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11.
Lúcia de Paula Célio L Silva Daniela Carlos Camila Matias-Peres Carlos A Sorgi Edson G Soares Patrícia RM Souza Carlos RZ Bladés Fábio CS Galleti Vânia LD Bonato Eduardo DC Gonçalves Érika VG Silva Lúcia H Faccioli 《Genetic vaccines and therapy》2007,5(1):1-7
The great challenges for researchers working in the field of vaccinology are optimizing DNA vaccines for use in humans or large animals and creating effective single-dose vaccines using appropriated controlled delivery systems. Plasmid DNA encoding the heat-shock protein 65 (hsp65) (DNAhsp65) has been shown to induce protective and therapeutic immune responses in a murine model of tuberculosis (TB). Despite the success of naked DNAhsp65-based vaccine to protect mice against TB, it requires multiple doses of high amounts of DNA for effective immunization. In order to optimize this DNA vaccine and simplify the vaccination schedule, we coencapsulated DNAhsp65 and the adjuvant trehalose dimycolate (TDM) into biodegradable poly (DL-lactide-co-glycolide) (PLGA) microspheres for a single dose administration. Moreover, a single-shot prime-boost vaccine formulation based on a mixture of two different PLGA microspheres, presenting faster and slower release of, respectively, DNAhsp65 and the recombinant hsp65 protein was also developed. These formulations were tested in mice as well as in guinea pigs by comparison with the efficacy and toxicity induced by the naked DNA preparation or BCG. The single-shot prime-boost formulation clearly presented good efficacy and diminished lung pathology in both mice and guinea pigs. 相似文献
12.
Carmen Fernandez-Becerra Joel Lelievre Mireia Ferrer Nuria Anton Richard Thomson Cristina Peligero Maria Jesus Almela Marcus VG Lacerda Esperanza Herreros Hernando A del Portillo 《Memórias do Instituto Oswaldo Cruz》2013,108(6):801-803
The production of fully functional human red cells in vitro from haematopoietic
stem cells (hHSCs) has been successfully achieved. Recently, the use of hHSCs
from cord blood represented a major improvement to develop the continuous
culture system for Plasmodium vivax. Here, we demonstrated that
CD34+hHSCs from peripheral blood and bone marrow can be expanded and
differentiated to reticulocytes using a novel stromal cell. Moreover, these
reticulocytes and mature red blood cells express surface markers for entrance of
malaria parasites contain adult haemoglobin and are also permissive to invasion
by P. vivax and Plasmodium falciparum
parasites. 相似文献
13.
Virus encoded RNA-silencing suppressors (RSSs) are the key components evolved by the viruses to counter RNA-silencing defense of plants. Whitefly-transmitted begomoviruses infecting tomato crop code for five different proteins, ORF AC4, ORF AC2 and ORF AV2 in DNA-A component, ORF BV1 in DNA-B and ORF βC1 in satellite DNA β which are predicted to function as silencing suppressors. In the present study suppressor function of ORF βC1 of three betasatellites Tomato leaf curl Bangalore betasatellite ToLCBB-[IN:Hess:08], Cotton leaf curl Multan betasatellite CLCuMB–[IN:Sri:02] and Luffa leaf distortion betasatellite LuLDB-[IN:Lu:04] were examined. Agroinfiltration of GFP-silenced Nicotiana tabaccum cv. Xanthi with the cells expressing βC1 protein resulted in reversal of silenced GFP expression. GFP-siRNA level was more than 50-fold lower compared to silenced plants in plants infiltrated with βC1 gene from ToLCBB. However, in the case of 35S-βC1 CLCuMB and 35S-βC1 LuLDB construct, although GFP was expressed, siRNA level was not reduced, indicating that the step at which βC1 interfere in RNA-silencing pathway is different. 相似文献
14.
Resistance of nicotiana benthamiana to phytophthora infestans is mediated by the recognition of the elicitor protein INF1 总被引:11,自引:0,他引:11 下载免费PDF全文
Phytophthora infestans, the agent of potato and tomato late blight disease, produces a 10-kD extracellular protein, INF1 elicitin. INF1 induces a hypersensitive response in a restricted number of plants, particularly those of the genus Nicotiana. In virulence assays with different P. infestans isolates, five Nicotiana species displayed resistance responses. In all of the interactions, after inoculation with P. infestans zoospores, penetration of an epidermal cell was observed, followed by localized necrosis typical of a hypersensitive response. To determine whether INF1 functions as an avirulence factor in these interactions, we adopted a gene-silencing strategy to inhibit INF1 production. Several transformants deficient in inf1 mRNA and INF1 protein were obtained. These strains remained pathogenic on host plants. However, in contrast to the wild-type and control transformant strains, INF1-deficient strains induced disease lesions when inoculated on N. benthamiana. These results demonstrate that the elicitin INF1 functions as an avirulence factor in the interaction between N. benthamiana and P. infestans. 相似文献
15.
Xin Hui S. Chan Ilsa L. Haeusler Yan Naung Win James Pike Borimas Hanboonkunupakarn Maryam Hanafiah Sue J. Lee Abdoulaye Djimd Caterina I. Fanello Jean-Ren Kiechel Marcus VG Lacerda Bernhards Ogutu Marie A. Onyamboko Andr M. Siqueira Elizabeth A. Ashley Walter RJ Taylor Nicholas J. White 《PLoS medicine》2021,18(9)
BackgroundAmodiaquine is a 4-aminoquinoline antimalarial similar to chloroquine that is used extensively for the treatment and prevention of malaria. Data on the cardiovascular effects of amodiaquine are scarce, although transient effects on cardiac electrophysiology (electrocardiographic QT interval prolongation and sinus bradycardia) have been observed. We conducted an individual patient data meta-analysis to characterise the cardiovascular effects of amodiaquine and thereby support development of risk minimisation measures to improve the safety of this important antimalarial.Methods and findingsStudies of amodiaquine for the treatment or prevention of malaria were identified from a systematic review. Heart rates and QT intervals with study-specific heart rate correction (QTcS) were compared within studies and individual patient data pooled for multivariable linear mixed effects regression.The meta-analysis included 2,681 patients from 4 randomised controlled trials evaluating artemisinin-based combination therapies (ACTs) containing amodiaquine (n = 725), lumefantrine (n = 499), piperaquine (n = 716), and pyronaridine (n = 566), as well as monotherapy with chloroquine (n = 175) for uncomplicated malaria. Amodiaquine prolonged QTcS (mean = 16.9 ms, 95% CI: 15.0 to 18.8) less than chloroquine (21.9 ms, 18.3 to 25.6, p = 0.0069) and piperaquine (19.2 ms, 15.8 to 20.5, p = 0.0495), but more than lumefantrine (5.6 ms, 2.9 to 8.2, p < 0.001) and pyronaridine (−1.2 ms, −3.6 to +1.3, p < 0.001). In individuals aged ≥12 years, amodiaquine reduced heart rate (mean reduction = 15.2 beats per minute [bpm], 95% CI: 13.4 to 17.0) more than piperaquine (10.5 bpm, 7.7 to 13.3, p = 0.0013), lumefantrine (9.3 bpm, 6.4 to 12.2, p < 0.001), pyronaridine (6.6 bpm, 4.0 to 9.3, p < 0.001), and chloroquine (5.9 bpm, 3.2 to 8.5, p < 0.001) and was associated with a higher risk of potentially symptomatic sinus bradycardia (≤50 bpm) than lumefantrine (risk difference: 14.8%, 95% CI: 5.4 to 24.3, p = 0.0021) and chloroquine (risk difference: 8.0%, 95% CI: 4.0 to 12.0, p < 0.001). The effect of amodiaquine on the heart rate of children aged <12 years compared with other antimalarials was not clinically significant. Study limitations include the unavailability of individual patient-level adverse event data for most included participants, but no serious complications were documented.ConclusionsWhile caution is advised in the use of amodiaquine in patients aged ≥12 years with concomitant use of heart rate–reducing medications, serious cardiac conduction disorders, or risk factors for torsade de pointes, there have been no serious cardiovascular events reported after amodiaquine in widespread use over 7 decades. Amodiaquine and structurally related antimalarials in the World Health Organization (WHO)-recommended dose regimens alone or in ACTs are safe for the treatment and prevention of malaria.In this meta-analysis, Xin Hui Supanee Chan and colleagues investigate the cardiovascular effects of amodiaquine and structurally-related antimalarials using individual patient data from trials. 相似文献
16.
Andre M Siqueira Janieldo A Cavalcante Shelia Vítor-Silva Roberto C Reyes-Lecca Aline C Alencar Wuelton M Monteiro Márcia AA Alexandre Mour?o Maria Paula G Caterina Guinovart Quique Bassat Maria das Gra?as C Alecrim Marcus VG Lacerda 《Memórias do Instituto Oswaldo Cruz》2014,109(5):569-576
Anaemia is amongst the major complications of malaria, a major public health problem
in the Amazon Region in Latin America. We examined the haemoglobin (Hb)
concentrations of malaria-infected patients and compared it to that of
malaria-negative febrile patients and afebrile controls. The haematological
parameters of febrile patients who had a thick-blood-smear performed at an infectious
diseases reference centre of the Brazilian Amazon between December 2009-January 2012
were retrieved together with clinical data. An afebrile community control group was
composed from a survey performed in a malaria-endemic area. Hb concentrations and
anaemia prevalence were analysed according to clinical-epidemiological status and
demographic characteristics. In total, 7,831 observations were included. Patients
with Plasmodium falciparum infection had lower mean Hb
concentrations (10.5 g/dL) followed by P. vivax-infected individuals
(12.4 g/dL), community controls (12.8 g/dL) and malaria-negative febrile patients
(13.1 g/dL) (p < 0.001). Age, gender and clinical-epidemiological status were
strong independent predictors for both outcomes. Amongst malaria-infected
individuals, women in the reproductive age had considerably lower Hb concentrations.
In this moderate transmission intensity setting, both vivax and falciparum malaria
are associated with reduced Hb concentrations and risk of anaemia throughout a wide
age range. 相似文献