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Dose-dependent Way (dose-dependent + way)
Selected AbstractsSpurious associations in oral epidemiological research: the case of dental flossing and obesityJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 8 2006P. P. Hujoel Abstract Background: Individuals with increased oral health awareness may also have increased general health awareness, and vice versa. Such associations between oral and general health awareness has the potential to induce spurious associations in oral epidemiological research. Objective: To assess the extent to which oral self-care patterns and general health awareness are confounded, we investigated the association between flossing and obesity, two lifestyle factors that are unlikely to be causally related. Methods: A cross-sectional study of 1497 individuals presenting for an initial periodontal exam by the specialist. Self-reported flossing behaviors and body mass index (BMI) categories were related using logistic regression models. Results: After adjustment for confounding variables, lack of daily flossing was associated in a dose-dependent way with morbid obesity (odds ratio (OR), 20.3; 95% confidence interval (CI), 2.7,154.0), obesity (OR, 2.1; 95% CI, 1.5,2.9), and being overweight (OR, 1.7; 95% CI, 1.3,2.2). When restricting to never smokers, a significant relationship between obesity and lack of flossing remained. Conclusion: The strong associations between two causally unrelated oral and general lifestyle characteristics indicate that simplistic epidemiologic methodology is unlikely to provide insights into causal mechanisms of oral diseases or oral-systemic relationships. [source] The effect of hyaluronic acid on IL-1,-induced chondrocyte apoptosis in a rat model of osteoarthritisJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 12 2008Pang-Hu Zhou Abstract The purpose of this article was to study the effect of hyaluronic acid (HA) on chondrocyte apoptosis in a rat osteoarthritis in vitro model (exposure to IL-1,) and explore its mechanism. A rat in vitro model of osteoarthritis (OA) was established using 10 ng/mL IL-1, as a modulating and chondrocyte apoptosis inducing agent. Different doses of HA (10, 20, and 40 µg/mL) were added 1 h prior to the addition of IL-1, to a monolayer culture of freshly isolated juvenile rat chondrocytes. The ratio of apoptotic cell death was surveyed by Annexin V-FITC and propidium iodide double-labeling FACS analysis. The mitochondrial membrane potential of chondrocytes was evaluated by rhodamine-123 fluorescence. The mitochondrial function was evaluated through detecting the ATP production by a luciferase assay. The reverse transcription polymerase chain reaction (RT-PCR) was performed to measure mRNA expression levels of inducible oxide synthase (iNOS). HA could inhibit IL-1,-induced chondrocyte apoptosis in our cell culture model system. It was showed that addition of HA to the medium was able in a dose-dependent way to reduce the impairment of the mitochondrial membrane potential and to restore mitochondrial ATP production. This study shows that HA could suppress in a dose-dependent way chondrocyte apoptosis in our IL-1,-induced osteoarthritis model. The suppression of inflammatory cytokine activity within the joint might be one important mechanism of the clinical action of intraarticular injection of HA in the treatment of OA. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res [source] Systemic and splanchnic haemodynamic effects of sildenafil in an in vivo animal model of cirrhosis support for a risk in cirrhotic patientsLIVER INTERNATIONAL, Issue 1 2004Isabelle Colle Abstract: Objectives: Sildenafil is a selective inhibitor of the cGMP-specific phosphodiesterase type V (PDE-V) in the corpus cavernosum. PDE-V is also present in the mesenteric artery. Cirrhosis is complicated by a splanchnic vasodilation attributed to a local overproduction of nitric oxide (NO). As sildenafil potentiates the effects of NO, it may further decrease mesenteric vascular tone and increase portal venous blood flow. The aim is to evaluate the effects of sildenafil on the systemic and splanchnic haemodynamics in an experimental model of cirrhosis. Methods: Secondary biliary cirrhosis was induced in male Wistar rats by common bile duct ligation (CBDL, n=8); control rats were sham-operated (sham, n=7). The mean arterial pressure (MAP), portal venous pressure (PVP) and arterial mesenteric blood flow (MBF) were measured after intramesenteric (0.01,10 mg/kg) and after intravenous (i.v.) (0.01,10 mg/kg) administration of sildenafil. Results: Baseline PVP was significantly higher in CBDL than in sham rats, whereas baseline MAP tended to be lower and MBF tended to be higher in CBDL compared with sham rats. Both intramesenteric and i.v. injection of sildenafil significantly decreased MAP and increased MBF and PVP in a dose-dependent way. The decrease in MAP was significantly less important in CBDL than in sham rats. The increase in MBF was importantly lower in CBDL than in sham rats. PVP tended to increase more significantly in sham rats than in CBDL. Conclusion: Sildenafil increases MBF and PVP and induces systemic hypotension. The effects are less pronounced in cirrhosis, suggesting vascular hyporesponsiveness to sildenafil. Although the rise in PVP in cirrhotic animals is smaller than in controls, it may present a risk for haemorrhagic complications. Further studies are necessary before prescribing sildenafil to patients with cirrhosis. [source] Is inhibition of VEGF165 sufficient to inhibit scar formation after trabeculectomy?ACTA OPHTHALMOLOGICA, Issue 2009T VAN BERGEN Purpose We have previously shown that VEGF plays a role in scar formation after glaucoma surgery and that inhibition of all VEGF-isoforms by bevacizumab is able to reduce scar formation. This study was designed to elucidate the exact role of VEGF165 in scar formation after trabeculectomy. The effect of pegaptanib (Pfizer), which specifically blocks VEGF165, was investigated in vitro and in vivo. Methods The effect of pegaptanib on Tenon fibroblasts and HUVEC in vitro was determined using a WST-1 proliferation assay. The effect of the aptamer was also investigated in vivo in a rabbit model for glaucoma surgery by studying angiogenesis, inflammation and collagen deposition. Results A dose-dependent reduction of HUVEC proliferation was seen after pegaptanib administration in vitro (P<0.05 with a dose of at least 0,3 mg/ml). A concentration of 2 mg/ml pegaptanib was necessary to inhibit the proliferation of Tenon fibroblasts. The aptamer also significantly reduced blood vessel density 3 days after surgery in a rabbit model of trabeculectomy (P=0.001). There were no significant differences in inflammation and collagen deposition in the treated eyes compared to control. Conclusion Whereas HUVEC cells were inhibited by pegaptanib in a dose-dependent way, Tenon fibroblasts were only inhibited at the highest dose. A single administration of pegaptanib at the time of trabeculectomy reduced postoperative angiogenesis, but not inflammation or collagen deposition. Further studies using repeated pegaptanib injections are necessary to investigate whether the lack of effect of pegaptanib on scarring was due to a shorter working time of pegaptanib compared to bevacizumab, or due to the difference in their effect on the various VEGF isoforms. [source] | ||||||||||