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51.
Confounding and interaction effect of Treponema denticola salivary carriage in chronic periodontitis
MC Martínez‐Pabón A Martínez‐Gaviria DM Isaza‐Guzmán CE Muskus‐López SI Tobón‐Arroyave 《Oral diseases》2010,16(3):278-285
Oral Diseases (2010) 16 , 278–285 Aim: To evaluate the salivary carriage of Treponema denticola and its association with demographic variables in the etiopathogenesis of chronic periodontitis. Subjects and methods: Ninety‐seven chronic periodontitis (CP) patients and a control group of 51 healthy subjects (HC) were selected. Periodontal status was assessed by criteria based on probing depth, attachment loss, extent, and severity of periodontal breakdown. A polymerase chain reaction method was used to determine the occurrence of T. denticola in saliva samples. Risk indicators for CP were assessed individually and adjusted for confounding and/or interaction using a logistic regression model. Results: Although univariate analysis revealed a positive association of age ≥30 years, smoking, and salivary carriage of T. denticola with CP, after logistic regression analysis, the association between age ≥30 years/smoking and CP persisted, whereas salivary carriage of T. denticola failed to achieve statistical significance. An interaction effect was significantly detected between these three variables. Conclusion: Although salivary carriage of T. denticola may be a risk indicator for CP, its pathogenicity should not be exclusively endorsed to its detection in saliva, but it might be associated with the synergistic biological interaction of the bacterium with some demographic characteristics of the susceptible host. 相似文献
52.
I Sayers J Hawley CE Stewart CK Billington A Henry JR Leighton-Davies SJ Charlton IP Hall 《British journal of pharmacology》2009,158(1):277-286
Background and purpose:
Indacaterol is a novel β2-adrenoceptor agonist in development for the treatment of chronic obstructive pulmonary disease. The aim of this study was to investigate the comparative pharmacology of indacaterol in recombinant cells expressing the common polymorphic variants of the human β2-adrenoceptor and in human primary airway smooth muscle (ASM) cells.Experimental approach:
Chinese hamster ovarian-K1 cell lines expressing high and low levels of the common human β2-adrenoceptor variants were generated [Gly16-Glu27-Val34-Thr164(GEVT), RQVT, GQVT] and also the rare GQVI variant. Human primary ASM cells were isolated from explants of trachealis muscle. Adenosine-3′,5′-cyclic-monophosphate production was used as an outcome measure.Key results:
In both the low- and high-expression recombinant GEVT ‘wild type’ cell lines indacaterol is a high-efficacy agonist. Salmeterol and formoterol were identified as low- and high-efficacy agonists, respectively, and showed similar potencies to indacaterol irrespective of the β2-adrenoceptor genotype. The I164 variant cell line was associated with a reduced capacity to generate adenosine-3′,5′-cyclic-monophosphate in response to β2-adrenoceptor agonist. In the human primary ASM cells indacaterol gave a maximal response intermediate between that of salmeterol and formoterol.Conclusions and implications:
These data demonstrate that indacaterol is a high-efficacy agonist in recombinant cell systems but acts with lower efficacy in human primary ASM cells. No marked genotype-dependent effects were observed for common variants; however, changes in I164 receptor activity were identified, which were dependent on the level of expression of β2-adrenoceptors. 相似文献53.
CE Vitor CP Figueiredo DB Hara AF Bento TL Mazzuco JB Calixto 《British journal of pharmacology》2009,157(6):1034-1044
Background and purpose:
α- and β-amyrin are pentacyclic triterpenes found in plants and are known to exhibit pronounced anti-inflammatory effects. Here, we evaluated the effects of a 1:1 mixture of α- and β-amyrin (α,β-amyrin) on an experimental model of colitis in mice.Experimental approach:
Colitis was induced in Swiss male mice by trinitrobenzene sulphonic acid (TNBS) and followed up to 72 h; animals were treated systemically with α,β-amyrin, dexamethasone or vehicle. Macro- and microscopic damage, myeloperoxidase activity and cytokine levels were assessed in colons. Histological sections were immunostained for cyclooxygenase-2 (COX-2), vascular endothelial growth factor, phospho-p65 nuclear factor-κB (NF-κB) and phospho-cyclic AMP response element-binding protein (CREB)Key results:
TNBS-induced colitis was associated with tissue damage, neutrophil infiltration and time-dependent increase of inflammatory mediators. Treatment with α,β-amyrin (3 mg·kg−1, i.p.) or dexamethasone (1 mg·kg−1, s.c.) consistently improved tissue damage scores and abolished polymorphonuclear cell infiltration. α,β-Amyrin, like dexamethasone, significantly diminished interleukin (IL)-1β levels and partially restored IL-10 levels in colon tissues 72 h after colitis induction, but only α,β-amyrin reduced vascular endothelial growth factor expression by immunohistochemistry. The colonic expression of COX-2 at 24 h and that of phospho-NF-κB and phospho-CREB (peaking at 6 h) after colitis induction were consistently inhibited by both α,β-amyrin and dexamethasone.Conclusions and implications:
Systemic administration of α,β-amyrin exerted a marked and rapid inhibition of TNBS-induced colitis, related to the local suppression of inflammatory cytokines and COX-2 levels, possibly via inhibition of NF-κB and CREB-signalling pathways. Taken together, our data suggest a potential use of α,β-amyrin to control inflammatory responses in bowel disease. 相似文献54.
55.
56.
57.
MA Vieira-Coelho MP Serr?o J Afonso CE Pinto E Moura 《British journal of pharmacology》2009,158(3):726-737
Background and purpose:
This study investigates the role of α2-adrenoceptor subtypes, α2A, α2B and α2C, on catecholamine synthesis and catabolism in the central nervous system of mice.Experimental approach:
Activities of the main catecholamine synthetic and catabolic enzymes were determined in whole brains obtained from α2A-, α2B- and α2C-adrenoceptor knockout (KO) and C56Bl\7 wild-type (WT) mice.Key results:
Although no significant differences were found in tyrosine hydroxylase activity and expression, brain tissue levels of 3,4-dihydroxyphenylalanine were threefold higher in α2A- and α2C-adrenoceptor KO mice. Brain tissue levels of dopamine and noradrenaline were significantly higher in α2A and α2CKOs compared with WT [WT: 2.8 ± 0.5, 1.1 ± 0.1; α2AKO: 6.9 ± 0.7, 1.9 ± 0.1; α2BKO: 2.3 ± 0.2, 1.0 ± 0.1; α2CKO: 4.6 ± 0.8, 1.5 ± 0.2 nmol·(g tissue)−1, for dopamine and noradrenaline respectively]. Aromatic L-amino acid decarboxylase activity was significantly higher in α2A and α2CKO [WT: 40 ± 1; α2A: 77 ± 2; α2B: 40 ± 1; α2C: 50 ± 1, maximum velocity (Vmax) in nmol·(mg protein)−1·h−1], but no significant differences were found in dopamine β-hydroxylase. Of the catabolic enzymes, catechol-O-methyltransferase enzyme activity was significantly higher in all three α2KO mice [WT: 2.0 ± 0.0; α2A: 2.4 ± 0.1; α2B: 2.2 ± 0.0; α2C: 2.2 ± 0.0 nmol·(mg protein)−1·h−1], but no significant differences were found in monoamine oxidase activity between all α2KOs and WT mice.Conclusions and implications:
In mouse brain, deletion of α2A- or α2C-adrenoceptors increased cerebral aromatic L-amino acid decarboxylase activity and catecholamine tissue levels. Deletion of any α2-adrenoceptor subtypes resulted in increased activity of catechol-O-methyltransferase. Higher 3,4-dihydroxyphenylalanine tissue levels in α2A and α2CKO mice could be explained by increased 3,4-dihydroxyphenylalanine transport. 相似文献58.
59.
IJ Webb ; CE Eickhoff ; AD Elias ; LJ Ayash ; CA Wheeler ; GN Schwartz ; GD Demetri ; KC Anderson 《Transfusion》1996,36(2):160-167
BACKGROUND: Peripheral blood progenitor cells (PBPCs) are commonly collected and used to reconstitute hematopoiesis after high-dose chemotherapy. However, strategies for optimal collection and assessment of leukapheresis components are not standardized. STUDY DESIGN and METHODS: Hematopoietic progenitor cell assays were performed on 369 leukapheresis components collected from 95 patients who had received doxorubicin-based chemotherapy and/or granulocyte-colony-stimulating factor (G-CSF). Precollection patient hematologic values, leukapheresis collection values, component hematopoietic progenitor cell assays, and patient outcome measures were summarized. The kinetics of mononuclear cell (MNC) and PBPC mobilization were assessed among four patient groups. RESULTS: Patient group was a significant predictor of the peripheral blood MNC count on the day of collection (p<0.0001), and that value was a significant predictor of granulocyte-macrophage– colony-forming unit (CFU-GM) yield (p<0.0001). This relationship between the peripheral blood MNC count on the day of collection and CFU- GM yield differed according to patient group (p<0.0001). CFU-GM made up a larger fraction of peripheral blood MNCs collected from patients who received chemotherapy plus G-CSF than collected from those who received G-CSF alone. Moreover, the peripheral blood MNC count and the corresponding CFU-GM yield increased significantly on consecutive days of collection in patient groups receiving chemotherapy and G-CSF but were unchanged or decreased in patients receiving G-CSF alone. CONCLUSION: The relationship between peripheral blood MNC count and leukapheresis component CFU-GM yield differed significantly between patients who received chemotherapy and G-CSF and those who received G- CSF alone for the mobilization of PBPCs. Patient peripheral blood MNC count and component CFU-GM yield are useful for both assessing and suggesting revisions to PBPC mobilization and collection strategies. 相似文献
60.
Pramana IA Latzin P Schlapbach LJ Hafen G Kuehni CE Nelle M Riedel T Frey U 《European journal of medical research》2011,16(5):223-230