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Purpose: Cisplatin-etoposide treatment is recommended as a first line in small cell lung cancer patients (SCLC). However, the prognosis is poor and the dosing is not tailored beyond the body surface area, which is related with indeterminate cisplatin exposure-response relationship. We aimed to evaluate cisplatin pharmacokinetics (PK) and the exposure to unbound cisplatin in SCLC patients using the informative priors, and assess the relationship between the cisplatin exposure and probability of neutropenia. Methods: Observational clinical study was performed including 17 cisplatin-treated SCLC patients. External population cisplatin PK models were identified and NONMEM® software and $PRIOR subroutine were used for the model evaluation. The bias and precision of the model-predicted cisplatin concentrations were evaluated. The best models were combined in a final model including several sets of informative priors, which was used to estimate individual cisplatin exposure, analyze the relationship between the exposure and neutropenia and simulate several cisplatin dosing regimens in a virtual patient cohort. Results: The models by Urien with the informative priors best fitted the data. The individual cisplatin exposure ranged between 2430 and 4560 μg*h/L. There was a trend of increasing probability of neutropenia and febrile neutropenia with increasing cisplatin exposure. Approximately 50%, 75% and 90% of patients receiving 60 mg/m2, 70 mg/m2 and 80 mg/m2, respectively, achieved the previously identified exposure threshold of 2860 μg*h/L. Conclusion: We developed a tool to individualize cisplatin dosing based on the estimated probability of neutropenia. The benefit of more intense dosing regimens in SCLC patients should be further assessed. Bibliografija: str. 311-313. Abstract. ARRS ARRS

Microplastics found in the environment are often covered with a biofilm, which makes their analysis difficult. Therefore, the biofilm is usually removed before analysis, which may affect the microplastic particles or lead to their loss during the procedure. In this work, we used laser-based analytical techniques and evaluated their performance in detecting, characterizing, and classifying pristine and aged microplastics with a developed biofilm. Five types of microplastics from different polymers were selected (polyamide, polyethylene, polyethylene terephthalate, polypropylene, and polyvinyl chloride) and aged under controlled conditions in freshwater and wastewater. The development of biofilm and the changes in the properties of the microplastic were evaluated. The pristine and aged microplastics were characterized by standard methods (e.g., optical and scanning electron microscopy, and Raman spectroscopy), and then laser-induced breakdown spectroscopy (LIBS) and laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) were used. The results show that LIBS could identify different types of plastics regardless of the ageing and major biotic elements of the biofilm layer. LA-ICP-MS showed a high sensitivity to metals, which can be used as markers for various plastics. In addition, LA-ICP-MS can be employed in studies to monitor the adsorption and desorption (leaching) of metals during the ageing of microplastics. The use of these laser-based analytical techniques was found to be beneficial in the study of environmentally relevant microplastics.

In this study, we investigated the interactions between titanium dioxide (nTiO2) and zinc oxide (nZnO) nanoparticles and polyethylene microplastics (MPs) with respect to their adsorption and subsequent desorption in aquatic media. Adsorption kinetic models revealed rapid adsorption of nZnO compared to nTiO2, while nTiO2 was adsorbed to a greater extent – four times more nTiO2 (67%) was adsorbed on MPs than nZnO (16%). The low adsorption of nZnO can be explained by the partial dissolution of zinc from nZnO in the form of Zn(II) and/or Zn(II) aqua-hydroxo complexes (e.g. [Zn(OH)]+, [Zn(OH)3]−, [Zn(OH)4]2−), which were not adsorbed on MPs. Adsorption isotherm models indicated that the adsorption process is controlled by physisorption for both nTiO2 and nZnO. The desorption of nTiO2 was low (up to 27%) and not pH dependent, and only nanoparticles were desorbed from the MPs surface. On the other hand, the desorption of nZnO was pH dependent at a slightly acidic pH (pH = 6), 89% of the adsorbed zinc was desorbed from the MPs surface and the majority were in the form of nanoparticles at a slightly alkaline pH (pH = 8.3), 72% of the zinc was desorbed, but the majority were in the soluble form of Zn(II) and/or Zn(II) aqua-hydroxo complexes. These results demonstrated the complexity and variability of interactions between MPs and metal engineered nanoparticles and contribute to a better understanding of their fate in the aquatic environment.

When microplastics enter aquatic ecosystems they are submitted to environmental aging which change their properties. Especially colonization by microorganisms alter their properties in term of density and adsorption properties. Hence the aim of the study was to evaluate the adsorption and leaching properties of virgin and aged microplastics. Silver (in form of silver nitrate) was selected as a model metal used for adsorption study. Results showed that silver is quickly adsorbed on both types of microplastics while aged microplastics adsorbed significantly more silver than virgin ones. However, also leaching of silver from aged particles proceeds much faster - after 48 hours in Steinberg medium (pH = 5.8), only 23.7% of silver was leached out from virgin microplastics in comparison to 45.6% leached out from aged microplastics. In OECD medium (pH = 7.3) leaching was minimal. Our results showed that aging of microplastics and development of biofilm can significantly alter their properties and thus it is necessary to enhance our knowledge about microplastics’ aging in the aquatic environment, which is still far from well-understood.

From the early precipitation-based techniques, introduced more than a century ago, to the latest development of enzymatic bio- and nano-sensor applications, the analysis of phytic acid and/or other inositol phosphates has never been a straightforward analytical task. Due to the biomedical importance, such as antinutritional, antioxidant and anticancer effects, several types of methodologies were investigated over the years to develop a reliable determination of these intriguing analytes in many types of biological samples; from various foodstuffs to living cell organisms. The main aim of the present work was to critically overview the development of the most relevant analytical principles, separation and detection methods that have been applied in order to overcome the difficulties with specific chemical properties of inositol phosphates, their interferences, absence of characteristic signal (e.g., absorbance), and strong binding interactions with (multivalent) metals and other biological molecules present in the sample matrix. A systematical and chronological review of the applied methodology and the detection system is given, ranging from the very beginnings of the classical gravimetric and titrimetric analysis, through the potentiometric titrations, chromatographic and electrophoretic separation techniques, to the use of spectroscopic methods and of the recently reported fluorescence and voltammetric bio- and nano-sensors.

Silver nanoparticles (Ag NPs), incidentally or intentionally released to soil ecosystems, have the potential to accumulate in organisms. Due to the great variety of natural (field) soil and its interactions with Ag NPs, the few available biokinetic studies performed on standard soils are not sufficient for an environmentally relevant assessment of Ag NP bioaccumulation. In this study, we analyzed the biokinetics of pristine and sulfidized Ag NPs (Ag2S NPs) in two arthropod species with different routes of exposure to soil contaminants (isopodPorcellio scaberand springtailFolsomia candida) exposed to 4 different soils, widely differing in chemical and physical properties. Using the biokinetic constant of uptake as proxy for bioavailability, we found soil pH and soil texture to be the strongest predictors of Ag bioavailability to isopods and springtails, respectively. Both organisms accumulated Ag when exposed to pristine Ag NPs, which suggests a risk for food-chain accumulation of Ag. In contrast, no Ag bioaccumulation was detected in the case of the poorly soluble Ag2S NPs, which is the more environmentally relevant form of Ag NPs. Our study corroborates the dominant role of dissolution in Ag NP bioavailability and draws attention to the biological differences between different soil dwelling organisms modulating their Ag NP exposure.

The main goal of the study was to evaluate the avoidance behaviour of isopods (Porcellio scaber) to food or soil contaminated with different nanoparticles (NPs): Ag-NPs, sulfidized Ag-NPs (Ag2S-NPs) or CeO2-NPs. These NPs are characterized by different physiochemical properties, and antimicrobial and toxic potentials. Isopods were exposed in three scenarios: (i) 14 d feeding test where animals were fed solely on contaminated leaves; (ii) 14 d food selection test where leaves spiked with NPs were offered simultaneously with uncontaminated leaves; and (iii) 48 h soil avoidance test where animals could choose between uncontaminated and soil spiked with NPs. The isopods decreased feeding on Ag-NP contaminated food and clearly avoided contact with Ag-NP contaminated soil. Substantial accumulation of Ag in the body of isopods was found both in feeding and food selection test. This means that food selection might mitigate but could not prevent Ag accumulation in woodlice. In contrast, no such behavioural response of isopods was found for CeO2-NP. These data suggest that the presence of metal ions in the case of Ag-NPs may be the main reason for differential behaviour. Interestingly, moderate avoidance behaviour was observed also towards Ag2S-NPs although no Ag+ was detected in stock suspensions. This avoidance was not statistically significant and needs to be further explored. Behavioural test with isopods showed again their value in estimation of potential adverse effects of pollutants comparable to collembolans and earthworms.

Extensive production of nanomaterials of various properties needs to be coupled with rapid toxicity testing in order to provide information about their potential risks to the environment and human health. Miniaturization of toxicity tests may accelerate economical testing of nanomaterials, but is not a common practice. We describe a case study to miniaturize a commonly used toxicity test with plant duckweed Lemna minor. 6-well, 12-well and 24-well culture plates were used to assess their potential use for the duckweed toxicity test with potassium chloride as reference material. The results were compared to the standard test design using 100 mL glass beakers. The comparison showed that the best agreement was with the 6-well vessels. This set-up was further used for toxicity testing of zinc oxide nanoparticles (ZnO NP) and zinc chloride. Zinc was not adsorbed onto either glass or plastic walls of the miniaturized system. We assume that in both vessels a fast agglomeration and settling of ZnO NP took place. Linear regression and statistical testing indicated a good correlation between the toxicity results obtained in the standard test and miniaturized 6-well vessels. The miniaturization of the test system for assessing the biological effect of nanomaterials on Lemna minor could become an appropriate alternative to the traditionally used high volume vessels.

The formation of metal complexes with phytic acid is a complex process that depends strongly on the metal-to-ligand molar ratio, pH value and consequent protonation level of the phytate ligand as well as accompanying side reactions, in particular metal hydrolysis and precipitation of the formed coordination compounds. In the present work, the potentiometric titration technique was used in combination with a detailed analysis of the equivalent point dependencies for selected biologically relevant monovalent and divalent cations from the groups of alkaline earths and transition metals, namely: Mg(II), Zn(II), Fe(II), Cu(I), and Cu(II) ions. The investigation of complex formation mechanism, the evaluation of the species formed, and the identification of other side reactions was based on the examination of three distinct equivalent points, which were detectable by alkalimetric titrations of phytic acid in the presence of selected metal ions. It has been demonstrated that alkaline earth metals interact with different binding site(s) than the transition metals, and experiments with both oxidation states of copper revealed similar complexing characteristics, which depend mainly on the ionic radius (and not on the ionic charge as initially expected). Quantitative data on phytate complexation, hydroxide formation and complex precipitation are presented herein for all metals studied, including Cu(I), which was investigated for the first time by means of alkalimetric titration.

The high annual production and use of cerium(IV) oxide nanoparticles (nCeO2s) may lead to their atmospheric release and substantial deposition on plants. This poses a potential threat to pollinators. We investigated the effects of nCeO2-spiked food (2–500 mg L−1) on summer and winter honeybees (Apis mellifera carnica) after chronic 9 days' oral exposure. Acetylcholinesterase (AChE) and glutathione S-transferase (GST) activities were measured in different body compartments (heads, thoraces, and haemolymph). The activity of AChE was assessed in salt-soluble (SS) (containing soluble and membrane AChE) and detergent-soluble (DS) (predominantly membrane-bound AChE) fractions. Exposure of honeybees to nCeO2-spiked food had no significant effects on survival up to 500 mg L−1 (

Understanding the adsorption of amino acids (AAs) onto magnetic iron-oxide nanoparticles (SPIONs) is important not only for the preparation of the aqueous suspensions, but also for understanding the interactions at the bionano interface. In this investigation the adsorption of aspartic acid (Asp) and lysine (Lys) onto SPIONs was studied, based on a characterization of the suspension properties, i.e., measurements of the ξ-potential, the hydrodynamic size, and the osmolality, and by direct HPLC analysis of the AA in the supernatants and at the nanoparticles of the ultracentrifuged suspensions. The results show that the AAs adsorb onto the SPIONs in the form of large molecular associates, which decisively influence the nanoparticles’ surface properties. A measurement of the freezing-point depression using a Knauer osmometer proved that the molecular associates are already formed in the AA aqueous solutions.

Electrochemical and transport properties of the pure 1-butyl-3-methylimidazolium dicyanamide ionic liquid, [bmim][DCA], and its binary liquid mixtures with γ-butyrolactone (GBL) were studied at temperatures from (273.15 to 323.15) K at atmospheric pressure over the whole composition range. Electrical conductivity data were correlated using Arrhenius, Casteel–Amis and Vogel–Tammann–Fulcher equations. Several semi-empirical models (quasi-Arrhenius and Bahe–Varela model) were also tested. Electrochemical stability of {[bmim][DCA] + GBL} was also investigated. It was found that addition of GBL do not reduce electrochemical stability of investigated solution. All the results obtained for {[bmim][DCA] + GBL} are compared with those reported for binary mixtures of GBL and ionic liquids with dicyanamide, [DCA]−, and bis(trifluoromethylsulfonyl)imide, [TFSI]−, anions. At the compositions where maximum of conductivity is observed, difference in conductivity between [DCA]− and [TFSI]− based ionic liquids + GBL mixtures is around 70%. It was found that type of the cation (imidazolium and pyrrolidinium) do not influence the electrical conductivity of the mixture.

In the last decade, different bio-materials have been investigated for ability to remove metals from aqueous solution. In this study, waste fungal biomass (WFB) was evaluated as a biosorbent for the accumulation and removal of lead and cadmium ions. The biomass being investigated was obtained after the production of Ganoderma lucidum fruiting bodies and was made from residues of the fungus and cultivation substrate. Light microscope and field emission scanning electron microscopy were used in the determination of WFB morphology. The surface area and pore size were determined with the Brunauer–Emmett–Teller and Barret–Joyner–Halenda methods, respectively. WFB was used as an adsorbent directly after drying and after the pre-treatment with three different chemical procedures, which increased removal efficiency from 87% and 84% to 93% and 97% for Pb(II) and Cd(II), respectively. The rate of the adsorption fitted well to a pseudo-second-order kinetic model. In addition, the Freundlich adsorption isotherm model was found to fit the experimental data. It was concluded that WFB represents a promising alternative for the removal of lead and cadmium ions from aqueous solutions.

Microplastics are very complex pollutants; they can be made of many polymer types and exist in various shapes and sizes. When they enter the environment they are affected by biotic and abiotic factors that cause their properties to change. In this context, the aim of our study was to evaluate the extent to which biofouling affects the properties and toxicity of microplastics. Cosmetic polyethylene microbeads were incubated in stream water for four weeks resulting in biofouling and aging. Subsequently, the changes in properties (sinking, particle size, adsorption, and leaching of model metal - silver) and the microplastics toxicity to daphnids Daphnia magna and duckweed Lemna minor were evaluated. Pristine microplastics did not affect daphnids but they significantly affected the root growth of duckweed. On the other hand, reference natural particles (beech sawdust) did not show any negative effects. We observed significant differences in the properties of aged versus pristine microplastics. When compared to pristine microplastics, aged microplastics adsorbed more silver and the subsequent leaching of silver was more intensive, especially in the medium with an acidic pH. Microplastics with adsorbed silver had a high ecotoxicological potential and at environmentally relevant concentrations affected both daphnids and duckweed. This study suggests that biofouling is an important parameter that affects microplastics properties, pollutant adsorption and release into the environment, and toxicity. Overall, there are significant alterations of the microplastics properties, behaviour, and fate in the environment.

The electrochemical behavior of Fe(III) in the presence of phytate ligand was investigated by cyclic voltammetry on the polycrystalline gold and mercury drop electrodes in the pH range between 1.5 and 10, and ligand to metal molar ratio from 0 to 20. Complexation of Fe(III) and Fe(II) by phytate ligand (L) reflects in (i) shift of the formal potential E 0′ of the Fe(III)/Fe(II) redox couple into the negative direction, and (ii) an increased irreversibility of the redox processes. Change of the formal potential originate from higher stability of the Fe(III)L complex with respect to Fe(II)L complex, however, due to the slow charge transfer control of the redox processes apparent stability constants calculated from voltammetric data may lead to an overestimation of their true values. Irreversible reduction of Fe(III)L to Fe(II)L is diffusion controlled and involves one proton per one electron on both electrodes. Reduction of Fe(III) phytate complex to Fe(II)L depends on the pH and at pH III H 5 L] 4– species, but at higher pH less protonated [Fe III H 3 L] 6– become the major reacting species. An almost stepwise change of the reduction peak potential for more than 0.8 V into the negative direction around pH 5 indicate that both reactants have quite different stability and/or structure. We predicted that electronic configuration and affinity of Fe(III) ions for the octahedral coordination induce the inversion of phytate ligand from its equatorial to the axial conformation which form more than ten orders of magnitude more stable Fe(III)L complexes. Fe(II)L intermediate generated on the electrode is strongly adsorbed on both gold and mercury electrodes, and totally irreversible reduction of Fe(II)L complex to the Fe metal was observable at mercury electrode as well. From Fe(III/II)L peak analysis on the mercury electrode the cathodic charge transfer coefficient of 0.68 was found, for [Fe III H 3 L] 6– reacting species the diffusion coefficient of (9.1 ± 0.1) × 10 −7 cm 2 /s was estimated, and the rate constant k 0 of 7.8 × 10 −5 cm/s was calculated.

A profound understanding of the Au dissolution process is a prerequisite for optimal utilization of Au-based materials. This goes for either increasing the corrosion stability of materials in the sectors where the long-term functionality of Au is needed or decreasing the corrosion stability where the recovery of the Au component is crucial. By employing an extremely sensitive online analytical system, consisting of an electrochemical flow cell coupled to an inductively coupled plasma mass spectrometry, in situ potential-resolved dissolution of Au in the ppb range is enabled. A comparative study of two Au based materials, (i) a polycrystalline Au disk and (ii) carbon-supported Au nanoparticles, is presented. As a probe, chloride ions were used to elucidate the distinct differences in the corrosion behavior of the two analogues.