Modulation of osteoblast differentiation and function by the P2X4 receptor

Bone cells are known to express multiple P2 receptor subtypes, and the functional effects of receptor activation have been described for many of these. One exception is the P2X4 receptor, which despite strong expression in osteoblasts and osteoclasts, has no defined functional activity. This study used the selective P2X4 receptor antagonists, 5-BDBD and PSB-12062, to investigate the role of this receptor in bone. Both antagonists (≥ 0.1 μM) dose-dependently decreased bone formation by 60–100%. This was accompanied by a ≤ 70% decrease in alkaline phosphatase activity, a ≤ 40% reduction in cell number, and a ≤ 80% increase in the number of adipocytes present in the culture. The analysis of gene expression showed that levels of osteoblast marker genes (e.g. Alpl, Bglap) were decreased in 5-BDBD treated cells. Conversely, expression of the adipogenic transcription factor PPARG was increased 10-fold. In osteoclasts, high doses of both antagonists were associated with a reduction in osteoclast formation and resorptive activity by ≤ 95% and ≤ 90%, respectively. Taken together, these data suggest that the P2X4 receptor plays a role in modulating bone cell function. In particular, it appears to influence osteoblast differentiation favouring the osteogenic lineage over the adipogenic lineage

Induction of insulin-like growth factor 2 expression in a mesenchymal cell line co-cultured with an ameloblast cell line

Various growth factors have been implicated in the regulation of cell proliferation and differentiation during tooth development. It has been unclear if insulin-like growth factors (IGFs) participate in the epithelium–mesenchyme interactions of tooth development. We previously produced three-dimensional sandwich co-culture systems (SW) containing a collagen membrane that induce the differentiation of epithelial cells. In the present study, we used the SW system to analyze the expression of IGFs and IGFRs. We demonstrate that IGF2 expression in mesenchymal cells was increased by SW. IGF1R transduces a signal; however, IGF2R does not transduce a signal. Recombinant IGF2 induces IGF1R and IGF2R expression in epithelial cells. IGF1R expression is increased by SW; however, IGF2R expression did not increase by SW. Thus, IGF2 signaling works effectively in SW. These results suggest that IGF signaling acts through the collagen membrane on the interaction between the epithelium and mesenchyme. In SW, other cytokines may be suppressed to induce IGF2R induction. Our results suggest that IGF2 may play a role in tooth differentiation

Opportunities for topical antimicrobial therapy: permeation of canine skin by fusidic acid

BACKGROUND: Staphylococcal infection of the canine epidermis and hair follicle is amongst the commonest reasons for antimicrobial prescribing in small animal veterinary practice. Topical therapy with fusidic acid (FA) is an attractive alternative to systemic therapy based on low minimum inhibitory concentrations (MICs, commonly <0.03 mg/l) documented in canine pathogenic staphylococci, including strains of MRSA and MRSP (methicillin-resistant Staphylococcus aureus and S. pseudintermedius). However, permeation of canine skin by FA has not been evaluated in detail. This study aimed to define the degree and extent of FA permeation in canine skin in vitro from two sites with different hair follicle density following application of a licensed ophthalmic formulation that shares the same vehicle as an FA-betamethasone combination product approved for dermal application in dogs. Topical FA application was modelled using skin held in Franz-type diffusion cells. Concentrations of FA in surface swabs, receptor fluid, and transverse skin sections of defined anatomical depth were determined using high-performance liquid chromatography and ultraviolet (HPLC-UV) analysis. RESULTS: The majority of FA was recovered by surface swabs after 24 h, as expected (mean ± SEM: 76.0 ± 17.0%). FA was detected within 424/470 (90%) groups of serial sections of transversely cryotomed skin containing follicular infundibula, but never in 48/48 (100%) groups of sections containing only deeper follicular structures, nor in receptor fluid, suggesting that FA does not permeate beyond the infundibulum. The FA concentration (mean ± SEM) in the most superficial 240 μm of skin was 2000 ± 815 μg/g. CONCLUSIONS: Topically applied FA can greatly exceed MICs for canine pathogenic staphylococci at the most common sites of infection. Topical FA therapy should now be evaluated using available formulations in vivo as an alternative to systemic therapy for canine superficial bacterial folliculitis.Peer reviewedFinal Published versio

Gastric cancer surgery: Billroth I or Billroth II for distal gastrectomy?

<p>Abstract</p> <p>Background</p> <p>The selection of an anastomosis method after a distal gastrectomy is a highly debatable topic; however, the available documentation lacks the necessary research based on a comparison of early postoperative complications. This study was conducted to investigate the difference of early postoperative complications between Billroth I and Billroth II types of anastomosis for distal gastrectomies.</p> <p>Methods</p> <p>A total of 809 patients who underwent distal gastrectomies for gastric cancer during four years were included in the study. The only study endpoint was analysis of in-patients' postoperative complications. The risk adjusted complication rate was compared by POSSUM (Physiological and operative severity score for enumeration of morbidity and mortality) and the severity of complications was compared by Rui Jin Hospital classification of complication.</p> <p>Results</p> <p>Complication rate of Billroth II type of anastomosis was almost double of that in Billroth I (P = 0.000). Similarly, the risk adjusted complication rate was also higher in Billroth II group. More severe complications were observed and the postoperative duration was significantly longer in Billroth II type (P = 0.000). Overall expenditure was significantly higher in Billroth II type (P = 0.000).</p> <p>Conclusion</p> <p>Billroth II method of anastomosis was associated with higher rate of early postoperative complications. Therefore, we conclude that the Billroth I method should be the first choice after a distal gastrectomy as long as the anatomic and oncological environment of an individual patient allows us to perform it. However more prospective studies should be designed to compare the overall surgical outcomes of both anastomosis methods.</p

Mindfulness based interventions in multiple sclerosis: a systematic review

&lt;b&gt;Background&lt;/b&gt; Multiple sclerosis (MS) is a stressful condition; depression, anxiety, pain and fatigue are all common problems. Mindfulness based interventions (MBIs) mitigate stress and prevent relapse in depression and are increasingly being used in healthcare. However, there are currently no systematic reviews of MBIs in people with MS. This review aims to evaluate the effectiveness of MBIs in people with MS.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Methods&lt;/b&gt; Systematic searches were carried out in seven major databases, using both subject headings and key words. Papers were screened, data extracted, quality appraised, and analysed by two reviewers independently, using predefined criteria. Study quality was assessed using the Cochrane Collaboration risk of bias tool. Perceived stress was the primary outcome. Secondary outcomes include mental health, physical health, quality of life, and health service utilisation. Statistical meta-analysis was not possible. Disagreements were adjudicated by a third party reviewer.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Results&lt;/b&gt; Three studies (n = 183 participants) were included in the final analysis. The studies were undertaken in Wales (n = 16, randomised controlled trial - (RCT)), Switzerland (n = 150, RCT), and the United States (n = 17, controlled trial). 146 (80%) participants were female; mean age (SD) was 48.6 (9.4) years. Relapsing remitting MS was the main diagnostic category (n = 123, 67%); 43 (26%) had secondary progressive disease; and the remainder were unspecified. MBIs lasted 6–8 weeks; attrition rates were variable (5-43%); all employed pre- post- measures; two had longer follow up; one at 3, and one at 6 months. Socio-economic status of participants was not made explicit; health service utilisation and costs were not reported. No study reported on perceived stress. All studies reported quality of life (QOL), mental health (anxiety and depression), physical (fatigue, standing balance, pain), and psychosocial measures. Statistically significant beneficial effects relating to QOL, mental health, and selected physical health measures were sustained at 3- and 6- month follow up.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusion&lt;/b&gt; From the limited data available, MBIs may benefit some MS patients in terms of QOL, mental health, and some physical health measures. Further studies are needed to clarify how MBIs might best serve the MS population.&lt;p&gt;&lt;/p&gt

Ocean forced variability of Totten Glacier mass loss

This is the author accepted manuscript. The final version is available from the Geological Society of London via the DOI in this record.A large volume of the East Antarctic Ice Sheet drains through the Totten Glacier (TG) and is thought to be a potential source of substantial global sea level rise over the coming centuries. We show the surface velocity and heightof the floating part of TG, which buttresses the grounded component, have varied substantially over two decades (1989–2011), with variations in surface height strongly anti-correlated with simulated basal melt rates (r=0.70, p<0.05). Coupled glacier/ice-shelf simulations confirm ice flow and thickness respond to both basal melting of the ice shelf and grounding on bed obstacles. We conclude the observed variability of TG is primarily ocean-driven. Ocean warming in this region will lead to enhanced ice-sheet dynamism and loss of upstream grounded ice.This work was supported by, Australian Antarctic Division projects 3103, 4077, 4287 and 4346, National Computing Infrastructure grant m68, NSF grant ANT-0733025, NASA grant NNX09AR52G (Operation Ice Bridge), NERC grant NE/F016646/1, NERC fellowship NE/G012733/2, the Jackson School of Geoscience, the Jet Propulsion Laboratory and the G. Unger Vetlesen Foundation. This research was also supported by the Australian Government’s Cooperative Research Centres Programme through the Antarctic Climate & Ecosystems Cooperative Research Centre. The work is also supported under the Australian Research Councils Special Research Initiative for Antarctic Gateway Partnership SR140300001. Landsat 4 and 7 images courtesy of the U.S. Geological Survey. This is UTIG contribution 2486. Thanks to Benoit Legresy for useful discussions

Theoretical study of the insulating oxides and nitrides: SiO2, GeO2, Al2O3, Si3N4, and Ge3N4

An extensive theoretical study is performed for wide bandgap crystalline oxides and nitrides, namely, SiO_{2}, GeO_{2}, Al_{2}O_{3}, Si_{3}N_{4}, and Ge_{3}N_{4}. Their important polymorphs are considered which are for SiO_{2}: $\alpha$-quartz, $\alpha$- and $\beta$-cristobalite and stishovite, for GeO_{2}: $\alpha$-quartz, and rutile, for Al_{2}O_{3}: $\alpha$-phase, for Si_{3}N_{4} and Ge_{3}N_{4}: $\alpha$- and $\beta$-phases. This work constitutes a comprehensive account of both electronic structure and the elastic properties of these important insulating oxides and nitrides obtained with high accuracy based on density functional theory within the local density approximation. Two different norm-conserving \textit{ab initio} pseudopotentials have been tested which agree in all respects with the only exception arising for the elastic properties of rutile GeO_{2}. The agreement with experimental values, when available, are seen to be highly satisfactory. The uniformity and the well convergence of this approach enables an unbiased assessment of important physical parameters within each material and among different insulating oxide and nitrides. The computed static electric susceptibilities are observed to display a strong correlation with their mass densities. There is a marked discrepancy between the considered oxides and nitrides with the latter having sudden increase of density of states away from the respective band edges. This is expected to give rise to excessive carrier scattering which can practically preclude bulk impact ionization process in Si_{3}N_{4} and Ge_{3}N_{4}.Comment: Published version, 10 pages, 8 figure