Enhanced Cytotoxic Effect of Doxorubicin Conjugated to Glutathione-Stabilized Gold Nanoparticles in Canine Osteosarcoma—In Vitro Studies

Osteosarcoma (OSA) is the most common malignant bone neoplasia in humans and dogs. In dogs, treatment consists of surgery in combination with chemotherapy (mostly carboplatin and/or doxorubicin (Dox)). Chemotherapy is often rendered ineffective by multidrug resistance. Previous studies have revealed that Dox conjugated with 4 nm glutathione-stabilized gold nanoparticles (Au-GSH-Dox) enhanced the anti-tumor activity and cytotoxicity of Dox in Dox-resistant feline fibrosarcoma cell lines exhibiting high P-glycoprotein (P-gp) activity. The present study investigated the influence of Au-GSH-Dox on the canine OSA cell line D17 and its relationship with P-gp activity. A human Dox-sensitive OSA cell line, U2OS, served as the negative control. Au-GSH-Dox, compared to free Dox, presented a greater cytotoxic effect on D17 (IC₅₀ values for Au-GSH-Dox and Dox were 7.9 μg/mL and 15.2 μg/mL, respectively) but not on the U2OS cell line. All concentrations of Au-GSH (ranging from 10 to 1000 μg/mL) were non-toxic in both cell lines. Inhibition of the D17 cell line with 100 μM verapamil resulted in an increase in free Dox but not in intracellular Au-GSH-Dox. The results indicate that Au-GSH-Dox may act as an effective drug in canine OSA by bypassing P-gp.     

Investigation of the quantitative properties of the quadrupole orthogonal acceleration time-of-flight mass spectrometer with electrospray ionisation using 3,4-methylenedioxymethamphetamine

This paper describes the investigation of the potential of a quadrupole orthogonal acceleration time-of-flight mass spectrometer (Q-TOF) equipped with an atmospheric pressure ionisation interface for quantitative measurements of small molecules separated by reversed phase liquid chromatography. To this end, the detection limits and linear dynamic range in particular were studied in an LC/MS/MS experiment using 3,4-methylenedioxymethamphetamine standards and 3,4-methylenedioxyethylamphetamine for internal standardisation. In a second phase, the experiment was repeated with real biological extracts (whole blood, serum, and vitreous humour). A calibration for 3,4-methylenedioxymethamphetamine and its metabolite 3,4-methylenedioxyamphetamine was prepared in each of these matrices again using 3,4-methylenedioxyethylamphetamine as internal standard. The resulting quantitative data were compared with those obtained by liquid chromatography with fluorescence detection for the same extracts. The Q-TOF results revealed excellent sensitivity and a linear dynamic range of nearly four decades (2-10 000 pg on-column, r(2) = 0.9998, 1/x weighting). Furthermore, all the calibration curves prepared in biological material were superimposable, LC/MS/MS and LC-fluorescence, and the quantitative results for actual samples compared very favourably. It was concluded that the Q-TOF achieves a linear dynamic range for quantitative LC/MS/MS work exceeding that of fluorescence detection and at much better absolute sensitivity. Copyright 1999 John Wiley & Sons, Ltd.     

Preparative Electrosynthesis of Strong Oxidizers at Boron-Doped Diamond Electrode in Anhydrous HF

The use of the boron-doped diamond electrode as a sufficiently stable electrode for electrochemical measurements/synthesis in liquid anhydrous hydrogen fluoride medium is reported. Electrooxidation of silver(I) has been studied in this solvent by using classical transient electrochemical methods and impedance spectroscopy. It has been found that faradaic currents related to silver(I) oxidation and the fluorine evolution reaction are reasonably separated at the potential scale, which allows efficient electrosynthesis of Ag^IIF₂, a powerful oxidizer. Impedance spectroscopy measurements provide insight into complex mechanism of AgF₂ formation. The procedure for electrosynthesis is provided for the first time in both galvanostatic and potentiostatic condition.     

Expedient Synthesis of Oxaboracyclic Compounds Based on Naphthalene and Biphenyl Backbone and Phase-Dependent Luminescence of their Chelate Complexes

The approach to a series of six- and seven-membered oxaboraheterocycles based on naphthalene or biphenyl backbones was developed. The key synthetic step involved Br/Li exchange in respective potassium (bromoaryl)trifluoroborates followed by quenching with selected electrophiles (CO₂, DMF, Me₂Si(H)Cl) and hydrolytic workup. Two ring-expanded benzoxaborole congeners were obtained by an additional reduction step with LiAlH₄ or NaBH₄. The obtained boracyclic compounds were characterized in detail by NMR spectroscopy and single-crystal X-ray diffraction. Specifically, biphenyl-based systems show dynamic behaviour interpreted in terms of inversion of non-planar seven-membered boraheterocycles. The acidity of the obtained compounds varies very strongly (pK_a ranges from 3.1–9.6) depending on their structure. Due to the enhanced boron Lewis acidity, selected compounds were used as a basis for luminescent complexes with 8-hydroxyquinoline. A strong phase-dependent variation of emission-band maximum (480–527 nm) and photoluminescence quantum yield (10–95 %) was observed, which was rationalized in terms of specific aggregation effects.     

Search for Lorentz invariance and CPT violation with the MINOS far detector

We searched for a sidereal modulation in the MINOS far detector neutrino rate. Such a signal would be a consequence of Lorentz and CPT violation as described by the standard-model extension framework. It also would be the first detection of a perturbative effect to conventional neutrino mass oscillations. We found no evidence for this sidereal signature, and the upper limits placed on the magnitudes of the Lorentz and CPT violating coefficients describing the theory are an improvement by factors of 20-510 over the current best limits found by using the MINOS near detector.     

Measurement of neutrino oscillations with the MINOS detectors in the NuMI beam

This Letter reports new results from the MINOS experiment based on a two-year exposure to muon neutrinos from the Fermilab NuMI beam. Our data are consistent with quantum-mechanical oscillations of neutrino flavor with mass splitting |Deltam2| = (2.43+/-0.13) x 10(-3) eV2 (68% C.L.) and mixing angle sin2(2theta) > 0.90 (90% C.L.). Our data disfavor two alternative explanations for the disappearance of neutrinos in flight: namely, neutrino decays into lighter particles and quantum decoherence of neutrinos, at the 3.7 and 5.7 standard-deviation levels, respectively.     

Specific volume of bisphenol C-2 polycarbonate

The molecular weight (M) dependence of specific volume (v_sp) for bisphenol C-2 polycarbonate (BCPC) is described. It has been confirmed that the Fox-Flory relation v_sp=A₀ + (A₁/M) is satisfied at 296 K, i.e. below the glass transition temperature of BCPC (441 K). The specific volume data for BCPC have been determined and compared with the corresponding data for bisphenol A polycarbonate.