Translocation of a gut pathobiont drives autoimmunity in mice and humans.

Despite multiple associations between the microbiota and immune diseases, their role in autoimmunity is poorly understood. We found that translocation of a gut pathobiont, Enterococcus gallinarum, to the liver and other systemic tissues triggers autoimmune responses in a genetic background predisposing to autoimmunity. Antibiotic treatment prevented mortality in this model, suppressed growth of E. gallinarum in tissues, and eliminated pathogenic autoantibodies and T cells. Hepatocyte-E. gallinarum cocultures induced autoimmune-promoting factors. Pathobiont translocation in monocolonized and autoimmune-prone mice induced autoantibodies and caused mortality, which could be prevented by an intramuscular vaccine targeting the pathobiont. E. gallinarum-specific DNA was recovered from liver biopsies of autoimmune patients, and cocultures with human hepatocytes replicated the murine findings; hence, similar processes apparently occur in susceptible humans. These discoveries show that a gut pathobiont can translocate and promote autoimmunity in genetically predisposed hosts.

[Sacral neuromodulation in urology - development and current status]. / Sakrale Neuromodulation in der Urologie - Entwicklung und aktueller Stand.

Sacral neuromodulation (SNM) in urology is employed to treat refractory lower urinary tract dysfunction as well as chronic pelvic pain. Electrical stimulation of the sacral afferents (S2 - S4) causes activation and conditioning of higher autonomic and somatic neural structures and thereby influences the efferents controlling the urinary bladder, the rectum and their related sphincter systems. It is therefore possible to treat overactivity as well as hypocontractility and functional bladder neck obstruction. SNM treatment is conducted biphasically. Initially, test electrodes are placed to evaluate changes in micturition and pain parameters. If, in this first phase - called peripheral nerve evaluation (PNE test) - sufficient improvements are observed, the patient progresses to phase two which involves implantation of the permanent electrodes and impulse generator system. In recent years, the "two stage approach" with initial implantation of the permanent electrodes has been favoured as it increases treatment success rates. Long-term success rates of SNM vary significantly in the literature (50 - 80 %) due to heterogeneous patient populations as well as improved surgical approaches. With the introduction of "tined lead electrodes" (2002), tissue damage is reduced to a minimum. Technical innovation, financial feasibility (reimbursed in Germany since 2004) and wider application, especially in otherwise therapy-refractory patients or complex dysfunctions of the pelvis, have established SNM as a potent treatment option in urology.

Interactions between apoptotic signal transduction and capacitation in human spermatozoa.

BACKGROUND: Capacitation of sperm is a prerequisite for successful fertilization, determined by hyperactivated motility, increased tyrosine phosphorylation (TyrP) and membrane changes. However, the exact molecular mechanism is not fully clarified. The calpain-calmodulin-system is essential for membrane fusion during capacitation. Recently, interactions with caspase (CP) activation, a main feature of apoptotic cells, were postulated. The objective of our study was to examine interactions between apoptosis signalling and the calpain-calmodulin-system during capacitation. METHODS: Semen samples from 20 healthy donors were incubated in human tubal fluid at 37 degrees C, 5% CO(2) for 3 h without additives (control), with 3% BSA (capacitation), 10 microM calpain-inhibitor III, 20 microM CP-1 inhibitor or 20 microM calmodulin-antagonist. Capacitation was monitored by computer assisted sperm motion analyzer, chlortetracycline (CTC)-assay and western blot (TyrP). Activation of caspases and integrity of transmembrane mitochondrial potential (TMP) were evaluated by flow cytometry. RESULTS: Capacitation, as measured by CTC assay, increased TyrP levels and hyperactivation, resulted in inactivation of CP-9, CP-3 and improved integrity of the TMP. Inhibition of calpain and CP-1 during capacitation reduced the capacitation-related parameters, but did not lead to apoptosis. Inhibition of calmodulin resulted in blocking of capacitation and stimulation of apoptosis. CONCLUSION: Interaction of the capacitation and apoptosis signalling systems seems to enable the capacitation process by prevention of apoptosis.

Nanofibers as carrier systems for antimicrobial microemulsions. Part I: fabrication and characterization.

Antimicrobial nanofibers were prepared by solubilizing an antimicrobial essential oil (eugenol; 0.75-1.5 wt %) in surfactant micelles (Surfynol 465; 5-10 wt %) to form eugenol-containing microemulsions. Microemulsions were mixed with a nonionic synthetic polymer (poly(vinyl alcohol), PVA; M(w) = 130 kDa, degree of hydrolysis approximately 87%) and solutions subjected to electrospinning to induce nanofiber formation. Solution properties, fiber morphology, and composition of nanofibers were determined. The surface conductivity and viscosity of the polymer solutions increased, while surface tension decreased as both surfactant and eugenol concentration increased. Material deposited on the collector plate consisted primarily of nanofibers with a circular cross section with some surface roughness, although some bead defects were observed. The mean fiber diameters ranged from 57 to 126 nm with fibers having a broad diameter distribution (10-280 nm). The mean diameter of the nanofibers decreased with increasing surfactant concentration and decreasing eugenol concentration. Transmission electron microscopy indicated that microemulsion droplets were homogenously dispersed throughout the nanofibers. Results suggest that electrospun nanofibers may serve as carrier vehicles for microemulsions containing solubilized lipophilic functional compounds such as bioactives, antimicrobials, antioxidants, flavors, and pharmaceuticals.