Comparison of the Toxicity of Pristine Graphene and Graphene Oxide,Using Four Biological Models

There are numerous applications of graphene in biomedicine and they can be classified into several main areas: delivery systems, sensors, tissue engineering and biological agents. The growing biomedical field of applications of graphene and its derivates raises questions regarding their toxicity. We will demonstrate an analysis of the toxicity of two forms of graphene using four various biological models: zebrafish (Danio rerio) embryo, duckweed (Lemna minor), human HS-5 cells and bacteria (Staphylococcus aureus). The toxicity of pristine graphene (PG) and graphene oxide (GO) was tested at concentrations of 5, 10, 20, 50 and 100 µg/mL. Higher toxicity was noted after administration of high doses of PG and GO in all tested biological models. Hydrophilic GO shows greater toxicity to biological models living in the entire volume of the culture medium (zebrafish, duckweed, S. aureus). PG showed the highest toxicity to adherent cells growing on the bottom of the culture plates—human HS-5 cells. The differences in toxicity between the tested graphene materials result from their physicochemical properties and the model used. Dose-dependent toxicity has been demonstrated with both forms of graphene.     

Effect of body mass and clothing on decomposition of pig carcasses

Carcass mass and carcass clothing are factors of potential high forensic importance. In casework, corpses differ in mass and kind or extent of clothing; hence, a question arises whether methods for post-mortem interval estimation should take these differences into account. Unfortunately, effects of carcass mass and clothing on specific processes in decomposition and related entomological phenomena are unclear. In this article, simultaneous effects of these factors are analysed. The experiment followed a complete factorial block design with four levels of carcass mass (small carcasses 5–15 kg, medium carcasses 15.1–30 kg, medium/large carcasses 35–50 kg, large carcasses 55–70 kg) and two levels of carcass clothing (clothed and unclothed). Pig carcasses (N?=?24) were grouped into three blocks, which were separated in time. Generally, carcass mass revealed significant and frequently large effects in almost all analyses, whereas carcass clothing had only minor influence on some phenomena related to the advanced decay. Carcass mass differently affected particular gross processes in decomposition. Putrefaction was more efficient in larger carcasses, which manifested itself through earlier onset and longer duration of bloating. On the other hand, active decay was less efficient in these carcasses, with relatively low average rate, resulting in slower mass loss and later onset of advanced decay. The average rate of active decay showed a significant, logarithmic increase with an increase in carcass mass, but only in these carcasses on which active decay was driven solely by larval blowflies. If a blowfly-driven active decay was followed by active decay driven by larval Necrodes littoralis (Coleoptera: Silphidae), which was regularly found in medium/large and large carcasses, the average rate showed only a slight and insignificant increase with an increase in carcass mass. These results indicate that lower efficiency of active decay in larger carcasses is a consequence of a multi-guild and competition-related pattern of this process. Pattern of mass loss in large and medium/large carcasses was not sigmoidal, but rather exponential. The overall rate of decomposition was strongly, but not linearly, related to carcass mass. In a range of low mass decomposition rate increased with an increase in mass, then at about 30 kg, there was a distinct decrease in rate, and again at about 50 kg, the rate slightly increased. Until about 100 accumulated degree-days larger carcasses gained higher total body scores than smaller carcasses. Afterwards, the pattern was reversed; moreover, differences between classes of carcasses enlarged with the progress of decomposition. In conclusion, current results demonstrate that cadaver mass is a factor of key importance for decomposition, and as such, it should be taken into account by decomposition-related methods for post-mortem interval estimation.     

Stereoselective disposition of the geometric isomers of a novel lipoxygenase cyclo-oxygenase inhibitor in dog and photochemical interconversion of its isomers

A sensitive (10 ng/mL) and specific high-performance liquid chromatographic (HPLC) assay, with electrochemical (EC) detection, for the geometric isomers of 3-hydroxy-N-(2-phenyl-2-(2-thienyl)ethenyl-5-(trifluoromethyl)benzo(b) thiophene-2-carboxamide in dog and human plasma has been developed. Both isomers strongly absorb light, leading to an efficient E in equilibrium Z photoisomerization. After iv administration of a single isomer (Z) to a dog, only the Zisomer was detected in plasma; no in vivo conversion to the E isomer was observed. However, when a mixture of the E and Z isomers (58.6:41.4) was administered in the same manner to the same dog, the E:Z ratio decreased significantly to 47.5:52.5 six hours after drug administration, indicating stereoselective disposition of the isomers. The elimination of the E isomer was found to be faster than that of the Z isomer.     

Cell tagging with clinically approved iron oxides: feasibility and effect of lipofection, particle size, and surface coating on labeling efficiency

PURPOSE: To evaluate the effect of lipofection, particle size, and surface coating on labeling efficiency of mammalian cells with superparamagnetic iron oxides (SPIOs). MATERIALS AND METHODS: Institutional Review Board approval was not required. Different human cell lines (lung and breast cancer, fibrosarcoma, leukocytes) were tagged by using carboxydextran-coated SPIOs of various hydrodynamic diameters (17-65 nm) and a dextran-coated iron oxide (150 nm). Cells were incubated with increasing concentrations of iron (0.01-1.00 mg of iron [Fe] per milliliter), including or excluding a transfection medium (TM). Cellular iron uptake was analyzed qualitatively at light and electron microscopy and was quantified at atomic emission spectroscopy. Cell visibility was assessed with gradient- and spin-echo magnetic resonance (MR) imaging. Effects of iron concentration in the medium and of lipofection on cellular SPIO uptake were analyzed with analysis of variance and two-tailed Student t test, respectively. RESULTS: Iron oxide uptake increased in a dose-dependent manner with higher iron concentrations in the medium. The TM significantly increased the iron load of cells (up to 2.6-fold, P < .05). For carboxydextran-coated SPIOs, larger particle size resulted in improved cellular uptake (65 nm, 4.37 microg +/- 0.08 Fe per 100 000 cells; 17 nm, 2.14 microg +/- 0.06 Fe per 100 000 cells; P < .05). Despite larger particle size, dextran-coated iron oxides did not differ from large carboxydextran-coated particles (150 nm, 3.81 microg +/- 0.46 Fe per 100 000 cells; 65 nm, 4.37 microg +/- 0.08 Fe per 100 000 cells; P > .05). As few as 10 000 cells could be detected with clinically available MR techniques by using this approach. CONCLUSION: Lipofection-based cell tagging is a simple method for efficient cell labeling with clinically approved iron oxide-based contrast agents. Large particle size and carboxydextran coating are preferable for cell tagging with endocytosis- and lipofection-based methods.     

Telomerase activity in urine sediments as a tool for noninvasive detection of bladder cancer

Telomerase is extensively investigated as potential diagnostic and prognostic marker in human tumors. In this study, we determined telomerase activity in histological specimens and voided urine of 52 human bladder cancers. Using the PCR-ELISA method telomerase activity was found in 21 (88%) of the 24 tumor tissues and in the corresponding sediments from voided urine of patients with superficial bladder carcinoma (Ta/T1). In case of muscle-invasive tumors (T2-T4), telomerase activity was found in 27 (96%) of the 28 tumor tissues and in 26 (93%) of the 28 urine sediments. Enzyme activity was not detected in 13 control urine sediments. Telomerase activity was not significantly associated with clinicopathological parameters supporting the diagnostic rather than prognostic value of this marker in bladder cancer. The present study demonstrates that telomerase activity detection in voided urine has high potential for noninvasive diagnosis of superficial bladder tumors.     

Sunitinib in combination with clarithromycin or azithromycin – is there a risk of interaction or not?

BackgroundMacrolides are the most widely prescribed antibiotics. Clarithromycin is a well-known inhibitor of cytochrome P450 CYP3A4 and causes numerous drug interactions that are not found for azithromycin. CYP3A4 is involved in the metabolism of the new oral multikinase inhibitor sunitinib and its active N-desethyl metabolite (SU012662). This study investigated the effects of oral single dose of clarithromycin or azithromycin on the pharmacokinetics of sunitinib.MethodsRabbits were subjected to one of three study drug groups: sunitinib + clarithromycin (n = 6), sunitinib + azithromycin (n = 6), or sunitinib (n = 6). The rabbits were treated with sunitinib in the oral dose of 25 mg. Plasma concentrations of sunitinib were measured with validated HPLC method with UV detection.ResultsComparison of the sunitinib C_max for the sunitinib + clarithromycin group with that of the sunitinib group gave a ratio of 94.4% [90% confidence interval (CI) (76.1, 117.1)]; for the sunitinib + azithromycin group, the ratio was 106.2% (90% CI 85.5, 131.7). Comparison of the sunitinib AUC_0-t of the sunitinib + clarithromycin and sunitinib + azithromycin groups with that of the sunitinib group showed ratios of 86.86% (90% CI 69.7, 108.3) and 99.8% (90% CI 80.1, 124.5), respectively.ConclusionsNo significant effect of the coadministration of clarithromycin or azithromycin on the pharmacokinetics of sunitinib in rabbits was found in this study.