Inflammatory mediators involved in the paw edema and hyperalgesia induced by Batroxase, a metalloproteinase isolated from Bothrops atrox snake venom.

Snake venom metalloproteinases have been described as responsible for several inflammatory effects. In this study, we investigated the edema and hyperalgesia induced in rats by Batroxase, a P-I metalloproteinase from Bothrops atrox venom, along with possible inflammatory mediators involved in these responses. Batroxase or sterile saline was injected into rat paws and the edema and hyperalgesic effects were evaluated for 6h by using a plethysmometer and a Von Frey system, respectively. Batroxase induced significant edematogenic and hyperalgesic peak responses in the first hours after administration. The inflammatory mediators involved in these responses were assayed by pretreatment of animals with synthesis inhibitors or receptor antagonists. Peak responses were significantly reduced by administration of the glucocorticoid dexamethasone, the H1 receptor antagonist diphenhydramine and the FLAP inhibitor MK-886. Rat paws injected with compound 48/80, a mast cell degranulating agent, followed by Batroxase injection resulted in significant reduction of the edema and hyperalgesia. However, Batroxase itself induced minor degranulation of RBL-2H3 mast cells in vitro. Additionally, the inflammatory responses did not seem to be related to prostaglandins, bradykinin or nitric oxide. Our results indicate a major involvement of histamine and leukotrienes in the edema and hyperalgesia induced by Batroxase, which could be related, at least in part, to mast cell degranulation.

Randomized controlled trial of cough test versus no cough test in the tension-free vaginal tape procedure: effect upon voiding dysfunction and 12-month efficacy.

INTRODUCTION AND HYPOTHESIS: This is a prospective randomized controlled trial of cough versus no cough test in the tension-free vaginal tape (TVT) procedure to determine its effect upon voiding dysfunction and 12-month efficacy. METHODS: The trial was conducted in a single tertiary urogynecology unit. Women ≥21 years old with primary urodynamic stress incontinence without voiding dysfunction were considered eligible. Participants were randomized to undergo the TVT procedure using either an intraoperative cough test or using no intraoperative cough test. Our hypothesis was that postoperative voiding dysfunction would be more common in the "no cough test" arm. The primary outcome was proportion of patients successfully completing a trial of void (TOV) within 24 h of catheter removal. Efficacy at 12 months comprised the secondary outcome. Participants were randomized using a computer-generated randomization sequence by an independent party who was not the operating surgeon. Due to the nature of the intervention to be tested, neither the patients nor the operating surgeons were blinded to the randomization process during the procedure. RESULTS: This trial is reported according to the recommendations of the 2010 CONSORT statement. In total, 94 women were recruited over a 4-year study period. Of these, 92 women were randomized (47 in the "cough" group and 45 in the "no cough" group). In one case, the TVT procedure was abandoned intraoperatively, leaving 91 women who underwent analysis. There was no significant difference in the proportion of women with a successful TOV within 24 h between the two arms (79% in the "cough" group versus 71% in the "no cough" group; p = 0.47). Efficacy data at 12 months were not significantly different between groups. CONCLUSION: Our data suggest that the performance of the intraoperative cough test during the TVT procedure does not reduce the incidence of postoperative voiding dysfunction (as determined by successful TOV within 24 h) nor affect efficacy. The removal of the cough test from the standard TVT technique may be appropriate.

Subtraction MR images in a multiple sclerosis multicenter clinical trial setting.

PURPOSE: To explore the applicability of subtraction magnetic resonance (MR) images to (a) detect active multiple sclerosis (MS) lesions, (b) directly quantify lesion load change, and (c) detect treatment effects (distinguish treatment arms) in a placebo-controlled multicenter clinical trial by comparing the subtraction scheme with a conventional pair-wise comparison of nonregistered MR images. MATERIALS AND METHODS: Forty-six pairs of MR studies in 40 patients (31 women; mean age, 31.9 years) from a multicenter clinical trial were used. The clinical trial was approved by local ethics review boards, and all subjects gave written informed consent. Active MS lesions were scored by two independent raters, and lesion load measurements were conducted by using semiautomated software. Lesion counts were evaluated by using the Wilcoxon signed rank test, interrater agreement was evaluated by using the intraclass correlation coefficient (ICC), and treatment (interferon beta-1b) effect was evaluated by using the Mann-Whitney U test. RESULTS: When subtraction images were used, there was a 1.7-fold increase in the detection of positive active lesions, as compared with native image pairs, and significantly greater interobserver agreement (ICC = 0.98 vs 0.91, P < .001). Subtraction images also allowed direct quantification of positive disease activity, a measure that provided sufficient power to distinguish treatment arms (P = .012) compared with the standard measurement of total lesion load change on native images (P = .455). CONCLUSION: MR image subtraction enabled detection of higher numbers of active MS lesions with greater interobserver agreement and exhibited increased power to distinguish treatment arms, as compared with a conventional pair-wise comparison of nonregistered MR images.

Seroprevalence of hepatitis C virus infection among indigent urban pregnant women in Zimbabwe.

OBJECTIVE: To estimate the seroprevalence of hepatitis C virus (HCV) infection among indigent pregnant women. DESIGN: A serological survey study of indigent pregnant women admitted for labour and delivery. SETTING: Harare Maternity Hospital, Harare, Zimbabwe. SUBJECTS: A random sample of 1,607 women, delivering at the hospital during the study period agreed to participate in the research. Serum samples were available for 1,591 women. MAIN OUTCOME MEASURES: Serum samples were tested for the presence of antibodies to HCV using a second generation agglutination assay and a third generation enzyme immuno-assay (EIA). RESULTS: Of the 1,591 women tested 25 (1.6%) were anti-HCV positive (95% confidence interval 1.0% to 2.2%). The frequency of anti-HCV positives was associated with maternal age (p = 0.0202) and maternal syphilis status (p = 0.020). Gravidas aged 25 to 29 years had the highest anti-HCV seroprevalence (3.4%) as compared with gravidas of other age categories (1.0% to 1.5%). Women with serologic evidence of syphilis infection during the index pregnancy had an increased prevalence of anti-HCV as compared with those women without evidence of syphilis infection (7.9% versus 1.4%, p = 0.020). There was some evidence (p = 0.094) that a positive prior history of delivering a stillborn infant was also associated with an increased prevalence of anti-HCV (4.1% vs 1.4%). Other maternal characteristics, including hepatitis B virus carriage status, parity, and whether she had received prenatal care during the index pregnancy were not determinants of maternal anti-HCV status. CONCLUSIONS: Overall, hepatitis C antibody was detected in 1.6% of indigent women delivering at Harare Maternity Hospital. This proportion of anti-HCV positive pregnant women is similar to estimates published for North American and European women. Factors positively associated with maternal seropositivity in our population included maternal age (between 25 to 29 years), prior history of delivering a stillborn infant, and seropositivity for syphilis during the index pregnancy. Given the relatively low seroprevalence of HCV and the fact that risk factors for HCV infection remain largely unknown, more studies are needed to identify high risk populations likely to benefit from HCV screening and treatment programmes.