Poly(d,l-lactide)/polyethylene glycol micro/nanofiber mats as paclitaxel-eluting carriers: preparation and characterization of fibers, in vitro drug release, antiangiogenic activity and tumor recurrence prevention.

Poly(d,l-lactide)/polyethylene glycol (PLA/PEG) micro/nanofibers loaded with paclitaxel (PTX, 10 wt%) were prepared by needless electrospinning technology, which allows large scale production for real medicinal practice. The fiber structure and properties were investigated by several methods including scanning electron microscopy, nitrogen adsorption/desorption isotherm measurements, differential scanning calorimetry, and X-ray diffraction measurements to examine their morphology (fiber diameter distribution, specific surface area, and total pore volume), composition, drug-loading efficiency, and physical state. An HPLC-UV method was optimized and validated to quantify in vitro PTX release into PBS. The results showed that the addition of PEG into PLA fibers promoted the release of higher amounts of hydrophobic PTX over prolonged time periods compared to fibers without PEG. An in vitro cell assay demonstrated the biocompatibility of PLA/PEG fibrous materials and showed significant cytotoxicity of PTX-loaded PLA/PEG fibers against a human fibrosarcoma HT1080 cell line. The chick chorioallantoic membrane assay proved that PTX-loaded fibers exhibited antiangiogenic activity, with a pronounced effect in the case of the PEG-containing fibers. In vivo evaluation of PTX-loaded PLA/PEG fibers in a human fibrosarcoma recurrence model showed statistically significant inhibition in tumor incidence and growth after primary tumor resection compared to other treatment groups.

Dip TIPS as a facile and versatile method for fabrication of polymer foams with controlled shape, size and pore architecture for bioengineering applications.

The porous polymer foams act as a template for neotissuegenesis in tissue engineering, and, as a reservoir for cell transplants such as pancreatic islets while simultaneously providing a functional interface with the host body. The fabrication of foams with the controlled shape, size and pore structure is of prime importance in various bioengineering applications. To this end, here we demonstrate a thermally induced phase separation (TIPS) based facile process for the fabrication of polymer foams with a controlled architecture. The setup comprises of a metallic template bar (T), a metallic conducting block (C) and a non-metallic reservoir tube (R), connected in sequence T-C-R. The process hereinafter termed as Dip TIPS, involves the dipping of the T-bar into a polymer solution, followed by filling of the R-tube with a freezing mixture to induce the phase separation of a polymer solution in the immediate vicinity of T-bar; Subsequent free-drying or freeze-extraction steps produced the polymer foams. An easy exchange of the T-bar of a spherical or rectangular shape allowed the fabrication of tubular, open- capsular and flat-sheet shaped foams. A mere change in the quenching time produced the foams with a thickness ranging from hundreds of microns to several millimeters. And, the pore size was conveniently controlled by varying either the polymer concentration or the quenching temperature. Subsequent in vivo studies in brown Norway rats for 4-weeks demonstrated the guided cell infiltration and homogenous cell distribution through the polymer matrix, without any fibrous capsule and necrotic core. In conclusion, the results show the "Dip TIPS" as a facile and adaptable process for the fabrication of anisotropic channeled porous polymer foams of various shapes and sizes for potential applications in tissue engineering, cell transplantation and other related fields.

Comparison of one-step and sequentially irradiated ultrahigh-molecular-weight polyethylene for total joint replacements.

Structure and properties of several ultrahigh-molecular-weight polyethylenes (UHMWPEs), which were crosslinked either by standard, single-step irradiation or by newer, several-step irradiation (sequential irradiation), were compared. To verify the results, the same characterization was carried out for commercially available UHMWPE liners made of sequentially irradiated polymer (X3™, Stryker, Mahwah, NJ) and one-step irradiated polymer (denoted as PE-IMC, produced by Beznoska, Kladno, Czech Republic). The structure was studied by a number of spectroscopic, diffraction, thermal, and microscopic methods. Mechanical properties were assessed by small-punch, microhardness and, wear testing. Our results suggested that sequential irradiation followed by annealing did not lead to unusual structure at the molecular or supermolecular level. Consequently, all measured mechanical properties, including wear resistance, were comparable with one-step irradiated UHMWPEs.

Occurrence of perfluoroalkyl substances in fish and water from the Svitava and Svratka rivers, Czech Republic.

Perfluoroalkyl substances (PFHxS, FHUEA, PFOA, PFOS, FOSA, N-methyl FOSA and PFNA) from seven sites on the Svitava and Svratka rivers in the Brno conurbation (Czech Republic) were determined in fish blood plasma and water. Concentrations of PFHxS, FHUEA, FOSA, and N-methyl FOSA were below detection limits. Major compound in fish blood was PFOS (38.9-57.8 ng mL(-1)), followed by PFNA and PFOA. In water, the major compound detected was PFOA (1.7-178.0 ng mL(-1)), followed by PFOS and PFNA. A significant (p < 0.05) correlation for PFOA concentration in blood plasma and water was found (r = 0.74).

Effect of metals, with special attention of Cd, content of the Svitava and Svratka rivers on levels of thiol compounds in fish liver and their use as biochemical markers.

OBJECTIVES: The aim of this study was to assess the effect of metals, with special attention of cadmium (Cd), content of the Svitava and Svratka rivers (Czech Republic) on levels of thiol compounds such as metallothioneins (MT), glutathione (GSH/GSSG), and cysteine (Cys) concentrations in chub (Leuciscus cephalus L.) liver and their use as biomarkers. DESIGN: Levels of thiol compounds in fish liver were determined by the differential pulse voltammetry Brdicka reaction. Cadmium content in L. cephalus liver was measured by atomic absorption spectometry (AAS) with electrothermal atomization. The contents of thiols and Cd were correlated with the Cd and metals content of river bottom sediments. RESULTS: Results were inconsistent with those of experimental studies. Correlations between liver Cd content and MT, Cys, GSSG were not significant in any locality (p > 0.05). Cd liver content was negatively (p< 0.05) correlated with GSH at one (Zidlochovice) of the seven tested sites. GSH and GSSG correlated negatively in five localities (p > 0.05). Correlations between Cd in sediment and Cys and GSSG (p > 0.05), and MT was negative (p< 0.05). The relationship between sum of metals value and MT was negative (p< 0.05), similarly with GSSG (p > 0.05). CONCLUSION: Many factors influence content of MT, GSH, and GSSG, and data for Cd were equivocal. Monitoring the aquatic ecosystem to identify metal content using thiol compounds in fish liver as biomarkers is complex. More relevant data including laboratory experiments will be required to assess most of the factors influencing thiols and their relevance to Cd contamination.

Fish biochemical markers as a tool for pollution assessment on the Svitava and Svratka rivers, Czech Republic.

OBJECTIVES: The study was designed to assess the pollution of the Svitava and Svratka rivers in and around the industrial city of Brno (Czech Republic) by persistent organic pollutants using selected biochemical markers in chub. DESIGN: Levels of selected biochemical markers were measured in liver and plasma samples of chub. The concentrations of persistent organic pollutants (POPs) were determined in bottom sediment, semi-permeable membrane devices (SPMDs) and muscle samples, and consequently used for correlation with biochemical markers. RESULTS: Significant alterations (p < 0.05) in some biochemical markers were observed and associated with combined exposure to pollutants. The highest levels of pollutants were found at sites situated downstream from Brno. The most widespread changes were identified in the function of phase I detoxifying enzymes. Significant positive correlations were observed in cytochrome P450 content and DDT concentration in the semi-permeable membrane device (p = 0.019, rs = 0.886), and between ethoxyresorufin-O-deethylase activity and content of DDT (p = 0.041, rs = 0.352) and polychlorinated biphenyls (p = 0.034, rs = 0.365) in muscle tissues of indicator fish. CONCLUSION: The results presented in our study indicate the highest contamination of sites situated downstream from Brno, where the intensive industrial and agricultural activities as well as domestic waste and sewage most probably comprise the main impact sources of the enhanced level of pollutants and some biochemical markers in fish.

Effect of cadmium chloride on metallothionein levels in carp.

Due to anthropogenic activities, heavy metals still represent a threat for various trophic levels. If aquatic animals are exposed to heavy metals, we can obviously observe considerable toxicity. It is well known that organisms treated with heavy metals synthesize low molecular mass compounds rich in cysteine. In this work the effects of cadmium chloride (2.5, 5, 7.5, 10 and 12.5 mg/L) on common carp (Cyprinus carpio) was investigated. We determined cadmium content in tissue of muscle, liver and kidney by atomic absorption spectrometry with electrothermal atomization and content of metallothionein (MT) in the same tissues by the Brdicka reaction. Electrochemical methods can be considered as suitable and sensitive tools for MT determination in carp tissues. Results of our study showed a gradually enhancing of cadmium content in muscle with time and dose of cadmium chloride in water. MT levels in liver reached both high levels (above 130 ng/g) in fish exposed to 2.5, 5 and 7.5 mg/L and low level (to 50 ng/g) in fish exposed to 10 and 12.5 mg/L of cadmium chloride. This finding confirms that the synthesis of metallothioneins and binding capacity of these proteins is restricted.

Can thiol compounds be used as biomarkers of aquatic ecosystem contamination by cadmium?

Due to anthropogenic activities, heavy metals still represent a threat for various trophic levels. If aquatic animals are exposed to heavy metals we can obviously observe considerable toxicity. It is well known that an organism affected by cadmium (Cd) synthesize low molecular mass thiol compounds rich in cysteine (Cys), such as metallothioneins (MT) and glutathione (GSH/GSSG). The aim of this study was to summarize the effect of Cd on level of thiol compounds in aquatic organisms, and evaluate that the concentrations of thiol compounds are effective indicators of Cd water pollution and explain their potential use in biomonitoring applications.

Perfluorinated compounds: occurrence and risk profile.

Perfluorinated compounds (PFCs) such as perfluoro-octane sulphonate (PFOS) and perfluorooctanoic acid (PFOA) are emerging environmental pollutants, arising mainly from their use as surface treatment chemicals, polymerization aids and surfactants. They are ubiquitous, persistent and bioaccumulative in the environment. Perfluorinated compounds are being proposed as a new class of POPs. Although tests in rodents have demonstrated numerous negative effects of PFCs, it is unclear if exposure to perfluorinated compounds may affect human health. This review provides an overview of the recent toxicology and toxicokinetics, monitoring data now available for the environment, wildlife, and humans and attempts to explain the mechanisms of action of PFCs.

Structural changes of UHMWPE after e-beam irradiation and thermal treatment.

Ultra-high molecular weight polyethylene (UHMWPE) was irradiated with accelerated electrons (1 MeV in air) using high dose rates (> 25 kGy/min) and thin specimens (thickness 1 mm). Parts of the specimens were remelted (200 degrees C for 10 min; 150 degrees C for 0, 2, 10, 30, 60 min). All specimens were stored in nitrogen in the dark at 5 degrees C. Supermolecular structure, extent of crosslinking, oxidative degradation, and macroradical content were studied by a number of methods (SAXS, WAXS, SEM, DSC, FTIR, ESR, TGA, solubility experiments, image analysis). The results obtained with irradiated samples were compared with those obtained with irradiated and remelted samples. It was confirmed that crosslinking predominates over chain scission at very high dose rates, even if the irradiation is performed in air. Discrepancies concerning supermolecular structure changes in UHMWPE after irradiation and thermal treatment, found in various studies in the literature, are discussed. A simple model, which describes and explains all supermolecular structure changes, is introduced. An effective way of eliminating residual macroradicals in UHMWPE is proposed.