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A study was conducted to examine the influence of hydraulic retention time (HRT) and solid retention time (SRT) on the removal of tetracycline in the activated sludge processes. Two lab-scale sequencing batch reactors (SBRs) were operated to simulate the activated sludge process. One SBR was spiked with 250 microg/L tetracycline, while the other SBR was evaluated at tetracycline concentrations found in the influent of the wastewater treatment plant (WWTP) where the activated sludge was obtained. The concentrations of tetracyclines in the influent of the WWTP ranged from 0.1 to 0.6 microg/L. Three different operating conditions were applied during the study (phase 1-HRT: 24 h and SRT: 10 days; phase 2-HRT: 7.4 h and SRT: 10 days; and phase 3-HRT: 7.4 h and SRT: 3 days). The removal efficiency of tetracycline in phase 3 (78.4 +/- 7.1%) was significantly lower than that observed in phase 1 (86.4 +/- 8.7%) and phase 2 (85.1 +/- 5.4%) at the 95% confidence level. The reduction of SRT in phase 3 while maintaining a constant HRT decreased tetracycline removal efficiency. Sorption kinetics reached equilibrium within 24 h. Batch equilibrium experiments yielded an adsorption coefficient (Kads) of 8400 +/- 500 mL/g and a desorption coefficient (Kdes) of 22 600 +/- 2200 mL/g. No evidence of biodegradation for tetracycline was observed during the biodegradability test, and sorption was found to be the principal removal mechanism of tetracycline in activated sludge.

The antimicrobial moenomycin, commonly used as a growth promoter in livestock, was isolated from medicated chicken feed. The purified extract was subjected to reversed-phase liquid chromatographic separation followed by structural characterization using ion-trap mass spectrometry (ITMS), which allowed identification of five moenomycins (A, A12, C1, C3, and C4) as the major components. The fragmentation patterns of the protonated and deprotonated moenomycin molecules, as well as of a series of sodium adducts, were investigated using ITMS after electrospray ionization. While the protonated molecules [M+H]+ proved highly unstable and underwent extensive in-source fragmentation, isolation and activation of the [M--H]- ions (m/z 1580 for moenomycin-A) yielded simple mass spectra with a dominant base peak corresponding to the loss of the carboxy-glycol and the C25-hydrocarbon chain (m/z 1152 for moenomycin-A). Further study of this fragment ion in an MS3 experiment gave rise to a peculiar product ion (m/z 902 for moenomycin-A) that was attributed to the expulsion of a carbohydrate moiety representing a central building block of the linear molecule. In positive ion mode the generation of the mono-sodiated adduct ions, [M+Na]+, was promoted by amending the mobile phase with 100 microM sodium acetate, but this also resulted in higher adducts of the type [M+2Na--H]+ and [M+3Na--2H]+ arising from the formation of the sodium salts of the phosphate acid diester and subsequently of the carboxylic acid. Substantial differences among the fragment-rich product ion profiles of the three species were observed, and could in part be traced back to the mode of complexation of the additional sodium cation(s).

A comprehensive study on the fragmentation pattern of the antimicrobial growth promoter avilamycin A was conducted in a quadrupole ion trap mass spectrometer equipped with an electrospray ionization (ESI) source. Performing multiple-stage experiments on the deprotonated molecule (m/z 1401) and its principal product ions showed that a sequential shortening of the oligosaccharide backbone took place, which can be attributed to the localization of the negative charge in the terminal dichloroisoeverninic acid. Under (+)-ESI conditions, avilamycin A readily formed an intense sodium-cationized molecule, [M + Na](+) (m/z 1425). Structural elucidation of the second-, third- and fourth-generation fragment ions revealed that all of the structures shared a common molecular portion comprising a central monosaccharide. This observation allowed us to assign confidently the complexation site of the alkali metal cation. In addition to the monosodiated molecule, the full-scan mass spectral acquisition also yielded a less abundant disodiated molecule, [M - H + 2Na](+) (m/z 1447). Multiple-stage experiments on this ion indicated that the second sodium ion compensates for the negative charge located at either of two positions within the molecule. While deprotonation of the phenolic hydroxyl group in the dichloroisoeverninic acid moiety was suggested to be driven by charge stabilization in the aromatic ring (in analogy with the deprotonated molecule in the (-)-ESI mode), the deprotonation at an alpha-carbon of an ester side-chain substituent in the oligosaccharide part was believed to provide a stable chelation-like coordination site for the cation.

—In annual accounts and management reports, financial figures are used predominantly both in commercial and nonprofit companies in order to give a true and fair view of a company's assets, profits and financial position. As a result, the financial success is a key performance indicator – a figure which, usually, is quite low in the case of nonprofit companies [1]. However, such companies strive to reach content-oriented goals primarily, for instance performance quality, training success and employee satisfaction. As content-oriented goals are their basis of legitimacy, there should be possibilities to calculate whether they are met [2]. Basic prerequisite for such a calculation are specified details about the company’s mission statement, its content-oriented goals (from an economic, business, social or environmental point of view), its commercial goals (concerning profitability, liquidity and financial security) and its standards to measure objectives [3]. On this basis, it becomes possible to set targets and to incorporate the defined goals into a monitoring and reporting system [4]. Beyond achieving a profit, a social kind of success becomes interesting in such cases, which can be expressed as the so-called Social Profit. For example, this key figure can be measured by comparing costs and benefits attributed to the support of people in need. Benefits calculations takes avoided social spending into account, for example due to the prevention of homelessness, imprisonment or psychiatric clinic stays. The calculation also takes account of the effects of an individual’s rehabilitation and restored working abilities on the partaking in working and social life – which in the long run benefit society as a whole as well as tax payers [5]. Company goals, target groups, possible activities and their effects are of interest to calculate the Social Profit. However, several assumptions must be made about future political and economic developments. The following case study approaches to define and apply the concept “Social Profit”. Index Terms: Content-oriented objectives, Impact, Legitimation, Private and public investments, Social economy enterprises, Social Profit, Social Return on Investment

A knowledge-based design strategy led to the discovery of several new series of potent and orally bioavailable CRTh2 antagonists where a bicyclic heteroaromatic ring serves as the central core. Structure–kinetic relationships (SKR) opened up the possibility of long receptor residence times.

In this study, four unapproved analogues of Sildenafil (SDF) were photodegraded under synthetic sunlight in artificial freshwater. Homosildenafil (H-SDF), hydroxyhomo-sildenafil (HH-SDF), norneosildenafil (NR-SDF) and thiosildenafil (T-SDF) were selected because they are frequently detected as adulterants in natural herbal products. Using UPLC-Orbitrap (Q Exactive)-MS, six photoproducts common to H-SDF, HH-SDF and T-SDF and nine unique transformation products of different molecular weights were identified based on their high-resolution (+)ESI product ion spectra. Mass spectral analysis of deuterated H-SDF, labeled on the N-ethyl group, allowed to gain mechanistic insight into the fragmentation pathway of the substituted piperazine ring and to support the postulated photoproduct structures. The mass spectral fragmentation confirmed the stepwise destruction of the piperazine ring eventually producing a sulfonic acid derivative (C17 H20 N4 O5 S: 392.1151 Da). In contrast, the photodegradation of NR-SDF, which lacks a piperazine ring in its structure, formed only two prominent photoproducts originating from N,N-dealkylation of the sulfonamide followed by hydrolysis. The current work constitutes the first study on the photodegradation of analogs of erectile dysfunction drugs and the first detection of two transformation products (m/z 449 and 489) in environmental samples.

After liquid chromatographic (LC) separation, electrospray ionization mass spectrometry (ESI-MS) was investigated for the determination of the amphoteric surfactant cocamidopropylbetaine (CAPB). In the positive ion mode the molecule formed the adduct ions [M + H]+, [M + Na]+ and [M + K]+. Adducts of these cations were also detected with decreasing abundance as dimer and trimer clusters. Additionally, doubly charged molecular ions with different combinations of cations were identified. It was noticed that the relative abundances of individual cation adducts were not reproducible, apparently owing to varying contents of alkali metal ions originating from the solvent and the sample. Under negative ionization, the major molecular ion was [M − H]−. Higher clusters formed by two and three surfactant molecules, i.e. [2M − H]− and [3M − H]− were likewise registered. The tendency to form clusters in both positive and negative ion modes, even at 0.1 mg l−1 levels, was attributed to strong electrostatic interactions between the zwitterionic head groups. Further evidence for this assumption was provided by the detection of a fragment formed from [2M − H]− which contained the two charged head groups. Studies were undertaken in the negative ion mode on the concentration- and orifice voltage-dependent monomer, dimer and trimer formation of C12-CAPB in order to evaluate potential issues in using the ion [M − H]− mode for quantitative analysis. Finally, the established (−)-LC/ESI-MS method was applied to follow up the primary degradation of CAPB in a laboratory-scale fixed-bed bioreactor (FBBR) spiked with a test concentration of 10 mg l−1. Direct analysis without sample pretreatment revealed that higher alkyl homologues were more prone to adsorption. Primary biodegradation of all alkyl homologues was completed after a period of 4 days. Selected lyophilized FBBR samples were examined for the presence of transient or stable degradation intermediates, but no metabolite could be identified. Copyright © 2001 John Wiley & Sons, Ltd.

Linear alkylbenzenesulfonates (LASs) were determined in wastewaters and coastal waters by solid-phase extraction, using two different sample preparation protocols depending on the sample treated, followed by capillary electrophoresis and ultraviolet detection (CE-UV). The linear range of the proposed method varied from 3 to 53 and from 25 to 495 microg/l, depending on the compound, with a limit of detection of 1 microg/l when 250 ml of coastal water was preconcentrated. [M-H]- ions were used for CE-MS confirmation after quantification by CE-UV. CE-MS diagnostic ions were the same ones used in LC-electrospray (ESI) MS and corresponded to m/z 297, 311, 325 and 339 for C10, C11, C12 and C13 LASs, respectively. LASs were determined in wastewater samples of the influent and effluent of three wastewater treatment plants (WWTPs), two of them using biological treatment with secondary settlement and receiving mainly domestic wastewaters whereas one of the plants was operated with physicochemical treatment and received mainly industrial wastewaters. LASs were also analyzed in two samples from coastal waters of the bay of Cadiz (Spain) receiving untreated domestic effluents. All samples were also analyzed by LC-ESI-MS and the results are compared with the CE-UV method developed in this work. The concentration levels of total LASs varied from 988 to 1309 microg/l in the influents of WWTPs, whereas in the effluents the concentrations varied from 136 to 197 microg/l. The levels of LASs in coastal wastewaters of the bay of Cadiz varied from 739 to 911 microg/l, indicating that the wastewaters discharged into the bay did not undergo any treatment at all.

Alkyl glucamides (AGs) were analyzed by reversed-phase liquid chromatography (LC) coupled to mass spectrometry with electrospray ionization (ESMS). Analytes were separated according to the chain length of two homologs, C12- and C14-glucamide. Mass spectrometric detection in the positive ion mode exhibited higher overall sensitivity where, apart from fragments, different molecular and quasi-molecular ions were obtained. However, application of the negative ion mode offered advantages in terms of reproducibility and extent of information when analyzing environmental samples. Therefore, a simple and sensitive analytical methodology was developed for the determination of AGs in municipal sewage treatment plant influent and effluent based on solid-phase enrichment, LC separation and negative ion ESMS quantification. After preconcentration of 100 ml of aqueous sample, the recoveries using polymeric LiChrolut EN cartridges exceeded 89%. A quantification limit of 0.1 µg l−1 was achieved. Studies on the biodegradability and metabolic pathway of C10-glucamide were carried out on a laboratory-scale microbial test unit under aerobic conditions. A postulated metabolism including ω-oxidation of the alkyl chain followed by subsequent β-oxidations was checked by LC/ESMS. Identification and formation of ‘C4-glucamide acid’ as a degradation intermediate was confirmed by mass spectrometric studies. Higher homolog acids such as C10-, C8- and C6-glucamide acids, which should be predicted precursors of C4-glucamide acid, and any other metabolites, were not detectable, presumably owing to rapid breakdown. Copyright © 2000 John Wiley & Sons, Ltd.

Alkyl polyglucosides (APGs) were analyzed by reversed-phase liquid chromatography coupled to mass spectrometry with electrospray ionization. Analytes were separated according to the chain length of the alkyl homologues, whereas the separation of isomeric forms of the glucose moiety was achieved partially. Depending on the structure of the glucose ring the alkyl monoglucosides show a distinct affinity in terms of the formation of sodium and ammonium adduct ions. Metabolism of isomer pure alkyl monoglucosides was studied on a testfilter device to gather information about the degradation behavior and to obtain eventually poorly degradable metabolites. In spite of unsuccessful detection of any metabolites such as “polyglucoside alcanoic acids”, a degradation pathway was proposed including the cleavage of the glucosidic bond as initial step. In addition, a method for the determination of APGs in municipal waste water effluent was developed using solid-phase extraction on reversed-phase material. Recovery rates were in the range of 66 to 98% for three spiked alkyl monoglucosides and a quantitation limit of 0.2 μg l−1 was achieved.

High throughput screening identified the pyrazole-4-acetic acid substructure as CRTh2 receptor antagonists. Optimisation of the compounds uncovered a tight SAR but also identified some low nanomolar inhibitors.

The objective of this introductory chapter is to provide basic knowledge to environmental scientists involved in studying occurrence, fate, and effects of pharmaceuticals with respect to aspects pertaining to modern Drug Discovery and Development. It provides a concise picture of fundamental terms used in pharmacokinetics and drug metabolism, and describes the role of physicochemical properties as the key determinants of absorption, distribution, metabolism, and excretion (ADME) of drugs. The role of drug metabolism in Drug Discovery is highlighted and the most common drug-metabolizing enzymes are portrayed. In the last part of this chapter, the position of major pharmaceutical companies on the presence of pharmaceuticals in the environment and their view on possible adverse effects on aquatic organisms and human health are reviewed.

Effects of alpha-melanocyte-stimulating hormone (alpha-MSH), beta-melanocyte-stimulating hormone (beta-MSH), beta-lipotropin (beta-LPH), and beta-endorphin (beta-EPH) at concentrations from 10(-9) M up to 10(-6) M on human adipose tissue lipoprotein lipase (LPL) were studied in a cell-free system. alpha-MSH and beta-MSH did not exert any effect on LPL; no degradation of these peptides in the incubation medium could be detected by HPLC analysis. beta-LPH and beta-EPH failed to alter enzyme activity. However, HPLC analysis revealed an unspecific rapid degradation of the peptides due to the activity of tissue proteases. Therefore, the protease inhibitors amastatin, antipain, APMSF, and TPCK were tested at concentrations of 10(-5), 10(-4), and 10(-3) M for their efficacy to inhibit degradation. None of the inhibitors was able to substantially reduce proteolysis of beta-LPH, as was the case with amastatin, APMSF, and TPCK for beta-EPH. However, antipain at 10(-4) M preserved at least 20% of the initial peptide concentration from proteolysis up to 150 min. Antipain caused a decrease in lipoprotein lipase activity (LPLA), which was dependent on concentration. The adverse effect of antipain at concentrations of 10(-4) M on LPL was completely abolished by beta-EPH at a concentration of 10(-6) M.

Recent publications on pharmaceutical monitoring are increasingly covering the field of illicit drugs and lately the forensic evaluation of designing illegal analogs of lifestyle drugs like the phosphodiesterase type 5 (PDE-5) inhibitors Viagra (sildenafil), Levitra (vardenafil) and Cialis (tadalafil). Recently, the presence of all three erectile dysfunction treatment drugs has been reported in wastewaters at very low concentrations. In the environment, contaminants undergo various physical or chemical processes classified into abiotic (photolysis, hydrolysis) and biotic (biodegradation) reactions. Thus, changes in the chemical structure lead to the formation of new transformation products, which may persist in the environment or be further degraded. This study describes the photolysis of sildenafil (SDF) and its human metabolite N-demethylsildenafil (DM-SDF) under simulated solar radiation (Xenon lamp). Following chromatographic separation of the irradiated samples, eight photoproducts in the SDF samples and six photoproducts for DM-SDF were detected and characterized. The combination of ultra performance liquid chromatography-electrospray ionization-quadrupole time-of-flight-mass spectrometry (UPLC-ESI-QToF-MS), liquid chromatography-atmospheric pressure chemical ionization-triple quadrupole mass spectrometry (LC-APCI-QqQ-MS) and hydrogen/deuterium-exchange experiments allowed to propose plausible chemical structures for the photoproducts, taking into account the characteristic fragmentation patterns and the accurate mass measurements. These mass spectral data provided sound evidence for the susceptibility of the piperazine ring toward photodegradation. A gradual breakdown of this heterocyclic structure gave rise to a series of products, which in part were identical for SDF and DM-SDF. The sulfonic acid, as the formal product of sulfonamide hydrolysis, was identified as key intermediate in the photolysis pathway. In both drug/metabolite molecules, phototransformation processes taking place beyond the sulfonamide group were deemed to be of minor relevance.

There is a lack of quantitative information on the effectiveness of selective-logging practices in ameliorating effects of logging on faunal communities. We conducted a large-scale replicated field study in 3 selectively logged moist semideciduous forests in West Africa at varying times after timber extraction to assess post logging effects on amphibian assemblages. Specifically, we assessed whether the diversity, abundance, and assemblage composition of amphibians changed over time for forest-dependent species and those tolerant of forest disturbance. In 2009, we sampled amphibians in 3 forests (total of 48 study plots, each 2 ha) in southwestern Ghana. In each forest, we established plots in undisturbed forest, recently logged forest, and forest logged 10 and 20 years previously. Logging intensity was constant across sites with 3 trees/ha removed. Recently logged forests supported substantially more species than unlogged forests. This was due to an influx of disturbance-tolerant species after logging. Simultaneously Simpson's index decreased, with increased in dominance of a few species. As time since logging increased richness of disturbance-tolerant species decreased until 10 years after logging when their composition was indistinguishable from unlogged forests. Simpson's index increased with time since logging and was indistinguishable from unlogged forest 20 years after logging. Forest specialists decreased after logging and recovered slowly. However, after 20 years amphibian assemblages had returned to a state indistinguishable from that of undisturbed forest in both abundance and composition. These results demonstrate that even with low-intensity logging (≤3 trees/ha) a minimum 20-year rotation of logging is required for effective conservation of amphibian assemblages in moist semideciduous forests. Furthermore, remnant patches of intact forests retained in the landscape and the presence of permanent brooks may aid in the effective recovery of amphibian assemblages.

The brand represents the image of products and companies and meanwhile even of universities. One has to differentiate between comprehensive, regional and specialized universities as well as between the university public, the scientific community and the general public. Most important is the positioning of a university in and by the scientific world. A university can gain an excellent reputation when it has excellent scholars and students. The university needs performance centers for scientific activities with autonomy of human resources, organization and finances. Given such an infrastructure the scientists will become innovators instead of conservers.

Objectives: Toxic oil syndrome (TOS) is a disease that appeared in Spain in 1981. Epidemiological work traced the origin to the ingestion of aniline-adulterated rapeseed oil, fraudulently marketed and sold as edible oil. It affected more than 20,000 people with over 400 deaths in the first 2 years. In 2001 evidence was presented that genetic factors could play a role in the susceptibility of individuals to the disease. Thus, a prospective study on the differences in gene expression in sera between control versus TOS-affected populations, both originally exposed to the toxic oil, was undertaken in our laboratory. Methods: Differential protein expression was analyzed by two-dimensional electrophoresis (2-DE). Problems related with serum analysis by 2-DE were addressed to improve protein detection in the gel images. Three new commercial systems for albumin depletion were tested to optimize the detection of minor proteins. The use of nonionic reductants or the presence of thiourea in the gels, were also tested. Results: From the resulting optimized images, a group of 329 major gel spots was located, matched and compared with serum samples. Thirty-five of these protein spots were found to be under- or over-expressed in TOS patients (threefold increase or decrease). Proteins in these spots were identified by matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) peptide map fingerprinting and database search. Several haptoglobin (Hp) isoforms were found to be differentially expressed, showing expression phenotypes that could be related with TOS. Resolution of the homologous α-1s and α-1f chains, with a mass difference of only 0.043 Da, was obtained after guanidation of the protein with O-methylisourea. We applied this procedure to the study of the distribution of the Hp alleles HP 2, HP 1s and HP 1f in control versus TOS-affected populations. The MALDI-TOF proteotyping method was validated by a parallel analysis of the serum samples by 2-DE. Conclusions: Data obtained from 54 TOS cases and 48 controls indicate significant differences in the distribution of Hp phenotypes in the two populations. Haptoglobin phenotypes have been reported to have biological and clinical consequences and have been described as risk factors for several diseases. Consequently, it was concluded that haptoglobin polymorphism could play a role in TOS. © 2010 Elsevier Ireland Ltd. All Rights Reserved., This work was supported by WHO projects EU/03/016989 and EU 05/025039.

This article describes the photolysis of azithromycin, a macrolide antibiotic with reported occurrence in environmental waters, under simulated solar radiation. The photodegradation followed first-order reaction kinetics in five matrices examined. In HPLC water, the degradation rate was the slowest (half-life: 20 h), whereas in artificial freshwater supplemented with nitrate (5 mg L−1) or humic acids (0.5 mg L−1) the degradation of azithromycin was enhanced by factors of 5 and 16, respectively, which indicated the role of indirect photolysis involving the formation of highly reactive species. Following chromatographic separation on a UPLC system, the characterization of the transformation products was accomplished using high-resolution QqToF-MS analysis. The presence of seven photoproducts was observed and their formation was postulated to originate from (bis)-N-demethylation in the desosamine sugar, O-demethylation in the cladinose sugar, combinations thereof, as well as from hydrolytic cleavages of the desosamine and/or cladinose residue. Two of these photoproducts could also be detected in natural photodegradation process in river water which was spiked with azithromycin.

The highly polar, nonionic X-ray contrast agent iopromide (C(18)H(24)N(3)O(8)I(3); 791 Da) is resistant to microbial degradation during the activated sludge process in wastewater treatment plants and hence is released into the aquatic environment. Against this background, the present study was conducted to evaluate the phototransformation, potentially constituting the most relevant removal mechanism in rivers and streams. The photolysis of the iodinated aromatic compound was investigated in a Suntest solar simulator using aqueous solutions. Following a 120-min irradiation period, an almost complete primary degradation of iopromide gave rise to a series of photoproducts that were chromatographed on a reversed-phase UPLC and subsequently characterized by a combination of accurate mass measurements on a ESI-QqToF-MS instrument and H/D-exchange experiments. This analytical approach facilitated confident identification of eight prominent products with the following elemental compositions and molecular weights: C(18)H(25)N(3)O(9)I(2) (681 Da); C(18)H(25)N(3)O(8)I(2) (665 Da); C(17)H(23)N(3)O(8)I(2) (651 Da); C(18)H(24)N(3)O(9)I (553 Da); C(17)H(24)N(3)O(8)I (525 Da); C(15)H(20)N(3)O(6)I (465 Da); C(14)H(18)N(3)O(6)I (451 Da); and C(18)H(25)N(3)O(9) (427 Da). Their formation was the result of four principal photoreactions: (1) gradual, and eventually complete, deiodination of the aromatic ring; (2) substitution of the halogen by a hydroxyl group; (3) N-dealkylation of the amide in the hydroxylated side chain; and (4) oxidation of a methylene group in the hydroxylated side chain to the corresponding ketone. In conclusion, the findings of the artificial sunlight irradiation experiments indicated that in real environmental settings iopromide might suffer partial or even complete deiodination.

Background 80–100% of patients with multiple sclerosis (MS) display a polyspecific, intrathecal humoral immune response against a broad panel of viral agents including antibodies to measles, rubella and varicella zoster virus as its three most abundant components (called MRZ reaction [MRZR]). However, a positive MRZR reaction can also be found in some patients with CNS vasculitis, another rare autoimmune condition, raising the question whether this marker is really of high specificity for MS as previously claimed or whether it just represents a non-specific marker of CNS autoimmunity. Besides MS and CNS vasculitis, paraneoplastic neurological disorders (PND) represent the best recognized models of CNS autoimmunity. Objective To investigate MRZR for the first time in patients with PND. Patients and methods Forty-two patients with MS and 34 with PND were compared in this study. The intrathecal synthesis of antibodies against measles, rubella, and varicella zoster virus was detected by calculation of the respective antibody indices (AI). Results A positive MRZ reaction as defined by a combination of at least two positive AIs was present in 37/42 patients with MS, but in none of the patients with PND ( p p Conclusions Our results confirm that MRZR is not a general marker of CNS autoimmunity. Taking into account the very rarity of CNS vasculitis as well the lack of MRZR positivity in infectious inflammatory CNS conditions as previously demonstrated, MRZR might indeed be a promising marker of MS. Further investigations on MRZR in more rare autoimmune conditions, which were not available for analysis in this study, are now warranted to refine further the specificity of this parameter.

ABSOLVENTUM MANNHEIM e. V. wurde 1995 gegrundet und zahlt inzwischen rund 4.500 Mitglieder. Der Grundung ging eine Umfrage unter den Studierenden und Absolventen1 voraus. Die Grunder handelten zeitgemas im Sinne der Nachfrage- bzw. Kundenorientierung. Die Idee sties auf grose Resonanz. Viele der Befragten auserten den Wunsch, auch uber ihre Universitatsausbildungszeit hinaus untereinander und mit der Universitat verbunden zu bleiben.

Proteolytic shedding of the immunostimulatory NKG2D ligands MICA and MICB from cancer cells constitutes a novel immune escape strategy that diminishes antitumor reactivity by NKG2D-bearing cytotoxic lymphocytes. In consequence, serum levels of soluble MICA and MICB are frequently found to be elevated in cancer disease.As the diagnostic potential depends strongly on the organ-specific benign diseases and is affected by diseases involved in marker metabolism, both markers were analyzed by ELISA in sera of 141 patients with hepatic autoimmune diseases (34 autoimmune hepatitis, 35 primary sclerosing cholangitis, 72 primary biliary cirrhosis), 18 patients with acute bacterial infections, 21 patients with renal insufficiency, 13 patients with cholestasis and 62 healthy individuals.Similarly to healthy controls (median sMICA30 pg/mL; sMICB30 pg/mL), low levels of both markers were generally found in sera of patients with hepatic autoimmune diseases. In contrast, significantly elevated concentrations of sMICA and sMICB were observed in sera of patients with acute infections (median sMICA 890 pg/mL; sMICB 111 pg/mL), in those with renal insufficiency (sMICA 195 pg/mL; sMICB 50 pg/mL), and in those with cholestasis (sMICA 1058 pg/mL; sMICB 146 pg/mL).While hepatic autoimmune diseases have no general impact on the amount of circulating sMICA and sMICB, acute bacterial infections, renal insufficiency and cholestasis can lead to notably elevated serum levels of the NKG2D ligands.

Intravenous immunoglobulin (IVIg) preparations are increasingly used for therapy of several neuroimmunologic diseases. IVIg therapy is considered safe, although serious side effects like aseptic meningitis, cerebral vasospasm, or ischemic encephalopathy have been reported. These side effects are frequently associated with neutrophilic pleocytosis in the cerebrospinal fluid (CSF), suggesting a neutrophil-mediated mechanism. To elucidate the potential role of neutrophil activation, we analyzed IVIg preparations from 5 different commercial sources for the presence of antineutrophil cytoplasmic antibody (ANCA)–like immunoglobulins against ethanol-fixed peripheral-blood neutrophils, purified human antigens, and a panel of human and nonhuman tissues. All IVIg batches tested (n = 13) contained atypical ANCAs (IgG titer up to 1:2048, IgA up to 1:512). Moreover, all preparations were capable of inducing hydrogen peroxide production in TNFα-primed human neutrophils, with a significant correlation (P < .005) between atypical ANCA titers in IVIg preparations and neutrophil activation. Fc-mediated binding and activation was ruled out by the use of IVIg-F(ab′)2 fragments. Our findings strongly suggest that in vivo activation of TNFα-primed neutrophils by atypical ANCAs of IVIg may contribute to the side effects of IVIg therapy and for the first time demonstrate that the activation of neutrophil granulocytes by IVIg occurs in an Fc receptor (FcR)–independent, hence antigen-dependent, way.

Commercial linear alkylbenzenesulfonate (LAS) contains 20 congeners of linear alkanes (C 10 to C 13 ) substituted subterminally with the 4-sulfophenyl moiety in any position from lateral to central. Parvibaculum lavamentivorans DS-1 T degrades each of eight laterally substituted congeners [e.g., 2-(4-sulfophenyl)decane (2-C10-LAS); herein, compounds are named systematically by chain length (e.g., C 10 ) and by the position of the substituent on the chain (e.g., position 2)] to a major sulfophenyl carboxylate [SPC; here 3-(4-sulfophenyl)butyrate (3-C4-SPC)] and two minor products, namely, the α,β-unsaturated SPC (SPC-2H, here 3-C4-SPC-2H) and the SPC+2C (here 5-C6-SPC) species (D. Schleheck, T. P. Knepper, K. Fischer, and A. M. Cook, Appl. Environ. Microbiol. 70:4053-4063). The degradation of centrally substituted congeners by strain DS-1 was examined in this work. 5-C10-LAS yielded not only the predicted 4-C8-SPC, 4-C8-SPC-2H, and 6-C10-SPC (about 70% of products) but also sulfophenyl dicarboxylates (SPdC), i.e., C6-, C8-, and C10-SPdC. These were identified by electrospray ionization-mass spectrometry (ESI-MS) after separation by high-pressure liquid chromatography (HPLC). ESI ion-trap MS and ESI-time of flight-MS were used to confirm the identities of key intermediates. Different mixtures of congeners obtained by separation of commercial LAS by HPLC were degraded, and the degradative products were compared. If a congener carried the sulfophenyl substituent on the 5, 6, or 7 position, SPdCs were formed as well as SPC, SPC-2H, and SPC+2C, whereas the substituent on the 2, 3, or 4 position yielded only SPC, SPC-2H, and SPC+2C. Some 50 products were generated from the 20 LAS congeners: 11 major SPCs, each with an SPC-2H and an SPC+2C (i.e., 33 SPC and SPC-2H species), and about 17 SPdC species. A large array of compounds, many in low quantities, is thus generated by P. lavamentivorans DS-1 during the degradation of commercial LAS.

8 pages, 2 tables, 5 figures.-- PMID: 17914752 [PubMed].-- Printed version published Nov 1, 2007., Supplementary information (PDF file, 2 pages, 1 fig, Word file, 2 pages, 1 fig) available at: http://pubs.acs.org/doi/suppl/10.1021/ac070891u, In the environment, organic micropollutants such as pharmaceuticals can be degraded via various biotic and abiotic transformation routes. In surface waters, for example, photodegradation may constitute a relevant natural attenuation process for drug residues that have been discharged from sewage treatment facilities. In the present work, the photochemical fate of the prodrug enalapril (376 Da, C(20)H(28)N2O5) and its active metabolite enalaprilat (348 Da, C(18)H(24)N2O5), a hypotensive cardioprotector previously reported to occur in contaminated rivers, was investigated in aqueous media under the influence of irradiation generated by a sunlight simulator. The experiments yielded three detectable photodegradates for enalapril (346 Da, 2 x 207 Da) whereas the photolysis of enalaprilat went hand in hand with the intermittent buildup of one photodegradate (304 Da). Fragmentation patterns of the parent compounds were established on a hybrid quadrupole-linear ion trap-mass spectrometer exploiting its MS3 capabilities. Accurate mass measurements recorded on a hybrid quadrupole-time-of-flight instrument in MS/MS mode allowed us to propose elemental compositions for the molecular ions of the degradates (346 Da, C(19)H(26)N2O4; 207 Da, C(12)H(17)NO2; 304 Da, C(17)H(24)N2O3) as well as of their fragment ions. Based on these complementary data sets from the two distinct mass spectrometric instruments, plausible structures were postulated for the four photodegradates. The compounds formed by enalapril corresponded to the loss of formaldehyde out of the proline residue (346 Da), cleavage of the central amide bond (207 Da) followed by migration of the ethylester side chain (207 Da) while decarboxylation of the free carboxylic acid was described for enalaprilat (304 Da). The study emphasized the potential of sunlight for breaking down an environmentally relevant drug and its metabolite., The work presented in this article was supported by the EU Project EMCO-INCO-CT-2004-509188) and by the Spanish Ministerio de Educación y Ciencia, Project EVITA (CTM2004-06255-CO3-01). This work reflects only the author’s views and the European Community is not liable for any use that may be made of the information contained therein. S.P. acknowledges a postdoctoral contract from I3P Program (Itinerario Integrado de Inserción Profesional); co-financed by CSIC and European Social Funds. S.P. acknowledges Roser Charler and Dori Fanjul, for their support with the MS instrumentation.

8 pages, 6 figures, 2 tables.-- PMID: 17996876 [PubMed].-- Printed version published on Dec 21, 2007., This study aimed to develop and optimize a method for the extraction and analysis of moenomycin antibiotics (a.k.a. flavomycin) in corn-based feed premix and in chicken litter. Moenomycin-A was isolated from chicken litter using pressurized liquid extraction followed by a solid-phase extraction (SPE) clean-up step. The highly lipophilic nature of moenomycin necessitated the use of the less hydrophobic sorbent, C4-based SPE cartridge, and a higher temperature elution solvent, methanol at 50ºC, in order to obtain satisfactory percent recoveries. After clean-up, the sample was analyzed by liquid chromatography–electrospray ionization–mass spectrometry (LC–ESI–MS). Various reversed-phase columns were examined, including C18, CN, perfluorinated C6, and a porous graphitic carbon. The set of conditions that gave the highest separation efficiency while still maintaining symmetrical peak shape was the C18 column using the H2O + 0.3% HCOOH and acetonitrile mobile phase., This material is based upon work supported by the National Science Foundation under grant no. 0233700. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the National Science Foundation. S.P. acknowledges a post-doctoral fellowship from the Spanish Ministry of Education, Culture and Science (EX2003-0687).

The inadequate response of immune cells to circulating apoptotic products, such as nucleosomal DNA fragments, is assumed to be a potent stimulus for the production of autoantibodies during the pathogenesis and progression of systemic lupus erythematosus (SLE). Here, we analyzed the levels of circulating nucleosomes, caspases, and C-reactive protein in sera of 244 individuals with various autoimmune diseases (155 with autoimmune hepatic disorders, 25 with ANCA-associated vasculitis, and 64 with various connective tissue diseases), and 32 healthy controls. Nucleosomes and caspase activities were significantly elevated in sera of patients with hepatic autoimmune diseases, connective tissue diseases, and particularly in ANCA-associated vasculitis when compared with healthy individuals. Nucleosomes showed a correlation with caspases, and caspases with C-reactive protein, but nucleosomes did not correlate with C-reactive protein. Serum levels of the apoptotic products, nucleosomes, and caspases are increased in various autoimmune diseases but may not be solely responsible for antinucleosome antibody production in SLE patients. It remains to be clarified whether qualitative changes in nucleosomes are linked with pathogenesis and disease progression in SLE.

Antineuronal antibody-associated paraneoplastic neurological syndromes (PaNSs) result from tumour-stimulated autoimmune attacks against components of the nervous system. The rare antineuronal antibody anti-Ri (ANNA-2) was initially thought to be closely associated with paraneoplastic opsoclonus–myoclonus syndrome. Recently, however, it has been found in several other PaNSs.1 First-line treatment in PaNSs is removal of the underlying tumour. Second-line treatment is immunosuppression, which, although extensively used, especially when no tumour is detected, is often ineffective. Often, patients die from relentlessly progressive PaNS rather than the underlying neoplasm.2 Here, we report the 2-year follow-up of an anti-Ri-positive steroid-responsive myeloneuropathy. No tumour was detected. Immunosuppressive treatment was tailored on the basis of clinical relapses, inflammatory changes in cerebrospinal fluid (CSF) and somatosensory evoked potentials (SEPs). A 65-year-old woman, a retired administrator, was referred to our department with a 10-month history of progressive gait difficulties and ascending sensory loss in her legs, eventually having become wheelchair bound. Her medical history was unremarkable apart from enlarged axillary lymph nodes that were excised 9 months earlier. Histological examination showed only inflammatory changes. She had received hormone replacement therapy for 11 years. She never smoked. On neurological examination, deep tendon reflexes were absent. She had spastic paraparesis with bilateral extensor plantar responses. Bilateral hypaesthesia for light touch up to the knees and diminished vibration sense were observed distally in her legs. Magnetic resonance imaging (MRI) showed symmetrical T2-hyperintense multisegmental (C6–TH3/TH8–TH12) cervicothoracal lesions of the spinal cord, with gadolinium enhancement restricted to the lateral parts (fig 1A). Cerebral …