Assessment of contaminants of emerging concern in European apex predators and their prey by LC-QToF MS wide-scope target analysis.

Apex predators are good indicators of environmental pollution since they are relatively long-lived and their high trophic position and spatiotemporal exposure to chemicals provides insights into the persistent, bioaccumulative and toxic (PBT) properties of chemicals. Although monitoring data from apex predators can considerably support chemicals' management, there is a lack of pan-European studies, and longer-term monitoring of chemicals in organisms from higher trophic levels. The present study investigated the occurrence of contaminants of emerging concern (CECs) in 67 freshwater, marine and terrestrial apex predators and in freshwater and marine prey, gathered from four European countries. Generic sample preparation protocols for the extraction of CECs with a broad range of physicochemical properties and the purification of the extracts were used. The analysis was performed utilizing liquid (LC) chromatography coupled to high resolution mass spectrometry (HRMS), while the acquired chromatograms were screened for the presence of more than 2,200 CECs through wide-scope target analysis. In total, 145 CECs were determined in the apex predator and their prey samples belonging in different categories, such as pharmaceuticals, plant protection products, per- and polyfluoroalkyl substances, their metabolites and transformation products. Higher concentration levels were measured in predators compared to prey, suggesting that biomagnification of chemicals through the food chain occurs. The compounds were prioritized for further regulatory risk assessment based on their frequency of detection and their concentration levels. The majority of the prioritized CECs were lipophilic, although the presence of more polar contaminants should not be neglected. This indicates that holistic analytical approaches are required to fully characterize the chemical universe of biota samples. Therefore, the present survey is an attempt to systematically investigate the presence of thousands of chemicals at a European level, aiming to use these data for better chemicals management and contribute to EU Zero Pollution Ambition.

Effects of wastewater-spiked nanoparticles of silver and titanium dioxide on survival, growth, reproduction and biochemical markers of Daphnia magna.

Silver (Ag) and titanium dioxide (TiO2) nanoparticles (NPs) are released into aquatic environments through wastewater treatment plants (WWTPs). Even though these NPs are mostly retained in WWTPs, a small fraction can be found in released effluents and may exert toxic effects on aquatic biota. Currently, the available information about the sublethal effects of wastewater-borne NPs on aquatic organisms is inconclusive and the importance of exposure media remains poorly understood. Previously, we demonstrated that rainbow trout juveniles chronically exposed to wastewater-borne AgNPs or TiO2NPs caused no effects on growth, but antioxidative stress mechanisms were triggered in fish organs. Accordingly, this study aimed to: (i) assess the chronic (21-d) effects of wastewater-borne AgNPs (0.3-23.5 µg L-1 Ag) and TiO2NPs (2.7-3.9 µg L-1 Ti) on survival, growth and reproduction of Daphnia magna; (ii) determine the short-term (96-h) effects of wastewater-borne AgNPs (30.3 µg L-1 Ag) and TiO2NPs (6.3 µg L-1 Ti) at the subcellular level (biochemical markers of neurotoxicity, anaerobic metabolism and oxidative stress); and (iii) compare the effects obtained in (i) and (ii) with the corresponding ones induced by effluent-supplemented and water-dispersed NPs. Total Ag and Ti levels were analytically quantified in all treatments. It was demonstrated that both wastewater-borne NPs are considered non-toxic to daphnids at tested concentrations, considering the endpoints at the individual (survival, growth, reproduction) and subcellular (biochemical markers) levels. Contrarily, when pristine forms of NPs were supplemented to effluents or water, concentration-dependent effects were noticed, particularly on cumulative offspring of daphnids. The significant effects on anaerobic metabolism and detoxification pathways caused by the effluent indicate background toxicity. Bearing in mind the achievement of a suitable risk assessment of NPs in aquatic environments, this combined approach looking at both the individual and subcellular levels responses come up with relevant information about the ecotoxicological harmlessness of wastewater-borne NPs in complex environmental matrices like WWTP effluents.

Nanopharmaceuticals (Au-NPs) after use: Experiences with a complex higher tier test design simulating environmental fate and effect.

The current environmental hazard assessment is based on the testing of the pristine substance. However, it cannot be excluded that (nano)pharmaceuticals are excreted into sewage during the use phase followed by entry into wastewater treatment plants (WWTPs). Sorption to sewage sludge or release via effluent can result in modified ecotoxicological effects which possibly can only be detected with a modified test approach. The objective of our study was to investigate a realistic exposure scenario for metallic nanoparticles (NPs) in pharmaceutical products, excreted into effluent, and released into the environment after treatment in WWTPs. The test approach was illustrated by using gold (Au) NPs. Effluent from model WWTPs were investigated in aquatic tests (Daphnia magna, fish cell lines). Sewage sludge was used as a sole food source (Eisenia fetida) or mixed with soil and used as test medium (soil microorganisms, Folsomia candida, Enchytraeus crypticus). To cover the aspect of regulation, the test systems described in OECD-test guidelines (OECD TG 201, 211, 220, 232, 249, 317) were applied. Modifications and additional test approaches were included to meet the needs arising out of the testing of nanomaterials and of the exposure scenarios. The results were assessed regarding the suitability of the test design and the toxicity of Au-NPs. Except for activated sludge as a sole food source for E.fetida, the selected test approach is suitable for the testing of nanomaterials. Additional information can be gained when compared to the common testing of the pristine nanomaterials in the standardized test systems. Effects of Au-NPs were observed in concentrations exceeding the modeled environmental.

Microbial Population Dynamics in Model Sewage Treatment Plants and the Fate and Effect of Gold Nanoparticles.

Adequate functioning of a sewage treatment plant (STP) is essential to protect the downstream aquatic environment (ECHA 2017), and information on the degradability of chemicals and their toxicity to activated sludge microorganisms is required. An environmental realistic higher tier test is a STP simulation test as described in OECD 303A (2001) which for nanoparticles can also be used to study their sorption behavior to activated sludge. However, information is limited on the influence of synthetic sewage on the microbial community of the activated sludge. A modified community can result in modifications of the sludge floccules affecting the sorption behavior. The main objective of our study was to show whether a representative microbial diversity remains under standardized test conditions as described in OECD 303A (2001) using synthetic sewage as influent. Furthermore, we investigated whether just considering the functional properties of a STP (elimination of dissolved organic carbon; nitrification), is sufficient for an assessment of gold nanoparticles (AuNPs) or whether the influence on microbial diversity also needs to be considered. AuNPs were used as a case study due to their rising medical applications and therefore increasing probability to reach the sewer and STP. The results can provide significant input for the interpretation of results from the regulatory point of view. To deliver these objectives, the general changes of the microbial population in activated sludge and its influence on the degradation activity (dissolved organic carbon (DOC) and inorganic nitrogen) using freshly collected sludge from the municipal STP in an artificial test system as a model STP in accordance with OECD 303A (2001) were assessed. Additionally, we evaluated the potential impact of AuNPs and its dispersant on the microbial composition and the overall impact on the function of the STP in terms of DOC degradation and nitrogen removal to observe if an assessment based on functional properties is sufficient. The bacteria composition in our study, evaluated at a class level, revealed commonly described environmental bacteria. Proteobacteria (ß, α, δ) accounted for more than 50% but also nitrifying bacteria as Nitrospira were present. Our results show that mainly within the first 7 days of an acclimatization phase by addition of synthetic sewage, the bacterial community changed. Even though AuNPs can have antibacterial properties, no adverse effects on the function and structure of the microorganisms in the STP could be detected at concentrations of increased modeled PEC values by a factor of about 10,000. Complementary to other metallic nanomaterials, gold nanomaterials also sorb to a large extent to the activated sludge. If activated sludge is used as fertilizer on agricultural land, gold nanoparticles can be introduced into soils. In this case, the effect on soil (micro)organisms must be investigated more closely, also taking into account the structural diversity.

Determination of low environmental free cyanide concentrations in freshwaters.

Cyanide compounds are naturally emitted into the environment in low levels by degradation processes or emitted from anthropogenic sources. In surface water, complex cyanide compounds as well as "free cyanide" are present. The latter term covers hydrogen cyanide and cyanide compounds which easily liberate hydrogen cyanide under slightly acidic conditions. Especially free cyanide may cause adverse effects in the environment. To exclude negative impacts on freshwater systems, in the context of the European Water Framework Directive (WFD), preventive regulatory activities for free cyanide are currently under discussion. However, established analytical methods for quantification of free cyanide only obtain limits of quantification (LOQs) in the range of 1 µg L-1. Thus, these methods are not sufficiently sensitive for a potential environmental quality standard (EQS) compliance monitoring at water concentrations below the current predicted no effect concentration (PNEC) level of free cyanide. In the present study, a standardized continuous flow analysis (CFA) method for quantification of low free cyanide concentrations was adapted by applying a special system which allows an ultra-sensitive photometric detection of a colored cyanide derivative. By this means, LOQs in a range of one magnitude below the PNEC are achievable. The method was validated according to ISO/IEC 17025 requirements. Free cyanide concentrations in tested surface water samples from a small river and a barrier lake with low anthropogenic influences were very low and clearly below the PNEC. The results prove that the adapted CFA method is suitable for the analysis of low concentration free cyanide in freshwaters and appropriate for a possible EQS compliance monitoring.

Chronic effects of wastewater-borne silver and titanium dioxide nanoparticles on the rainbow trout (Oncorhynchus mykiss).

Even though nanoparticles (NPs) are mostly removed by wastewater treatment plants, wastewater-borne NPs may show an altered toxicity to aquatic organisms. The main objectives of this work were: i) to assess the chronic (28 days) effects of wastewater-borne NPs of silver (AgNPs, 1.4-36.2 µg L-1) and titanium dioxide (TiO2NPs, 3.1-50.2 µg L-1) at the individual (growth) and biochemical (biomarkers of neurotoxicity, oxidative stress and energy metabolism) levels in rainbow trout Oncorhynchus mykiss; and ii) to compare them with their effluent-supplemented and water-dispersed counterparts. The total Ag and Ti levels were determined in several fish organs. The growth of O. mykiss was not affected by the NPs in any treatment, except a 29% increase at 5.5 µg L-1 of total Ag supplemented to effluents. The Ag level in organs of O. mykiss was significantly higher after exposure to water-dispersed AgNPs than their wastewater-borne or effluent-supplemented counterparts. No significant Ti uptake could be observed. Effluent-supplemented TiO2NPs (50.1 µg L-1 Ti) potentially induced neurotoxic effects, indicated by a 24% increase in acetylcholinesterase activity comparatively to controls. Energy reserves were unaffected by TiO2 treatments, while nearly all AgNP-containing treatments caused a depletion of total lipids, proteins and carbohydrates in the muscle, suggesting an increased energy demand for detoxification processes to cope with AgNPs. Besides NPs, the effluent matrix and dispersing agent (for AgNPs) induced significant effects on energetic reserves and oxidative stress, indicating background toxicity of both treatments at the biochemical level. Our study is the first to assess chronic effects of wastewater-borne NPs on rainbow trout. While no effects were found at the individual level, several biochemical markers were changed by the NPs exposure. Our results highlight the importance of using complex matrices for a reliable risk assessment of NPs in the aquatic environment.

Bioavailability of silver from wastewater and planktonic food borne silver nanoparticles in the rainbow trout Oncorhynchus mykiss.

Silver nanoparticles (AgNPs) are present in a wide field of applications and consumer products and are likely to be released into the environment, mainly via urban and industrial sewage due to their extensive use. Even though AgNPs are mostly retained within the sludge of wastewater treatment plants (WWTPs), a small amount of mainly sulfidized particles still enters the aquatic environment, where they can be taken up by various aquatic organisms and transferred along the food chain. In this study, uptake and bioavailability of Ag from AgNPs following aqueous and dietary exposure were investigated in the rainbow trout Oncorhynchus mykiss. AgNPs in the effluent of model WWTPs and in tap water were used to perform aqueous exposure studies. No significant Ag uptake into the gills and carcass of the analyzed fish could be found for wastewater-borne AgNPs. However, when added to tap water at a concentration of 12.4 µg L-1, a maximum total Ag tissue concentrations of around 100 µg kg-1 and 50 µg kg-1 in gills and carcass were measured, respectively. For the dietary exposure studies, freshwater zooplankton was exposed to AgNPs, and used for the preparation of food pellets with a total Ag concentration of 121.5 µg kg-1. During the feeding study with rainbow trout significant total Ag concentrations up to 34.3 µg kg-1 could be found in the digestive tract. However, only a limited transfer of Ag through the intestinal walls into the carcass could be detected. AgNPs in plankton and WWTP effluent were characterized by transmission electron microscopy (TEM) in combination with energy dispersive X-ray spectroscopy (EDX) and found to be sulfidized. This transformation most presumably has led to their limited bioavailability for fish. The results emphasize the importance of realistic test conditions for the risk assessment of AgNPs by the use of environmental matrices.

Correction to: Progress on bringing together raptor collections in Europe for contaminant research and monitoring in relation to chemicals regulation.

The correct affiliation of Sabrina Lo Brutto is shown in this paper.

Assessment of seafood contamination under the marine strategy framework directive: contributions of the German environmental specimen bank.

Descriptor 9 (D9) of the European Union Marine Strategy Framework Directive refers to the compliance of contaminant levels in fish and other seafood of a defined marine region or subregion with human health threshold values. This requires georeferenced samples that are often difficult to obtain when relying on commercial fisheries or programs designed for monitoring human exposure. The present study examines whether georeferenced samples of blue mussel (Mytilus edulis) and eelpout (Zoarces viviparus) fillet of the German environmental specimen bank (ESB) can be used in this context. The suitability of the ESB samples, procedures, and analytical methods is evaluated with respect to D9 requirements. Based on ESB data for the D9 relevant contaminants Pb, Cd, Hg, ∑4 PAHs, PCDD/Fs, dioxin-like (dl)-PCBs, and indicator non-dl-PCBs and the potentially relevant substances TBT, PFOS, PBDE, and HBCDD, the Good Environmental Status for D9 is assessed at the ESB sites in the North and Baltic Seas. The overall evaluation indicates that ESB samples are suitable for D9 assessment with the limitation that only coastal areas of the North and Baltic Seas are covered. Over a period of up to 30 years, concentrations of the D9 relevant contaminants were well below the maximum levels allowed for human consumption.

Long-term effects of sulfidized silver nanoparticles in sewage sludge on soil microflora.

The use of silver nanoparticles (AgNPs) in consumer products such as textiles leads to their discharge into wastewater and consequently to a transfer of the AgNPs to soil ecosystems via biosolids used as fertilizer. In urban wastewater systems (e.g., sewer, wastewater treatment plant [WWTP], anaerobic digesters) AgNPs are efficiently converted into sparingly soluble silver sulfides (Ag2 S), mitigating the toxicity of the AgNPs. However, long-term studies on the bioavailability and effects of sulfidized AgNPs on soil microorganisms are lacking. Thus we investigated the bioavailability and long-term effects of AgNPs (spiked in a laboratory WWTP) on soil microorganisms. Before mixing the biosolids into soil, the sludges were either anaerobically digested or directly dewatered. The effects on the ammonium oxidation process were investigated over 140 d. Transmission electron microscopy (TEM) suggested an almost complete sulfidation of the AgNPs analyzed in all biosolid samples and in soil, with Ag2 S predominantly detected in long-term incubation experiments. However, despite the sulfidation of the AgNPs, soil ammonium oxidation was significantly inhibited, and the degree of inhibition was independent of the sludge treatment. The results revealed that AgNPs sulfidized under environmentally relevant conditions were still bioavailable to soil microorganisms. Consequently, Ag2 S may exhibit toxic effects over the long term rather than the short term. Environ Toxicol Chem 2017;36:3305-3313. © 2017 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC.

Detoxification and sensing mechanisms are of similar importance for Cd resistance in Caenorhabditis elegans.

The present study employed mass spectrometry (ICP-MS) to measure the internal cadmium concentrations (Cdint) in Caenorhabditis elegans to determine Cd uptake from a Cd-containing environment as well as Cd release under Cd-free conditions. To analyze the functional role of several ATP binding cassette (ABC) transporters (e.g., HMT-1 and MRP-1) and phytochelatin synthase (PCS), we compared wild-type (WT) and different mutant strains of C. elegans. As a pre-test on selected mutant strains, several time-resolved experiments were performed to determine the survival rate and avoidance behavior of C. elegans under Cd stress, which confirmed the already known Cd sensitivity of the deletion mutants mrp-1Δ, pcs-1Δ, and hmt-1Δ. In addition, these experiments revealed flight reactions under Cd stress to be almost completely absent in mrp-1Δ mutants. The ICP-MS studies showed Cd uptake to be significantly higher in mrp-1Δ and WT than in hmt-1Δ. As Cd is ingested with food, food refusal due to very early Cd stress and its perception was likely the reason for the reduced Cd uptake of hmt-1Δ. Cd release (detoxification) was found to be maximal in mrp-1Δ, minimal in hmt-1Δ, and intermediate in WT. High mortality under Cd stress, food refusal, and minimal Cd release in the case of hmt-1Δ suggest a vital importance of the HMT-1/PCS-1 detoxification system for the survival of C. elegans under Cd stress. High mortality under Cd stress, absence of an avoidance behavior, missing food refusal, and maximal Cd release in the case of mrp-1Δ indicate that MRP-1 is less important for Cd detoxification under severe stress, but is probably important for Cd perception. Accordingly, our results suggest that the survival of WT under Cd stress (or possibly other forms of metal stress) primarily depends on the function of the HMT-1/PCS-1 detoxification system and the presence of a sensing mechanism to control the uptake of Cd (or other metals), which keeps internal Cd (or metal) concentrations under control, to some extent, for the timely mobilization of protection and repair systems.

A microcosm study to support aquatic risk assessment of nickel: Community-level effects and comparison with bioavailability-normalized species sensitivity distributions.

The aquatic risk assessment for nickel (Ni) in the European Union is based on chronic species sensitivity distributions and the use of bioavailability models. To test whether a bioavailability-based safe threshold of Ni (the hazardous concentration for 5% of species [HC5]) is protective for aquatic communities, microcosms were exposed to 5 stable Ni treatments (6-96 µg/L) and a control for 4 mo to assess bioaccumulation and effects on phytoplankton, periphyton, zooplankton, and snails. Concentrations of Ni in the periphyton, macrophytes, and snails measured at the end of the exposure period increased in a dose-dependent manner but did not indicate biomagnification. Abundance of phytoplankton and snails decreased in 48 µg Ni/L and 96 µg Ni/L treatments, which may have indirectly affected the abundance of zooplankton and periphyton. Exposure up to 24 µg Ni/L had no adverse effects on algae and zooplankton, whereas the rate of population decline of the snails at 24 µg Ni/L was significantly higher than in the controls. Therefore, the study-specific overall no-observed-adverse-effect concentration (NOAEC) is 12 µg Ni/L. This NOAEC is approximately twice the HC5 derived from a chronic species sensitivity distribution considering the specific water chemistry of the microcosm by means of bioavailability models. Thus, the present study provides support to the protectiveness of the bioavailability-normalized HC5 for freshwater communities.

Retrospective monitoring of mercury in fish from selected European freshwater and estuary sites.

Levels and trends of total mercury (THg) and methylmercury (MeHg) compounds in bream (Abramis brama) from different European sites were compared. Bream were collected between 2007 and 2013 in the estuaries of the rivers Scheldt (Netherlands), Rhône (France), Göta älv (Sweden), Tees (United Kingdom), and Mersey (UK), and in Lake Belau (Germany). A direct mercury analyzer was used to determine THg concentrations while MeHg was measured by gas chromatography/inductively coupled plasma-mass spectrometry applying stable isotope dilution. THg and MeHg in annual pool samples of bream ranged between 15.9 and 251 µg kg(-1) wet weight (ww) with lowest concentrations found at the reference site Lake Belau and highest in samples from the river Rhône. The EU environmental quality standard (EQS) of 20 µg kg(-1) ww was exceeded at all sites and in all years except at Lake Belau in 2012. Significantly decreasing trends over time were observed only in bream from the Rhône, while THg increased in bream from the Western Scheldt. The MeHg fractions of THg were always >80% and a significant difference between sites was detected only in one case (Rhône vs. Lake Belau).

Spatial and temporal trends of metals and arsenic in German freshwater compartments.

Cadmium, lead, mercury, copper, nickel, zinc, and arsenic were analyzed in suspended particulate matter (SPM), zebra mussels, and bream sampled yearly under the program of the German Environmental Specimen Bank (ESB) in the rivers Rhine, Elbe, Danube, Saar, Mulde, and Saale and in Lake Belau. Temporal and spatial trends were analyzed, correlations between metal levels in different specimen types assessed, and sampling sites ranked according to their metal levels by calculating a Multi-Metal Index (MMI) for every specimen type and site. SPM: Highest metal loads were detected in Mulde, Saale, and Elbe right downstream of the Saale confluence. In the Elbe, metal loads in SPM were mostly highest in the upper and middle section of the river while in Rhine and Saar concentrations increased downstream. Temporal trends since 2005 were detected only at three sites. Zebra mussel: MMIs were highest in the tidal section of the Elbe and the lower Rhine and lowest in Lake Belau and the upper Danube. Different temporal trends were detected since the early 1990s depending on site and metal. Bream: As, Pb, Cu, and Hg were analyzed in muscle tissue and Pb, Cd, Cu, and Zn in liver. For both tissues, MMIs were highest in Mulde and Saale and the lower and middle Elbe. Since the early 1990s, Hg, Pb, and Cu decreased in bream muscle at many sites while As increased at 6 of the 17 sites. The findings indicate that Hg, Pb, and Cu have obviously decreased in many freshwater ecosystems in recent years, whereas As and Ni levels have increased at several sites. Metal levels and temporal trends mostly differed between the specimen types under investigation and only few correlations between specimen types were detected. This underlines the importance of including different components of an ecosystem when assessing its environmental quality.

Properties of Halococcus salifodinae, an Isolate from Permian Rock Salt Deposits, Compared with Halococci from Surface Waters.

Halococcus salifodinae BIpT DSM 8989T, an extremely halophilic archaeal isolate from an Austrian salt deposit (Bad Ischl), whose origin was dated to the Permian period, was described in 1994. Subsequently, several strains of the species have been isolated, some from similar but geographically separated salt deposits. Hcc. salifodinae may be regarded as one of the most ancient culturable species which existed already about 250 million years ago. Since its habitat probably did not change during this long period, its properties were presumably not subjected to the needs of mutational adaptation. Hcc. salifodinae and other isolates from ancient deposits would be suitable candidates for testing hypotheses on prokaryotic evolution, such as the molecular clock concept, or the net-like history of genome evolution. A comparison of available taxonomic characteristics from strains of Hcc. salifodinae and other Halococcus species, most of them originating from surface waters, is presented. The cell wall polymer of Hcc. salifodinae was examined and found to be a heteropolysaccharide, similar to that of Hcc. morrhuae. Polyhydroxyalkanoate granules were present in Hcc. salifodinae, suggesting a possible lateral gene transfer before Permian times.

Multicenter study of pegylated liposomal doxorubicin in patients with cutaneous T-cell lymphoma.

BACKGROUND: In single center studies and case reports, it was shown that pegylated liposomal doxorubicin (PEG-DOXO) was effective as second-line therapy for patients with cutaneous T-cell lymphoma (CTCL). The objective of this study was to evaluate the efficacy and toxicity of single-agent PEG-DOXO as second-line chemotherapy in patients with CTCL. METHODS: A retrospective, multicenter study was performed evaluating 34 patients (31 male patients and 3 female patients). Twenty-seven patients received PEG-DOXO 20 mg/m(2), 5 patients received PEG-DOXO 20-30 mg/m(2), and 2 patients received PEG-DOXO 40 mg/m(2). PEG-DOXO was administered intravenously every 2 weeks in 6 patients, every 2-3 weeks in 4 patients, and every 4 weeks in 23 patients. One patient received only a single course of PEG-DOXO. Outcomes were evaluated, and adverse effects were recorded. RESULTS: Thirty-four patients received at least 1 cycle of PEG-DOXO. Disease was classified as mycosis fungoides in 28 patients, mycosis fungoides with follicular mucinosis in 2 patients, small or medium-sized pleomorphic CTCL in 2 patients, Sèzary syndrome in 1 patient, and CD30 positive CTCL in 1 patient. Fifteen patients achieved a complete response (CR), including patients who achieved a CR and patients who achieved a CR defined by clinical criteria only with no biopsy (CRu), and 15 patients achieved a partial response (PR), resulting in a response rate (CRs, CRus, and PRs) of 88.2%. Two patients dropped out: one patient after a single PEG-DOXO infusion because of Grade 3 capillary leakage syndrome and one patient after two cycles because of a suicide attempt that was not related to treatment or to CTCL. All other patients received at least four cycles of PEG-DOXO. Overall survival was 17.8 months +/- 10.5 months (n = 33 patients), event-free survival was 12.0 months +/- 9.5 months, and disease-free survival was 13.3 +/- 10.5 months (n = 16 patients). Adverse effects were seen in 14 of 34 patients (41.2%); they were temporary and generally mild. Only 6 patients had Grade 3 or 4 adverse effects. CONCLUSIONS: This multicenter study provided evidence of high efficacy of PEG-DOXO monotherapy with a low rate of severe adverse effects compared with other chemotherapy protocols in patients with CTCL.

Decreased concentrations of serum phospholipid plasmalogens indicate oxidative burden of uraemic patients undergoing haemodialysis.

Experimental evidence indicates that uraemic patients undergoing haemodialysis are subject to increased oxidative stress. Plasmalogens are a phospholipid subclass found in cell membranes and plasma lipoproteins, which may work as an endogenous antioxidant. Using gas chromatography, we measured reduced portions of fatty aldehyde dimethyl acetals (16:0 DMA and 18:0 DMA, representing derivatives of plasmalogens) in fatty acid patterns of fasting serum phospholipids from 30 patients with chronic renal failure (CRF) receiving repeated ambulatory haemodialysis, as compared to 99 normal control subjects (CS). The highly significant difference of mean 16:0 DMA and 18:0 DMA values between CRF patients and CS (0.53 +/- 0.15 vs. 0.67 +/- 0.13, p < 0.001 and 0.33 +/- 0.11 vs. 0.40 +/- 0.11, p < 0.01, respectively) was lost when the patients were compared to subjects older than 85 (16:0 DMA) or 75 years (18:0 DMA). Weak, but significant inverse correlations with age or triglycerides were observed in blood serum of CS for 16:0 DMA and 18:0 DMA, respectively, but not of the patients. Partial correlation analysis indicated a mutually independent association of age and triglyceride values with serum plasmalogens in CS, but not in CRF patients. In conclusion, the reduced content of serum plasmalogen phospholipids of uraemic patients undergoing haemodialysis suggests an increased oxidative stress.