent results suggest broader biological activity may also be involved in the cardiovascular effects of this peptide Here we show that Bj PRO 10c enhances and sustains the generation of nitric made (NO) by regulating argininosuccinate synthase activity and thereby velocity of the citrulline NO cycle Bj PRO 10c-mediated effects not restricted to the cardiovascular system since NO production was also induced in cells of astroglial origin Bj PRO 10c was internalized by C6 astroglioma cells where it induces NO production and upregulation of the citrulline NO cycle cells in a dose dependent fashion In view of that, astroglial cells function as L arginine pool for NO production in neighboring neurons, we suggest a regulatory function for Bj PRO-10c on the metabolism of this gaseous neurotransmitter in the CNS Moreover, proliferation of astroglial cells was reduced in the presence of Bj PRO 10c however, cell death was not induced Since NO donors have been studied for the treatment of solid cancers Bj PRO 10c may serve as structural model for developing drugs to improve the effects of cancer therapy based on the peptide`s ability to augment NO production (C) 2010 Elsevier B V All rights reserved
Resumo:
Malignant melanoma has increased incidence worldwide and causes most skin cancer-related deaths. A few cell surface antigens that can be targets of antitumor immunotherapy have been characterized in melanoma. This is an expanding field because of the ineffectiveness of conventional cancer therapy for the metastatic form of melanoma. In the present work, antimelanoma monoclonal antibodies (mAbs) were raised against B16F10 cells (subclone Nex4, grown in murine serum), with novel specificities and antitumor effects in vitro and in vivo. MAb A4 (IgG2ak) recognizes a surface antigen on B16F10-Nex2 cells identified as protocadherin beta(13). It is cytotoxic in vitro and in vivo to B16F10-Nex2 cells as well as in vitro to human melanoma cell lines. MAb A4M (IgM) strongly reacted with nuclei of permeabilized murine tumor cells, recognizing histone 1. Although it is not cytotoxic in vitro, similarly with mAb A4, mAb A4M significantly reduced the number of lung nodules in mice challenged intravenously with B16F10-Nex2 cells. The V(H) CDR3 peptide from mAb A4 and V(L) CDR1 and CDR2 from mAb A4M showed significant cytotoxic activities in vitro, leading tumor cells to apoptosis. A cyclic peptide representing A4 CDR H3 competed with mAb A4 for binding to melanoma cells. MAb A4M CDRs L1 and L2 in addition to the antitumor effect also inhibited angiogenesis of human umbilical vein endothelial cells in vitro. As shown in the present work, mAbs A4 and A4M and selected CDR peptides are strong candidates to be developed as drugs for antitumor therapy for invasive melanoma.
Resumo:
Doxorubicin (DOX), a member of the anthracycline group, is a widely used drug in cancer therapy. The mechanisms of DOX action include topoisomerase II-poisoning, free radical release, DNA adducts and interstrand cross-link (ICL) formation. Nucleotide excision repair(NER) is involved in the removal of helix-distorting lesions and chemical adducts, however, little is known about the response of NER-deficient cell lines to anti-tumoral drugs like DOX. Wild type and XPD-mutated cells, harbouring mutations in different regions of this gene and leading to XP-D, XP/CS or TTD diseases, were treated with this drug and analyzed for cell cycle arrest and DNA damage by comet assay. The formation of DSBs was also investigated by determination of gamma H2AX foci. Our results indicate that all three NER-deficient cell lines tested are more sensitive to DOX treatment, when compared to wild type cells or XP cells complemented by the wild type XPD cDNA, suggesting that NER is involved in the removal of DOX-induced lesions. The cell cycle analysis showed the characteristic G2 arrest in repair-proficient MRC5 cell line after DOX treatment, whereas the repair-deficient cell lines presented significant increase in sub-G1 fraction. The NER-deficient cell lines do not show different patterns of DNA damage formation as assayed by comet assay and phosphorylated H2AX foci formation. Knock-down of topoisomerase II alpha with siRNA leads to increased survival in both MRC5 and XP cells, however, XP cell line still remained significantly more sensitive to the treatment by DOX. Our study suggests that the enhanced sensitivity is due to DOX-induced DNA damage that is subject to NER, as we observed decreased unscheduled DNA synthesis in XP-deficient cells upon DOX treatment. Furthermore, the complementation of the XPD-function abolished the observed sensitivity at lower DOX concentrations, suggesting that the XPD helicase activity is involved in the repair of DOX-induced lesions. (C) 2009 Elsevier B.V. All rights reserved.
Resumo:
This paper presents an overview of the results obtained during the Joint Experiments organized in the framework of the IAEA Coordinated Research Project on `Joint Research Using Small Tokamaks` that have been carried out on the tokamaks CASTOR at IPP Prague, Czech Republic (2005), T-10 at RRC `Kurchatov Institute`, Moscow, Russia (2006), and the most recent one at ISTTOK at IST, Lisbon, Portugal, in 2007. Experimental programmes were aimed at diagnosing and characterizing the core and the edge plasma turbulence in a tokamak in order to investigate correlations between the occurrence of transport barriers, improved confinement, electric fields and electrostatic turbulence using advanced diagnostics with high spatial and temporal resolution. On CASTOR and ISTTOK, electric fields were generated by biasing an electrode inserted into the edge plasma and an improvement of the global particle confinement induced by the electrode positive biasing has been observed. Geodesic acoustic modes were studied using heavy ion beam diagnostics on T-10 and ISTTOK and correlation reflectometry on T-10. ISTTOK is equipped with a gallium jet injector and the technical feasibility of gallium jets interacting with plasmas has been investigated in pulsed and ac operation. The first Joint Experiments have clearly demonstrated that small tokamaks are suitable for broad international cooperation to conduct dedicated joint research programmes. Other activities within the IAEA Coordinated Research Project on Joint Research Using Small Tokamaks are also overviewed.
Resumo:
We calculate the form factors and the coupling constant in the D*D rho vertex in the framework of QCD sum rules. We evaluate the three-point correlation functions of the vertex considering D, rho and D* mesons off-shell. The form factors obtained are very different but give the same coupling constant: g(D*D rho) = 4.3 +/- 0.9 GeV(-1). (C) 2011 Elsevier B.V. All rights reserved.
Resumo:
Assuming that nuclear matter can be treated as a perfect fluid, we study the propagation of perturbations in the baryon density. The equation of state is derived from a relativistic mean field model, which is a variant of the non-linear Walecka model. The expansion of the Euler and continuity equations of relativistic hydrodynamics around equilibrium configurations leads to differential equations for the density perturbation. We solve them numerically for linear and spherical perturbations and follow the propagation of the initial pulses. For linear perturbations we find single soliton solutions and solutions with one or more solitons followed by ""radiation"". Depending on the equation of state a strong damping may occur. We consider also the evolution of perturbations in a medium without dispersive effects. In this case we observe the formation and breaking of shock waves. We study all these equations also for matter at finite temperature. Our results may be relevant for the analysis of RHIC data. They suggest that the shock waves formed in the quark gluon plasma phase may survive and propagate in the hadronic phase. (C) 2009 Elseiver. B.V. All rights reserved.
Resumo:
We study the production of D (sJ) (2317) mesons in relativistic heavy ion collisions using the quark coalescence model. The predicted D (sJ) (2317) abundance depends sensitively on the quark structure of the D (sJ) (2317) meson. We have also evaluated the absorption cross sections of the D (sJ) (2317) meson by pi, rho, kaon and K* in a phenomenological hadronic model. We find that the final yield of D (sJ) (2317) mesons remains sensitive to its initial number produced from the quark-gluon plasma, providing thus the possibility of studying the quark structure of the D (sJ) (2317) meson and its production mechanism in relativistic heavy ion collisions.