Toxicity of differently sized and coated silver nanoparticles to the bacterium Pseudomonas putida: risks for the aquatic environment?

Aim of this study was to describe the toxicity of a set of different commercially available silver nanoparticles (AgNPs) to the gram-negative bacterium Pseudomonas putida (growth inhibition assay, ISO 10712) in order to contribute to their environmental hazard and risk assessment. Different AgNP sizes and coatings were selected in order to analyze whether those characteristics are determinants of nanoparticle toxicity. Silver nitrate was tested for comparison. In general Pseudomonas putida reacted very sensitive towards the exposure to silver, with an EC₀₅ value of 0.043 μg L^?1 for AgNO₃ and between 0.13 and 3.41 μg L^?1 for the different AgNPs (EC₅₀ values 0.16 μg L^?1 for AgNO₃, resp. between 0.25 and 13.4 μg L^?1 for AgNPs). As the ionic form of silver is clearly the most toxic, an environmental hazard assessment for microorganisms based on total silver concentration and the assumption that AgNPs dissolve is sufficiently protective. Neither specific coatings nor certain sizes could be linked to increasing or decreasing toxicity. The characterization of particle behavior as well as the total and dissolved silver content in the medium during the exposures was not possible due to the high sensitivity of Pseudomonas (test concentrations were below detection limits), indicating the need for further development in the analytical domain. Monitored silver concentrations in the aquatic environment span six orders of magnitude (0.1–120,000 ng L^?1), which falls into the span of observed EC₀₅ values and might hence indicate a risk to environmental bacteria.     

Determination of pethidine hydrochloride using potentiometric coated graphite and carbon paste electrodes

A new approach for lowering the detection limit of a pethidine ion‐selective electrode is presented. A coated graphite (CGE) and carbon paste (CPE) electrodes for pethidine ions based on pethidine‐phosphotungstate (PD‐PT) as ion‐pair complex are described. The sensors exhibit a Nernstian slope of 58.1 and 54.2 mVdecade^?1 for pethidine ion over a wide concentration range from 2.6 × 10^?7 to 1.0 × 10^?2 M and 2.1 × 10^?6 to 1.0 × 10^?2 M with a detection limit of 1.8 × 10^?7 M and 7.3 × 10^?7 M for pethidine coated graphite (PD‐CGE) and pethidine carbon paste electrode (PD‐CPE), respectively. These sensors exhibited a fast response time (about 5–8 s) and good stability. The standard electrode potentials, E^o, were determined at different temperatures and used to calculate the isothermal temperature coefficient (dE^o/dT) of the PD‐CGE and PD‐CPE, which was 0.0062 and 0.0071 V/ °C, respectively. Selectivity coefficients, determined by matched potential method (MPM) and separate solution method (SSM), showed high selectivity for pethidine hydrochloride (PDCl) over a large number of inorganic cations, organic cations, sugars, urine components, and some common drug excipients. The sensors were applied for determination of PDCl in ampoule and in spiked urine samples using potentiometric determination, standard addition and the calibration curve methods. The results obtained were satisfactory with excellent percentage recovery comparable and sometimes better than those obtained by other routine methods for the assay. Copyright © 2011 John Wiley & Sons, Ltd.     

Cellular uptake and toxicity effects of silver nanoparticles in mammalian kidney cells

The rapid progress and early commercial acceptance of silver‐based nanomaterials is owed to their biocidal activity. Besides embracing the antimicrobial potential of silver nanoparticles (AgNPs), it is imperative to give special attention to the potential adverse health effects of nanoparticles owing to prolonged exposure. Here, we report a detailed study on the in vitro interactions of citrate‐coated AgNPs with porcine kidney (Pk15) cells. As uncertainty remains whether biological/cellular responses to AgNPs are solely as a result of the release of silver ions or whether the AgNPs themselves have toxic effects, we investigated the effects of Ag⁺ on Pk15 cells for comparison. Next, we investigated the cellular uptake of both AgNPs and Ag⁺ in Pk15 cells at various concentrations applied. The detected Ag contents in cells exposed to 50 mg l^?1 AgNPs and 50 mg l^?1 Ag⁺ were 209 and 25 µg of Ag per 10⁶ cells, respectively. Transmission electron microscopy (TEM) images indicated that the Pk15 cells internalized AgNPs by endocytosis. Both forms of silver, nano and ionic, decreased the number of viable Pk15 cells after 24 h in a dose‐dependent manner. In spite of a significant uptake into the cells, AgNPs had only insignificant toxicity at concentrations lower than 25 mg l^?1, whereas Ag⁺ exhibited a significant decrease in cell viability at one‐fifth of this concentration. The Comet assay suggested that a rather high concentration of AgNP (above 25 mg l^?1) is able to induce genotoxicity in Pk15 cells. Further studies must seek deeper understanding of AgNP behavior in biological media and their interactions with cellular membranes. Copyright © 2014 John Wiley & Sons, Ltd.     

Novel nano-insulin formulation modulates cytokine secretion and remodeling to accelerate diabetic wound healing

Little is known about insulin's wound healing capability in normal as well as diabetic conditions. We here report specific interaction of silver nanoparticles (AgNPs) with insulin by making a ~2?nm thick coat around the AgNPs and its potent wound healing efficacy. Characterization of the interaction of human insulin with silver nanoparticles showed confirmed alteration of amide-I in insulin whereas amide-II and III remained unaltered. Further, nanoparticles protein interaction kinetics showed spontaneous interaction at physiological temperature with ΔG, ΔS, Ea and Ka values ?7.48, 0.076, 3.84 kcal mol^?1 and 6?×?10⁵?s^?1 respectively. Insulin loaded AgNPs (IAgNPs) showed significant improvement in healing activity in vitro (HEKa cells) and in vivo (Wister Rats) in comparison with the control in both normal and diabetic conditions. The underlying mechanism was attributed to a regulation of the balance between pro (IL-6, TNFα) and anti-inflammatory cytokines (IL-10) at the wound site to promote faster wound remodeling.     

新诺明分子印迹传感器的制备及应用研究

目的以吡咯为单体在玻碳电极表面电聚合一种新诺明分子印迹膜。方法研究了聚吡咯、新诺明浓度、扫描圈数及扫描速率对印迹膜制备的影响,并探讨检测液的pH值、乙腈与水的体积比对响应电流的影响。采用循环伏安法及电化学交流阻抗技术对分子印迹膜进行表征。结果在最佳实验条件下新诺明的浓度在2．50×10^-5～7．50×10^-4mol·L^-1及7．50×10^-4～2．00×10^-3mol·L^-1内时,差分脉冲伏安法的峰电流响应值呈现线性关系（线性相关系数分别为0．9958和0．99671,检出限（S／N=3）为2．80×10^-6mol·L^-1。结论印迹电极也显示出较好的选择性、重复性、稳定性。将此印迹传感器对复方新诺明药品中磺胺甲嗯唑的含量进行了测定,回收率在94．2％～105．0％。     

Determination of total mercury in seafood by ion-selective electrodes based on a thiol functionalized ionic liquid

A mercury(II) ion-selective electrode with an ionic liquid (IL), 1-methyl-2-butylthioimidazolium bis(trifluoromethanesulphonyl)imide ([C₁C₄Sim]NTf₂) as active material was constructed. Parameters affecting the performance of the electrodes such as the dosages of the IL and carbon nanotubes and the aqueous pH values were investigated. Experimental results indicated that the optimal composition of the electrode filling material was 47.6% [C₁C₄Sim]NTf₂, 47.6% tetrabutylphosphonium bis(trifluoromethanesulphonyl)imide (TBPNTf₂) and 4.8% carboxylic multi-walled carbon nanotubes (MWCNTs-COOH). Under the selected conditions, the proposed electrodes showed a good linear response in the concentration range of 10^?10–10^?5 mol L^?1 and had a detection limit of 4.1 × 10^?11 mol L^?1. No great interference from common metal ions was found. The proposed electrodes were applied to determine Hg²⁺ in seafood samples; the results were comparable to those of the direct mercury analyzer.     

Brain‐targeted distribution and high retention of silver by chronic intranasal instillation of silver nanoparticles and ions in Sprague–Dawley rats

The wide applications of silver nanoparticles (AgNPs) have been concerned regarding their unintentional toxicities. Different exposure modes may cause distinct accumulation, retention and elimination profiles, which are closely related with their toxicities. Unlike silver accumulation profiles through other regular administration modes, the biodistribution, accumulation and elimination of AgNPs by intranasal instillation are not fully understood. This study conducted intranasal instillation of polyvinylpyrrolidone‐coated AgNPs in neonatal Sprague–Dawley rats at doses of 1 and 0.1 mg kg^?1 day^?1 for 4 and 12 weeks, respectively. The 4‐week recovery was also designed after the 12‐week exposure. Silver concentrations in the main tissues or organs were periodically monitored. Parallel exposures using silver ion were performed for the comparative studies. No physiological alterations were observed in AgNP exposures. In comparison, 1 mg kg^?1 day^?1 silver ions decreased body weight gain and caused mortality of 18.2%, showing ionic silver had a relatively higher toxicity than AgNPs. A relatively higher silver accumulation was observed in silver ion groups than AgNP groups. The silver ion release could not fully explain silver accumulation in AgNP exposures, showing silver distribution caused by particulate silver occurred in vivo. The highest silver concentration was in the liver at week 4, while it shifted to the brain after a 12‐week exposure. Dose‐related silver accumulation occurred for both AgNP and silver ion groups. The time course revealed a uniquely high concentration and retention of brain silver, implying chronic intranasal instillation caused brain‐targeted silver accumulation. These findings provided substantial evidence on the potential neuronal threat from the intranasal administration of AgNPs or silver colloid‐based products. Copyright © 2015 John Wiley & Sons, Ltd.     

Role of Nanostructures for Anti-proliferation of Bacteria and Their Quantitative Study Validated by Statistical Analysis

The simple and sensitive UV–visible spectrophotometric analytical methods have been adopted for the determination and validation of ZnO nanostructures (nanorods (NRs), nanosphere (NSs), and nanonuts (NNTs)), concentration, which are used to control the bacterial growth of Escherichia coli. This method is based on processing conditions of nanostructures of ZnO using precursors zinc acetate dihydrate (Zn(AC₂)₂·2H₂O), zinc nitrate hexahydrate (Zn(NO₃)₂·6H₂O), sodium hydroxide, hexamethylenetetramine (HMT), methanol, etc. The optical density (OD) of the resulting solution of ZnO nanostructures with E. coli bacteria were measured at 600 nm against the reagent blank, prepared under the same conditions. The use of statistical analysis for evaluation of the resulting solution (ZnO-NRs, ZnO-NSs, and ZnO-NNTs with E. coli) was optimized and validated by various operational parameters. Beer’s law was followed (Concentration range from 0.25–2.0 μg ml^?1) with apparent molar absorptivity of 4.38?×?10² l mol^?1 cm^?1 for ZnO-NRs, 2.70?×?10² l mol^?1 cm^?1 for ZnO-NSs, and 3.10?×?10² l mol^?1 cm^?1 for ZnO-NNTs, respectively. The calibration curve shows linearity over the concentration range of 0.25–1.50 μg ml^?1 for ZnO-NRs and 0.25–2.0 μg ml^?1 for ZnO-NSs and ZnO-NNTs. Detection limit (LOD) and quantitation limit (LOQ) were found to be 0.022:0.068 μg ml^?1 for ZnO-NRs, 0.028:0.087 μg ml^?1 for ZnO-NSs, and 0.044:0.137 μg ml^?1 for ZnO-NNTs analyzed by spectrophotometric method, respectively.     

Assessment of total silver and silver nanoparticle extraction from medical devices

There is concern over the release of silver nanoparticles (AgNPs) from medical devices due to their potential toxicological consequences inside the body. Towards developing the exposure component of a risk assessment model, the purpose of this study was to determine the amount and physical form of silver released from medical devices. Scanning electron microscopy was used to confirm that three of five marketed medical devices contained nanosilver coatings (mean feature sizes 115–341 nm). Aqueous device extracts (water, saline and human plasma) were analyzed with inductively coupled plasma mass spectrometry, ultraviolet–visible spectroscopy, dynamic light scattering, transmission electron microscopy, and nanoparticle tracking analysis. The amount of silver extracted from the devices ranged from 1 × 10⁻¹ to 1 × 10⁶ ng/cm² (conditions ranged from 37 to 50 °C, over one hour to seven days). The results further indicated that one of the five devices (labeled MD1) released significantly more AgNPs than the other devices. This data suggests that some but not all devices that are formulated with nanosilver may release detectable levels of AgNPs upon extraction. Further work is underway to quantitate the proportion of silver released as AgNPs and to incorporate this data into a risk assessment for AgNP exposure from medical devices.     

Acute toxic effects and gender‐related biokinetics of silver nanoparticles following an intravenous injection in mice

This study evaluated the acute toxicity and biokinetics of intravenously administered silver nanoparticles (AgNPs) in mice. Mice were exposed to different dosages of AgNPs (7.5, 30 or 120 mg kg^?1). Toxic effects were assessed via general behavior, serum biochemical parameters and histopathological observation of the mice. Biokinetics and tissue distribution of AgNPs were evaluated at a dose of 120 mg kg^?1 in both male and female mice. Inductively coupled plasma–mass spectrometry (ICP‐MS) was used to determine silver concentrations in blood and tissue samples collected at predetermined time intervals. After 2 weeks, AgNPs exerted no obvious acute toxicity in the mice. However, inflammatory reactions in lung and liver cells were induced in mice treated at the 120 mg kg^?1 dose level. The highest silver levels were observed in the spleen, followed by liver, lungs and kidneys. The elimination half‐lives and clearance of AgNPs were 15.6 h and 1.0 ml h^?1 g^?1 for male mice and 29.9 h and 0.8 ml h^?1 g^?1 for female mice. These results indicated that AgNPs could be distributed extensively to various tissues in the body, but primarily in the spleen and liver. Furthermore, there appears to be gender‐related differences in the biokinetic profiles in blood and distribution in lungs and kidneys following an intravenous injection of AgNPs. The data from this study provides information on toxicity and biodistribution of AgNPs following intravenous administration in mice, which represents the worst case scenario of toxicity among all the different administration routes, and may shed light in the future use of products containing AgNPs in humans. Copyright © 2012 John Wiley & Sons, Ltd.     

Caffeic acid phenethyl ester attenuates IgE-induced immediate allergic reaction

Caffeic acid phenethyl ester (CAPE) is the active component of honey bee propolis extracts. The results of the current study demonstrate that CAPE attenuated immunoglobulin (Ig)E-mediated allergic response in mast cells. Oral administration of CAPE inhibited IgE-mediated passive cutaneous anaphylaxis. CAPE effectively reduced both histamine and serotonin (5-HT)-induced vascular permeability in rats. CAPE also reduced histamine and leukotrienes (LTs) release from isolated rat peritoneal mast cells. Moreover, CAPE suppressed contraction induced by histamine (3 × 10^?8–3 × 10^?5 M), 5-HT (3 × 10^?9–10^?6 M) and adenosine (3 × 10^?8–10^?5 M) in guinea pig tracheal zigzag. These findings provide evidence that CAPE may serve as an effective therapeutic agent for allergic diseases.     

Toxicological interactions of silver nanoparticles and organochlorine pesticides in mouse peritoneal macrophages

Nanotechnology occupies a prominent space in economy and science due to the beneficial properties of nanomaterials. However, nanoparticles may pose risks to living organisms due to their adsorption and pro-oxidative properties. The aim of the current study was to investigate the effects of polymer-coated silver nanoparticles (AgNPs) and organochlorine pesticides (OCPs), as well as their combined effects on mouse peritoneal macrophages. Macrophages were isolated and exposed to three concentrations of AgNPs (groups: N1?=?30, N2?=?300 and N3?=?3000?ng.ml^?1), two concentrations of OCPs (groups: P1?=?30 and P2?=?300?ng.ml^?1) and the six possible combinations of these two contaminants for 24?h. AgNPs had irregular shape, Feret diameter of 8.7?±?7.5?nm and zeta potential of ?28.7?±?3.9?mV in water and ?10.7?±?1.04?mV in culture medium. OCP mixtures and the lower concentrations of AgNPs had no detectable effects on cell parameters, but the highest AgNPs concentration showed high toxicity (trypan blue and MTT assays) resulting in morphological changes, increase of nitric oxide levels and phagocytic index. Foremost, the association of N3 and P2 led to distinct effects from those observed under single exposure.     

The acute toxic effects of silver nanoparticles on myocardial transmembrane potential,INa and IK1 channels and heart rhythm in mice

This study focused on the potential toxicity of silver nanoparticles (AgNPs) on cardiac electrophysiology which is rarely investigated. We found that AgNPs (10^?9–10^?6?g/ml) concentration-dependently depolarized the resting potential, diminished the action potential, and finally led to loss of excitability in mice cardiac papillary muscle cells in vitro. In cultured neonatal mice cardiomyocytes, AgNPs (10^?9–10^?7?g/ml) concentration-dependently decreased the Na⁺ currents (I_Na), accelerated the activation, and delayed the inactivation and recovery of Na⁺ channels from inactivation within 5?min. AgNPs at 10^?8?g/ml also rapidly decreased the inwardly rectifying K⁺ currents (I_K1) and delayed the activation of I_K1 channels. Intravenous injection of AgNPs at 3?mg/kg only decreased the heart rate, while at ≥4?mg/kg sequentially induced sinus bradycardia, complete atrio-ventricular conduction block, and cardiac asystole. AgNPs at 10^?10–10^?6?g/ml did not increase reactive oxygen species (ROS) generation and only at 10^?6?g/ml mildly induced lactate dehydrogenase (LDH) release in the cardiomyocytes within 5?min. Endocytosis of AgNPs by cardiomyocytes was not observed within 5?min, but was observed 1?h after exposing to AgNPs. Comparative Ag⁺ (≤0.02% of the AgNPs) could not induce above toxicities. We conclude that AgNPs exert rapid toxic effects on myocardial electrophysiology and induce lethal bradyarrhythmias. These acute toxicities are likely due to direct effects of AgNPs on ion channels at the nano-scale level, but not caused by Ag⁺, ROS, and membrane injury. These findings provide warning to the nanomedical practice using AgNPs.     

A validated capillary electrophoretic method for the determination of indacaterol and its application to a pharmaceutical preparation

Indacaterol is a new inhaled ultra-long acting ${\beta }_2$-agonist. It has been recently approved in the European Union for the treatment of chronic obstructive pulmonary disease. This paper reports, for the first time, a method for the determination and validation of Indacaterol (IND) using an internal standard in capsules. Capillary electrophoretic separation was performed on an uncoated fused-silica capillary (50 cm effective length, 75 μm i.d.) and background electrolyte composed of 20 mmol L^?1 of sodium tetraborate buffer, 15% (v/v) methanol (pH = 10.0) with the application of 20 kV of potential; 10 s at 5 × 10³ N m^?2 (50 mbar) of injection time; and wavelength of 200 nm and 25 °C of temperature. The linearity was evaluated in the range of 4.90 × 10^?6 mol L^?1 (2.50 μg mL^?1) and 3.94 × 10^?5 mol L^?1 (20.00 μg mL^?1), with R = 0.9993 for inter-day. LOD and LOQ values were 2.18 × 10^?8 mol L^?1 (0.011 μg mL^?1) and 7.25 × 10^?8 mol L^?1 (0.037 μg mL^?1) for inter-day, respectively. The precision values were 0.50–1.06% for intra-day and 2.12% for inter-day as RSD%. The accuracy was tested by the standard addition method with the recovery values being between 98.79 and 99.09 as percentages with RSD% interval of 0.01–0.80. The developed method was validated according to ICH guidelines. Indacaterol was successfully determined in Arcapta^® capsule dosage form by the validated CE method with a relative error of 0.28%. The result was within the requirements of the USP 34-NF29. Therefore, the validated method may be used for the determination of Indacaterol in its capsules in quality control laboratories.     

Pt-MWCNT modified carbon electrode strip for rapid and quantitative detection of H2O2 in food

A single-use screen-printed carbon electrode strip was designed and fabricated. Nanohybrids, prepared by deposition of platinum (Pt) nanoparticles on multi-wall carbon nanotube (MWCNT), was modified on the surface of screen-printed carbon electrode for the development of a fast, sensitive and cost-effective hydrogen peroxide (H₂O₂) detection amperometric sensor strip. With Pt-MWCNT nanohybrids surface modification, current generated in response to H₂O₂ by the screen-printed carbon electrode strip was enhanced 100 fold with an applied potential of 300 mV. Quality of as-prepared electrode strip was assured by the low coefficient of variation (CV) (<5%) of currents measured at 5 s. Three linear detection ranges with sensitivity of 75.2, 120.7, and 142.8 μA mM^?1 cm^?2 were observed for H₂O₂ concentration in the range of 1–15 mM, 0.1–1 mM, and 10–100 μM, respectively. The lowest H₂O₂ concentration could be measured by the as-prepared strip was 10 μM. H₂O₂ levels in green tea infusion and pressed Tofu could be rapidly detected with results comparable to that measured by ferrous oxidation xylenol orange (FOX) assay and peroxidase colorimetric method.     

Biogenic synthesis of silver nanoparticles and their synergistic effect with antibiotics: a study against gram-positive and gram-negative bacteria

The development of a reliable green chemistry process for the biogenic synthesis of nanomaterials is an important aspect of current nanotechnology research. Silver nanoparticles (AgNPs) have been known for their inhibitory and bactericidal effect. Resistance to antimicrobial agents by pathogenic bacteria has emerged in recent years and is a major challenge for the health care industry. In the present investigation the use of the fungus Trichoderma viride for the extracellular biosynthesis of AgNPs from silver nitrate solution is reported. It was observed that the aqueous silver (Ag⁺) ions, when exposed to a filtrate of T. viride, were reduced in solution, thereby leading to formation of extremely stable AgNPs. These AgNPs were characterized by means of several techniques. The nanoparticles show maximum absorbance at 420 nm on ultraviolet-visible spectra. The presence of proteins was identified by Fourier transform–infrared spectroscopy. The reduction of Ag⁺ ions to elemental silver was characterized by x-ray photoelectron spectrophotometry. Electrokinetic measurements (zeta potential) of AgNPs as a function of pH in 1 × 10^?3 mol dm^?3 aqueous solution were evaluated. The transmission electron micrograph revealed the formation of polydispersed nanoparticles of 5–40 nm, and the presence of elemental silver was confirmed by energy-dispersed spectroscopy analysis. The nanoparticles were also evaluated for their increased antimicrobial activities with various antibiotics against gram-positive and gram-negative bacteria. The antibacterial activities of ampicillin, kanamycin, erythromycin, and chloramphenicol were increased in the presence of AgNPs against test strains. The highest enhancing effect was observed for ampicillin against test strains. The result showed that the combination of antibiotics with AgNPs have better antimicrobial effects. A mechanism was also proposed to explain this phenomenon.From the Clinical EditorSilver nanoparticles (Ag NP-s) represent an important nanomedicine-based advance in the fight against polyresistent bacteria. In this study, the fungus Trichoderma viride was utilized for extracellular biosynthesis of extremely stable Ag Nps. The antibacterial activities of kanamycin, erythromycin, chloramphenicol and especially of ampicillin were increased in the presence of Ag NPs against test strains.     

Evaluating the effects of diclofenac sodium and etodolac on renal hemodynamics with contrast-enhanced ultrasonography: a pilot study

Purpose

Contrast-enhanced ultrasonography (CEUS) is a novel approach used for measuring organ perfusion changes. Studies using CEUS to assess the effects of non-steroidal anti-inflammatory drugs (NSAIDs) on renal blood flow (RBF) have not yet been conducted. We aimed to evaluate the effects of NSAIDs on the renal hemodynamics of healthy subjects with CEUS.

Methods

We performed CEUS using the bolus injection method in a total of 10 healthy subjects. Measurements were completed over two study days in a randomized, crossover manner. On each study day, CEUS was performed twice, before and after the administration of NSAIDs. Subjects received an injection of contrast medium and images were recorded. A region-of-interest (ROI) was selected within the renal cortex, signal intensity in the ROI of the kidney was measured and a time-intensity curve (TIC) was automatically generated with attached software.

Results

The mean (±SD) peak intensity decreased significantly after an administration of diclofenac sodium (from 26.0?×?10^?4?±?17.4?×?10^?4 AU to 19.2?×?10^?4?±?12.0?×?10^?4 AU; P?=?0.022), but not significantly with etodolac (from 26.5?×?10^?4?±?9.7?×?10^?4 AU to 25.9?×?10^?4?±?20.8?×?10^?4 AU; P?=?0.474). The mean (±SD) percent reduction in intensity following diclofenac sodium administration was significantly reduced compared with etodolac administration (22.2?±?20.5 % vs. 3.4?±?8.9 %, P?=?0.037).

Conclusions

These finding suggests that diclofenac sodium (P?=?0.022), but not etodolac (P?=?0.474), affects renal hemodynamics even in healthy subjects.     

Towards disposable sensors for drug quality control: Dextromethorphan screen‐ printed electrodes

A simple, rapid, reliable, and reproducible method for mass production of disposable sensors using screen‐printing technology is described. Homemade printing has been characterized and optimized on the basis of effects of the modifier and plasticizers. The fabricated bi‐electrode potentiometric strip containing both working and reference electrode was used as dextromethorphan (DXM) sensor. The proposed sensors worked satisfactorily in the concentration range from 10^?5 to 10^?2 mol L^?1 with detection limit reaching 6 × 10^?6 mol L^?1 and adequate shelf life of 8 months. DXM was determined in pharmaceutical formulations under batch and flow injection analysis (FIA) conditions with sampling output 120 h^?1. Copyright © 2010 John Wiley & Sons, Ltd.     

Silver nanoparticles inhaled during pregnancy reach and affect the placenta and the foetus

Recently, interest for the potential impact of consumer-relevant engineered nanoparticles on pregnancy has dramatically increased. This study investigates whether inhaled silver nanoparticles (AgNPs) reach and cross mouse placental barrier and induce adverse effects. Apart from their relevance for the growing use in consumer products and biomedical applications, AgNPs are selected since they can be unequivocally identified in tissues. Pregnant mouse females are exposed during the first 15 days of gestation by nose-only inhalation to a freshly produced aerosol of 18–20?nm AgNPs for either 1 or 4?h, at a particle number concentration of 3.80?×?107 part./cm^?3 and at a mass concentration of 640?μg/m³. AgNPs are identified and quantitated in maternal tissues, placentas and foetuses by transmission electron microscopy coupled with energy-dispersive X-ray spectroscopy and single-particle inductively coupled plasma mass spectrometry. Inhalation of AgNPs results in increased number of resorbed foetuses associated with reduced oestrogen plasma levels, in the 4?h/day exposed mothers. Increased expression of pregnancy-relevant inflammatory cytokines is also detected in the placentas of both groups. These results prove that NPs are able to reach and cross the mouse placenta and suggest that precaution should be taken with respect to acute exposure to nanoparticles during pregnancy.     

Synthesis of a novel phosphate analog of 20-hydroxylecdysone with potent hypoglycemic activity

A novel, water-soluble 20-hydroxylecdysono-20,22-phosphoric acid 2 and its sodium salt 3 were designed and synthesized from 20-hydroxylecdysone 1 in six steps and with 67% overall yield. The synthesized phosphoric acid 2 exhibited hypoglycemic activity >40-fold more potent than that of 20-hydroxylecdysone 1 at concentrations between 2 × 10^? 7 and 2 × 10^? 8 mol/l in a glucose consumption test in HepG2 cells. At a concentration of 2 × 10^? 9 mol/l, phosphoric acid 2 was still active, causing a maximum increase in glucose consumption of more than 500%, while 20-hydroxylecdysone 1 was inactive.