Inflammasome sensor NLRP1 controls rat macrophage susceptibility to Toxoplasma gondii

Toxoplasma gondii is an intracellular parasite that infects a wide range of warm-blooded species. Rats vary in their susceptibility to this parasite. The Toxo1 locus conferring Toxoplasma resistance in rats was previously mapped to a region of chromosome 10 containing Nlrp1. This gene encodes an inflammasome sensor controlling macrophage sensitivity to anthrax lethal toxin (LT) induced rapid cell death (pyroptosis). We show here that rat strain differences in Toxoplasma infected macrophage sensitivity to pyroptosis, IL-1β/IL-18 processing, and inhibition of parasite proliferation are perfectly correlated with NLRP1 sequence, while inversely correlated with sensitivity to anthrax LT-induced cell death. Using recombinant inbred rats, SNP analyses and whole transcriptome gene expression studies, we narrowed the candidate genes for control of Toxoplasma-mediated rat macrophage pyroptosis to four genes, one of which was Nlrp1. Knockdown of Nlrp1 in pyroptosis-sensitive macrophages resulted in higher parasite replication and protection from cell death. Reciprocally, overexpression of the NLRP1 variant from Toxoplasma-sensitive macrophages in pyroptosis-resistant cells led to sensitization of these resistant macrophages. Our findings reveal Toxoplasma as a novel activator of the NLRP1 inflammasome in rat macrophages

Can the outcome of pelvic-floor rehabilitation in patients with fecal incontinence be predicted?

Purpose: Pelvic-floor rehabilitation does not provide the same degree of relief in all fecal incontinent patients. We aimed at studying prospectively the ability of tests to predict the outcome of pelvic-floor rehabilitation in patients with fecal incontinence. Materials and methods: Two hundred fifty consecutive patients (228 women) underwent medical history and a standardized series of tests, including physical examination, anal manometry, pudendal nerve latency testing, anal sensitivity testing, rectal capacity measurement, defecography, endoanal sonography, and endoanal magnetic resonance imaging. Subsequently, patients were referred for pelvic-floor rehabilitation. Outcome of pelvic-floor rehabilitation was quantified by the Vaizey incontinence score. Linear regression analyses were used to identify candidate predictors and to construct a multivariable prediction model for the posttreatment Vaizey score. Results: After pelvic-floor rehabilitation, the mean baseline Vaizey score (18, SD±3) was reduced with 3.2 points (p<0.001). In addition to the baseline Vaizey score, three elements from medical history were significantly associated with the posttreatment Vaizey score (presence of passive incontinence, thin stool consistency, primary repair of a rupture after vaginal delivery at childbed) (R2, 0.18). Th

Usefulness of 3D transperineal ultrasound in severe stenosis of the anal canal: preliminary experience in four cases

BACKGROUND: Organic or functional anal canal stenoses are uncommon conditions that occur in the majority of cases as a consequence of anal diseases. A proper assessment is fundamental for decision making; however, proctological examination and endoanal ultrasound are often unfeasible or very difficult to perform even under local or general anesthesia. We therefore began to use 3D transperineal ultrasound to assess patients. The aim of this study was to compare the results of evacuation proctography and 3D transperineal ultrasound in patients with severe anal canal stenosis. METHODS: Four consecutive patients with high-grade anal canal stenosis were evaluated using both proctography and 3D transperineal ultrasound with a micro-convex transducer between March and June 2011. RESULTS: In all cases, 3D transperineal ultrasound provided detailed information on the length and level of stenosis and on the integrity of the anal sphincters. CONCLUSIONS: Our preliminary experience suggests that 3D transperineal ultrasound makes it possible to plan optimal surgical treatment