Nevertheless, LCL-30 was an efficacious and safe agent. Future studies should further elaborate on the mechanism of cell selleckchem death and aim to identify an alternative application route as well as more effective partners for combination treatment. Acknowledgments We thank Stefan Heinrich, Gerd Kullak, Daniel Fetz, Peter Gehrig, Riem Ha (University and University Hospital Zurich), J��rgen Schiller, Jan Hengstler (University Leipzig), Besim Ogretmen, Tarek Taha, and Sergei Novgorodov (Medical University South Carolina) for helpful discussions, and Valentin Rousson (Department of Biostatistics, Institute for Social and Preventive Medicine, University of Zurich) for statistical advice. Furthermore, we are grateful to Udo Ungeth��m, Marion Bawohl, Claas B?rger (University Hospital Zurich), and Barbara Rembiesa (Medical University of South Carolina) for technical assistance.

This work was supported by Sassella Foundation, Zurich, Switzerland (to FD) and the National Cancer Institute, Bethesda, MD (Grant IPO1CA097132 to AB and YAH)
Ascending infection of the upper female genital tract with Gram-negative bacteria causes pelvic inflammatory disease (PID) or endometritis in women, with the influx of neutrophils and macrophages leading to accumulation of pus in the uterine lumen [1]. Female genital tract infections with Gram-negative bacteria are also an important cause of infertility, pre-term labour and chronic pelvic pain [2]. Bacteria such as Chlamydia trachomatis are well adapted to colonise the human endometrium and disease models have been established in mice using infusion of bacteria [3].

Alternatively, pathogen-associated molecules such as lipopolysaccharide can be used in vivo to establish PID in mice [4], [5]. Ascending infection of the female genital tract with a wide range of bacteria occurs in almost all cattle after parturition [6], [7]. This infection often leads to disease of the upper female genital tract, which can be called pelvic inflammatory disease or metritis [8]. Indeed, about 40% of animals develop PID within a week of parturition, and ~20% have endometritis that persists for >3 weeks [9]. Infection of the endometrium with Gram-negative Escherichia coli is the first step in the disease process for developing PID in cattle, preceding infection by the other bacteria such as Arcanobacterium pyogenes [6], [10]. The presence of E.

coli is associated with the acute phase protein response, the severity of PID and the extent of the infertility [6], [7], [10]. There is a wide genetic diversity of E. coli in the environment and feces [11], [12]. So, the widely held assumption was that these genetically diverse fecal E. coli randomly and opportunistically contaminate the endometrium to Anacetrapib cause PID. However, there are well characterised pathogenic strains of diarrheagenic E.