Interference of endocrine disrupting chemicals with aromatase CYP19 expression or activity, and consequences for reproduction of teleost fish

Many natural and synthetic compounds present in the environment exert a number of adverse effects on the exposed organisms, leading to endocrine disruption, for which they were termed endocrine disrupting chemicals (EDCs). A decrease in reproduction success is one of the most well-documented signs of endocrine disruption in fish. Estrogens are steroid hormones involved in the control of important reproduction-related processes, including sexual differentiation, maturation and a variety of others. Careful spatial and temporal balance of estrogens in the body is crucial for proper functioning. At the final step of estrogen biosynthesis, cytochrome P450 aromatase, encoded by the cyp19 gene, converts androgens into estrogens. Modulation of aromatase CYP19 expression and function can dramatically alter the rate of estrogen production, disturbing the local and systemic levels of estrogens. In the present review, the current progress in CYP19 characterization in teleost fish is summarized and the potential of several classes of EDCs to interfere with CYP19 expression and activity is discussed. Two cyp19 genes are present in most teleosts, cyp19a and cyp19b, primarily expressed in the ovary and brain, respectively. Both aromatase CYP19 isoforms are involved in the sexual differentiation and regulation of the reproductive cycle and male reproductive behavior in diverse teleost species. Alteration of aromatase CYP19 expression and/or activity, be it upregulation or downregulation, may lead to diverse disturbances of the above mentioned processes. Prediction of multiple transcriptional regulatory elements in the promoters of teleost cyp19 genes suggests the possibility for several EDC classes to affect cyp19 expression on the transcriptional level. These sites include cAMP responsive elements, a steroidogenic factor 1/adrenal 4 binding protein site, an estrogen-responsive element (ERE), half-EREs, dioxin-responsive elements, and elements related to diverse other nuclear receptors (peroxisome proliferator activated receptor, retinoid X receptor, retinoic acid receptor). Certain compounds including phytoestrogens, xenoestrogens, fungicides and organotins may modulate aromatase CYP19 activity on the post-transcriptional level. As is shown in this review, diverse EDCs may affect the expression and/or activity of aromatase cyp19 genes through a variety of mechanisms, many of which need further characterization in order to improve the prediction of risks posed by a contaminated environment to teleost fish population.

Pain drawings in somatoform-functional pain

Background Pain drawings are a diagnostic adjunct to history taking, clinical examinations, and biomedical tests in evaluating pain. We hypothesized that somatoform-functional pain, is mirrored in distinctive graphic patterns of pain drawings. Our aim was to identify the most sensitive and specific graphic criteria as a tool to help identifying somatoform-functional pain. Methods We compared 62 patients with somatoform-functional pain with a control group of 49 patients with somatic-nociceptive pain type. All patients were asked to mark their pain on a pre-printed body diagram. An investigator, blinded with regard to the patients’ diagnoses, analyzed the drawings according to a set of numeric or binary criteria. Results We identified 13 drawing criteria pointing with significance to a somatoform-functional pain disorder (all p-values ≤ 0.001). The most specific and most sensitive criteria combination for detecting somatoform-functional pain included the total number of marks, the length of the longest mark, and the presence of symmetric patterns. The area under the ROC-curve was 96.3% for this criteria combination. Conclusion Pain drawings are an easy-to-administer supplementary technique which helps to identify somatoform-functional pain in comparison to somatic-nociceptive pain.

Evaluation of late results in breast reconstruction by latissimus dorsi flap and prosthesis implantation

BACKGROUND: Breast reconstruction by latissimus dorsi myocutaneous flap in combination with a prosthesis is a widely used, well-established procedure. Short- and medium-term evaluation after this procedure is well described in the literature, but there have been no evaluations of the late course (over 10 years) published until now. METHODS: In a retrospective study, 68 patients operated on by means of this technique at the authors' institution from 1981 to 1993 resulting in a minimal follow-up of 10 years were included. Patients were invited to an interrogation, clinical examination, and photographic documentation (n = 51). Incidence of late flap or prosthesis-related complications, number of and indications for corrective procedures, and the correlation of the patients' subjective judgment and objective results in the late course have been the main interest of the authors' survey. RESULTS: The authors found that 50 percent of the patients needed a late reoperation for change or removal of the prosthesis. Seven (10 percent) of 68 patients needed a definitive removal of the implant in the late course. Assessment of the photographic documentation of the late result by four nonprofessionals showed that the objective aesthetic results of a considerable number of the authors' reconstructions were not sufficient. CONCLUSION: The procedure combines two basic techniques of reconstructive surgery, the soft-tissue restoration by a pedicled flap as the autologous reconstructive component and the volume reconstruction by prosthesis. Therefore, these patients are subject to a cumulation of the basic morbidity of the two techniques. The authors conclude that the indication for this procedure should be restricted to patients not qualifying for "pure" reconstructive techniques.

Concentration- and time-dependent effects of the synthetic estrogen, 17alpha-ethinylestradiol, on reproductive capabilities of the zebrafish, Danio rerio

Partial or full life-cycle tests are needed to assess the potential of endocrine-disrupting compounds (EDCs) to adversely affect development and reproduction of fish. Small fish species such as zebrafish, Danio rerio, are under consideration as model organisms for appropriate test protocols. The present study examines how reproductive effects resulting from exposure of zebrafish to the synthetic estrogen 17alpha-ethinylestradiol (EE2) vary with concentration (0.05 to 10 ng EE2 L(-1), nominal), and with timing/duration of exposure (partial life-cycle, full life-cycle, and two-generation exposure). Partial life-cycle exposure of the parental (F1) generation until completion of gonad differentiation (0-75 d postfertilization, dpf) impaired juvenile growth, time to sexual maturity, adult fecundity (egg production/female/day), and adult fertilization success at 1.1 ng EE2 L(-1) and higher. Lifelong exposure of the F1 generation until 177 dpf resulted in lowest observed effect concentrations (LOECs) for time to sexual maturity, fecundity, and fertilization success identical to those of the developmental test (0-75 dpf), but the slope of the concentration-response curve was steeper. Reproduction of zebrafish was completely inhibited at 9.3 ng EE2 L(-1), and this was essentially irreversible as a 3-mo depuration restored fertilization success to only a very low rate. Accordingly, elevated endogenous vitellogenin (VTG) synthesis and degenerative changes in gonad morphology persisted in depurated zebrafish. Full life-cycle exposure of the filial (F2) generation until 162 dpf impaired growth, delayed onset of spawning and reduced fecundity and fertilization success at 2.0 ng EE2 L(-1). In conclusion, results show that the impact of estrogenic agents on zebrafish sexual development and reproductive functions as well as the reversibility of effects, varies with exposure concentration (reversibility at < or = 1.1 ng EE2 L(-1) and irreversibility at 9.3 ng EE2 L(-1)), and between partial and full life-cycle exposure (exposure to 10 ng EE2 L(-1) during critical period exerted no permanent effect on sexual differentiation, but life-cycle exposure did).

Estimation of sex and age of "virtual skeletons"--a feasibility study

This article presents a feasibility study with the objective of investigating the potential of multi-detector computed tomography (MDCT) to estimate the bone age and sex of deceased persons. To obtain virtual skeletons, the bodies of 22 deceased persons with known age at death were scanned by MDCT using a special protocol that consisted of high-resolution imaging of the skull, shoulder girdle (including the upper half of the humeri), the symphysis pubis and the upper halves of the femora. Bone and soft-tissue reconstructions were performed in two and three dimensions. The resulting data were investigated by three anthropologists with different professional experience. Sex was determined by investigating three-dimensional models of the skull and pelvis. As a basic orientation for the age estimation, the complex method according to Nemeskéri and co-workers was applied. The final estimation was effected using additional parameters like the state of dentition, degeneration of the spine, etc., which where chosen individually by the three observers according to their experience. The results of the study show that the estimation of sex and age is possible by the use of MDCT. Virtual skeletons present an ideal collection for anthropological studies, because they are obtained in a non-invasive way and can be investigated ad infinitum.

Adaptive rather than non-adaptive evolution of Mimulus guttatus in its invasive range

Adaptive and non-adaptive evolutionary processes are likely to play important roles in biological invasions but their relative importance has hardly ever been quantified. Moreover, although genetic differences between populations in their native versus invasive ranges may simply reflect different positions along a genetic latitudinal cline, this has rarely been controlled for. To study non-adaptive evolutionary processes in invasion of Mimulus guttatus, we used allozyme analyses on offspring of seven native populations from western North America, and three and four invasive populations from Scotland and New Zealand, respectively. To study quantitative genetic differentiation, we grew 2474 plants representing 17 native populations and the seven invasive populations in a common greenhouse environment under temporarily and permanently wet soil conditions. The absence of allozyme differentiation between the invasive and native range indicates that multiple genotypes had been introduced to Scotland and New Zealand, and suggests that founder effects and genetic drift played small, if any, roles in shaping genetic structure of invasive M. guttatus populations. Plants from the invasive and native range did not differ in phenology, floral traits and sexual and vegetative reproduction, and also not in plastic responses to the watering treatments. However, plants from the invasive range produced twice as many flower-bearing upright side branches than the ones from the native populations. Further, with increasing latitude of collection, vegetative reproduction of our experimental plants increased while sexual reproduction decreased. Plants from the invasive and native range shared these latitudinal clines. Because allozymes showed that the relatedness between native and invasive populations did not depend on latitude, this suggests that plants in the invasive regions have adapted to the local latitude. Overall, our study indicates that quantitative genetic variation of M. guttatus in its two invasive regions is shaped by adaptive evolutionary processes rather than by non-adaptive ones. (C) 2007 Gesellschaft fur Okologie. Published by Elsevier GmbH. All rights reserved.

Differential effects of anti-hypertensive treatment on the retinal microcirculation: an Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) sub- study

Changes in the retinal microcirculation are associated with hypertension and predict cardiovascular mortality. There are few data describing the impact of antihypertensive therapy on retinal vascular changes. This substudy of the Anglo-Scandinavian Cardiac Outcomes Trial compared the effects of an amlodipine-based regimen (373 patients) with an atenolol-based regimen (347 patients) on retinal microvascular measurements made from fundus photographs. The retinal photographs were taken at a stage in the trial when treatments were stable and blood pressure was well controlled. Amlodipine-based treatment was associated with a smaller arteriolar length:diameter ratio than atenolol-based treatment (13.32 [10.75 to 16.04] versus 14.12 [11.27 to 17.81], median [interquartile range]; P<0.01). The association remained significant after adjustment for age, sex, cholesterol, systolic and diastolic blood pressures, body mass index, smoking, and statin treatment. This effect appeared to be largely attributable to shorter retinal arteriolar segment lengths in the amlodipine-treated group and is best explained by the vasodilator effects of amlodipine causing the visible emergence of branching side vessels. Photographic assessment of the retinal vascular network may be a useful approach to evaluating microvascular structural responses in clinical trials of antihypertensive therapy.

Augmented environments for the targeting of hepatic lesions during image-guided robotic liver surgery

BACKGROUND Stereotactic navigation technology can enhance guidance during surgery and enable the precise reproduction of planned surgical strategies. Currently, specific systems (such as the CAS-One system) are available for instrument guidance in open liver surgery. This study aims to evaluate the implementation of such a system for the targeting of hepatic tumors during robotic liver surgery. MATERIAL AND METHODS Optical tracking references were attached to one of the robotic instruments and to the robotic endoscopic camera. After instrument and video calibration and patient-to-image registration, a virtual model of the tracked instrument and the available three-dimensional images of the liver were displayed directly within the robotic console, superimposed onto the endoscopic video image. An additional superimposed targeting viewer allowed for the visualization of the target tumor, relative to the tip of the instrument, for an assessment of the distance between the tumor and the tool for the realization of safe resection margins. RESULTS Two cirrhotic patients underwent robotic navigated atypical hepatic resections for hepatocellular carcinoma. The augmented endoscopic view allowed for the definition of an accurate resection margin around the tumor. The overlay of reconstructed three-dimensional models was also used during parenchymal transection for the identification of vascular and biliary structures. Operative times were 240 min in the first case and 300 min in the second. There were no intraoperative complications. CONCLUSIONS The da Vinci Surgical System provided an excellent platform for image-guided liver surgery with a stable optic and instrumentation. Robotic image guidance might improve the surgeon's orientation during the operation and increase accuracy in tumor resection. Further developments of this technological combination are needed to deal with organ deformation during surgery.

Copying, emergence, and digital reproduction

This talk combines concepts of the copying of manuscripts in the age before mechanical reproduction (as described in W. Benjamin’s famous Artwork-essay), of the emergence of non-vertical evolution (as to be found in textual ‘contamination’ and in horizontal gene transfer alike), and of the electronic reproduction of such phenomena (as presented in scholarly digital editions and phylogenetic trees). The guiding idea is that ‘copying’, ‘emergence’, and ‘(digital) reproduction’ enable variation depending on particular physical or biological forms, on contextual or environmental conditions, as well as on user habits or receptive fields. – Is it possible to develop a theory of copying and reproduction on this base? The material of the talk will be drawn from the Parzival-Project, a critical electronic edition of an Arthurian romance, composed by the German poet Wolfram von Eschenbach shortly after 1200 and transmitted in over eighty witnesses.

Stuck in Mobility? Fragmented Journeys of Migrants without Chances of Admission in Europe

This paper is about young migrants without chance of being granted legal residence status in the Schengen zone. Previous observations suggest that some migrants, whose country of origin leaves them with low chances of receiving asylum or in fact any type of residence permit, exhibit a highly complex migration pattern that is characterised by 1) durable “transit” across Europe, which is a multi-linear movement according to opportunities that open up along the journey; 2) a high degree of flexibility, as they have to respond to suddenly changing conditions, such as work opportunities, rejection of asylum claims, detention or deportation, and 3) switching between different legal statuses, such as asylum seeker, sans papiers or detainee. The experiences of these young adults thus show a deep ambivalence between a sense of autonomy, on the one hand, and of profound hope and powerlessness, on the other. The Dublin Convention intends to limit such a hypermobility of migrants but seems to fail in many cases. Simultaneously it provokes some of the movements by sending asylum seekers and irregular migrants back to their first country of arrivals. Given the fact that little is known about these fragmented journeys inside of the Schengen area, this ethnographic study produces novel data on a highly pertinent migration pattern, the impact of the European migration management on individual migrants as well as the inter-relatedness of the asylum regime and irregular migration in Europe. At the same time these fragmented journeys are an excellent example to discuss mobility as a resource on the one hand (since it enables this specific migrant group to extend their presence in Europe) and as a handicap on the other (since it impedes the building of stable social networks, the planning of the future, etc.).