Quantitative Bestimmung von 19-Norsteroiden nach peroraler und sublingualer Applikation von Norandrostendion und Norandrostendiol Eine klinische Studie zum Metabolismus von Nandrolon-Prohormonen

Zusammenfassung: Seit 1994 erlaubt der Dietary Supplement Health and Education Act in den USA Prohormon-Präparate als Nahrungsergänzungsmittel zu vertreiben. Diese werden zumeist als Vorstufen anabol androgener Steroide beworben und vorwiegend von Sportlern mit dem Ziel des Kraftzuwachses und einer Steigerung der sportlichen Leistungsfähigkeit konsumiert. Ziel der vorliegenden Arbeit war es, innerhalb einer klinischen Studie wissenschaftliche Daten über den in vivo Metabolismus der auf der Doping-Liste stehenden Nandrolon-Prohormone Norandrostendion (ND, Estr-4-en-3,17-dione) und Norandrostendiol (NDiol, Estr-4-en-3(,17(-diol) zu erheben. Dazu wurden acht männlichen Probanden ND- und NDiol-haltige Nahrungsergänzungsmittel verabreicht. Daran anschließende Blutuntersuchungen mittels gaschromatographisch/massenspektrometrischer Analyse erlaubten die Indentifizierung und Quantifizierung der aus der Prohormon-Einnahme resultierenden Metaboliten. Insbesondere konnte die im Phase-I-Metabolismus erfolgte enzymatische Umsetzung zu pharmakologisch aktivem Nandrolon bestätigt werden. Speziell die sublinguale NDiol-Aufnahme resultierte bei allen Probanden kurzfristig in Nandrolon-Spiegeln, die mit einer therapeutischen Nandrolon-Therapie vergleichbar sind. Abstract: Since The Dietary Supplement Health and Education Act came into force in 1994 prohormones have been available as nutritional supplements for over-the-counter sales in the USA. Prohormones are marketed as assumed precursers of anabolic androgenic steroids and are consumed mostly by athletes to enhance muscle mass and athletic performance. To evaluate the in vivo metabolism of the nandrolone-prohormones norandrostenedione (ND, estr-4-ene-3,17-dione) and norandrostenediol (NDiol, estr-4-ene-3(,17(-diol) different nutritional supplements containing ND and NDiol were administered to eight healthy male volunteers within a clinical study. Subsequent blood analyses by gas chromatography/mass spectrometry enabled the identification and quantification of generated metabolites resulting from the ingestion of ND and NDiol. Particularly the conversion to pharmacologically active nandrolone was confirmed. Especially after sublingual application of NDiol all volunteers have been temporary exposed to pharmacologically relevant plasma concentrations of nandrolone comparable to acute therapeutic nandrolone administration

Systematic review of interventions for the secondary prevention and treatment of emotional abuse of children by primary carers

Background Emotional abuse (or psychological maltreatment, as it is more commonly called in the US) is an inadequately researched and poorly understood concept, despite increasing awareness about the harm it can cause to children‟s lives. Although it unifies and underpins all types of maltreatment it also occurs alone and when it does, tends to elude detection and intervention. There have to date been no systematic reviews of the literature on the secondary prevention and treatment involving the parents or primary carers of emotionally abused children. Objective The objective of the review was to identify studies that evaluate the effectiveness of interventions in the secondary prevention and treatment of child emotional abuse involving the parents or primary carers of children aged 0 – 19 years. Methods Studies were included if they involved any intervention which was directed at emotionally abusive parenting and that measured change in (i) emotional unavailability (ii) negative attributions (i.e. that involve the parent attributing negative intentions, beliefs or attitudes toward the child); (iii) developmentally inappropriate interactions; (iv) lack of recognition of children‟s boundaries; (v) inconsistency of parenting role; (vi) missocialisation or consistent failure to promote the child‟s social adaptation. The primary outcomes evaluated involved proxy measures of a range of parent, family and child outcomes including parental psychopathology, parenting attitudes and practices, family functioning and/or child behaviour and the child‟s development and adaptation. . A broad search strategy was developed in order to identify as many relevant studies as possible. An electronic search of a wide range of databases was carried about. No study type was excluded. The search was augmented by direct contact with academics and practitioners known in this field. The search included studies written in English, Spanish, French and German. Studies were included if the intervention was described, and the impact on at least one indicator of emotional abuse was assessed. Included studies were critically appraised by two reviewers using standard criteria. Data were extracted using a standard proforma, and a qualitative synthesis of results was carried out. Results The initial search yielded 4248 publications of potential interest. Of these, 175 were obtained for possible inclusion or as background material. A total of 21 studies of 18 interventions, met all the inclusion criteria. A further 43 studies were relevant, but did not meet all of the inclusion criteria. Studies were organised according to the type of emotional abuse targeted: emotionally abusive parenting; parents of infants with faltering growth; missocialisation: parenting interventions with substance-abusing mothers. Twelve included studies had quantitative designs. Of these, 6 comprised randomised controlled trials; 1 comprised a follow-up of a randomised controlled trial; 2 were controlled studies; and 3 had one-group pre- and post-designs. The remaining 9 were case studies. Included studies involved a wide range of interventions. The 8 studies for parents which address emotionally abusive parenting (rejection, misattribution, parent-child role reversal and anger management) involved evaluations of cognitive-behavioural training (CBT), behavioural training and parent-infant psychotherapy. Two further case studies involved cognitive-behavioural training, mentalisation and family-based therapy. The 9 interventions with parents of infants with faltering growth evaluated CBT, behavioural training, parent infant psychotherapy and interaction guidance; lay home visitors, and a range of therapeutic options based on the diagnostic condition of the parents. The 3 studies of interventions for substance abusing mothers evaluated a relational psychotherapy group for mothers, and a residential treatment for substance abuse with a parenting component. The sample sizes for quantitative studies were small and ranged from 17 to 98 participants. Ten interventions involved mothers alone, while a further 11 included fathers, either at the outset or at a later stage, and in 3 cases extended family members. Interventions for emotionally abusing parents The findings from the 8 included studies evaluating CBT, psychotherapy, and behavioural approaches suggest that group-based CBT may be an effective means of intervening with this group of parents, although it cannot currently be recommended with parents experiencing symptoms of severe psychopathology. While one comparative study showed a psychotherapeutic intervention to be more effective than a CBT focused intervention, the outcomes measured in this study (i.e. parent and child representations) favoured the former. Behavioural case work involving the use of problem-solving techniques may also have a role to play with some parents, although further research is still needed. Interventions to enhance parental sensitivity The findings from a systematic review of 81 interventions that aimed at enhancing parental sensitivity and / or infant attachment found strong evidence that short term (less than 16 sessions) interventions, with a behavioural focus and aimed exclusively at enhancing maternal sensitivity were also most effective in enhancing infant attachment security. This supports the notion of a causal role of sensitivity in shaping attachment. Interventions that included fathers as well as mothers showed higher effect sizes but results are tentative since they are based on a small number of small scale trials. Parental behaviours associated with faltering growth Nine studies evaluated a range of interventions with parents of babies with faltering growth including interaction guidance, home visiting; parent-child psychotherapy, behavioural casework and multi-component interventions. The findings show that interaction guidance and parent-infant psychotherapy may be potentially effective means of working with this group of clients along with behavioural casework, but that further research is needed before these can be recommended. Missocialisation: Parenting interventions for substance-abusing parents 5 studies (one of which was a 6-month follow-up) evaluated interventions for substance abusing mothers, including a relational psychotherapy group and a residential treatment for substance abusing adults with a parenting component. The findings show that initial gains made in the former were not sustained at 6-months and few benefits from residential intervention. Conclusions Emotional abuse is a complex issue resulting in part from learned behaviours, psychopathology and/or unmet emotional needs in the parents, and often compounded by factors in the families‟ immediate and wider social environment. As such, a „one-approach-fits-all‟ is unlikely to lead to sustained change. The evidence base is weak, but suggests that some caregivers respond well to cognitive behavioural therapy. However, the characteristics that define these parents are not clear. There is currently no evidence to support the use of this intervention alone in the treatment of severely emotionally abusive parents. Some of the evidence suggests that a certain form of emotional abuse (for example, highly negative parent affect, which may be expressed as frightened and frightening behaviours in the parent) stemming from unresolved trauma and loss, is less amenable to CBT. There is some evidence that interaction guidance and psychotherapeutic approaches can generate change in parents with more severe psychopathology. Further research is urgently needed to evaluate the benefits of both psychotherapeutic and cognitive behavioural interventions, including those which take the form of family therapy, with parents at the more severe end of the spectrum, with fathers, and with older children. There is also a need to gain further understanding about which forms of emotional abuse respond best to different treatments

Bacteria producing contractile phage tail-like particles (CPTPs) are promising alternatives to conventional pesticides

Diese Übersichtsarbeit verfolgt das Ziel, über bakterielle kontraktile Phagenderivate (englisch CPTPs) und ihr Potenzial als effiziente und Schadorganismus-spezifische Alternativen zu konventionellen chemischen Pflanzenschutzmitteln in der Land-/Forstwirtschaft und im Gartenbau zu informieren. CPTPs werden von verschiedenen Bakterien in diversen Habitaten für den interbakteriellen Konkurrenzkampf sowie zur Beeinflussung eukaryotischer Wirte, wie Pilze und Insekten, verwendet. Diese Arbeit präsentiert interessante und bemerkenswerte Beispiele für den vielfältigen Einsatz von CPTPs als leistungsfähige biologische Bekämpfungsmittel. Wir stellen die verschiedenen Typen von CPTPs vor und legen einen besonderen Fokus auf diejenigen, die eine Wirkung gegen Schadinsekten besitzen. Zusätzlich stellen wir zwei kürzlich etablierte Webservices vor, die das permanent wachsende Wissen über CPTPs mit einem Auswahlverfahren für die besten Bakterienkandidaten kombinieren, um eine zielgerichtete Anwendung der CPTPs in der nachhaltigen Pflanzenproduk­tion zu ermöglichen.This mini-review aims at raising the interest in contractile phage tail-like particles (CPTPs) of bacteria as an efficient and pest-specific alternative to conventional chemical pesticides in agriculture, horticulture and forestry. CPTPs are used by various bacteria in diverse environments for interbacterial competition or for manipulation of eukaryotic hosts, such as fungi or insects. This review gives examples for the versatile use of CPTPs as powerful biological control agents. We introduce the different types of CPTPs with a special focus on those with activity against insect plant pests. In addition, we present two currently established web services that combine the permanently increasing knowledge on CPTPs with a selection approach of the best candidate bacteria for targeted CPTP application in sustainable plant production

Mono-ADP-ribosylation sites of human CD73 inhibit its adenosine-generating enzymatic activity

CD73-derived adenosine plays a major role in damage-induced tissue responses by inhibiting inflammation. Damage-associated stimuli, such as hypoxia and mechanical stress, induce the cellular release of ATP and NA

Organ-on-a-chip: Determine feasibility of a human liver microphysiological model to assess long-term steroid metabolites in sports drug testing

A fundamental challenge in preventive doping research is the study of metabolic pathways of substances banned in sport. However, the pharmacological predictions obtained by conventional in vitro or in vivo animal studies are occasionally of limited transferability to humans according to an inability of in vitro models to mimic higher order system physiology or due to various species-specific differences using animal models. A more recently established technology for simulating human physiology is the organ-on-a-chip principle. In a multichannel microfluidic cell culture chip, 3-dimensional tissue spheroids, which can constitute artificial and interconnected microscale organs, imitate principles of the human physiology. The objective of this study was to determine if the technology is suitable to adequately predict metabolic profiles of prohibited substances in sport. As model compounds, the frequently misused anabolic steroids, stanozolol and dehydrochloromethyltestosterone (DHCMT) were subjected to human liver spheroids in microfluidic cell culture chips. The metabolite patterns produced and circulating in the chip media were then assessed by LC-HRMS/(MS) at different time points of up to 14 days of incubation at 37 degrees C. The overall profile of observed glucurono-conjugated stanozolol metabolites excellently matched the commonly found urinary pattern of metabolites, including 3 ' OH-stanozolol-glucuronide and stanozolol-N-glucuronides. Similarly, but to a lower extent, the DHCMT metabolic profile was in agreement with phase-I and phase-II biotransformation products regularly seen in postadministration urine specimens. In conclusion, this pilot study indicates that the organ-on-a-chip technology provides a high degree of conformity with traditional human oral administration studies, providing a promising approach for metabolic profiling in sports drug testing

Updated stomatal flux and flux-effect models for wheat for quantifying effects of ozone on grain yield, grain mass and protein yield

Field measurements and open-top chamber experiments using nine current European winter wheat cultivars provided a data set that was used to revise and improve the parameterisation of a stomatal conductance model for wheat, including a revised value for maximum stomatal conductance and new functions for phenology and soil moisture. For the calculation of stomatal conductance for ozone a diffusivity ratio between O3 and H2O in air of 0.663 was applied, based on a critical review of the literature. By applying the improved parameterisation for stomatal conductance, new flux-effect relationships for grain yield, grain mass and protein yield were developed for use in ozone risk assessments including effects on food security. An example of application of the flux model at the local scale in Germany shows that negative effects of ozone on wheat grain yield were likely each year and on protein yield in most years since the mid 1980s