Untersuchungen am Bergfried von Schloss Weesenstein

Die bauhistorische Untersuchung beschäftigt sich mit den verschiedenen Phasen des Weesensteiner Bergfrieds. Zunächst wird der eiförmige Grundriss erklärt und mit kriegerischen Auseinandersetzungen in Verbindungen gebracht. Im Zuge der Dohnaschen Fehde wurde die Burg Weesenstein mit Steinkugeln beschossen. Abschließend werden die Befunde in den historischen Kontext eingebettet. Grundrisse, Zeichnungen und Fotografien illustrieren die Ausführungen

Die bauliche Entwicklung des Brücken- und Torhausbereiches von Schloss Weesenstein vom 15. Jahrhundert bis ins 18. Jahrhundert

Mittelalterliche Bautätigkeiten an der Burg Weesenstein benötigten einen stabilen und sichereren Transportweg. Bei Bauuntersuchungen des Brücken- und Torhausbereiches konnten fünf Bauphasen festgestellt werden. Beschrieben wird der Zustand um 1400, die erste Erweiterung gegen 1500, die zweite Erweiterung im 16. Jahrhundert, die dritte Erweiterungsphase im 17. Jahrhundert und die baulichen Veränderungen im 18. Jahrhundert. Die Erklärungen werden durch Fotografien und grafische Darstellungen unterstützt

»Verschütteter« und »Tiefer Keller«: Bauhistorische Untersuchungen im Kellerbereich der Albrechtsburg in Meißen

Der Beitrag fasst die Ergebnisse der bauhistorischen Forschungen in zwei Kellerbereichen im Zuge der Sanierung der Albrechtsburg Meißen zusammen. Besondere Ausführungen gelten den Schießscharten der zweiten Hälfte des 15. Jahrhunderts im „Tiefen Keller“

Forschungen im »Burgareal« von Schloss Weesenstein

Der Aufsatz befasst sich mit Untersuchungen in den Gewölben am Felsengang. Im ältesten Weesensteiner Schlossinventar werden die drei Gewölbe erwähnt. Bis ins 19. Jahrhundert dienten sie als Bier- und Weinkeller. Bei der bauhistorischen Untersuchung war zu klären, ob es sich um einen nur partiell fassbaren oder raumgreifenden Befund handelt, inwieweit die schwarzbraune Putzoberfläche datierbar ist und welcher Raumnutzung sie ihre Entstehung verdankt. Diese Fragen standen auch unter dem Aspekt einer neuen musealen Gestaltung dieses Raumes

Alterations in endogenous progesterone metabolism associated with spontaneous very preterm delivery

Study question: Do maternal serum levels of progesterone metabolites early in pregnancy correspond to an increased risk for very preterm delivery prior to 32 weeks? Summary answer: Maternal serum levels of 11-deoxycorticosterone (DOC) measured during the late first trimester or early second trimester correlate with an increased risk for preterm delivery prior to 32 weeks, and the correlation becomes stronger when the ratio of DOC to 16-alpha-hydroxyprogesterone was measured. What is known already: Progesterone is a pro-gestational steroid hormone that has been shown to decrease the risk of preterm birth in some pregnant women. Progesterone is metabolized by the body into various metabolites including members of the mineralocorticoid and glucocorticoid families. Our group has previously demonstrated that some progesterone metabolites enhance myometrial contractility in an ex vivo system, while others result in myometrial relaxation. The current exploratory study was designed to determine if pre-specified metabolites of progesterone measured early in pregnancy were associated with a woman's risk for delivery prior to 32 weeks, which is referred to as a very preterm delivery. Study design size duration: The Building Blocks of Pregnancy Biobank (BBPB) is a biorepository at Indiana University (IU) that follows women prospectively through their pregnancy. A variety of biospecimens are collected at various time points during a woman's pregnancy. Women participating in the IU BBPB who were enrolled after 8 weeks' gestation with pregnancy outcome data were eligible for participation. Participants/materials setting methods: Women delivering prior to 37 weeks (preterm) and at or after 37 weeks (term) who had blood samples collected during the late first trimester/early second trimester and/or during the early third trimester were identified. These samples were then processed for mass spectroscopy, and the amount of progesterone and progesterone metabolites in the samples were measured. Mean values of each measured steroid metabolite were calculated and compared among women delivering at less than 32 weeks, less than 37 weeks and greater than or equal to 37 weeks. Receiver operating characteristic (ROC) curves were constructed and threshold levels determined for each compound to identify a level above or below which best predicted a woman's risk for delivery prior to 32 and prior to 37 weeks. Mann-Whitney U nonparametric testing with Holm-Bonferroni correction for multiple comparisons was utilized to identify steroid ratios that could differentiate women delivering spontaneously at less than 32 weeks from all other pregnancies. Main results and the role of chance: Steroid hormone levels and pregnancy outcome data were available for 93 women; 28 delivering prior to 32 weeks, 40 delivering between 32 0/7 and 36 6/7 weeks and 25 delivering at or greater than 37 weeks: the mean gestational age at delivery within the three groups was 27.0, 34.4 and 38.8 weeks, respectively. Among women delivering spontaneously at less than 37 weeks, maternal 11-deoxycorticosterone (DOC) levels drawn in the late first trimester/early second trimester were significantly associated with spontaneous preterm delivery prior to 32 weeks; a threshold level of 47.5 pg/ml had 78% sensitivity, 73% specificity and an AUC of 0.77 (P = 0.044). When DOC levels were analyzed as a ratio with other measured steroid hormones, the ratio of DOC to 16-alpha-hydroxyprogesterone among women delivering spontaneously prior to 37 weeks was able to significantly discriminate women delivering prior to 32 weeks from those delivering at or greater than 32 weeks, with a threshold value of 0.2 with 89% sensitivity, 91% specificity and an AUC of 0.92 (P = 0.002). When the entire study cohort population was considered, including women delivering at term and women having an iatrogenic preterm delivery, the ratio of DOC to 16-alpha-hydroxyprogesterone was able to discriminate women delivering spontaneously prior to 32 weeks from the rest of the population at a threshold of 0.18 and 89% sensitivity, 59% specificity and an AUC of 0.81 (P = 0.003). Limitations reasons for caution: This is a discovery study, and the findings have not been validated on an independent cohort. To mitigate issues with multiple comparisons, we limited our study to pre-specified metabolites that are most representative of the major metabolic pathways for progesterone, and adjustments for multiple comparisons were made. Wider implications of the findings: Spontaneous preterm birth is increasingly being recognized to represent a common end pathway for a number of different disease phenotypes that include infection, inflammation, premature rupture of the membranes, uterine over distension, cervical insufficiency, placental dysfunction and genetic predisposition. In addition to these phenotypes, longitudinal changes in the maternal-fetal hypothalamic-pituitary-adrenal (HPA) axis also likely contribute to a significant proportion of the disease burden of spontaneous preterm birth. Here, we demonstrate that differential production of steroid metabolites is associated with very early preterm birth. The identified biomarkers may hint at a pathophysiologic mechanism and changes in the maternal-fetal dyad that result in preterm delivery. The early identification of abnormal changes in HPA axis metabolites may allow for targeted interventions that reverse the aberrant steroid metabolic profile to a more favorable one, thereby decreasing the risk for early delivery. Further research is therefore required to validate and extend the results presented here. Study funding/competing interests: Funding for this study was provided from the Office of the Vice Chancellor for Research at IUPUI, 'Funding Opportunities for Research Commercialization and Economic Success (FORCES) grant'.Both A.S.P. and C.A.G. are affiliated with Nixxi, a biotech startup. The remaining authors report no conflict of interest

Progesterone Metabolites Produced by Cytochrome P450 3A Modulate Uterine Contractility in a Murine Model

Objective: We seek to characterize the effect of progesterone metabolites on spontaneous and oxytocin-induced uterine contractility. Study Design: Spontaneous contractility was studied in mouse uterine horns after treatment with progesterone, 2α-hydroxyprogesterone, 6β-hydroxyprogesterone (6β-OHP), 16α-hydroxyprogesterone (16α-OHP), or 17-hydroxyprogesterone caproate (17-OHPC) at 10−9 to 10−6 mol/L. Uterine horns were exposed to progestins (10−6 mol/L), followed by increasing concentrations of oxytocin (1-100 nmol/L) to study oxytocin-induced contractility. Contraction parameters were compared for each progestin and matched vehicle control using repeated measures 2-way analysis of variance. In vitro metabolism of progesterone by recombinant cytochrome P450 3A (CYP3A) microsomes (3A5, 3A5, and 3A7) identified major metabolites. Results: Oxytocin-induced contractile frequency was decreased by 16α-OHP (P = .03) and increased by 6β-OHP (P = .05). Progesterone and 17-OHPC decreased oxytocin-induced contractile force (P = .02 and P = .04, respectively) and frequency (P = .02 and P = .03, respectively). Only progesterone decreased spontaneous contractile force (P = .02). Production of 16α-OHP and 6β-OHP metabolites were confirmed in all CYP3A isoforms tested. Conclusion: Progesterone metabolites produced by maternal or fetal CYP3A enzymes influence uterine contractility

Bacteria localization and chorion thinning among preterm premature rupture of membranes.

OBJECTIVE: Bacterial colonization of the fetal membranes and its role in pathogenesis of membrane rupture is poorly understood. Prior retrospective work revealed chorion layer thinning in preterm premature rupture of membranes (PPROM) subjects. Our objective was to prospectively examine fetal membrane chorion thinning and to correlate to bacterial presence in PPROM, preterm, and term subjects. STUDY DESIGN: Paired membrane samples (membrane rupture and membrane distant) were prospectively collected from: PPROM = 14, preterm labor (PTL = 8), preterm no labor (PTNL = 8), term labor (TL = 10), and term no labor (TNL = 8), subjects. Sections were probed with cytokeratin to identify fetal trophoblast layer of the chorion using immunohistochemistry. Fluorescence in situ hybridization was performed using broad range 16 s ribosomal RNA probe. Images were evaluated, chorion and choriodecidua were measured, and bacterial fluorescence scored. Chorion thinning and bacterial presence were compared among and between groups using Student's t-test, linear mixed effect model, and Poisson regression model (SAS Cary, NC). RESULTS: In all groups, the fetal chorion cellular layer was thinner at rupture compared to distant site (147.2 vs. 253.7 µm, p<0.0001). Further, chorion thinning was greatest among PPROM subjects compared to all other groups combined, regardless of site sampled [PPROM(114.9) vs. PTL(246.0) vs. PTNL(200.8) vs. TL(217.9) vs. TNL(246.5)]. Bacteria counts were highest among PPROM subjects compared to all other groups regardless of site sampled or histologic infection [PPROM(31) vs. PTL(9) vs. PTNL(7) vs. TL(7) vs. TNL(6)]. Among all subjects at both sites, bacterial counts were inversely correlated with chorion thinning, even excluding histologic chorioamnionitis (p<0.0001 and p = 0.05). CONCLUSIONS: Fetal chorion was uniformly thinner at rupture site compared to distant sites. In PPROM fetal chorion, we demonstrated pronounced global thinning. Although cause or consequence is uncertain, bacterial presence is greatest and inversely correlated with chorion thinning among PPROM subjects

Midregional pro-adrenomedullin plasma concentrations are blunted in severe preeclampsia

Levels of the peptide hormone adrenomedullin (AM) are elevated during normal pregnancy, but whether this differs during complications of pregnancy remains unresolved. AM can be quantified by measuring its preprohormone byproduct, midregional pro-adrenomedullin (MR-proADM). MR-pro ADM has shown prognostic value as a biomarker of heart failure, sepsis, and community-acquired pneumonia. Given the relevance of AM to pregnancy, we tested the hypothesis that MR-proADM provides a biomarker for preeclampsia. We find that MR-proADM plasma concentrations are blunted in severe preeclampsia and that MR-proADM is similarly effective as established biomarkers endoglin and placental growth factor at discriminating patients with severe preeclampsia from controls