Hexabromcyclododecan

Das Ziel dieser Arbeit war die Untersuchung des enantiomerenspezifischen Umweltverhaltens des Flammschutzmittels Hexabromcyclododecan (HBCD). Zu Beginn erfolgte daher die Optimierung und Validierung eines enantiomerenspezifischen Analysenverfahrens für die Bestimmung von HBCD in Biota. Die errechneten mittleren Wiederfindungen lagen im Bereich von 100-102 % und die Nachweisgrenzen zwischen 0,131 und 0,255 pg g-1. Untersuchungen zur ubiquitären Verteilung von HBCD erfolgten an Eiern der Silbermöwe deutscher Nord- und Ostseeinseln (Probenahme 1988-2008). In allen Fällen dominierte alpha-HBCD das Diastereomerenmuster, wobei eine bevorzugte Anreicherung von (-)-alpha-HBCD sowie ein zeitlicher Trend aller Enantiomeren-Gehalte festgestellt wurde. Zur Klärung der Frage einer Bioakkumulation sowie -isomerisierung der HBCD-Stereoisomere erfolgten Langzeit-Fütterungsversuche an Spiegelkarpfen. Die Untersuchungen ergaben eine signifikante Akkumulation des jeweils gefütterten HBCD-Enantiomers, jedoch konnte die Hypothese der Bioisomerisierung nicht bestätigt werden. Ein weiterer Schwerpunkt lag in Untersuchungen zur cytochromabhängigen enantiomerenspezifischen Biotransformation von HBCD im Rahmen des Metabolismus an Lebermikrosomen diverser Spezies. Hier konnte gezeigt werden, dass HBCD dem Phase I-Metabolismus unterliegt und hydroxyliert wird. Dabei weist jedes HBCD-Enantiomer ein spezifisches Metabolitenmuster auf, was eine Zuordnung der hydroxylierten Verbindungen zum entsprechenden HBCD-Enantiomer erlaubt. Anhand von Zeitreihen sowie der Berechnung von Halbwertszeiten konnte der Verdacht eines enantiomerenspezifischen Metabolismus in Richtung einer Anreicherung von (-)-alpha- und (+)-gamma-HBCD bestätigt werden. Inkubationsansätze mit reinen Cytochrom (CYP)-Isoformen sowie molekülmechanische Berechnungen legen die Vermutung nahe, dass dem CYP3A4 eine Schlüsselrolle bei der Metabolisierung von HBCD zukommt.The main emphasis of this thesis was on the enantio-specific environmental behaviour of the polybrominated flame retardant hexabromocyclododecane (HBCD). Initially, an enantio-specific analytical method for the determination of HBCD in biota was optimised and validated. The calculated mean recoveries ranged from 100 to 102 % and the limits of detection are in the range of 0.131 to 0.255 pg g-1. First investigations of the ubiquitous environmental distribution of HBCD were performed using herring gull eggs from different islands in the North and Baltic Sea (sampling 1988 to 2008). In all cases alpha-HBCD was the predominant diastereomer. Significant deviations from the racemic mixture revealed a preferred enrichment of the first eluting (-)-alpha-HBCD. In addition, a temporal trend of HBCD levels was observed. To clarify the issue of accumulation as well as bioisomerisation of HBCD stereoisomers, a long-term feeding study with mirror carps was performed. The results showed an accumulation of each initially fed HBCD enantiomer, but hypothesis of a bioisomerisation could not be confirmed. Another important focus of this work was to study the cytochrome-dependent enantio-specific biotransformation of HBCD enantiomers in various species of liver microsomes. It was shown that HBCD is subject to phase I metabolism. In the course of this process, HBCD is metabolised to hydroxylated products, whereas each HBCD enantiomer results in a specific metabolite pattern allowing the allocation of the corresponding hydroxylated compounds. Investigation of time series as well as the calculation of half-lives, the hypothesis of an enantio-specific metabolism towards an enrichment of (-)-alpha- and (+)-gamma-HBCD could be confirmed. Incubation mixtures with pure cytochrome (CYP) isoforms, as well as molecular mechanic calculations suggest that CYP3A4 plays a key role in the biotransformation processes of HBCD

Satisfaction with the local service point for care: results of an evaluation study

PURPOSE: The market of care increases and is characterized by complexity. Therefore, service points, such as the ‘Zentrale Anlaufstelle Pflege (ZAPf)’ in Nuremberg, are helpful for clients to get orientation. The purpose of the presentation is to show the results of an evaluation study about the clients' satisfaction with the offers of ZAPf. STUDY: Satisfaction with service may be measured with the SERVQUAL concept introduced by Parasuraman et al. (1988). They found out five dimensions of quality (tangibles, reliability, responsiveness, assurances and empathy). We took these dimensions in our study. The study focuses on the quality of service and the benefits recognized by clients. In spring 2007, we conducted 67 interviews by phone, based on a half standardized questionnaire. Statistical analysis was conducted using SPSS. RESULTS: The clients want to get information about care in general, financial and legal aspects, alternative care arrangement (e.g. ambulant, long-term care) and typical age-related diseases. They show a high satisfaction with the service provided. Their benefits are to get information and advice, to strengthen the ability of decision taking, to cope with changing situations in life, and to develop solutions. CONCLUSIONS: The results show that the quality of service is on a high level. Critical success factors are the interdisciplinary cooperation at the service point, based on a regularly and open exchange of information. Every member focuses on an optimal individual solution for the client. Local professional service points act as networkers and brokers. They serve not only for the clients' needs but also support the effective and efficient provision of optimized care

Analytical techniques combined with chemometrics for authentication and determination of contaminants in condiments : A review

Spices and herbs play an important role as flavorings, colorants, and also as bioactive compounds used in medicine and cosmetics. The presence of common contaminants, e.g., mycotoxins, pesticide residues, heavy metals, and the adulterants, e.g., azo dyes, filth and extraneous matter have been permanently monitored in condiments in order to control their quality, compliance to market, and safety to human health. The present paper shows a comprehensive overview of the analytical methods, based on the modern instrumental techniques and the most perspective statistical tools, based on univariate and multivariate (chemometrics) statistics, used for qualitative and quantitative determination of contaminant levels and for the authentication issues of different spices and herbs, discriminated by their geographic or biological origin. The review comprises more than sixty studies covering the last decade, describing the benefits of different analytical methods including multidimensional (non-targeted and targeted) approaches combined with multivariate chemometric techniques for the assessment of contaminants in spices and herbs in relation to research of their safety and quality issues. The methods based on multivariate data description and regression techniques are among the most promising techniques for the authentication of spices/herbs and determination of their contamination or adulteration risks with potential hazards.</p

Procalcitonin: Inflammatory Biomarker for Assessing the Severity of Community-Acquired Pneumonia – A Clinical Observation in Geriatric Patients

Community-acquired pneumonia is a common disease of the elderly and involves a high mortality risk. Demographic developments are creating new challenges for acute medical treatment strategies in geriatric patients with their underlying multimorbidity. In addition to the diagnostic parameters recorded on hospital admission, such as white cell count and C-reactive protein, procalcitonin, more than the risk scores CRB- and CURB-65 evaluated to date, appears to be a promising parameter for assessing the severity of pneumonia in elderly patients to allow early detection of severe courses and initiation of suitable treatment. The decisive factor is the dynamic course of the procalcitonin values over 3 consecutive days, as demonstrated in this case series

Increased orbitofrontal cortex activation associated with "pro-obsessive" antipsychotic treatment in patients with schizophrenia

Background: Patients with schizophrenia have an approximately 10-fold higher risk for obsessive–compulsive symptoms (OCS) than the general population. A large subgroup seems to experience OCS as a consequence of second-generation antipsychotic agents (SGA), such as clozapine. So far little is known about underlying neural mechanisms.Methods: To investigate the role of SGA treatment on neural processing related to OCS in patients with schizophrenia, we stratified patients according to their monotherapy into 2 groups (group I: clozapine or olanzapine; group II: amisulpride or aripiprazole). We used an fMRI approach, applying a go/no-go task assessing inhibitory control and an n-back task measuring working memory.Results: We enrolled 21 patients in group I and 19 patients in group II. Groups did not differ regarding age, sex, education or severity of psychotic symptoms. Frequency and severity of OCS were significantly higher in group I and were associated with pronounced deficits in specific cognitive abilities. Whereas brain activation patterns did not differ during working memory, group I showed significantly increased activation in the orbitofrontal cortex (OFC) during response inhibition. Alterations in OFC activation were associated with the severity of obsessions and mediated the association between SGA treatment and co-occurring OCS on a trend level.Limitations: The main limitation of this study is its cross-sectional design.Conclusion: To our knowledge, this is the first imaging study conducted to elucidate SGA effects on neural systems related to OCS. We propose that alterations in brain functioning reflect a pathogenic mechanism in the development of SGA-induced OCS in patients with schizophrenia. Longitudinal studies and randomized interventions are needed to prove the suggested causal interrelations.publishe

Reduced activation in ventral striatum and ventral tegmental area during probabilistic decision-making in schizophrenia

Patients with schizophrenia suffer from deficits in monitoring and controlling their own thoughts. Within these so-called metacognitive impairments, alterations in probabilistic reasoning might be one cognitive phenomenon disposing to delusions. However, so far little is known about alterations in associated brain functionality. A previously established task for functional magnetic resonance imaging (fMRI), which requires a probabilistic decision after a variable amount of stimuli, was applied to 23 schizophrenia patients and 28 healthy controls matched for age, gender and educational levels. We compared activation patterns during decision-making under conditions of certainty versus uncertainty and evaluated the process of final decision-making in ventral striatum (VS) and ventral tegmental area (VTA). We replicated a pre-described extended cortical activation pattern during probabilistic reasoning. During final decision-making, activations in several fronto- and parietocortical areas, as well as in VS and VTA became apparent. In both of these regions schizophrenia patients showed a significantly reduced activation. These results further define the network underlying probabilistic decision-making. The observed hypo-activation in regions commonly associated with dopaminergic neurotransmission fits into current concepts of disrupted prediction error signaling in schizophrenia and suggests functional links to reward anticipation. Forthcoming studies with patients at risk for psychosis and drug-naive first episode patients are necessary to elucidate the development of these findings over time and the interplay with associated clinical symptoms.publishe

Metamemory in schizophrenia: retrospective confidence ratings interact with neurocognitive deficits

Prior studies with schizophrenia patients described a reduced ability to discriminate between correct and false memories in terms of confidence compared to control groups. This metamemory bias has been associated with the emergence and maintenance of delusions. The relation to neuropsychological performance and other clinical dimensions is incompletely understood. In a cross-sectional study, metamemory functioning was explored in 32 schizophrenia patients and 25 healthy controls. Metamemory was assessed using a verbal recognition task combined with retrospective confidence level ratings. Associations of metamemory performance with six neuropsychological domains (executive functioning/problem solving, speed of processing, working memory, verbal and visual learning, and attention/vigilance) and psychopathological measures were analyzed. Results revealed a significantly smaller discrepancy between confidence ratings for correct and incorrect recognitions in the patient group. Furthermore, patients showed significantly lower recognition accuracy in the metamemory task and marked deficits in all neuropsychological domains. Across all participants, metamemory performance significantly correlated with executive functioning and working memory. No associations with delusions were found. This data confirms prior findings of metamemory biases in schizophrenia. Selective neuropsychological abilities seem to be modulating factors of metamemory functioning. Longitudinal studies in at risk mental state and first-episode patients are needed to reveal causal interrelation

Complete Trebouxia ITS alignment

Complete Trebouxia ITS alignment (n=2356), clades 'A', 'G', 'I', and 'S'