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81.
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
82.
Ngiik Tiong 《European journal of pharmaceutics and biopharmaceutics》2009,73(3):373-384
The aim of this study was to investigate the use of liquisolid technique in improving the dissolution profiles of naproxen in a solid dosage form. This study was designed to evaluate the effects of different formulation variables, i.e. type of non-volatile liquid vehicles and drug concentrations, on drug dissolution rates. The liquisolid tablets were formulated with three different liquid vehicles, namely Cremophor® EL (polyoxyl 35 castor oil), Synperonic® PE/L61 (poloxamer 181, polyoxyethylene-polyoxypropylene copolymer) and poly ethylene glycol 400 (PEG400) at two drug concentrations, 20%w/w and 40%w/w. Avicel® PH102 was used as a carrier material, Cab-o-sil® M-5 as a coating material and maize starch as a disintegrant. The empirical method as introduced by Spireas and Bolton (1999) [1] was applied strictly to calculate the amounts of coating and carrier materials required to prepare naproxen liquisolid tablets. Quality control tests, i.e. uniformity of tablet weight, uniformity of drug content, tablet hardness, friability test, disintegration and dissolution tests were performed to evaluate each batch of prepared tablets. In vitro drug dissolution profiles of the liquisolid formulations were studied and compared with conventional formulation, in simulated gastric fluid (pH 1.2) and simulated intestinal fluid (pH 7.2) without enzyme. Stability studies were carried out to evaluate the stability of the tablets under humid conditions. Differential scanning calorimetry and Fourier transform infrared were used to investigate physicochemical interaction between naproxen and the excipients. It was found that liquisolid tablets formulated with Cremophor® EL at drug concentration of 20%w/w produced high dissolution profile with acceptable tablet properties. The stability studies showed that the dissolution profiles of liquisolid tablets prepared with Cremophor® EL were not affected by ageing significantly. Furthermore, DSC revealed that drug particles in liquisolid formulations were completely solubilised. 相似文献
83.
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84.
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85.
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89.
Crist WM; Shuster JJ; Falletta J; Pullen DJ; Berard CW; Vietti TJ; Alvarado CS; Roper MA; Prasthofer E; Grossi CE 《Blood》1988,72(6):1891-1897
The immunophenotypes of lymphoblasts from children with newly diagnosed T-cell acute lymphoid leukemia (T-ALL, n = 101) or T-cell non-Hodgkin lymphoma (T-NHL, n = 31) were analyzed to correlate stage of thymocyte differentiation with clinical features and outcome. The 67 boys and 34 girls with T-ALL were 1 month to 18 years old (median, 8 years) with leukocyte counts ranging from 2 to 810 x 10(9)/L (median, 55 x 10(9)/L). Eighteen of these patients were black, and 70 had a mediastinal mass. Twenty-six boys and five girls with a median age of 9 years (range, 1 to 20 years) had T-NHL. Seven of these patients were black, and 24 had a mediastinal mass. The distributions of thymocyte developmental stages (early [CD7+], intermediate [CD1+ and/or CD4+ and/or CD8+], and mature [CD3+]) in cases of T-ALL and T-NHL were significantly different: 34%, 43%, and 23% v 6%, 62%, and 32% (P = .02). A comparison of the patients' clinical features according to the maturational stage of thymocytes failed to disclose significant differences in the majority of characteristics studied. However, patients with mature-stage T-NHL, with or without the addition of subjects with mature-stage T-ALL, were less likely to have a mediastinal mass (P = .02 for both comparisons). Those with intermediate-stage T-cell malignancy (T-ALL and T-NHL combined) were the subgroup most likely to have a mediastinal mass (P = .01). Response to remission induction therapy was significantly worse in the T-ALL subgroup with an early-stage phenotype: a failure rate of 21% v 0% and 6% for the two more differentiated phenotypic subgroups (P = .007). Event-free survival was not affected by thymocyte maturational stage in cases of either T-ALL or T-NHL. Despite evidence of clinical heterogeneity among the maturational stages of T-cell malignancies in children, these developmental subdivisions do not appear to be critical determinants of outcome once remission is achieved. We conclude that such phenotypes need not be included in the stratification plans for clinical trials using common induction treatment. 相似文献
90.
MA Vieira-Coelho MP Serr?o J Afonso CE Pinto E Moura 《British journal of pharmacology》2009,158(3):726-737