2,687 research outputs found

    Roles of FGFR3 during morphogenesis of Meckel's cartilage and mandibular bones

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    AbstractTo address the functions of FGFR2 and FGFR3 signaling during mandibular skeletogenesis, we over-expressed in the developing chick mandible, replication-competent retroviruses carrying truncated FGFR2c or FGFR3c that function as dominant negative receptors (RCAS-dnFGFR2 and RCAS-dnFGFR3). Injection of RCAS-dnFGFR3 between HH15 and 20 led to reduced proliferation, increased apoptosis, and decreased differentiation of chondroblasts in Meckel's cartilage. These changes resulted in the formation of a hypoplastic mandibular process and truncated Meckel's cartilage. This treatment also affected the proliferation and survival of osteoprogenitor cells in osteogenic condensations, leading to the absence of five mandibular bones on the injected side. Injection of RCAS-dnFGFR2 between HH15 and 20 or RCAS-dnFGFR3 at HH26 did not affect the morphogenesis of Meckel's cartilage but resulted in truncations of the mandibular bones. RCAS-dnFGFR3 affected the proliferation and survival of the cells within the periosteum and osteoblasts. Together these results demonstrate that FGFR3 signaling is required for the elongation of Meckel's cartilage and FGFR2 and FGFR3 have roles during intramembranous ossification of mandibular bones

    STUDY OF THE ANTI-HYPERLIPIDEMIC EFFECT OF THE COMBINED ADMINISTRATION OF THREE NATURAL EXTRACTS IN A POLOXAMER-407 HYPERLIPIDEMIC MODEL AND THEIR LC-ESI-MS/MS2 AND HPLC PROFILING

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    Objective: Dyslipidaemia is considered a high-risk factor for inducing atherosclerosis and cardiovascular diseases (CVDs). This study aims to investigate the anti-hyperlipidemic effect of the co-administration of the ethanol extracts of both ginger (root and rhizome) and leek (leaves and bulbs) in addition to the aqueous extract of gum arabic.  Methods: Rats were divided into eight groups: Hyperlipidaemia was induced in rats by a single intraperitoneal injection of Poloxamer 407 (P-407) [1 g/kg], negative control [saline injected], hyperlipidemic control [P-407 injected], positive control [Atorvastatin 70 mg/kg], groups four, five and six received ginger extract (400 mg/kg), leek extract (500 mg/kg) and gum arabic aqueous extract (7.5 g/kg) respectively and groups seven and eight received a co-administration of ginger, leek and gum arabic extracts at doses A and B respectively. Lipid profile was monitored. The profiling of all the tested extracts was performed by LC-ESI/MS and HPLC. Results: A significant anti-hyperlipidemic activity (P<0.05) was seen for group eight among all the tested groups producing ≈54%, 72%, 50% and 72% decrease in the measured parameters total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL) and very-low-density lipoprotein (VLDL) respectively. An overall of 56 and 45 compounds were tentatively identified in the ethanol extracts of ginger and leek, respectively. Galactose and arabinose sugars were found to be the major saccharides in gum arabic and glucuronic acid was the major polyuronide part. Conclusion: the co-administration of a group of natural extracts in the given concentration proved to be more effective than the use of synthetic drugs or the use of a single component.&nbsp

    Statistical Mechanics of the Chinese Restaurant Process: lack of self-averaging, anomalous finite-size effects and condensation

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    The Pitman-Yor, or Chinese Restaurant Process, is a stochastic process that generates distributions following a power-law with exponents lower than two, as found in a numerous physical, biological, technological and social systems. We discuss its rich behavior with the tools and viewpoint of statistical mechanics. We show that this process invariably gives rise to a condensation, i.e. a distribution dominated by a finite number of classes. We also evaluate thoroughly the finite-size effects, finding that the lack of stationary state and self-averaging of the process creates realization-dependent cutoffs and behavior of the distributions with no equivalent in other statistical mechanical models.Comment: (5pages, 1 figure

    Meta-analysis: insulin sensitizers for the treatment of non-alcoholic steatohepatitis

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    Aliment Pharmacol Ther 2010; 32: 1211–1221Non-alcoholic fatty liver disease generally has a benign course; however, patients with non-alcoholic steatohepatitis (NASH) may progress to cirrhosis and hepatocellular carcinoma. Currently, there is a lack of consensus about optimal NASH treatment.To assess the efficacy of insulin-sensitizing agents on histological and biochemical outcomes in randomized control trials of biopsy-proven NASH.Multiple online databases and conference abstracts were searched. Random effects meta-analyses were performed, with assessment for heterogeneity and publication bias.Nine trials were included; five trials using thiazolidinediones (glitazones), three using metformin and one trial using both drugs. There was no publication bias. Compared with controls, glitazones resulted in improved steatosis (WMD = 0.57, 95% CI 0.36–0.77, P  = <0.001), hepatocyte ballooning (WMD = 0.36, 95% CI 0.24–0.49, P  < 0.001) and ALT (WMD = 16.4, 95% CI 7.7–25.0, P  < 0.001), but not inflammation ( P  = 0.09) or fibrosis ( P  = 0.11). In patients without diabetes, glitazones significantly improved all histological and biochemical outcomes, most importantly including fibrosis (WMD = 0.29, 95% CI 0.078–0.51, P  = 0.008). Metformin failed to improve any pooled outcome.Treatment of NASH with glitazones, but not metformin, demonstrates a significant histological and biochemical benefit, especially in patients without diabetes. Additional studies are needed to investigate long-term outcomes of glitazone therapy in patients without diabetes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/79251/1/j.1365-2036.2010.04467.x.pd
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