885 resultados para Inducers of resistance


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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

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The goal of treatment of chronic hepatitis C is to achieve a sustained virological response, which is defined as exhibiting undetectable hepatitis C virus (HCV) RNA levels in serum following therapy for at least six months. However, the current treatment is only effective in 50% of patients infected with HCV genotype 1, the most prevalent genotype in Brazil. Inhibitors of the serine protease non-structural protein 3 (NS3) have therefore been developed to improve the responses of HCV-infected patients. However, the emergence of drug-resistant variants has been the major obstacle to therapeutic success. The goal of this study was to evaluate the presence of resistance mutations and genetic polymorphisms in the NS3 genomic region of HCV from 37 patients infected with HCV genotype 1 had not been treated with protease inhibitors. Plasma viral RNA was used to amplify and sequence the HCV NS3 gene. The results indicate that the catalytic triad is conserved. A large number of substitutions were observed in codons 153, 40 and 91; the resistant variants T54A, T54S, V55A, R155K and A156T were also detected. This study shows that resistance mutations and genetic polymorphisms are present in the NS3 region of HCV in patients who have not been treated with protease inhibitors, data that are important in determining the efficiency of this new class of drugs in Brazil.

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background. The prevalence of resistance to imipenem and ceftazidime among Pseudomonas aeruginosa isolates is increasing worldwide.objective. Risk factors for nosocomial recovery ( defined as the finding of culture- positive isolates after hospital admission) of imipenemresistant P. aeruginosa ( IRPA) and ceftazidime- resistant P. aeruginosa ( CRPA) were determined.design. Two separate case- control studies were conducted. Control subjects were matched to case patients ( ratio, 2: 1) on the basis of admission to the same ward at the same time as the case patient. Variables investigated included demographic characteristics, comorbid conditions, and the classes of antimicrobials used.setting. The study was conducted in a 400- bed general teaching hospital in Campinas, Brazil that has 14,500 admissions per year. Case patients and control subjects were selected from persons who were admitted to the hospital during 1992 - 2002.results. IRPA and CRPA isolates were obtained from 108 and 55 patients, respectively. Statistically significant risk factors for acquisition of IRPA were previous admission to another hospital ( odds ratio [ OR], 4.21 [ 95% confidence interval {CI}, 1.40- 12.66];), hemodialysis Pp. 01 ( OR, 7.79 [ 95% CI, 1.59- 38.16];), and therapy with imipenem ( OR, 18.51 [ 95% CI, 6.30- 54.43];), amikacin ( OR, 3.22 Pp. 01 P !.001 [ 95% CI, 1.40- 7.41];), and/ or vancomycin ( OR, 2.48 [ 95% CI, 1.08- 5.64];). Risk factors for recovery of CRPA were Pp. 005 Pp. 03 previous admission to another hospital ( OR, 18.69 [ 95% CI, 2.00- 174.28];) and amikacin use ( OR, 3.69 [ 95% CI, 1.32- 10.35]; Pp. 01). Pp. 01conclusion. Our study suggests a definite role for several classes of antimicrobials as risk factors for recovery of IRPA but not for recovery of CRPA. Limiting the use of only imipenem and ceftazidime may not be a wise strategy to contain the spread of resistant P. aeruginosa strains.

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O uso de cateter intermitente representa um procedimento muito utilizado em ambiente hospitalar. Este estudo, de natureza experimental, teve como propósito a análise comparativa entre o cateter intermitente, preenchido com solução de heparina 100 U/ml e o preenchido com soro fisiológico 0,9%. Foi realizado um estudo comparativo, avaliando a formação de coágulos e se estes estivessem presentes seriam quantificados. Para tanto, foram utilizados quatro grupos de 7 coelhos, da linhagem Norfolk, sendo realizado acesso venoso em veia auricular conectado ao dispositivo de infusão múltipla. em dois destes grupos, foi usada solução salina; em um grupo, caso fosse encontrada resistência, esta seria forçada; no outro, esta resistência não seria forçada. Nos dois outros grupos, foi usada solução de heparina; em um grupo, caso fosse encontrada resistência, esta seria forçada; no outro esta resistência não seria forçada. O cateter intermitente foi mantido por 72 horas e, a cada 12 horas foi infundida água destilada, simulando a administração de medicamento. Durante o experimento foram observadas as seguintes variáveis: presença da formação de coágulos, comprimento do coágulo, peso fresco do coágulo, peso seco do coágulo, contagem plaquetária e desconforto. Na análise estatística feita pelo método não paramétrico Kruskal-Wallis, com nível de significância de sigma = 5%, não foi encontrada diferença significativa entre os grupos e momentos. Pôde-se constatar a presença de formação de coágulo em todos os grupos independentemente da solução de preenchimento. Concluímos, principalmente, que há necessidade de elaboração de novas normas e rotinas na utilização de cateter intermitente.

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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

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A inflamação ocular é uma das principais causas de perda visual e cegueira. As uveítes constituem um grupo complexo e heterogêneo de doenças caracterizadas por inflamação dos tecidos intraoculares. O olho pode ser o único órgão envolvido ou a uveíte pode ser parte de uma doença sistêmica. A etiologia é desconhecida em um número significativo de casos, que são considerados idiopáticos. Modelos animais têm sido desenvolvidos para estudar a fisiopatogênese da uveíte autoimune devido às dificuldades na obtenção de tecidos de olhos humanos inflamados para experimentos. Na maioria desses modelos, que simulam as uveítes autoimunes em humanos, a uveíte é induzida com proteínas específicas de fotorreceptores (antígeno-S, proteína ligadora de retinoide do interfotoreceptor, rodopsina, recoverina e fosducina). Antígenos não retinianos, como proteínas associadas à melanina e proteína básica de mielina, são também bons indutores de uveíte em animais. Entender os mecanismos básicos e a patogênese dessas doenças oculares é essencial para o desenvolvimento de novas formas de tratamento das uveítes autoimunes e de novos agentes terapêuticos. Nesta revisão serão abordados os principais modelos experimentais utilizados para o estudo de doenças inflamatórias oculares autoimunes.

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Dengue and dengue hemorrhagic fever, vector-borne diseases transmitted by the mosquito Aedes aegypti, are presently important public health problems in Brazil. As the strategy for disease control is based on vector control through the use of insecticides, the development of resistance is a threat to programs efficacy. The objective of this study was to compare the Aedes aegypti susceptibility in nine vector populations from the state of São Paulo and seven from Northeast region of Brazil, since there was a difference on group of insecticide used between the areas. Bioassays with larvae and adult were performed according to the World Health Organization methods.The results showed higher resistance levels to organophosphates group in populations from the Northeast region where this group was used for both larvae and adult control than in São Paulo where organophosphates were used for larvae and pyretroids for adult control. Resistance to pyretroids in adults was widespread in São Paulo after ten years of use of cypermethrin while in vector populations from the Northeast region it was punctual. The difference in resistance profile between the areas is in accordance to the group of insecticide used.

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

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Objective. To evaluate the content of inorganic particles and the flexural strength of new condensable composites for posterior teeth in comparison to hybrid conventional composites.Method. The determination of the content of inorganic particles was performed by mass weighing of a polymerized composite before and after the elimination of the organic phase. The volumetric particle content was determined by a practical method based on Archimedes' principle, which calculates the volume of the composite and their particles by differential mass measured in the air and in water. The flexural. strength of three points was evaluated according to the norm ISO 4049:1988.Results. The results showed the following filter content: Alert, 67.26%; Z-100, 65.27%; Filtek P 60, 62.34%; Ariston pHc, 64.07%; Tetric Ceram, 57.22%; Definite, 54.42%; Solitaire, 47.76%. In the flexural strength test, the materials presented the following decreasing order of resistance: Filtek P 60 (170.02 MPa) > Z-100 (151.34 MPa) > Tetric Ceram (126.14 MPa) = Alert (124.89 MPa) > Ariston pHc (102.00 MPa) = Definite (93.63 MPa) > Solitaire (56.71 MPa).Conclusion. New condensable composites for posterior teeth present a concentration of inorganic particles similar to those of hybrid composites but do not necessarily present higher flexural strength. (C) 2003 Elsevier B.V. Ltd. Alt rights reserved.

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Late leaf spot (LLS), caused by the fun.-us Cercosporidium personatum, is one of the most severe diseases in peanut (Arachis hypogaea). The vast majority of commercial cultivars do not exhibit satisfactory levels of resistance to the pathogen, whereas non-commercial genotypes cv. 850 and cv. 909 are resistant to LLS and show symptoms similar to hypersensitive response (HR) lesions. In the present study, we investigated the molecular components of the initial stages of the resistance by gene expression profiling using suppression subtractive hybridization and differential screening of cDNA macroarray techniques. Gene expression analyses have allowed us to identify more than 700 peanut unique expressed sequence taus (EST) involved in several aspects of the early stages of C. personatum pathogenesis, such as components of defense signaling pathways, gene expression regulators, cell cycle controlling genes and components of the biosynthesis of transducer and antimicrobial compounds. The most significantly induced gene corresponds to a novel O'-methyltranferase, suggesting its involvement in the production of local lesions in C. personatum-resistant A. hypogea genotypes. Taken together, our results contribute to elucidate the defense strategies of peanut and provide the framework for the generation of pathogen-resistant peanut cultivars. (C) 2007 Elsevier B.V. All rights reserved.

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Staphylococcus aureus is the main agent of infections during peritoneal dialysis (PD). The presence of S. aureus in the nasal cavity has been extensively studied and suggested as a risk factor of dialysis-related infections, whereas coagulase-negative Staphylococcus (CNS) species are frequently considered part of the normal human microbiota. The aim of this study was to identify Staphylococcus in the nasal cavity, pericatheter skin and peritoneal effluent from PD patients, as well as to evaluate the antimicrobial activity evolution in vitro. Thirty-two chronic PD patients were observed during 12 months and had nasal and pericatheter skin samples collected for culture. When peritonitis was detected, samples were also collected from the peritoneal effluent for culture. The activity of several antimicrobial drugs (penicillin G, oxacillin, cephalothin, ofloxacin, netilmicin and vancomycin) against different Staphylococcus species was measured by using the agar drug diffusion assay (Kirby-Bauer method). Staphylococcus was separated into S. aureus, S. epidermidis and other CNS species in order to determine the in vitro resistance level. S. epidermidis resistance to oxacillin progressively increased during the study period (p < 0.05). Resistance to ofloxacin was inexpressive, whereas resistance to netilmicin and vancomycin was not detected. of the oxacillin-resistant species (n = 74), 83% were S. epidermidis, 13% other CNS and 4% S. aureus (p < 0.05). Regarding multidrug resistant strains (n = 45), 82% were S. epidermidis, 13% other CNS, and 5% S. aureus (p < 0.05). This study shows the relevance of resistance to oxacillin and CNS multi-drug resistance, particularly concerning S. epidermidis, in PD patients.

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The present study evaluated Nelore cattle with different degrees of resistance to natural infections by gastrointestinal nematodes. One hundred weaned male cattle, 11-12 months of age, were kept on the same pasture and evaluated from October 2003 to February 2004. Faecal and blood samples were collected for parasitological, haematological and immunological tests. In February 2004, the 10 most resistant and the 10 most susceptible animals were selected based on individual means of nematode faecal egg counts (FEC). Such animals were slaughtered for worm burden determination and nematode species identification. The repeatability estimates for FEC (+/- S.D.), log-transformed FEC and packed-cell volume (PCV) in all animals were 0.3 (+/- 0.05), 0.26 (+/- 0.04) and 0.42 (+/- 0.05), respectively. The resistant group showed lower FEC and worm burdens than the susceptible group (P < 0.05). There were no significant differences between groups regarding mean body weight, weight gain, PCV and total serum protein values (P > 0.05). The resistant group showed higher total serum IgE levels (P < 0.05) and higher mean eosinophil blood counts. However, the latter was statistically significant only 42 days after the beginning of the study. Nematodes Cooperia punctata and Haemonchus placei were predominant and the correlation between Cooperia and Haemonchus burdens was 0.64 (P < 0.05), which indicated that animals presenting increased numbers of one of those genera probably had increased numbers of the other. The current study provides further evidence of IgE active role in nematode immunity and suggests that total serum IgE level might serve as an additional marker to select Nelore cattle that are responsive to H. placei and C. punctata infections. (C) 2007 Elsevier B.V. All rights reserved.

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The objective of this study was to determine the level of resistance of Haemonchus contortus and Trichostrongylus colubriformis in sheep to levamisole albendazole ivermectin moxidectin closantel and trichlorfon The parasites were isolated from sheep naturally infected by gastrointestinal nematodes and were then kept in monospecifically infected lambs for production of infective larvae (L3) of both species Forty-two lambs at three months of age were simultaneously artificially infected with 4000 L3 of H contortus and 4000 L3 of T colubriformis The animals were allocated Into seven groups with six animals each that received one of the following treatments Group 1-control no treatment Group 2-moxidectin (0 2 mg/kg body weight (BW)) Group 3-closantel (10 mg/kg BW) Group 4-trichlorfon (100 mg/kg BW) Group 5-levamisole phosphate (4 7 mg/kg BW) Group 6-albendazole (5 0 mg/kg BW) and Group 7-ivermectin (0 2 mg/kg BW) Nematode fecal egg counts (FEC) were carried out on the day of treatment and again at 3 7 10 and 14 days post-treatment on the same occasions composite fecal cultures were prepared for each group for production of L3 which were identified into genus The animals were sacrificed for worm counts at 14 days after treatment The efficacy of each treatment was calculated from the arithmetic mean of the FEC or worm burden of the treated group compared with the values of the control group Only trichlorfon and moxidectin treatments resulted in a significant reduction of H contortus recorded at necropsy (73% and 45% respectively) Moxidectin reduced T colubriformis worm burdens by 82% and albendazole by 19% All other anthelmintics resulted in no significant reduction in the numbers of worms found at necropsy In conclusion the Isolates of H contortus and T colubriformis showed multiple resistance to all groups of anthelmintics tested This is the first report based on the controlled efficacy test to show resistance of T colubriformis to macrocyclic lactones in Brazil (C) 2010 Elsevier B.V. All rights reserved