Preferential accumulation of inorganic elements in Amanita muscaria from North-eastern Poland.

Concentrations of Al, Ba, Cd, Ca, Co, Cu, Fe, K, Mg, Mn, Hg, Rb, Ag, Na, Sr and Zn were analysed in fruiting bodies of A. muscaria. This mushroom is considered conditionally edible, since parboiling can detoxify its fruiting bodies from the hallucinogens and render it edible. The specific purpose of the research is the little-known phenomenon of the variability of mineral composition of mushrooms for generations harvested in the same forest areas - both in terms of their nutritional value and anthropogenic influences. Fungal materials were digested in nitric acid and analysed by a validated methods using inductively coupled plasma optical emission spectrometer (ICP-OES) and cold - vapor atomic absorption spectroscopy (CV-AAS). A. muscaria collected in the same area over the period of four years showed fluctuations in the concentrations of the essential elements Co, Cu, Fe, K, Mn, Na and Zn (p < 0.05; U Mann-Whitney test), while only Ca and Mg (p > 0.05) levels were similar. In addition, concentrations of Ag, Al, Ba, Cd, Rb and Sr in fruiting bodies fluctuated, while remained at a similar level for Hg. It is important to note that statistically significant variations in levels of several inorganic elements accumulated in A. muscaria would imply a more careful consideration would be required when assessing the nutritional value of mushroom species.

Assessing multimedia/multipathway exposures to inorganic arsenic at population and individual level using MERLIN-Expo.

In this study, we report on model simulations performed using the newly developed exposure tool, MERLIN-Expo, in order to assess inorganic arsenic (iAs) exposure to adults resulting from past emissions by non-ferrous smelters in Belgium (Northern Campine area). Exposure scenarios were constructed to estimate external iAs exposure as well as the toxicologically relevant As (tAs, i.e., iAs, MMA and DMA) body burden in adults living in the vicinity of the former industrial sites as compared to adults living in adjacent areas and a reference area. Two scenarios are discussed: a first scenario studying exposure to iAs at the aggregated population level and a second scenario studying exposure at the individual level for a random sub-sample of subjects in each of the three different study areas. These two scenarios only differ in the type of human related input data (i.e., time-activity data, ingestion rates and consumption patterns) that were used, namely averages (incl. probability density functions, PDFs) in the simulation at population level and subject-specific values in the simulation at individual level. The model predictions are shown to be lower than the corresponding biomonitoring data from the monitoring campaign. Urinary tAs levels in adults, irrespective of the area they lived in, were under-predicted by MERLIN-Expo by 40% on average. The model predictions for individual adults, by contrast, under-predict the biomonitoring data by 7% on average, but with more important under-predictions for subjects at the upper end of exposure. Still, average predicted urinary tAs levels from the simulations at population level and at individual level overlap, and, at least for the current case, lead to similar conclusions. These results constitute a first and partial verification of the model performance of MERLIN-Expo when dealing with iAs in a complex site-specific exposure scenario, and demonstrate the robustness of the modelling tool for these situations.

In vivo degeneration and the fate of inorganic nanoparticles.

What happens to inorganic nanoparticles (NPs), such as plasmonic gold or silver, superparamagnetic iron oxide, or fluorescent quantum dot NPs after they have been administrated to a living being? This review discusses the integrity, biodistribution, and fate of NPs after in vivo administration. The hybrid nature of the NPs is described, conceptually divided into the inorganic core, the engineered surface coating comprising of the ligand shell and optionally also bio-conjugates, and the corona of adsorbed biological molecules. Empirical evidence shows that all of these three compounds may degrade individually in vivo and can drastically modify the life cycle and biodistribution of the whole heterostructure. Thus, the NPs may be decomposed into different parts, whose biodistribution and fate would need to be analyzed individually. Multiple labeling and quantification strategies for such a purpose will be discussed. All reviewed data indicate that NPs in vivo should no longer be considered as homogeneous entities, but should be seen as inorganic/organic/biological nano-hybrids with complex and intricately linked distribution and degradation pathways.

Physiologically Based Pharmacokinetic Model for Long-Circulating Inorganic Nanoparticles.

A physiologically based pharmacokinetic model was developed for accurately characterizing and predicting the in vivo fate of long-circulating inorganic nanoparticles (NPs). This model is built based on direct visualization of NP disposition details at the organ and cellular level. It was validated with multiple data sets, indicating robust inter-route and interspecies predictive capability. We suggest that the biodistribution of long-circulating inorganic NPs is determined by the uptake and release of NPs by phagocytic cells in target organs.

Selection of appropriate training and validation set chemicals for modelling dermal permeability by U-optimal design.

Quantitative structure-activity relationship (QSAR) models are being used increasingly in skin permeation studies. The main idea of QSAR modelling is to quantify the relationship between biological activities and chemical properties, and thus to predict the activity of chemical solutes. As a key step, the selection of a representative and structurally diverse training set is critical to the prediction power of a QSAR model. Early QSAR models selected training sets in a subjective way and solutes in the training set were relatively homogenous. More recently, statistical methods such as D-optimal design or space-filling design have been applied but such methods are not always ideal. This paper describes a comprehensive procedure to select training sets from a large candidate set of 4534 solutes. A newly proposed 'Baynes' rule', which is a modification of Lipinski's 'rule of five', was used to screen out solutes that were not qualified for the study. U-optimality was used as the selection criterion. A principal component analysis showed that the selected training set was representative of the chemical space. Gas chromatograph amenability was verified. A model built using the training set was shown to have greater predictive power than a model built using a previous dataset [1].

Environmental factors affecting the urinary excretion of inorganic arsenic in the general population.

OBJECTIVE: To assess the critical issues concerning the use of urinary inorganic arsenic (iAs), including As3, As5, monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA), as biomarker of internal dose in order to monitor environmental and occupational exposure to inorganic As, considering the influence of diet and drinking water on excretion of iAs. METHODS: The design protocol stipulated collection of weekly urine samples from 6 male subjects for 5 consecutive months. In all the urine samples, iAs was determined by Hydride Generation-Atomic Absorption Spectrophotometry (HG-AAS). In the subjects with iAs higher than 35 microg/L, Biological Exposure Index (BEI) proposed by the American Conference of Governmental Industrial Hygienists (ACGIH), urinary arsenic speciation was performed by HPLC-ICP-MS. Exposure to airborne As was evaluated monthly using personal environmental samplers worn for 8 hours. Throughout the study, the participants filled out a daily food diary, also detailing types of water drunk. RESULT: Exposure to airborne As was invariably below the limit of detection, equal to 1 ng/m3. A total of 77 urine samples were collected. iAs was always detectable and was higher in 7 urine samples, obtained from 5 of the 6 subjects examined, than the BEI. Among foods with a high As content, the intake of seafood and fish within 72 hours before providing the sample seems to be the principal source of the iAs concentrations, while the intake of rice or drinking water showed no influence on this biological marker. Instead, drinking wine within 24 hours before urine sample collection can cause a significant increase in the excretion of iAs. CONCLUSIONS: In populations that eat large amounts of fish and seafood, the use of iAs to monitor occupational and environmental exposure to inorganic As seems to present some problems, and urinary As speciation may be essential at least in cases with As measurements above the biological limit values. In any case, a diet sheet reporting all foods eaten within 3 days of urine collection seems to be an indispensable tool to ensure a correct interpretation of the results.

Nanoparticles through the skin: managing conflicting results of inorganic and organic particles in cosmetics and pharmaceutics.

Toxicity of nanoparticles is a current scientific issue because of the enhanced reactivity of nanomaterials and their possible easy penetration into the body arising from their small size. Because inorganic particles are present in sunscreen cosmetic products, attention has been focused on cutaneous penetration. But organic particles of various sizes are also used in pharmaceutical applications such as skin care and transdermal drug delivery. It appears that organic and inorganic particles penetrate the skin quite differently. The apparent discrepancy is addressed in this review focusing on skin penetration of inorganic sunscreen particles and organic particles for drug delivery. After a short description of the physicochemical properties of these particles, the skin penetration of both types is reviewed with emphasis on the mechanistic issues and the differences that could account for such conflicting results. It appears that investigations by cosmetic and pharmaceutical communities focused on the main issue, i.e., no toxicity in cosmetics and maximum activity of the drug in pharmaceutics. This leaves several fundamental issues as open questions and this does not allow a rigorous comparison between both types of material. While it is claimed that inorganic nanoparticles can only penetrate the outer layer of the skin, it appears that organic submicron particles and even microparticles reach the dermis in an in vitro cell. Besides particle size, the surface chemistry of the particles and the presence of other excipients in the formulations contribute to skin absorption.

Relative absorption and dermal loading of chemical substances: Consequences for risk assessment.

Quantification of skin absorption is an essential step in reducing the uncertainty of dermal risk assessment. Data from literature indicate that the relative dermal absorption of substances is dependent on dermal loading. Therefore, an internal exposure calculated with absorption data determined at a dermal loading not comparable to the actual loading may lead to a wrong assessment of the actual health risk. To investigate the relationship between dermal loading and relative absorption in a quantitative manner, 138 dermal publicly available absorption experiments with 98 substances were evaluated (87 in vitro, 51 in vivo; molecular weight between 40 and 950, logP between -5 and 13), with dermal loading ranging mostly between 0.001 and 10mg/cm(2). In 87 experiments (63%) an inverse relationship was observed between relative dermal absorption and dermal loading, with an average decrease of factor 33+/-69. Known skin irritating and volatile substances less frequently showed an inverse relationship between dermal loading and relative absorption.

Transport of methylmercury and inorganic mercury to the fetus and breast-fed infant.

It is well established that methylmercury (MeHg) and mercury vapor pass the placenta, but little is known about infant exposure via breast milk. We measured MeHg and inorganic mercury (I-Hg) in blood of Swedish mothers (n = 20) and their infants, as well as total mercury (T-Hg) in breast milk up to 13 weeks postpartum. Infant blood MeHg was highly associated with maternal blood MeHg at delivery, although more than twice as high. Infant MeHg decreased markedly until 13 weeks of age. Infant blood I-Hg was associated with, and about as high as, maternal blood I-Hg at delivery. Infant I-Hg decreased until 13 weeks. In breast milk, T-Hg decreased significantly from day 4 to 6 weeks after delivery but remained unchanged thereafter. At 13 weeks, T-Hg in breast milk was associated with infant MeHg but not with maternal MeHg. Conversely, T-Hg in breast milk was associated with maternal I-Hg but not with infant I-Hg. From the findings of the present study in which the exposure to both MeHg and I-Hg was low, we conclude that the exposure to both forms of mercury is higher before birth than during the breast-feeding period, and that MeHg seems to contribute more than I-Hg to infant exposure postnatally via breast milk.

Gallium and other main group metal compounds as antitumor agents.

Gallium has been the second metal to show activity against malignant tumors in humans soon after the establishment of platinum drugs in routine clinical practice. It has the unique property of inhibiting tumor growth as a simple cation, mainly because of its close resemblance to ferric iron. Even though its inability to shift between the trivalent and a divalent oxidation state precludes that gallium behaves as an iron analogue in every respect, it strongly interferes with cellular acquisition of iron from blood by competitive interaction with transferrin and transferrin receptor-mediated endocytosis. Furthermore, gallium also seems to affect intracellular availability of iron already taken up via this pathway, probably due to its inhibitory activity on vacuolar-type H(+)-ATPases. Apart from the consequences of iron deprivation, gallium exerts cytotoxic effects by direct interaction with the iron-dependent enzyme ribonucleotide reductase, resulting in reduced dNTP pools and inhibition of DNA synthesis. Both the abundance of transferrin receptors and upregulation of ribonucleotide reductase render tumors susceptible to gallium-induced cytotoxicity. However, some experimental findings raise the question whether these effects resulting from the iron-mimicking properties of gallium are solely responsible for its antineoplastic activity or whether additional mechanisms are involved, such as antimitotic effects which result from its capability of inhibiting tubulin polymerization. The limitations experienced with gallium nitrate and gallium chloride, which call for a prolonged exposure to low steady-state gallium levels in blood in order to adequately exploit the affinity of gallium to tumor tissues and to avoid severe toxic effects, may be overcome by oral gallium complexes such as tris(3-hydroxy-2-methyl-4H-pyran-4-onato)gallium(III) (gallium maltolate) or tris(8-quinolinolato)gallium(III) (KP46), which are currently being evaluated in clinical trials and show promise to initiate a revival of gallium in the clinical setting. These two investigational drugs, albeit differing in their complex stability, have both been developed with the intention of providing gallium in a form which allows sufficient intestinal absorption, but without altering its pharmacodynamic effects. Gallium complexes based on other rationales are scarce and, with regard to the well-known antineoplastic potential of this metal, noticeably under-explored. With the recent approval of arsenic trioxide for the second-line treatment of acute promyelocytic leukemia, the clinical revival of arsenic compounds, which have been the mainstay of antileukemic therapy before the age of modern cancer chemotherapy, has already begun. Currently, strong efforts are being made to explore the activity spectrum in other (less rare) malignancies and to gain a deeper insight into the mode of action. Although this development is currently focusing on arsenic trioxide, it should be suited to stimulate investigations into the therapeutic potential of other arsenic compounds as well.

[Sorption-frequency probes and biosensors for gas and liquid composition monitoring]. / Sorbtsionno-chastotnye datchiki i biosensory dlia kontrolia sostava gazov i zhidkikh sred.

The review deals with the problems of development of analytical equipment based on piezoelectric crystals. Consideration is given to the philosophy of determining inorganic and organic compounds, biologically active compounds, viruses, and bacteria with piezoelectric resonators. Described are methods of immobilization of the biological component, immersion-and-drying analysis, and sensor-assisted detection in the soluble phase.

The power of size. 2. Rate constants and equilibrium ratios for accumulation of inorganic substances related to species weight.

Most of the thousands of substances and species that risk assessment has to deal with are not investigated empirically because of financial, practical, and ethical constraints. To facilitate extrapolation, we have developed a model for concentration kinetics of inorganic substances as a function of the exposure concentration of the chemical and the weight and trophic level of the species. The ecological parameters and the resistances that substances encounter during diffusion in water layers were obtained from previous reviews. The other chemical parameters (the resistances for permeation of lipid layers) were calibrated in the present study on 1,062 rate constants for absorption from water, for assimilation from food, and for elimination. Data on all elements and species were collected, but most applied to aquatic species, in particular mollusks and fish, and to transition metals, in particular group IIB (Zn, Cd, Hg). Their ratio was validated on 92 regressions and nine geometric averages, representing thousands of (near-)equilibrium accumulation ratios from laboratory and field studies. Rate constants for absorption and elimination decreased with species weight at an exponent of about -0.25, known from ecological allometry. On average, uptake-rate constants decreased with about the reciprocal square root of the exposure concentration. About 71 and 30% of the variation in absorption and elimination was explained by the model, respectively. The efficiency for assimilation of elements from food appeared to be determined mainly by the food digestibility and the distribution over egested and digested fractions. (Near-)equilibrium accumulation and magnification ratios also decreased with the reciprocal square root of the exposure concentration. The level of the organism-solids concentrations ratios roughly varied between one and two orders of magnitude, depending on the number of elements and species groups investigated. Metal concentrations did not increase at higher trophic levels, with the exception of (methyl-)mercury. Organism-solids concentration ratios for terrestrial species tended to be somewhat lower than those for their aquatic equivalents. Food web accumulation, expressed as organism-organic solids and organism-food concentrations ratios, can therefore be only partly explained by ecological variables. The model is believed to facilitate various types of scientific interpretation as well as environmental risk assessment.

[Nutrition of wheat under wet injury and its regulation].

With pot experiment, this paper dealt with the effects of different nutrition regulations on nutrient absorption and crop yield of wheat under waterlogged condition. N, P, K, Zn, Cu uptakes by wheat were greatly inhibited by waterlogging. The total amounts of reusable elements N, P, K and Zn in leaves decreased obviously in stems but did not in ears, compared with control; while the total amount of element Cu in all parts was reduced by waterlogging. The yield of individual wheat plant was significantly reduced under waterlogging. Additional N-fertilizer or spraying N, P and K significantly increased the uptake of nutrients and the yield for Wanmai 19 under light waterlogging, but were not effective for Yanmai 158 under heavy waterlogging. A positive correlation was found between the yield of wheat under waterlogging and the N accumulation in leaves.

Formal analysis of electrogenic sodium, potassium, chloride and bicarbonate transport in mouse colon epithelium.

1. The mammalian colonic epithelium carries out a number of different transporting activities simultaneously, of which more than one is increased following activation with a single agonist. These separate activities can be quantified by solving a set of equations describing these activities, provided some of the dependent variables can be eliminated. Using variations in the experimental conditions, blocking drugs and comparing wild type tissues with those from transgenic animals this has been achieved for electrogenic ion transporting activity of the mouse colon. 2. Basal activity and that following activation with forskolin was measured by short circuit current in isolated mouse colonic epithelia from normal and cystic fibrosis (CF) mice. 3. Using amiloride it is shown that CF colons show increased electrogenic sodium absorption compared to wild type tissues. CF mice had elevated plasma aldosterone, which may be responsible for part or all of the increased sodium absorbtion in CF colons. 4. The derived values for electrogenic chloride secretion and for electrogenic potassium secretion were increased by 13 and 3 fold respectively by forskolin, compared to basal state values for these processes. 5. The loop diuretic, frusemide, completely inhibited electrogenic potassium secretion, but apparently only partially inhibited electrogenic chloride secretion. However, use of bicarbonate-free solutions and acetazolamide reduced the frusemide-resistant current, suggesting that electrogenic bicarbonate secretion accounts for the frusemide-resistant current. 6. It is argued that the use of tissues from transgenic animals is an important adjunct to pharmacological analysis, especially where effects in tissues result in the activation of more than one sort of response.