Os livros brancos da defesa da República Popular da China 1998-2010

Este estudo é uma análise da evolução das perceções de (in)segurança da República Popular da China (RPC), através da aferição quantitativa e qualitativa de expressões idiomáticas caracterizadoras da evolução do sistema internacional, as quais foram selecionadas e associadas a tais perceções, e que constam das sete edições do Livro Branco da Defesa publicadas pelo Conselho de Estado entre 1998 e 2010. Procura-se através de um enquadramento conceptual e metodológico derivado da análise crítica do discurso baseado nas teorias de Michel Foucault e de Norman Fairclough, bem como do da perceção de ameaças por parte dos Estados no sistema internacional formulado por Robert Jervis, identificar e justificar variações nas perceções de (in)segurança da RPC entre 1998 e 2010, concluindo-se que estas refletem uma visão de natureza essencialmente realista estrutural e Lockeana quanto à evolução do sistema internacional

Safety and on-treatment efficacy of telaprevir: the early access programme for patients with advanced hepatitis C

Background and aim Severe adverse events (AEs) compromise the outcome of direct antiviral agent-based treatment in patients with advanced liver fibrosis due to HCV infection. HEP3002 is an ongoing multinational programme to evaluate safety and efficacy of telaprevir (TVR) plus pegylated-interferon-alpha (PEG-IFN alpha) and ribavirin (RBV) in patients with advanced liver fibrosis caused by HCV genotype 1 (HCV-1).Methods 1782 patients with HCV-1 and bridging fibrosis or compensated cirrhosis were prospectively recruited from 16 countries worldwide, and treated with 12 weeks of TVR plus PEG-IFN/RBV, followed by 12 or 36 weeks of PEG-IFN and RBV (PR) alone dependent on virological response to treatment and previous response type.Results 1587 patients completed 12 weeks of triple therapy and 4 weeks of PR tail (53% cirrhosis, 22% HCV-1a). By week 12, HCV RNA was undetectable in 85% of naives, 88% of relapsers, 80% of partial responders and 72% of null responders. Overall, 931 patients (59%) developed grade 1-4 anaemia (grade 3/4 in 31%), 630 (40%) dose reduced RBV, 332 (21%) received erythropoietin and 157 (10%) were transfused. Age and female gender were the strongest predictors of anaemia. 64 patients (4%) developed a grade 3/4 rash. Discontinuation of TVR due to AEs was necessary in 193 patients (12%). Seven patients died (0.4%, six had cirrhosis).Conclusions in compensated patients with advanced fibrosis due to HCV-1, triple therapy with TVR led to satisfactory rates of safety, tolerability and on-treatment virological response with adequate managements of AEs.Janssen PharmaceuticsUniv Milan, Div Gastroenterol, Dept Med, Fdn IRCCS Ca Granda Osped Maggiore Policlin, Milan, ItalyHosp Univ 12 Octubre, Secc Aparato Digest, Madrid, SpainIM Sechenov First Moscow State Med Univ, EM Tareev Clin Nephrol Internal & Occupat Med, Moscow, RussiaUniversidade Federal de São Paulo, Viral Hepatitis Div Infect Dis, Outpatient Clin HIV, São Paulo, BrazilUniv Sydney, Royal Prince Alfred Hosp, AW Morrow Gastroenterol & Liver Ctr, Sydney, NSW 2006, AustraliaCharles Univ Prague, Fac Med 1, Dept Internal Med, Prague, Czech RepublicCent Mil Hosp Prague, Prague, Czech RepublicUniv Libre Brussels, Dept Gastroenterol Hepatopancreatol & Digest Onco, Erasme Univ Hosp, Liver Unit, Brussels, BelgiumCarol Davila Univ Med & Pharm, Natl Inst Infect Dis, Bucharest, RomaniaJanssen Pharmaceut, B-2340 Beerse, BelgiumJanssen Pharmaceut, Paris, FranceJanssen Res & Dev, Titusville, NJ USAJanssen Res & Dev, High Wycombe, Bucks, EnglandJanssen Cilag AG, Zug, SwitzerlandHannover Med Sch, D-30623 Hannover, GermanyUniversidade Federal de São Paulo, Viral Hepatitis Div Infect Dis, Outpatient Clin HIV, São Paulo, BrazilWeb of Scienc

Prevention and treatment for mucositis in bone marrow grafted patients: a systematic review and meta-analysis

Universidade Federal de São Paulo, São Paulo, BrazilUniversidade Federal de São Paulo, Brazilian Cochrane Ctr, São Paulo, BrazilUniversidade Federal de São Paulo, EPM, São Paulo, BrazilUniversidade Federal de São Paulo, Brazilian Cochrane Ctr, São Paulo, BrazilWeb of Scienc

Jacaranone Induces Apoptosis in Melanoma Cells via ROS-Mediated Downregulation of Akt and p38 MAPK Activation and Displays Antitumor Activity in Vivo

Background: Malignant melanoma is a deadly type of metastatic skin cancer with increased incidence over the past 30 years. Despite the advanced knowledge on the biology, immunobiology and molecular genetics of melanoma, the alternatives of treatment are limited with poor prognosis. On clinical trials, natural products and among them redox-active quinones have been tested in the attempt to control the growth of cancer cells. Recently, we isolated jacaranone from Pentacalia desiderabilis, a benzoquinone derivative that showed a broad antitumor activity and protective anti-melanoma effect in a syngeneic model. the purified substance is active at micromolar concentrations, is not hemolytic, and is not toxic in naive mice.Methodology/Principal Findings: the jacaranone antitumor activity was shown against several human cancer cell lines in vitro. Moreover, the induction of apoptosis in murine melanoma cells and jacaranone antitumor activity in vivo, in a melanoma experimental model, were also shown. Jacaranone renders antiproliferative and proapoptotic responses in tumor cells, by acting on Akt and p38 MAPK signaling pathways through generation of reactive oxygen species (ROS). the free radical scavenger N-acetyl-cysteine (NAC) was able to completely suppress cell death induced by jacaranone as it blocked Akt downregulation, p38 MAPK activation as well as upregulation of proapoptotic Bax. Notably, treatment of melanoma growing subcutaneously in mice with jacaranone significantly extended the mean survival times in a dose-dependent manner.Conclusions/Significance: the results provide evidence for the mechanisms of action of jacaranone and emphasize the potential use of this quinone for the treatment of melanoma

Natterins, a new class of proteins with kininogenase activity characterlized from Thalassophryne nattereri fish venom

A novel family of proteins with kininogenase activity and unique primary structure was characterized using combined pharmacological, proteomic and transcriptomic approaches of Thalassophryne nattercri fish venom. the major venom components were isolated and submitted to bioassays corresponding to its main effects: nociception and edema. These activities were mostly located in one fraction (MS3), which was further fractionated. the isolated protein, named natterin, was able to induce ederna, nociception and cleave human kininogen and kininogen-derived synthetic peptides, releasing kallidin (Lys-bradykinin). the enzymatic digestion was inhibited by kallikrein inhibitors as Trasylol and TKI. Natterin N-terminal peptide showed no similarity with already known proteins present in databanks. Primary structure of natterin was obtained by a transcriptomic approach using a representative cDNA library constructed from T nattereri venom glands. Several expressed sequence tags (ESTs) were obtained and processed by biomformatics revealing a major group (18%) of related sequences unknown to gene or protein sequence databases. This group included sequences showing the N-terminus of isolated natterin and was named Natterin family. Analysis of this family allowed us to identify five related sequences, which we called natterin 1-4 and P. Natterin I and 2 sequences include the N-terminus of the isolated natterin. Furthermore, internal peptides of natterin 1-3 were found in major spots of whole venom submitted to mass spectrometry/2DGE. Similarly to the ESTs, the complete sequences of natterins did not show any significant similarity with already described tissue kallikreins, kininogenases or any proteinase, all being entirely new. These data present a new task for the knowledge of the action of kininogenases and may help in understanding the mechanisms of T nattereri fish envenoming, which is an important medical problem in North and Northeast of Brazil. (C) 2005 Elsevier SAS. All rights reserved.Inst Butantan, Lab Imunopatol, BR-05503900 São Paulo, BrazilIPEN, CNEN SP, São Paulo, BrazilUniversidade Federal de São Paulo, São Paulo, BrazilUniv Virginia, Charlottesville, VA USAFiocruz MS, BR-21045900 Rio de Janeiro, BrazilUniversidade Federal de São Paulo, EPM, São Paulo, BrazilWeb of Scienc

Effect of pH on the Clarification of Stevia rebaudiana Bertoni Extract Using Alginate Beads

Stevia rebaudiana Bertoni is plant used for producing a natural sweetener. After extraction from leaves, stevia extract is dark in colour and must be clarified for better acceptance by consumers. Adsorption processes are widely employed in the clarification because they do not use organic solvents. In the present work, the use of alginate beads as an adsorbent was investigated. Experiments were carried out in a batch system in which the aqueous stevia extract was mixed with the alginate beads previously prepared by ionotropic gelation. The effect of pH on the adsorption process was evaluated and the performance of the beads was examined by colorimetric analysis (colour removal, turbidity removal and adsorption of stevia steviol glycosides), as well as by refractive analysis for determining the adsorption of soluble solids. The results showed that the alginate beads were capable of adsorbing both the stevia steviol glycosides and the pigments that colour the extract. The best results were observed at a pH value of 2.0.Univ Fed Sao Paulo, BR-09972270 Sao Paulo, BrazilUniv Estadual Oeste Parana, BR-85903000 Toledo, Parana, BrazilUniv Fed Sao Paulo, BR-09972270 Sao Paulo, BrazilWeb of Scienc

Anti-malarial, anti-trypanosomal, and anti-leishmanial activities of jacaranone isolated from Pentacalia desiderabilis (Vell.) Cuatrec. (Asteraceae)

Leishmaniasis, Chagas disease, and malaria affect the poorest population around the world, with an elevated mortality and morbidity. in addition, the therapeutic alternatives are usually toxic or ineffective drugs especially those against the trypanosomatids. in the course of selection of new anti-protozoal compounds from Brazilian flora, the CH2C12 phase from MeOH extract obtained from the leaves of Pentacalia desiderabilis (Vell.) Cuatrec. (Asteraceae) showed in vitro anti-leishmanial, anti-malarial, and anti-trypanosomal activities. the chromatographic fraction-ation of the CH2C12 phase led to the isolation of the bioactive compound, which was characterized as jacaranone [ methyl (1-hydroxy-4-oxo-2,5-cyclohexandienyl) acetate], by spectroscopic methods. This compound showed activity against promastigotes of Leishmania (L.) chagasi, Leishmania (V.) braziliensis, and Leishmania (L.). amazonensis showing an IC50 of 17.22, 12.93, and 11.86 mu g/mL, respectively. Jacaranone was also tested in vitro against the Trypanosoma cruzi trypomastigotes and Plasmodium falciparum chloroquine-resistant parasites (K1 strain) showing an IC50 of 13 and 7.82 mu g/mL, respectively, and was 3.5-fold more effective than benznidazole in anti-Trypanosoma cruzi assay. However, despite of the potential against promatigotes forms, this compound was not effective against amastigotes of L. (L.) chagasi and T. cruzi. the cytotoxicity study using Kidney Rhesus monkey cells, demonstrated that jacaranone showed selectivity against P. falciparum (21.75 mu g/mL) and a selectivity index of 3. the obtained results suggested that jacaranone, as other similar secondary metabolites or synthetic analogs, might be useful tolls for drug design for in vivo studies against protozoan diseases.MACKPESQUISAConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Univ Presbiteriana Mackenzie, Ctr Ciencias & Humanidades, BR-01302907 São Paulo, BrazilUniv Presbiteriana Mackenzie, Ctr Ciencias Biol & Saude, BR-01302907 São Paulo, BrazilInst Adolfo Lutz Registro, Lab Toxinol Aplicada Farmacos Antiparasitarios, Dept Parasitol, BR-01246000 São Paulo, BrazilNucl Estudos Malaria, BR-05403000 São Paulo, BrazilUniversidade Federal de São Paulo, Inst Ciencias Ambientais Quim & Farmaceut, BR-09972270 Diadema, SP, BrazilUniversidade Federal de São Paulo, Inst Ciencias Ambientais Quim & Farmaceut, BR-09972270 Diadema, SP, BrazilCNPq: 473405/2008-3CNPq: 477422/2009-8FAPESP: 06/57626-5FAPESP: 08/11496-9Web of Scienc