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Carla GS Saad Ana CM Ribeiro Julio CB Moraes Liliam Takayama Celio R Goncalves Marcelo B Rodrigues Ricardo M de Oliveira Clovis A Silva Eloisa Bonfa Rosa MR Pereira 《Arthritis research & therapy》2012,14(5):R216
Introduction
Sclerostin levels have been reported to be low in ankylosing spondylitis (AS), but there is no data regarding the possible role of this Wnt inhibitor during anti-tumor necrosis factor (TNF) therapy. The present study longitudinally evaluated sclerostin levels, inflammatory markers and bone mineral density (BMD) in AS patients under anti-TNF therapy.Methods
Thirty active AS patients were assessed at baseline, 6 and 12 months after anti-TNF therapy regarding clinical parameters, inflammatory markers, BMD and baseline radiographic damage (mSASSS). Thirty age- and sex-matched healthy individuals comprised the control group. Patients'' sclerostin levels, sclerostin binding low-density lipoprotein receptor-related protein 6 (LRP6) and BMD were evaluated at the same time points and compared to controls.Results
At baseline, AS patients had lower sclerostin levels (60.5 ± 32.7 vs. 96.7 ± 52.9 pmol/L, P = 0.002) and comparable sclerostin binding to LRP6 (P = 0.387) than controls. Improvement of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Metrology Index (BASMI), Ankylosing Spondylitis quality of life (ASQoL) was observed at baseline vs. 6 vs. 12 months (P < 0.01). Concomitantly, a gradual increase in spine BMD (P < 0.001) and a positive correlation between baseline mSASSS and spine BMD was found (r = 0.468, P < 0.01). Inflammatory parameters reduction was observed comparing baseline vs. 6 vs. 12 months (P <0.01). Sclerostin levels progressively increased [baseline (60.5 ± 32.7) vs. 6 months (67.1 ± 31.9) vs. 12 months (72.7 ± 32.3) pmol/L, P <0.001]. At 12 months, the sclerostin levels remained significantly lower in patients compared to controls (72.7 ± 32.3 vs. 96.70 ± 52.85 pmol/L, P = 0.038). Moreover, sclerostin serum levels at 12 months were lower in the 10 patients with high C reactive protein (CRP) (≥ 5 mg/l) compared to the other 20 patients with normal CRP (P = 0.004). Of note, these 10 patients with persistent inflammation also had lower sclerostin serum levels at baseline compared to the other patients (P = 0.023). Univariate logistic regression analysis demonstrated that AS patients with lower sclerostin serum levels had an increased risk to have high CRP at 12 months (odds ratio = 7.43, 95% CI 1.23 to 45.01, P = 0.020) than those with higher sclerostin values.Conclusions
Persistent low sclerostin levels may underlie continuous inflammation in AS patients under anti-TNF therapy. 相似文献14.
Welmaker GS Nelson JA Sabalski JE Sabb AL Potoski JR Graziano D Kagan M Coupet J Dunlop J Mazandarani H Rosenzweig-Lipson S Sukoff S Zhang Y 《Bioorganic & medicinal chemistry letters》2000,10(17):1991-1994
A series of 2,3,4,4a-tetrahydro-1H-pyrazino[1,2-a]quinoxalin-5-(6H)ones and 2,3,4,4a,5,6-hexahydro-1H-pyrazino[1,2-a]quinoxalines was shown to exhibit 5-HT2C agonist binding and functional activity. Compound 21R inhibited food intake over 2 h in fasted, male Sprague Dawley rats with ED50 values of 2 mg/kg (i.p.) and 10 mg/kg (p.o.). 相似文献
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Gene regulatory divergence among species estimated by altered developmental patterns in interspecific hybrids 总被引:4,自引:0,他引:4
Disturbances in the schedules of gene expression in developing
interspecific fish hybrids have been used to draw inferences about the
extent of gene regulatory divergence between species and about the degree
to which this gene regulatory divergence is correlated with structural gene
divergence, as estimated by genetic distance. Sperm from each of 10
different species representing six genera within the family Centrarchidae
was used to fertilize eggs of the Florida largemouth bass (Micropterus
salmoides floridanus). The genetic distances (D; Nei 1978) between the
parental species used to form the hybrids ranged from 0.133 to 0.974. The
developmental success and temporal patterns of gene expression of each of
the hybrids were compared with those of the Florida largemouth bass. As the
genetic distance between the paternal species and the Florida largemouth
bass increased, there was a general decline in developmental success in the
hybrid embryos as demonstrated by the observed reductions in the percentage
of hatching and by progressively earlier and more extensive morphological
abnormalities. Concomitantly, progressively more marked alterations in
developmental schedules of expression of 15 enzyme loci occurred in the
hybrids as the genetic distance between parental species increased.
However, observed deviations from this trend for a few species may
represent an uncoupling of the rates and modes of evolution of structural
genes from those for genes regulating developmental processes.
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EG Smirnova GS Muromtsev AV Osipenko EE Khavkin LS Yaguzhinsky 《Biochemistry. Biokhimii?a》1998,63(9):1021-1028
Activation of highly specific biochemical processes by simple chemical agents is demonstrated for morphogenesis (anlage and development of female gametophyte in cereal) and mitosis (in cell cultures and animal and plant tissues). The effects of these agents are tissue-specific. Structure--activity relationship is analyzed in this group of compounds. Thus, the phenomenon reveals the exact pathways of the influence of allelopathic and anthropogenic chemical agents on evolution of plant biocenoses. 相似文献
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M Kale R Ramsey-Goldman S Bernatsky MB Urowitz D Gladman PR Fortin M Petri E Yelin S Manzi S Edworthy O Nived S-C Bae D Isenberg A Rahman JG Hanly C Gordon S Jacobsen E Ginzler DJ Wallace GS Alarcón MA Dooley L Gottesman K Steinsson A Zoma J-L Senécal S Barr G Sturfelt L Dreyer L Criswell J Sibley JL Lee AE Clarke 《Arthritis research & therapy》2012,14(Z3):A15
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Conserved sequence motifs, alignment, and secondary structure for the third domain of animal 12S rRNA 总被引:17,自引:3,他引:14
Hickson RE; Simon C; Cooper A; Spicer GS; Sullivan J; Penny D 《Molecular biology and evolution》1996,13(1):150-169
Secondary structure models are an important step for aligning sequences,
understanding probabilities of nucleotide substitutions, and evaluating the
reliability of phylogenetic reconstructions. A set of conserved sequence
motifs is derived from comparative sequence analysis of 184 invertebrate
and vertebrate taxa (including many taxa from the same genera, families,
and orders) with reference to a secondary structure model for domain III of
animal mitochondrial small subunit (12S) ribosomal RNA. A template is
presented to assist with secondary structure drawing. Our model is similar
to previous models but is more specific to mitochondrial DNA, fitting both
invertebrate and vertebrate groups, including taxa with markedly different
nucleotide compositions. The second half of the domain III sequence can be
difficult to align precisely, even when secondary structure information is
considered. This is especially true for comparisons of anciently diverged
taxa, but well-conserved motifs assist in determining biologically
meaningful alignments. Patterns of conservation and variability in both
paired and unpaired regions make differential phylogenetic weighting in
terms of "stems" and "loops" unsatisfactory. We emphasize looking carefully
at the sequence data before and during analyses, and advocate the use of
conserved motifs and other secondary structure information for assessing
sequencing fidelity.
相似文献