10 resultados para BENZOTHIOPYRANOINDAZOLE ANTICANCER ANALOGS

em Universidade Federal do Rio Grande do Norte(UFRN)


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TORRES, F ; FILHO, M.S. ; ANTUNES, C. ; KALININE, E. ; ANTONIOLLI, E. ; PORTELA, Luis Valmor ; SOUZA, Diogo Onofre ; TORT, A. B. L. . Electrophysiological effects of guanosine and MK-801 in a quinolinic acid-induced seizure model. Experimental Neurology , v. 221, p. 296-306, 2010

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Heparan sulfate (HS) and Heparin (Hep) glycosaminoglycans (GAGs) are heterogeneous and highly charged polysaccharides. HS is structurally related to Hep but is much less substituted with sulfo groups than heparin and has a more varied structure (or sequence). Because of structural similiarities between these two polymers, they have been described together as heparinoids . Both chains bind a variety of proteins and mediate various physiologically important processes including, blood coagulation, cell adhesion and growth factor regulation. Heparinoids with structural characteristics similar to these described from HS and/or Hep from mammalian tissues have been isolated from different species of invertebrates, although only a few heparinoids from unusual sources have been characterized. The present study describes the presence of unusual heparinoids population from Artemia franciscana, isolated after proteolysis and fractionation by ion exchange resin and named, F-3.0M. The study model in vivo were hemostasis (rat tail scarification) and inflamatoty activity. The tests in vitro were used for coagulations assays (PT and APTT). The analyse of the heparinoids eluted with 3,0M NaCl showed electrophoretic migration in different buffer systems a single band with a behaviour intermediate between those of mammalian HEP and HS. The main products obtained from Artemia heparinoids after enzymatic degradation with heparitinases I and II from F. heparinum were N-sulphated disaccharides (∆U-GlcNS,6S/ ∆U,2S-GlcNS and ∆U-GlcNS) and N-acetylated disaccharides (∆U, GlcNAc). This heparinoid had a lower hemorrhagic effect (400μg/ml) when compared to unfractiionated heparins(25μg/ml).The results also suggest a negligible APTT activity of this heparinoid (62.2s). No action was observed on PT indicating that F-3.0M haven t action on the extrinsic pathway. The results showed that the fraction F- 3.0M have inhibitory effect on migration of leukocytes, 64.5% in the concentration of 10 μg/ml (P<0.001). The search for new heparin and/or heparan sulphates analogs devoid of anticoagulant activity is an atractive alternative and may open up a wide variety of new therapeutic applications

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The species of the genus Marsdenia, Apocynaceae, are widely used in folk medicine of several countries. In Brazil is found several species belonging to this genus. The in vitro antioxidant, anticoagulant and antiproliferative activities were evaluated to aqueous extracts of stalk, leaf and root of Marsdenia megalantha. In the total antioxidant capacity assay (expressed as ascorbic acid equivalents) the stalk extract showed 76.0 mg/g, while leaf and root extracts 141.3 mg/g and 57.0 mg/g, respectively. The stalk and leaf extracts showed chelating activity around 40% at 1.5 mg/mL, while root extract, at the same concentration showed, 17%. Only the leaf extract showed a significant ability in superoxide scavenging (80% at 0.8 mg/mL). Any extract was able in scavenge hydroxyl, as well anticoagulant activity. The antiproliferative activity of the extracts was evaluated against HeLa tumor cell line. The extracts inhibited in a dose-dependent manner the cell growth. However, the leaf extract showed 80% of inhibition at 1.0 mg/mL, while stalk and root extracts inhibited 63% and 30%, respectively. To assess the mechanism of cell death caused by the leaf extract in HeLa, was performed flow cytometry and western blot. The results show that leaf extract induces cell death by apoptosis through an activation caspase-independent pathway. These data indicate that stalk and leaf extracts obtained have potential to be used as antioxidants and anticancer drugs

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The drug targeting has been the subject of extensive studies in order to develop site-specific treatments that minimize side effects and become more effective anticancer therapy. Despite considerable interest in this class, drugs like antibiotics also have limitations, and have been neglected. Using new pharmaceutical technologies, the use of magnetic vectors appear as promising candidate for drug delivery systems in several studies. Small magnetic particles bound to the drug of interest can be modulated according to the orientation of a magnet outside the body, locating and holding in a specific site. In this work, we propose the use of High Energy Milling (HEM) for synthesis of a magnetic vector with characteristics suitable for biomedical applications by intravenous administration, and for the formation of an oxacillin-carrier complex to obtain a system for treating infections caused by Staphylococcus aureus. The results of the variation of milling time showed that the size and structural properties of the formed material change with increasing milling time, and in 60 hours we found the sample closest to the ideal conditions of the material. The vector-drug system was studied in terms of structural stability and antimicrobial activity after the milling process, which revealed the integrity of the oxacillin molecule and its bactericidal action on cultures of Staphylococcus aureus ATCC

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The 1988 Federal Constitution of Brazil by presenting the catalog of fundamental rights and guarantees (Title II) provides expressly that such rights reach the social, economic and cultural rights (art. 6 of CF/88) as a means not only to ratify the civil and political rights, but also to make them effective and practical in the life of the Brazilian people, particularly in the prediction of immediate application of those rights and guarantees. In this sense, health goes through condition of universal right and duty of the State, which should be guaranteed by social and economic policies aimed at reducing the risk of disease and other hazards, in addition to ensuring universal and equal access to actions and services for its promotion, protection and recovery (Article 196 by CF/88). Achieving the purposes aimed by the constituent to the area of health is the great challenge that requires the Health System and its managers. To this end, several policies have been structured in an attempt to establish actions and services for the promotion, protection and rehabilitation of diseases and disorders to health. In the mid-90s, in order to meet the guidelines and principles established by the SUS, it was established the Política Nacional de Atenção Oncológica PNAO, in an attempt to sketch out a public policy that sought to achieve maximum efficiency and to be able to give answers integral to effective care for patients with cancer, with emphasis on prevention, early detection, diagnosis, treatment, rehabilitation and palliative care. However, many lawsuits have been proposed with applications for anticancer drugs. These actions have become very complex, both in the procedural aspects and in all material ones, especially due to the highcost drugs more requested these demands, as well as need to be buoyed by the scientific evidence of these drugs in relation to proposed treatments. The jurisprudence in this area, although the orientations as outlined by the Parliament of Supreme Court is still in the process of construction, this study is thus placed in the perspective of contributing to the effective and efficient adjudication in these actions, with focus on achieving the fundamental social rights. Given this scenario and using research explanatory literature and documents were examined 108 lawsuits pending in the Federal Court in Rio Grande do Norte, trying to identify the organs of the Judiciary behave in the face of lawsuits that seeking oncology drugs (or antineoplastic), seeking to reconcile the principles and constitutional laws and infra constitutional involving the theme in an attempt to contribute to a rationalization of this judicial practice. Finally, considering the Rational Use of health demands and the idea of belonging to the Brazilian people SUS, it is concluded that the judicial power requires ballast parameters of their decisions on evidence-based medicine, aligning these decisions housing constitutional principles that the right to health and the scientific conclusions of efficacy, effectiveness and efficiency in oncology drugs, when compared to the treatments offered by SUS

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The study physical process that control the stellar evolution is strength influenced by several stellar parameters, like as rotational velocity, convective envelope mass deepening, and magnetic field intensity. In this study we analyzed the interconnection of some stellar parameters, as Lithium abundance A(Li), chromospheric activity and magnetic field intensity as well as the variation of these parameters as a function of age, rotational velocity, and the convective envelope mass deepening for a selected sample of solar analogs and twins stars. In particular, we analyzed the convective envelope mass deepening and the dispersion of lithium abundance for these stars. We also studied the evolution of rotation in subgiants stars, because its belong to the following evolutionary stage of solar analogs, and twins stars. For this analyze, we compute evolutionary models with the TGEC code to derive the evolutionary stage, as well as the convective envelope mass deepening, and derive more precisely the stellar mass, and age for this 118 stars. Our Investigation shows a considerable dispersion of lithium abundance for the solar analogs stars. We also realize that this dispersion is not by the convective zone deep, in this way we observed which the scattering of A(Li) can not be explained by classical theories of mixing in the convective zone. In conclusion we have that are necessary extra-mixing process to explain this decrease of Lithium abundance in solar analogs and twins stars. We analyzed the subgiant stars because this are the subsequent evolutionary stage after the solar analogs and twins stars. For this analysis, we compute the rotational period for 30 subgiants stars observed by Co- RoT satellite. For this task we apply two different methods: Lomb-Scargle algorithm, and the Plavchan Periodogram. We apply the TGEC code we compute models with internal distribution of angular momentum to confront the predict results with the models, and the observational results. With this analyze, we showed which solid body rotation models are incompatible with the physical interpretation of observational results. As a result of our study we still concluded that the magnetic field, convective envelope mass deepening, and internal redistribution of angular momentum are essential to explain the evolution of low-mass stars, and its observational characteristics. Based on population synthesis simulation, we concluded that the solar neighborhood presents a considerable quantity of solar twins when compared with the discovered set nowadays. Altogether we foresee the existence around 400 solar analogs in the solar neighborhood (distance of 100 pc). We also study the angular momentum of solar analogs and twins, in this study we concluded that added angular momentum from a Jupiter type planet, putted in the Jupiter position, is not enough to explain the angular momentum predicted by Kraft law (Kraft 1970)

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The study of solar-type stars also includes the familiar solar analogs and twins. These objects have been one of the major research subjects in astrophysics nowadays. A direct comparison of solar activity with chromospheric activity indices for a set of stars very similar to the Sun (twins and analogs) provides an excellent opportunity to study the evolution of stellar activity on timescales of the order of the lifetime on the main sequence. This work deals with the relationship between the abundance of lithium, chromospheric activity, X-ray emission and rotation period in terms of stellar ages. We explore the influence of stellar evolution in the global properties of the stars and the aspects linked to its coronal, chromospheric and magnetic activity. Our main objective is to probe the law of decay of each of these parameters based on a sample of stars classified as well-connected as analogs stars and solar twins.

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Matrix metalloproteinase-7 (MMP-7) and -9 (MMP-9) modulate important functions strictly related to the development, invasion and metastasis of several human cancers among them the squamous cell carcinoma of the tongue (SCCT). However, individual genetic factors such as the functional single nucleotide polymorphisms (SNPs) influence the pattern of protein expression of these MMPs and thus may be related to the variability observed in the clinical behavior of patients with SCCT. In this context, the present cross-sectional study aimed to evaluate the association between the frequency of the functional SNPs MMP-7 -181 A/G and MMP-9 -1562 C/T and the clinical (age, gender and metastasis) and pathological (malignancy histological grading and immunohistochemistry expression) features of SCCT cases. Genotyping of these SNPs were performed by PCR-RFLP on DNA samples from 71 cases of SCCT and 60 individuals without cancer who constitute the control group. Among the results of this research, it was observed that the frequency of the polymorphic alleles MMP-7 -181 G and MMP-9 -1562 T in SCCT patients was 28% and 12%, respectively, and the frequency of the heterozygotes A/G (PR = 2.00; p < 0.001) and C/T (PR = 1.54; p = 0.014) were significantly higher in the patient group than in the controls. The prevalence of patients carrying the combination of SNPs studied was significantly associated with SCCT cases (PR = 2.00; p = 0.011) and metastasis (PR = 2.00; p < 0.001). Furthermore, with the frequency of SNPs analyzed, the age, gender, histological grading and immunoreactivity of MMP-7 and MMP-9 formed clinical and pathological parameters relevant to the identification of population subgroups more related to the development of SCCT and metastasis. Based on these results, it is suggested that the protein expression levels of MMP-7 and -9 substantially influence the balance between their pro- and anticancer biological functions and hence the clinicopathological profile of the squamous cell carcinoma of the tongue

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This study proposes an observing program focused on the investigation of the stellar magnetism and dynamo evolution in cool active solar-like stars. More mainly in the solar analogs and twins. Observations of stars of our base were carried out with two spectropolarimeter (ESPaDOnS@CFHT and NARVAL@TBL). The analyse of stars in stage different allows an understanding of the dependence of magnetic activity on basic stellar parameters such as rotation, mass, age and depth of the convection zone. This study provides measures necessary for testing dynamo theories. The 65 targets for this project are solar type stars with mass spanning from 0:9 M=Mfi 1:075 solar masses and at different evolutionary stages. Our two main science objectives were, (i) To determine how the magnetic field evolved from the ZAMS to the TO (turn off) for stars with 0:9 M=Mfi 1:075; (ii) To determine the impact of convective depth and rotation on magnetic of cool stars of solar type. The main result from this study was the characterization of the dependence of magnetic field intensity as function of age, Rossby number and the convective zone deepening. This context, the availability of ESPaDOnS and NARVAL opens an exceptional possibility to study the magnetic properties of Sun-like stars by means of spectropolarimetric observations

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In the current work are presented the results about the study of digital mapping of analogs referents the fluvial oil reservoirs in the Açu Formation. With the regional recognizing in the south corner of Potiguar Basin was selected a area of 150 Km square in the west of Assu city. In this area was chosen the outcrops for the digital mapping and from the data fields and remote sensors were done the depositional architectural for the fluvial deposits, which it was named coarse meandering fluvial systems. In the deposits were individualized 3 (three) fluvial cycles, which they was separated by bounding surface of fifth order. Such cycles are preferentially sandy, with fining-upward sequence finished in flood plain deposits. Inner of the sandy levels of the filling channels were characterized least cycles, normaly incomplete, constituted by braided sandy bodies and bounding surfaces of fourth order. In the mapped area was chosen a outcrop with great exposition, where it was possible to see tipical deposits of filling channel and was in this outcrop that was done the digital mapping. In this outcrop was used diverse technics and tools, which they integrated sedimentological, altimetric (GPS, Total Station), LIDAR (Light Detection and Ranging), digital photomosaic of high resolution and of the inner geometries (Ground Penetration Radar) data sets. For the integrating, interpretation and visualization of data was used software GoCAD®. The final product of the outcrop digital mapping was the photorealistic model of part of the cliff (or slope) because the observed reflectors in the radargrams were absents. A part of bar oblique accretion was modeled according to GPR gride of 200x200 meters in the alluvial Assu river probable recent analog. With the data of inner geometries was developed the three-dimentional sedimentary architectural, where it was possible characterize sand sheet deposits and many hierarchy of braided channels. At last, simulations of sedimentary geometries and architectures of the Potiguar Basin Fluvial Reservoirs were done with PetBool software, in order to understand the capacity of this program in simulations with a lot of numbers of conditioning wells. In total, 45 simulations was acquired, where the time and the channel numbers increase in relation of the conditioning wells quantity. The deformation of the meanders was detected from the change of simulated dominion dimensions. The presence of this problem was because the relationship between the simulated dominion and the width of the meander