Mechanism and kinetics of halogenated compound removal by metallic iron: Transport in solution, diffusion and reduction within corrosion films.

A detailed kinetic model comprised of mass transport (ktra), pore diffusion (kdif), adsorption and reduction reaction (krea), was developed to quantitatively evaluate the effect of corrosion films on the removal rate (kobs) of halogenated compounds by metallic iron. Different corrosion conditions were controlled by adjusting the iron aging time (0 or 1 yr) and dissolved oxygen concentration (0-7.09 mg/L DO). The kobs values for bromate, mono-, di- and tri-chloroacetic acids (BrO3-, MCAA, DCAA and TCAA) were 0.41-7.06, 0-0.16, 0.01-0.53, 0.10-0.73 h-1, with ktra values at 13.32, 12.12, 11.04 and 10.20 h-1, kdif values at 0.42-5.82, 0.36-5.04, 0.30-4.50, 0.30-3.90 h-1, and krea values at 14.94-421.18, 0-0.19, 0.01-1.30, 0.10-3.98 h-1, respectively. The variation of kobs value with reaction conditions depended on the reactant species, while those of ktra, kdif and krea values were irrelevant to the species. The effects of corrosion films on kdif and krea values were responsible for the variation of kobs value for halogenated compounds. For a mass-transfer-limited halogenated compound such as BrO3-, an often-neglected kdif value primarily determined its kobs value when pore diffusion was the rate-limiting step of its removal. In addition, the value of kdif might influence product composition during a consecutive dechlorination, such as for TCAA and DCAA. For a reaction-controlled compound such as MCAA, an increased krea value was achieved under low oxic conditions, which was favorable to improve its kobs value. The proposed model has a potential in predicting the removal rate of halogenated compounds by metallic iron under various conditions.

Afatinib reverses multidrug resistance in ovarian cancer via dually inhibiting ATP binding cassette subfamily B member 1.

ABCB1-mediated multidrug resistance (MDR) remains a major obstacle to successful chemotherapy in ovarian cancer. Herein, afatinib at nontoxic concentrations significantly reversed ABCB1-mediated MDR in ovarian cancer cells in vitro (p < 0.05). Combining paclitaxel and afatinib caused tumor regressions and tumor necrosis in A2780T xenografts in vivo. More interestingly, unlike reversible TKIs, afatinib had a distinctive dual-mode action. Afatinib not only inhibited the efflux function of ABCB1, but also attenuated its expression transcriptionally via down-regulation of PI3K/AKT and MAPK/p38-dependent activation of NF-κB. Furthermore, apart from a substrate binding domain, afatinib could also bind to an ATP binding domain of ABCB1 through forming hydrogen bonds with Gly533, Gly534, Lys536 and Ala560 sites. Importantly, mutations in these four binding sites of ABCB1 and the tyrosine kinase domain of EGFR were not correlated with the reversal activity of afatinib on MDR. Given that afatinib is a clinically approved drug, our results suggest combining afatinib with chemotherapeutic drugs in ovarian cancer. This study can facilitate the rediscovery of superior MDR reversal agents from molecular targeted drugs to provide a more effective and safer way of resensitizing MDR.

[Pharmacokinetics of amphotericin B in the cerebrospinal fluid during continuous intrathecal administration for treatment of cryptococcal neoformans meningitis].

OBJECTIVE: To explore the pharmacokinetics of amphotericin B (AMB) in the cerebrospinal fluid (CSF) during continuous intrathecal administration of AMB for treatment of cryptococcal neoformans meningitis (CNM). METHODS: The concentration of AMB in the CSF was measured using reversed phase high performance liquid chromatography (RP-HPLC) in 3 patients receiving continuous intrathecal infusion of AMB for CNM. RESULTS: AMB concentrations in the CSF of the 3 patients exceeded the minimal inhibitory concentration (MIC) of AMB against Cryptococcus neoformans. The concentration-time curve showed that AMB concentration in the CSF underwent obvious variations on the first day of intrathecal infusion and after additional AMB doses, but maintained a stable level (0.61-1.21 µg/ml) on the next day. CONCLUSION: [corrected] Continuous intrathecal administration of AMB can enhance the drug concentration in the CSF and maintain a stable and effective drug level for treatment of CNM.

[Pharmacokinetics, tissue distribution and magnetic resonance's response characterstics of folic acid-O-carboxymethyl chitosan ultrasmall superparamagnetic iron oxide nanoparticles in mice and rats].

Folic acid-O-carboxymethyl chitosan ultrasmall superparamagnetic iron oxide nanoparticles (FA-OCMCS-USPIO-NPs) are a novel molecular targeting MR contrast agent. This paper reperts the pharmacokinetics and magnetic resonance response characteristics of FA-OCMCS-USPIO-NPs in normal rats and mice, and discussed its distributing regularity in animals, providing basis for tumor targeting imaging. O-phenanthroline method was used to determine iron content in rats' plasma and mice's organs following high and low doses of nanoparticles injected through tail vein, and the blood concentration-time curve was drawn, the calculated t1/2 of two groups were greater than 7 h. The results of tissue distribution showed that only a small part of nanoparticles were swallowed by the liver and spleen, while none in the heart, lung and kidney. At the same times, the phagocytosis of nanoparticles did not change with the dose. The results of MRI showed that renal excretion occurred 4 hours after injection, and signal to noise ratio (SNR) of liver and kidney returned to normal levels 24 hours after injection. There were no nanoparticles in the lungs. So a part of nanoparticles escaped from phagocytosis of liver and spleen, and it owned lower toxicity and longer half-life. indicated its use for tumor-targeting imaging. All of these indicated its use for tumor-targeting imaging.

[Preparation and characterization of superparamagnetic iron oxide nanoparticles].

OBJECTIVE: To determine the physical and magnetic properties of superparamagnetic iron oxide (SPIO) nanoparticle prepared in our laboratory and evaluate its possibility for use as contrast agents in magnetic resonance imaging (MRI). METHODS: The SPIO nanoparticle was obtained by means of classical coprecipitation in dextran solution and its size determined by electron microscopy and photon-correlation spectroscopy. The iron content was determined by phenanthroline photometry, and T(2) values as well as relaxivity evaluated with a clinical MR system at 1.5T. RESULTS: Dextran-coated magnetite particles with a hydrodynamic diameter of 85.9 nm were prepared. The iron core size was 15 nm and the formation of Fe(3)O(4) crystal in SPIO nanoparticles was confirmed by X-ray diffraction (XRD) analysis. These particles possessed some characteristics of superparamagnetic and show a smaller spin-spin relaxation, with relaxivity and saturation magnetization of 0.1567 mmol(-1)/ms(-1) and 80 emu/g Fe, respectively. CONCLUSIONS: A stable SPIO nanoparticle with a dextran coating have been developed, and in vitro evaluation of its physical and magnetic properties suggests its potential for use as the contrast agent in MRI.

[Sampling of exhaled gas after intravenous administration of octafluoropropane-containing human albumin micropheres in dogs].

OBJECTIVE: To develop a method for quantitative collection of exhaled gas in anesthetized dogs at given time following intravenous administration of octafluoropropane (OFP)-containing human albumin micropheres for assessing the gas kinetics of OFP. METHODS: OFP-containing albumin micropheres were administered intravenously at 0.4, 0.8 and 1.2 ml/kg, respectively, in anesthetized and ventilated dogs. The exhaled air samples were analyzed by gas chromatography-tandem mass spectrometry (GC-MS-MS). RESULTS: The correlation curve between the area under curve (AUC) and administered dose was roughly linear (Y=1162.5X-417.38, r square=0.949 9). The total recovery rate was (119.49-/+27.62)% which was not significantly different from the rate of 100% (P>0.05). GC-MS-MS was accurate, sensitive, precise and applicable for OFP determination. CONCLUSION: The sampling method is useful for characterizing OFP pharmacokinetics in dogs, and also applicable for studying the pharmacokinetics of other gas-containing drugs.

Effect of Changtong oral liquid on serum cytokine concentrations in rats with postoperative intestinal adhesion.

OBJECTIVE: To observe the effects of Changtong oral liquid (CTOL) on the serum levels of tumor necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta(1), interleukin (IL)-1beta, IL-4, IL-6 and IL-10 in rats with postoperative intestinal adhesions. METHODS: Fifty-four male Sprague-Dawley rats were randomized into 6 equal groups, namely the normal control, model, Simo decoction (SMD) groups and three CTOL groups of low, moderate, and high doses, respectively. Intestinal adhesion was induced in the rats of the groups other than the normal control group. The rats in the normal control and model groups received intragastric administration of distilled water (10 ml/kg), and those in the 4 treatment groups had SMD (10 ml/kg) and CTOL (at 4.3, 8.6 and 17.2 g/kg for low, moderate, and high dose groups, respectively). On day 7 after surgery, blood samples were obtained from the rats for measurement of serum cytokine levels with enzyme-linked immunosorbent assay followed by adhesion grading according to a 5-grade scale. RESULTS: CTOL evidently reduced the severity of postoperative adhesions and decreased the serum levels of the proinflammatory cytokines such as TNF-alpha, IL-1beta, TGF-beta(1) and IL-6. However, it had no significant impact on serum levels of the anti-inflammatory cytokines IL-4 and IL-10 in rats with postoperative adhesion. CONCLUSION: Significant indices for postoperative adhesion assessment are established, which provides the experimental basis for evaluating clinical therapeutic effects of postoperative adhesions as well as for developing new therapeutic drugs.