Non-viral Smad7 gene delivery and attenuation of postoperative peritoneal adhesion in an experimental model

Background: Postoperative intra-abdominal adhesion is associated with high morbidity and mortality. Smad7, a protein that occupies a strategic position in fibrogenesis, inhibits the transforming growth factor (TGF) β/Smad signalling pathway. In this study the therapeutic potential of exogenous Smad7 in preventing fibrogenesis in postoperative intra-abdominal adhesion was investigated. Methods: Intra-abdominal adhesion was induced in a rodent model by peritoneal abrasion. Smad7 was delivered into the peritoneal cavity by a non-viral ultrasound-microbubble-mediated naked gene transfection system. The effect of Smad7 transgene on adhesion formation was studied by measuring changes in TGF-β, fibrogenic factors, α-SMA and Smad2/3 activation in the anterior abdominal wall. Results: Four weeks after surgical abrasion, all rats developed significant peritoneal adhesion with enhanced TGF-β expression, increased levels of extracellular matrix components and activated myofibroblasts, accompanied by decreased Smad7 expression and increased Smad2/3 activation. In rats treated with the Smad7 transgene, the incidence and severity of peritoneal adhesion were significantly reduced, with biochemical downregulation of fibrogenic factors and inhibition of Smad2/3 activation. Serial quantitation using magnetic resonance imaging revealed a significant reduction in adhesion areas from day 14 onwards. Conclusion: Ultrasound-microbubble-mediated gene transfection provides timely targeted gene delivery for the treatment of postoperative peritoneal adhesions. Copyright © 2009 British Journal of Surgery Society Ltd. Published by John Wiley & Sons Ltd.postprin

MRI detection of peritoneal adhesion with dialysate enhancement

This study investigated the use of clinical peritoneal dialysis fluid (dialysate) as a peritoneal contrast agent to visualize peritoneal adhesions in rats at 7 Tesla. Intraperitoneal injection of dialysate (~0.1 mL/g) allowed the MR detection of peritoneal adhesions that were surgically induced in all rats studied (N = 6). MR measurements of adhesion surface areas correlated well with the postmortem estimations (R = 0.99). T1 and T2 values of undiluted dialysate were found to be 3017.5¡Ó35.3 ms and 108.4¡Ó2.0 ms, respectively. These findings demonstrated dialysate-enhanced MRI as a potentially valuable technique in clinical detection and evaluation of post-surgical peritoneal adhesion and to monitor therapeutic interventions (i.e., against peritoneal adhesion) in future preclinical research.published_or_final_versio

Jacobi-Predictor-Corrector Approach for the Fractional Ordinary Differential Equations

We present a novel numerical method, called {\tt Jacobi-predictor-corrector approach}, for the numerical solution of fractional ordinary differential equations based on the polynomial interpolation and the Gauss-Lobatto quadrature w.r.t. the Jacobi-weight function $\omega(s)=(1-s)^{\alpha-1}(1+s)^0$. This method has the computational cost O(N) and the convergent order $IN$, where $N$ and $IN$ are, respectively, the total computational steps and the number of used interpolating points. The detailed error analysis is performed, and the extensive numerical experiments confirm the theoretical results and show the robustness of this method.Comment: 24 pages, 5 figure

Expression and activities of three inducible enzymes in the healing of gastric ulcers in rats

Aim: To explore the roles of nitric oxide synthase (NOS), heme oxygenase (HO) and cyclooxygenase (COX) in gastric ulceration and to investigate the relationships of the expression and activities of these enzymes at different stages of gastric ulceration. Methods: Gastric ulcers (kissing ulcers) were induced by luminal application of acetic acid. Gastric tissue samples were obtained from the ulcer base, ulcer margin, and non-ulcerated area around the ulcer margin at different time intervals after ulcer induction. The mRNA expression and protein levels of inducible and constitutive isoforms of NOS, HO and COX were analyzed with RT-PCR and Western blotting methods. The activities of the total NOS, inducible NOS (iNOS), HO, and COX were also determined. Results: Differential expression of inducible iNOS, HO-1 and COX-2 and enzyme activities of NOS, HO and COX were found in the gastric ulcer base. High iNOS expression and activity were observed on day 1 to day 3 in severely inflamed ulcer tissues. Maximum expressions of HO-1 and COX-2 and enzyme activities of HO and COX lagged behind that of iNOS, and remained at high levels during the healing phase. Conclusion: The expression and activities of inducible NOS, HO-1 and COX-2 are found to be correlated to different stages of gastric ulceration. Inducible NOS may contribute to ulcer formation while HO-1 and COX-2 may promote ulcer healing.published_or_final_versio

Use of quercetin in animal feed : effects on the P-gp expression and pharmacokinetics of orally administrated enrofloxacin in chicken

Modulation of P-glycoprotein (P-gp, encoded by Mdr1) by xenobiotics plays central role in pharmacokinetics of various drugs. Quercetin has a potential to modulate P-gp in rodents, however, its effects on P-gp modulation in chicken are still unclear. Herein, study reports role of quercetin in modulation of P-gp expression and subsequent effects on the pharmacokinetics of enrofloxacin in broilers. Results show that P-gp expression was increased in a dose-dependent manner following exposure to quercetin in Caco-2 cells and tissues of chicken. Absorption rate constant and apparent permeability coefficient of rhodamine 123 were decreased, reflecting efflux function of P-gp in chicken intestine increased by quercetin. Quercetin altered pharmacokinetic of enrofloxacin by decreasing area under curve, peak concentration, and time to reach peak concentration and by increasing clearance rate. Molecular docking shows quercetin can form favorable interactions with binding pocket of chicken xenobiotic receptor (CXR). Results provide convincing evidence that quercetin induced P-gp expression in tissues by possible interaction with CXR, and consequently reducing bioavailability of orally administered enrofloxacin through restricting its intestinal absorption and liver/kidney clearance in broilers. The results can be further extended to guide reasonable use of quercetin to avoid drug-feed interaction occurred with co-administered enrofloxacin or other similar antimicrobials.Peer reviewedFinal Published versio

Momentum-resolved resonant inelastic soft X-ray scattering (qRIXS) endstation at the ALS

A momentum resolved resonant inelastic X-ray scattering (qRIXS) experimental station with continuously rotatable spectrometers and parallel detection is designed to operate at different beamlines at synchrotron and free electron laser (FEL) facilities. This endstation, currently located at the Advanced Light Source (ALS), has five emission ports on the experimental chamber for mounting the high-throughput modular soft X-ray spectrometers (MXS) [24]. Coupled to the rotation from the supporting hexapod, the scattered X-rays from 27.5° (forward scattering) to 152.5° (backward scattering) relative to the incident photon beam can be recorded, enabling the momentum-resolved RIXS spectroscopy. The components of this endstation are described in details, and the preliminary RIXS measurements on highly oriented pyrolytic graphite (HOPG) reveal the low energy vibronic excitations from the strong electron-phonon coupling at C K edge around σ* band. The grating upgrade option to enhance the performance at low photon energies is presented and the potential of this spectroscopy is discussed in summary

Nitrogen forms affect root structure and water uptake in the hybrid poplar

The study analyses the effects of two different forms of nitrogen fertilisation (nitrate and ammonium) on root structure and water uptake of two hybrid poplar (Populus maximowiczii x P. balsamifera) clones in a field experiment. Water uptake was studied using sap flow gauges on individual proximal roots and coarse root structure was examined by excavating 18 whole-root systems. Finer roots were scanned and analyzed for architecture. Nitrogen forms did not affect coarse-root system development, but had a significant effect on fine-root development. Nitrate-treated trees presented higher fine:coarse root ratios and higher specific root lengths than control or ammonium treated trees. These allocation differences affected the water uptake capacity of the plants as reflected by the higher sapflow rate in the nitrate treatment. The diameter of proximal roots at the tree base predicted well the total root biomass and length. The diameter of smaller lateral roots also predicted the lateral root mass, length, surface area and the number of tips. The effect of nitrogen fertilisation on the fine root structure translated into an effect on the functioning of the fine roots forming a link between form (architecture) and function (water uptake)

Eta Carinae and the Luminous Blue Variables

We evaluate the place of Eta Carinae amongst the class of luminous blue variables (LBVs) and show that the LBV phenomenon is not restricted to extremely luminous objects like Eta Car, but extends luminosities as low as log(L/Lsun) = 5.4 - corresponding to initial masses ~25 Msun, and final masses as low as ~10-15 Msun. We present a census of S Doradus variability, and discuss basic LBV properties, their mass-loss behaviour, and whether at maximum light they form pseudo-photospheres. We argue that those objects that exhibit giant Eta Car-type eruptions are most likely related to the more common type of S Doradus variability. Alternative atmospheric models as well as sub-photospheric models for the instability are presented, but the true nature of the LBV phenomenon remains as yet elusive. We end with a discussion on the evolutionary status of LBVs - highlighting recent indications that some LBVs may be in a direct pre-supernova state, in contradiction to the standard paradigm for massive star evolution.Comment: 27 pages, 6 figures, Review Chapter in "Eta Carinae and the supernova imposters" (eds R. Humphreys and K. Davidson) new version submitted to Springe

N-player quantum games in an EPR setting

The $N$-player quantum game is analyzed in the context of an Einstein-Podolsky-Rosen (EPR) experiment. In this setting, a player's strategies are not unitary transformations as in alternate quantum game-theoretic frameworks, but a classical choice between two directions along which spin or polarization measurements are made. The players' strategies thus remain identical to their strategies in the mixed-strategy version of the classical game. In the EPR setting the quantum game reduces itself to the corresponding classical game when the shared quantum state reaches zero entanglement. We find the relations for the probability distribution for $N$-qubit GHZ and W-type states, subject to general measurement directions, from which the expressions for the mixed Nash equilibrium and the payoffs are determined. Players' payoffs are then defined with linear functions so that common two-player games can be easily extended to the $N$-player case and permit analytic expressions for the Nash equilibrium. As a specific example, we solve the Prisoners' Dilemma game for general $N \ge 2$. We find a new property for the game that for an even number of players the payoffs at the Nash equilibrium are equal, whereas for an odd number of players the cooperating players receive higher payoffs.Comment: 26 pages, 2 figure

Strong signature of natural selection within an FHIT intron implicated in prostate cancer risk

Previously, a candidate gene linkage approach on brother pairs affected with prostate cancer identified a locus of prostate cancer susceptibility at D3S1234 within the fragile histidine triad gene (FHIT), a tumor suppressor that induces apoptosis. Subsequent association tests on 16 SNPs spanning approximately 381 kb surrounding D3S1234 in Americans of European descent revealed significant evidence of association for a single SNP within intron 5 of FHIT. In the current study, resequencing and genotyping within a 28.5 kb region surrounding this SNP further delineated the association with prostate cancer risk to a 15 kb region. Multiple SNPs in sequences under evolutionary constraint within intron 5 of FHIT defined several related haplotypes with an increased risk of prostate cancer in European-Americans. Strong associations were detected for a risk haplotype defined by SNPs 138543, 142413, and 152494 in all cases (Pearson's χ2 = 12.34, df 1, P = 0.00045) and for the homozygous risk haplotype defined by SNPs 144716, 142413, and 148444 in cases that shared 2 alleles identical by descent with their affected brothers (Pearson's χ2 = 11.50, df 1, P = 0.00070). In addition to highly conserved sequences encompassing SNPs 148444 and 152413, population studies revealed strong signatures of natural selection for a 1 kb window covering the SNP 144716 in two human populations, the European American (π = 0.0072, Tajima's D= 3.31, 14 SNPs) and the Japanese (π = 0.0049, Fay & Wu's H = 8.05, 14 SNPs), as well as in chimpanzees (Fay & Wu's H = 8.62, 12 SNPs). These results strongly support the involvement of the FHIT intronic region in an increased risk of prostate cancer. © 2008 Ding et al