The preparation, characterization, and pharmacokinetic studies of chitosan nanoparticles loaded with paclitaxel/dimethyl-β-cyclodextrin inclusion complexes.

A novel biocompatible and biodegradable drug-delivery nanoparticle (NP) has been developed to minimize the severe side effects of the poorly water-soluble anticancer drug paclitaxel (PTX) for clinical use. PTX was loaded into the hydrophobic cavity of a hydrophilic cyclodextrin derivative, heptakis (2,6-di-O-methyl)-β-cyclodextrin (DM-β-CD), using an aqueous solution-stirring method followed by lyophilization. The resulting PTX/DM-β-CD inclusion complex dramatically enhanced the solubility of PTX in water and was directly incorporated into chitosan (CS) to form NPs (with a size of 323.9–407.8 nm in diameter) using an ionic gelation method. The formed NPs had a zeta potential of +15.9–23.3 mV and showed high colloidal stability. With the same weight ratio of PTX to CS of 0.7, the loading efficiency of the PTX/DM-β-CD inclusion complex-loaded CS NPs was 30.3-fold higher than that of the PTX-loaded CS NPs. Moreover, it is notable that PTX was released from the DM-β-CD/CS NPs in a sustained-release manner. The pharmacokinetic studies revealed that, compared with reference formulation (Taxol(®)), the PTX/DM-β-CD inclusion complex-loaded CS NPs exhibited a significant increase in AUC(0→24h) (the area under the plasma drug concentration–time curve over the period of 24 hours) and mean residence time by 2.7-fold and 1.4-fold, respectively. Therefore, the novel drug/DM-β-CD inclusion complex-loaded CS NPs have promising applications for the significantly improved delivery and controlled release of the poorly water-soluble drug PTX or its derivatives, thus possibly leading to enhanced therapeutic efficacy and less severe side effects

Solutions of Several Coupled Discrete Models in terms of Lame Polynomials of Order One and Two

Coupled discrete models abound in several areas of physics. Here we provide an extensive set of exact quasiperiodic solutions of a number of coupled discrete models in terms of Lame polynomials of order one and two. Some of the models discussed are (i) coupled Salerno model, (ii) coupled Ablowitz-Ladik model, (iii) coupled saturated discrete nonlinear Schrodinger equation, (iv) coupled phi4 model, and (v) coupled phi6 model. Furthermore, we show that most of these coupled models in fact also possess an even broader class of exact solutions.Comment: 31 pages, to appear in Pramana (Journal of Physics) 201

Solutions of Several Coupled Discrete Models in terms of Lame Polynomials of Arbitrary Order

Coupled discrete models abound in several areas of physics. Here we provide an extensive set of exact quasiperiodic solutions of a number of coupled discrete models in terms of Lam\'e polynomials of arbitrary order. The models discussed are (i) coupled Salerno model, (ii) coupled Ablowitz-Ladik model, (iii) coupled $\phi^4$ model, and (iv) coupled $\phi^6$ model. In all these cases we show that the coefficients of the Lam\'e polynomials are such that the Lam\'e polynomials can be reexpressed in terms of Chebyshev polynomials of the relevant Jacobi elliptic function

Association between Low Density Lipoprotein Receptor-Related Protein 2 Gene Polymorphisms and Bone Mineral Density Variation in Chinese Population

Low density lipoprotein receptor-related protein 2 gene (LRP2) is located next to the genomic region showing suggestive linkage with both hip and wrist bone mineral density (BMD) phenotypes. LRP2 knockout mice showed severe vitamin D deficiency and bone disease, indicating the involvement of LRP2 in the preservation of vitamin D metabolites and delivery of the precursor to the kidney for the generation of 1α,25(OH)2D3. In order to investigate the contribution of LRP2 gene polymorphisms to the variation of BMD in Chinese population, a total of 330 Chinese female-offspring nuclear families with 1088 individuals and 400 Chinese male-offspring nuclear families with 1215 individuals were genotyped at six tagSNPs of the LRP2 gene (rs2389557, rs2544381, rs7600336, rs10210408, rs2075252 and rs4667591). BMD values at the lumbar spine 1–4 (L1-4) and hip sites were measured by DXA. The association between LRP2 polymorphisms and BMD phenotypes was assessed by quantitative transmission disequilibrium tests (QTDTs) in female- and male-offspring nuclear families separately. In the female-offspring nuclear families, rs2075252 and haplotype GA of rs4667591 and rs2075252 were identified in the nominally significant total association with peak BMD at L1-4; however, no significant within-family association was found between peak BMD at the L1-4 and hip sites and six tagSNPs or haplotypes. In male-offspring nuclear families, neither the six tagSNPs nor the haplotypes was in total association or within-family association with the peak BMD variation at the L1-4 and hip sites by QTDT analysis. Our findings suggested that the polymorphisms of LRP2 gene is not a major factor that contributes to the peak BMD variation in Chinese population

Diagnostic significance of CK19, TG, Ki67 and galectin-3 expression for papillary thyroid carcinoma in the northeastern region of China

<p>Abstract</p> <p>Background</p> <p>To evaluate the expression and differential diagnostic significance of CK19, TG, Ki67 and galectin-3 in papillary thyroid carcinoma (PTC) (metastatic and non metastatic), follicular adenoma and nodular goiter in patients from the northeastern part of China.</p> <p>Methods</p> <p>441 PTC specimens and 151 other benign thyroid specimens (97 cases of nodular goiter, 54 cases of nonmalignant follicular adenoma) were collected. Immunohistochemistry for CK19, TG, Ki67 and galectin-3 was performed.</p> <p>Results</p> <p>CK19, TG, Ki67 and galectin-3 expression was 96.37% (425/441), 82.77% (365/441), and 40.59% (179/441), 96.82% (427/441), respectively, for the PTC group and the expression of these markers in the benign thyroid lesions group was 25.83% (39/151), 79.47% (120/151), and 37.09% (56/151), 50.99% (77/151), respectively. The expression of CK19 and galectin-3 in PTC was much higher than that in the nonmalignant group (p < 0.05). However, the expression of TG, Ki67 did not differ among these two groups (p > 0.05). The diagnostic efficiency of CK19 and galectin-3 for PTC was 96.37% (537/592) and 84.63% (501/592). CK19 and galectin-3 expression rate in PTC was higher than that in benign disease cases.</p> <p>Conclusions</p> <p>The diagnostic efficiency of CK19 for PTC was slightly better than galectin-3. The utilization of these markers combined with morphologic evaluation may be helpful in the differential diagnosis of papillary thyroid carcinoma in the northeastern region of China.</p

Measurement of CP-violation asymmetries in D0 to Ks pi+ pi-

We report a measurement of time-integrated CP-violation asymmetries in the resonant substructure of the three-body decay D0 to Ks pi+ pi- using CDF II data corresponding to 6.0 invfb of integrated luminosity from Tevatron ppbar collisions at sqrt(s) = 1.96 TeV. The charm mesons used in this analysis come from D*+(2010) to D0 pi+ and D*-(2010) to D0bar pi-, where the production flavor of the charm meson is determined by the charge of the accompanying pion. We apply a Dalitz-amplitude analysis for the description of the dynamic decay structure and use two complementary approaches, namely a full Dalitz-plot fit employing the isobar model for the contributing resonances and a model-independent bin-by-bin comparison of the D0 and D0bar Dalitz plots. We find no CP-violation effects and measure an asymmetry of ACP = (-0.05 +- 0.57 (stat) +- 0.54 (syst))% for the overall integrated CP-violation asymmetry, consistent with the standard model prediction.Comment: 15 page

A Search for Dark Higgs Bosons

Recent astrophysical and terrestrial experiments have motivated the proposal of a dark sector with GeV-scale gauge boson force carriers and new Higgs bosons. We present a search for a dark Higgs boson using 516 fb-1 of data collected with the BABAR detector. We do not observe a significant signal and we set 90% confidence level upper limits on the product of the Standard Model-dark sector mixing angle and the dark sector coupling constant.Comment: 7 pages, 5 postscript figures, published version with improved plots for b/w printin

Increased Expression of Integrin-Linked Kinase Improves Cardiac Function and Decreases Mortality in Dilated Cardiomyopathy Model of Rats

AIMS: Integrin-linked kinase (ILK) is a multifunctional kinase linking the extracellular matrix to intracellular signaling pathways, whose activation in the heart gives rise to a number of functional consequences. The aim of this study is to demonstrate the therapeutic and survival benefit of cardiac ILK overexpression in a rat model of dilated cardiomyopathy. METHODS AND RESULTS: The dilated cardiomyopathy model was generated in rats by intraperitoneal administration of six equal doses of doxorubicin over a 2 week period. Five weeks after the first injection, echocardiographic analysis demonstrated impaired cardiac function and, at that point, recombinant adenoviral vector harboring ILK cDNA or vehicle was injected into the myocardium, and the rats re-studied 4 weeks later. Compared with vehicle injection, ILK treatment ameliorated inflammatory cell infiltration and cardiomyocyte degeneration, as well as left ventricular dilation and dysfunction. ILK treatment was also associated with a reduction in apoptosis and an increase in proliferation of cardiomyocytes, as well as decreased oxidative stress and autophagic vacuole accumulation. Importantly, mortality was lower in rats following ILK treatment than in those following vehicle injection. In cultured neonatal rat cardiomyocytes, we also found that ILK overexpression protected against doxorubicin-induced apoptosis, giving rise to an increase in their proliferation. CONCLUSIONS: These data demonstrate for the first time that ILK gene therapy improves cardiac function and survival in a model of dilated cardiomyopathy, and this may be mediated through suppression of inflammation, prevention of ventricular remodeling, inhibition of cardiomyocyte apoptosis and autophagy, and stimulation of cardiomyocyte proliferation