Etoposide: four decades of development of a topoisomerase II inhibitor

Podophyllin-containing materials have been used as folk medicines for centuries. In the 1950s, scientists began a search to identify a more effective podophyllotoxin derivative. These efforts eventually resulted in the development of a new class of antineoplastic agents which target the DNA unwinding enzyme, topoisomerase II. The history of the development of one of the first identified topoisomerase II inhibitors, etoposide, is reviewed in this paper. Critical developments in etoposide's mechanism of action, pharmacology and administration schedule are summarised. The clinical benefits of the recently marketed etoposide prodrug, etoposide phosphate (Etopophos) are also detailed. The current status of other clinically approved anticancer agents which target topoisomerase II is briefly reviewed.     

Clinical applications of anticancer drugs targeted to topoisomerase II

Agents which 'poison' the enzyme topoisomerase II, have proven to be useful drugs for cancer treatment. Six antineoplastic drugs, which target topoisomerase II (doxorubicin, daunorubicin, idarubicin, mitoxantrone, etoposide and teniposide) are currently approved for clinical use in the United States. In this paper, the strategies and goals of cancer chemotherapy are summarized for the non-clinician. The use, pharmacology and toxicity of each of the six currently approved topoisomerase II inhibiting agents are reviewed.     

Formulation and characterisation of nanosuspension of herbal extracts for enhanced antiradical potential

Nanotechnology is a promising technique to increase the bioavailability of herbal medicines. This paper presents the nanosuspension approach for increasing the aqueous solubility and thereby bioactivity of important herbal extracts. Nanosuspensions of the seeds of three plants extract (Silybum marianum, Elettaria cardamomum and Coriandrum sativum) were prepared by using polyvinyl alcohol (1.5% w/v) as a stabiliser. Prepared nanoparticles were characterised by scanning electron microscope. Activity of nanosuspension formulation was assessed by using four in vitro antioxidant assays. S. marianum, E. cardamomum and C. sativum particle size was observed to fall in range of 446.1 ± 112.6, 456.63 ± 339.2 and 432.1 ± 172.8 nm, respectively, most of the particles were having spherical shape and smooth topology. These synthesised nanoparticles were found to be more effective against quenching free radical than their crude extracts and standards [butylated hydroxyl toluene and ascorbic acid]. C. sativum nanosuspension showed most free radical scavenging potential against 2,2-diphenyl-1-picrylhdrazyl (DPPH) and superoxide free radical scavenging assays (IC₅₀ 0.59 ± 0.01 and 0.81 ± 0.11 mg/ml). S. marianum nanosuspension was found to be most effective against DPPH radicals scavenging (IC₅₀ 0.34 ± 0.02 mg/ml). It was concluded that nanosuspension of herbal medicines potentiates the antioxidant potential.     

Conducting carbon/polymer composites as a catalyst support for proton exchange membrane fuel cells

Carbon/poly(3,4‐ethylene dioxythiophene) (C/PEDOT) composites are synthesized by in situ chemical oxidative polymerization of EDOT monomer on carbon black in order to decrease carbon corrosion that occurred in carbon‐supported catalysts used in proton exchange membrane fuel cell. The effects of different dopants including polystyrene sulfonic acid, p‐toluenesulfonic acid and camphorsulfonic acid with the addition of ethylene glycol or dimethyl sulfoxide on the properties of the composites are investigated. The synthesized composites are characterized by X‐ray diffraction, Fourier transform infrared spectroscopy, thermogravimetric analysis, surface area analysis and scanning electron microscope. Electrical conductivity is determined by using the four‐point probe technique. Electrochemical oxidation characteristics of the synthesized C/PEDOT composites are investigated by cyclic voltammetry by applying 1.2 V for 24 h. The composite prepared at 25 °C with p‐toluenesulfonic acid and ethylene glycol shows the best carbon corrosion resistance. Platinum‐supported catalyst by using this composite was prepared using microwave irradiation technique, and it was seen that the prepared catalyst did not significantly lose its hydrogen oxidation and oxygen reduction reaction activities after electrochemical oxidation. Copyright © 2013 John Wiley & Sons, Ltd.     

Polymerization of epoxides catalyzed by a mixed‐valent iron trifluoroacetate [Fe3O(O2CCF3)6(H2O)3]

The readily available mixed‐valent iron trifluoroacetate complex [Fe₂^IIIFe^II(µ₃‐O)(O₂CCF₃)₆(H₂O)₃] is an effective catalyst for the polymerization of epoxides. A very small amount of the catalyst (1.0–0.01 mol%) could initiate the polymerization of cyclohexene oxide, cyclopentene oxide and epichlorohydrin. Based on quantitative end‐group analysis by ¹⁹F NMR spectroscopy, a Lewis acid (LA^⊕) catalyzed anionic reaction mechanism is proposed. Copyright © 2012 Society of Chemical Industry     

A Novel Sprague-Dawley Rat Model Presents Improved NASH/NAFLD Symptoms with PEG Coated Vitexin Liposomes

Chronic liver disease (CLD) is a global threat to the human population, with manifestations resulting from alcohol-related liver disease (ALD) and non-alcohol fatty liver disease (NAFLD). NAFLD, if not treated, may progress to non-alcoholic steatohepatitis (NASH). Furthermore, inflammation leads to liver fibrosis, cirrhosis, and hepatocellular carcinoma. Vitexin, a natural flavonoid, has been recently reported for inhibiting NAFLD. It is a lipogenesis inhibitor and activates lipolysis and fatty acid oxidation. In addition, owing to its antioxidant properties, it appeared as a hepatoprotective candidate. However, it exhibits low bioavailability and low efficacy due to its hydrophobic nature. A novel rat model for liver cirrhosis was developed by CCL4/Urethane co-administration. Vitexin encapsulated liposomes were synthesized by the ‘thin-film hydration’ method. Polyethylene glycol (PEG) was coated on liposomes to enhance stability and stealth effect. The diseased rats were then treated with vitexin and PEGylated vitexin liposomes, administered intravenously and orally. Results ascertained the liposomal encapsulation of vitexin and subsequent PEG coating to be a substantial strategy for treating liver cirrhosis through oral drug delivery.     

食糖市场营销战略分析

2005/06年制糖期全国食糖产量881.5万t,消费量估计达到1070万t,主产区白糖平均售价达到4500元/t,制糖企业取得很好效益.新形势下制糖行业将发生转变,一是食糖流通企业经过整合力量不断壮大,二是市场化、国际化程度逐步提高,三是食糖价格将总体走高,四是甜菜糖和淀粉糖将加速发展.在新形势下制糖企业必须努力提高市场竞争力,制定市场营销战略,重视销售网络渠道建设,不断扩大市场份额.     

Dark fermentative hydrogen production from sucrose and molasses

There are many factors affecting the dark fermentative hydrogen production. The interaction of these factors, that is, their combined effects, should be investigated for better design of the systems with stable and higher hydrogen yields. This study aimed to investigate the combined effects of initial substrate, pH, and biomass (or initial substrate to biomass) values on hydrogen production from sucrose and sugar‐beet molasses. Therefore, optimum initial chemical oxygen demand (COD), pH, and volatile suspended solids (VSS) or initial substrate to biomass (VSS) ratio (S/X_o) values leading to the highest dark fermentative hydrogen production were investigated in batch reactors. An experimental design approach (response surface methodology) was used. Results revealed that when sucrose was the substrate, maximum hydrogen production yield (HY) of 2.3 mol H₂/mol sucrose_added was obtained at initial pH of 7 and COD of 10 g/L. Initial S/X_o values studied (4–20 g COD/g VSS) had no effect on HY, while the initial pH was found as the parameter mostly affecting both HY and hydrogen production rate (HPR). When substrate was molasses, initial COD concentration was the only variable affecting HY and HPR. Maximum of both was achieved at 10 g/L initial COD. Initial VSS values studied (2.5–7.5 g/L) had no effect on HPR and HY. This study also indicated that molasses leads to homoacetogenesis for potentially containing intrinsic microorganism and/or natural constituents; thus, sucrose is more advantageous for hydrogen production via fermentation. Homoacetogenesis should be prevented for effective optimization via response surface methodology, if substrate is a natural carbon source potential to have intrinsic microorganisms. Copyright © 2017 John Wiley & Sons, Ltd.     

Size and expansion ratio analysis of micro nozzle gas flow

Size and expansion ratio effects on the flowfield are investigated for micro converging-diverging nozzles. Numerical computations are conducted by using two dimensional augmented Burnett equations and Navier-Stokes equations that were derived from the Boltzmann equation. The Maxwell-Smoluchowski slip boundary condition is used for adiabatic walls, and Steger-Warming flux vector splitting scheme is applied to the convective inviscid flux terms. The results from the augmented Burnett equation are compared with Navier-Stokes and Direct Simulation Monte Carlo (DSMC) results. Then, nozzle-size analysis is conducted for between 2 µm and 100 µm throat width. Influence of the Knudsen number is investigated, and temperature and Mach number variations are presented. In addition, the influence of the expansion ratio is studied with three (1.7:1, 3.4:1, and 6.8:1) different configurations. The results are compared with each other and an experimental data in the literature.