Preparation of As4S4/Fe3O4 nanosuspensions and in-vitro verification of their anticancer activity.

Multifunctional nanoparticulate systems, especially those used in medicine, are currently of great interest. In this work, the in-vitro anticancer activity of As4S4/Fe3O4 composites dispersed in a water solution of Poloxamer 407 on breast MCF-7 and tongue SCC-25 cancer cells was verified. An increase in apoptotic cells as a consequence of higher caspase activities, a decrease in mitochondrial membrane potential and an accumulation of cells in the G2/M and subG0/G1 phases were detected after treatment with the As4S4/Fe3O4 nanosuspensions. The sterically stabilized nanosuspensions were characterized in relation to their particle size distribution, zeta potential and long-term stability properties. The interaction between the solid and liquid phases of the nanosuspensions was also studied using Fourier transform infrared spectroscopy.

Preparation, properties and anticancer effects of mixed As4S4/ZnS nanoparticles capped by Poloxamer 407.

Arsenic sulfide compounds have a long history of application in a traditional medicine. In recent years, realgar has been studied as a promising drug in cancer treatment. In this study, the arsenic sulfide (As4S4) nanoparticles combined with zinc sulfide (ZnS) ones in different molar ratio have been prepared by a simple mechanochemical route in a planetary mill. The successful synthesis and structural properties were confirmed and followed via X-ray diffraction and high-resolution transmission electron microscopy measurements. The morphology of the particles was studied via scanning electron microscopy and transmission electron microscopy methods and the presence of nanocrystallites was verified. For biological tests, the prepared As4S4/ZnS nanoparticles were further milled in a circulation mill in a water solution of Poloxamer 407 (0.5wt%), in order to cover the particles with this biocompatible copolymer and to obtain stable nanosuspensions with unimodal distribution. The average size of the particles in the nanosuspensions (~120nm) was determined by photon cross-correlation spectroscopy method. Stability of the nanosuspensions was determined via particle size distribution and zeta potential measurements, confirming no physico-chemical changes for several months. Interestingly, with the increasing amount of ZnS in the sample, the stability was improved. The anti-cancer effects were tested on two melanoma cell lines, A375 and Bowes, with promising results, confirming increased efficiency of the samples containing both As4S4 and ZnS nanocrystals.

Effect of verapamil on baroreflex sensitivity and on cardiovascular variability.

OBJECTIVE: Epidemiological evidence indicates that depressed baroreflex sensitivity and heart rate variability are associated with reduced survival secondary to coronary heart disease as well as with an increased risk of developing coronary heart disease. In view of the conflicting data in the literature concerning the effect of calcium channel antagonists on autonomic balance, we evaluated the effect of verapamil on heart rate and blood pressure variability, and on baroreflex sensitivity. METHODS: Baroreflex sensitivity was studied in 11 rabbits (27 series) under slight sedation induced by pentobarbital infusion (5 mg/kg/hour), both with a steady-state method using phenylephrine-induced blood pressure ramps, and by spectral analysis estimating the transfer function from mean arterial blood pressure to heart rate. Mean arterial blood pressure in the femoral artery, heart rate, and a microphotoelectric plethysmogram of the capillary network of rabbit's ears were simultaneously recorded during the entire experiment. Baroreflex sensitivity was measured before and after 30 min of verapamil infusion (20 micrograms/kg/min). RESULTS: Verapamil-reduced baroreflex sensitivity measured by steady-state (2.6 +/- 0.2-1.7 +/- 0.2 beats/min/mmHg, mean +/- SEM) and transfer function methods (19.0 +/- 3.1-5.3 +/- 0.9; control vs. verapamil infusion, p < 0.001), and increased cardiovascular variability as estimated both by standard deviation in mean arterial blood pressure (2.0 +/- 0.1-4.0 +/- 0.4 mm Hg) and standard deviation in heart rate (6.5 +/- 1.0-9.8 +/- 1.1 bpm; p < 0.05). Verapamil increased heart rate (+3%; p < 0.05), reduced systemic mean arterial blood pressure (-12%; p < 0.05), and mean arterial blood pressure swings induced by increasing doses of phenylephrine bolus injections (-6% to -15%; p < 0.05). The reduction was larger for larger blood pressure ramps and exceeded the systemic arterial pressure reduction induced by verapamil infusion. A nonsignificant trend towards an increase in microcirculation was observed. CONCLUSIONS: Besides the direct cardiodepressant and vasodilatatory action of verapamil, its suppressive effect on baroreflex sensitivity should be taken into account, since this sensitivity might contribute to an increased risk of cardiac morbidity and mortality.