Upregulation of TLR2 and TLR4 in the human adrenocortical cells differentially modulates adrenal steroidogenesis.

Rapid activation of adrenal steroid release plays a pivotal role in an organism's first line of defense during sepsis. Adrenal gland function is often suppressed in critically ill patients and negatively impacts the overall survival rate. Increasingly, experimental and clinical evidence suggests that Toll-like receptors (TLRs), components of the innate immune system, play a key role in the mediation of systemic responses to invading pathogens during sepsis. In the present study, we aimed to elucidate the effect of TLR2, TLR4 and CD14 upregulation on adrenocortical cell steroidogenesis. We found that TLR4 and CD14 but not TLR2 overexpression in NCI-H295R cells inhibited basal and acute cortisol and aldosterone production. This effect could be partially explained by reduced expression of enzymes involved in the synthesis of latter steroids--CYP11B1 and CYP11B2. Together, these data suggest that TLR upregulation in the steroid producing cells may be involved in the adrenal gland dysfunction during sepsis.

Pubovaginal cutaneous fascial sling procedure for stress urinary incontinence: 10 years' experience.

OBJECTIVES: There is a considerable lack of consensus regarding indications and long-term efficacy of the many techniques for treating urinary stress incontinence. We report the long-term results of a modified pubovaginal sling procedure. METHODS: From 1989 to 1998, 129 consecutive patients underwent a pubovaginal sling by two urologists. 86 of the subjects (67%) replied to a questionnaire designed to assess the outcome of the procedure and the subjective satisfaction with the operative result. During surgery we performed a modified sling procedure using a cutaneous strip strengthened by rectus fascia and placed with almost no tension. Special care was taken not to lacerate or damage but support the urethral musculature. We routinely did an anterior vaginoplasty, and posterior vaginoplasty if necessary. RESULTS: Mean patient age was 56.8 years, mean follow-up 39 months, mean parity 2.1, previous surgery 0.4. Improvement rates were determined as follows ('Are you satisfied with the operation?'): Significantly reduced incontinence (i.e. 50-100% improvement) was found in 65.2%, slight reduction (10-40% improvement) in 15.2%, no change in 17.4% and worsening in 2.2% of all 103 cases. The majority of all complications were wound infections. CONCLUSION: Despite the considerable failure rate, the substantial improvement in the quality of life of almost two thirds of the patients during a 3-year follow-up recommends a pubovaginal sling as a treatment option for urinary incontinence.