Berberine modulates expression of mdr1 gene product and the responses of digestive track cancer cells to Paclitaxel

Berberine is the major constituent of Coptis chinese and is commonly used in Chinese herbal medicine to treat patients with gastrointestinal disorders. In this study, using flow cytometry, we have found that a 24-h berberine treatment up-regulated the multidrug-resistant transporter (pgp-170) expression in two oral (KB, OC2), two gastric (SC-M1, NUGC-3) and two colon (COLO 205, CT 26) cancer cell lines. Decreased retention of rhodamine 123 was observed in berberine-treated cells as compared to vehicle control. To examine whether the berberine modulated pgp-170 expression in cancer cells is associated with changes in drug resistance, we determined the cytotoxicity, cell cycle progression and cell morphology of Paclitaxel-treated cells. Paclitaxel (1 nM–10 μM) treatment for 24 h induced cytotoxicity in OC2, SC-M1 and COLO 205 cells in a dose-dependent manner. Pretreatment of cells with 32 μM berberine for 24 h prior to Paclitaxel treatment resulted in increased viability as compared to that of Paclitaxel-treated cells. In addition, Paclitaxel-induced apoptosis and/or G2/M arrest in these three cancer cell lines. Pretreatment of cells with berberine prior to Paclitaxel blocked the Paclitaxel-induced cell cycle responses and morphological changes. These results together suggest that berberine modulated the expression and function of pgp-170 that leads to reduced response to Paclitaxel in digestive track cancer cells. © 1999 Cancer Research Campaig

Return-volume dynamics in UK futures

It is widely acknowledged in the financial literature that trading in asset markets is mainly induced by the arrival of new information. However, the contemporaneous and dynamic empirical relationships between volume and returns in futures data, with attendant implications for futures market microstructure, remain largely unresolved due to the inconclusive nature of the extant empirical literature. The present paper examines these relationships from the perspective of competing hypotheses in the context of data for three LIFFE futures contracts over a variety of intra-day frequencies. These results indicate not only a positive contemporaneous relationship between volume and absolute returns but also bidirectional causality for most series and frequencies, consistent with the sequential arrival of information hypothesis, but with different speeds of information dissemination across the three markets. Further examination of the contemporaneous and dynamic relationships between volume and actual returns reveals only limited evidence of any statistically significant associations implying market inefficiency, and consistent with an inverse association between informational asymmetry and market efficiency.

Physicochemical Characteristics, Cytotoxicity, and Antioxidant Activity of Three Lipid Nanoparticulate Formulations of Alpha-lipoic Acid

Exogenously supplied alpha-lipoic acid (LA) has proven to be effective as an antioxidant. In an effort to develop a water-soluble formulation for topical administration, LA was formulated in the form of solid lipid nanoparticles (SLN), nanostructure lipid carriers (NLC), and nanoemulsion (NE) and characterized in terms of physical and biological properties. Mean particle size of 113, 110, and 121 nm were obtained for NE, NLC, and SLN, respectively, with narrow size distribution. Zeta potential was approximately in the range of −25 to −40 mV. Disc and spherical structures of nanoparticles were observed by cryo-scanning electron microscopy. Entrapment efficiency of LA in three formulations was found to be more than 70%. After 120 days of storage at 25°C, physical stability of all formulations remained unchanged whereas the entrapment efficiency of SLN and NLC could be maintained, suggesting relative long-term stability. Prolonged release of LA formulation following the Higuchi model was found where a faster release was observed from NE compared with that of SLN and NLC. More than 80% of cell survivals were found up to 1 μM of LA concentrations. Antioxidant activity analysis demonstrated that all LA-loaded formulations expressed antioxidant activity at a similar magnitude as pure LA. These results suggest that chosen compositions of lipid nanoparticles play an important role on drug loading, stability, and biological activity of nanoparticles. Both SLN and NLC demonstrated their potential as alternative carriers for aqueous topical administration of LA