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Ana Cecilia AX De-Oliveira Renato S Carvalho Flavio HM Paixão Hellen S Tavares Luciana S Gueiros Carolina M Siqueira Francisco JR Paumgartten 《Malaria journal》2010,9(1):1-17
Background
The mechanisms by which malaria up and down-regulates CYP activities are not understood yet. It is also unclear whether CYP activities are modulated during non-lethal malaria infections. This study was undertaken to evaluate the time course of CYP alterations in lethal (Plasmodium berghei ANKA) and non-lethal (Plasmodium chabaudi chabaudi) murine malaria. Additionally, hypotheses on the association of CYP depression with enhanced nitric oxide (NO) production, and of CYP2a5 induction with endoplasmic reticulum dysfunction, enhanced haem metabolism and oxidative stress were examined as well.Methods
Female DBA-2 and C57BL/6 mice were infected with P.berghei ANKA or P. chabaudi and killed at different post-infection days. Infection was monitored by parasitaemia rates and clinical signs. NO levels were measured in the serum. Activities of CYP1a (ethoxyresorufin-O-deethylase), 2b (benzyloxyresorufin-O-debenzylase), 2a5 (coumarin-7-hydroxylase) and uridine-diphosphoglucuronyl-transferase (UGT) were determined in liver microsomes. Glutathione-S-transferase (GST) activity and concentrations of gluthatione (GSH) and thiobarbituric acid-reactive substances (TBARS) were determined in the liver. Levels of glucose-regulated protein 78 (GRP78) were evaluated by immunoblotting, while mRNAs of haemoxygenase-1 (HO-1) and inducible nitric oxide synthase (iNOS) were determined by quantitative RT-PCR.Results
Plasmodium berghei depressed CYP1a and 2b and induced 2a5 in DBA-2 mice. In P.berghei-infected C57BL/6 mice CYP activities remained unaltered. In both strains, GST and UGT were not affected by P.berghei. Plasmodium c. chabaudi depressed CYP1a and 2b and induced 2a5 activities on the day of peak parasitaemia or near this day. CYP2a5 induction was associated with over-expression of HO-1 and enhanced oxidative stress, but it was not associated with GRP78 induction, a marker of endoplasmic reticulum stress. Plasmodium chabaudi increased serum NO on days near the parasitaemia peak in both strains. Although not elevating serum NO, P.berghei enhanced iNOS mRNA expression in the liver.Conclusion
Down-regulation of CYP1a and 2b and induction of 2a5 occurred in lethal and non-lethal infections when parasitaemia rates were high. A contribution of NO for depression of CYP2b cannot be ruled out. Results were consistent with the view that CYP2a5 and HO-1 are concurrently up-regulated and suggested that CYP2a5 induction may occur in the absence of enhanced endoplasmic reticulum stress. 相似文献25.
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Antibodies to citrullinated proteins and differences in clinical progression of rheumatoid arthritis
van der Helm-van Mil AH Verpoort KN Breedveld FC Toes RE Huizinga TW 《Arthritis research & therapy》2005,7(5):R949-R958
Antibodies to citrullinated proteins (anti-cyclic-citrullinated peptide [anti-CCP] antibodies) are highly specific for rheumatoid
arthritis (RA) and precede the onset of disease symptoms, indicating a pathogenetic role for these antibodies in RA. We recently
showed that distinct genetic risk factors are associated with either anti-CCP-positive disease or anti-CCP-negative disease.
These data are important as they indicate that distinct pathogenic mechanisms are underlying anti-CCP-positive disease or
anti-CCP-negative disease. Likewise, these observations raise the question of whether anti-CCP-positive RA and anti-CCP-negative
RA are clinically different disease entities. We therefore investigated whether RA patients with anti-CCP antibodies have
a different clinical presentation and disease course compared with patients without these autoantibodies. In a cohort of 454
incident patients with RA, 228 patients were anti-CCP-positive and 226 patients were anti-CCP-negative. The early symptoms,
tender and swollen joint count, and C-reactive protein level at inclusion, as well as the swollen joint count and radiological
destruction during 4 years of follow-up, were compared for the two groups. There were no differences in morning stiffness,
type, location and distribution of early symptoms, patients' rated disease activity and C-reactive protein at inclusion between
RA patients with and without anti-CCP antibodies. The mean tender and swollen joint count for the different joints at inclusion
was similar. At follow-up, patients with anti-CCP antibodies had more swollen joints and more severe radiological destruction.
Nevertheless, the distribution of affected joints, for swelling, bone erosions and joint space narrowing, was similar. In
conclusion, the phenotype of RA patients with or without anti-CCP antibodies is similar with respect to clinical presentation
but differs with respect to disease course. 相似文献
27.
Sofie HM Manders Wietske Kievit Eddy Adang Herman L Brus Hein J Bernelot Moens Andre Hartkamp Lidy Hendriks Elisabeth Brouwer Henk Visser Harald E Vonkeman Jos Hendrikx Tim L Jansen Rene Westhovens Mart AFJ van de Laar Piet LCM van Riel 《Arthritis research & therapy》2015,17(1)
IntroductionFor patients with rheumatoid arthritis (RA) whose treatment with a tumour necrosis factor inhibitor (TNFi) is failing, several biological treatment options are available. Often, another TNFi or a biological with another mode of action is prescribed. The objective of this study was to compare the effectiveness and cost-effectiveness of three biologic treatments with different modes of action in patients with RA whose TNFi therapy is failing.MethodsWe conducted a pragmatic, 1-year randomised trial in a multicentre setting. Patients with active RA despite previous TNFi treatment were randomised to receive abatacept, rituximab or a different TNFi. The primary outcome (Disease Activity Score in 28 joints) and the secondary outcomes (Health Assessment Questionnaire Disability Index and 36-item Short Form Health Survey scores) were analysed using linear mixed models. Cost-effectiveness was analysed on the basis of incremental net monetary benefit, which was based on quality-adjusted life-years (calculated using EQ-5D scores), and all medication expenditures consumed in 1 year. All analyses were also corrected for possible confounders.ResultsOf 144 randomised patients, 5 were excluded and 139 started taking abatacept (43 patients), rituximab (46 patients) or a different TNFi (50 patients). There were no significant differences between the three groups with respect to multiple measures of RA outcomes. However, our analysis revealed that rituximab therapy is significantly more cost-effective than both abatacept and TNFi over a willingness-to-pay range of 0 to 80,000 euros.ConclusionsAll three treatment options were similarly effective; however, when costs were factored into the treatment decision, rituximab was the best option available to patients whose first TNFi treatment failed. However, generalization of these costs to other countries should be undertaken carefully.
Trial registration
Netherlands Trial Register number NTR1605. Registered 24 December 2008.Electronic supplementary material
The online version of this article (doi:10.1186/s13075-015-0630-5) contains supplementary material, which is available to authorized users. 相似文献28.
Obara MT Barata JM da Silva NN Ceretti Júnior W Urbinatti PR da Rosa JA Jurberg J Galvão C 《Memórias do Instituto Oswaldo Cruz》2007,102(1):13-19
The objective of this work was to analyze the morphological, morphometrical, and histological characteristics of eggs of four triatomine bugs species still not studied, in order to understand phylogenetic aspects and to facilitate parameters used in taxonomy, with the purpose of a specific and generic characterization of these vectors in public health. The eggs of each species had come from the collections of the Laboratory of Triatomine bugs and Culicid mosquitoes of the Faculdade de Saúde Pública - USP (Faculty of Public Health/USP). The morphologic studies were carried out through optic microscopy (OM) and scanning electronic microscopy (SEM). The eggs were measured with the help of the digital paquimeter Starrett 727. In relation to histological measures, Microtome Leica RM 2145 was used. Similarities were evidenced in the exocorial architecture of the eggs when they were studied by OM and SEM. This similarity among the eggs suggests a recent speciation, probably derived from common ancestry, representing a monophyletic group. Some structures were also detected by the histological cuts. The study has contributed to the magnification and recognition in generic and specific terms of the Triatominae subfamily. These new data will be able to subsidize a better understanding to determine roles for each vector species and to facilitate parameters to be used in taxonomy. 相似文献
29.
Erin N Smith Kristen Jepsen Mahdieh Khosroheidari Laura Z Rassenti Matteo D’Antonio Emanuela M Ghia Dennis A Carson Catriona HM Jamieson Thomas J Kipps Kelly A Frazer 《Genome biology》2014,15(7)
Accurate allele frequencies are important for measuring subclonal heterogeneity and clonal evolution. Deep-targeted sequencing data can contain PCR duplicates, inflating perceived read depth. Here we adapted the Illumina TruSeq Custom Amplicon kit to include single molecule tagging (SMT) and show that SMT-identified duplicates arise from PCR. We demonstrate that retention of PCR duplicate reads can imply clonal evolution when none exists, while their removal effectively controls the false positive rate. Additionally, PCR duplicates alter estimates of subclonal heterogeneity in tumor samples. Our method simplifies PCR duplicate identification and emphasizes their removal in studies of tumor heterogeneity and clonal evolution.
Electronic supplementary material
The online version of this article (doi:10.1186/s13059-014-0420-4) contains supplementary material, which is available to authorized users. 相似文献30.
Femke HM Prince Vivian P Bykerk Nancy A Shadick Bing Lu Jing Cui Michelle Frits Christine K Iannaccone Michael E Weinblatt Daniel H Solomon 《Arthritis research & therapy》2012,14(2):R68-8