Local stress anomaly in the Bavarian Molasse Basin

Background: The characterization of fault zones in the Bavarian Molasse Basin plays a major role for further geothermal reservoir development. Hence, their identification, geological origin, and hydraulic characterization are discussed extensively. Methods: Stress indicators and fractures are interpreted from image and caliper logs of three highly deviated wells at the Sauerlach site. We transform the identified stress field into the borehole coordinate system and compare the observed orientation to the modeled stress field which assumes a homogeneous borehole surrounding. Results: High breakout occurrence, cross-cutting fractures, and a fracture orientation from N-S to NNE-SSW are observed in Sauerlach Th1. In Sauerlach Th2 and Th3, fractures strike primarily ENE-WSW and N-S to NNE-SSW. Drilling-enhanced natural fractures and drilling-induced tensile fractures are observed in all three wells and indicate the orientation of tensile stress at the borehole wall. In Sauerlach Th2 and Th3, stress transformation indicates a S$_{H}$-dir. ~ N 10°E in a strike-slip stress regime. The modeled stress orientations match the observed orientations within the well Sauerlach Th1 if either S$_{H}$-dir. is N 320°E in a strike-slip regime or S$_{H}$-dir. is N 10°E in a normal faulting regime. Conclusion: This approach improves the detection of the local stress field especially for non-vertical wells, which has, in combination with the facture pattern, a major impact on the hydraulic system of the geothermal reservoir

Vaginal expression of efflux transporters and the potential impact on the disposition of microbicides in vitro and in rabbits

In order to reach sufficiently high tissue concentrations and thus be effective, vaginally applied anti-HIV microbicides that are active at the level of the immune cells must permeate across the cervicovaginal mucosal layer. Cellular efflux transporters, such as Pgp, BCRP, and MRP-2, have been demonstrated to greatly affect drug disposition at different sites in the body including the intestine and the blood-brain barrier; their possible role on drug uptake from the female genital tract, however, has not been elucidated yet. In the present study, the protein expression of Pgp, BCRP, and MRP-2 in endocervical and vaginal tissue of premenopausal women was confirmed by Western blot analysis. To enable the assessment of transporter effects in vitro, the identification of an appropriate cervicovaginal cell line was pursued. The cervical SiHa cell line was observed to express mRNA of the 3 studied transporters, but only MRP-2 was found to be active. Consequently, the established Caco-2 cell line was utilized as an alternative in which the interaction of 10 microbicide candidates with the efflux transporters was studied. Darunavir, saquinavir, and maraviroc were identified as Pgp and MRP-2 substrates. The impact of Pgp on in vivo drug disposition was further examined for the model Pgp substrate talinolol in rabbits. Its vaginal uptake was significantly reduced by Pgp-mediated efflux when formulated in a neutral but not in an acidic gel. Our findings indicate the expression of a functional Pgp transporter in the vaginal mucosa that may severely reduce the vaginal uptake of Pgp substrates, including certain microbicide candidates, especially in women with an increased vaginal pH