The acyclic CB1R inverse agonist taranabant mediates weight loss by increasing energy expenditure and decreasing caloric intake.

Cannabinoid 1 receptor (CB1R) inverse agonists are emerging as a potential obesity therapy. However, the physiological mechanisms by which these agents modulate human energy balance are incompletely elucidated. Here, we describe a comprehensive clinical research study of taranabant, a structurally novel acyclic CB1R inverse agonist. Positron emission tomography imaging using the selective CB1R tracer [(18)F]MK-9470 confirmed central nervous system receptor occupancy levels ( approximately 10%-40%) associated with energy balance/weight-loss effects in animals. In a 12-week weight-loss study, taranabant induced statistically significant weight loss compared to placebo in obese subjects over the entire range of evaluated doses (0.5, 2, 4, and 6 mg once per day) (p < 0.001). Taranabant treatment was associated with dose-related increased incidence of clinical adverse events, including mild to moderate gastrointestinal and psychiatric effects. Mechanism-of-action studies suggest that engagement of the CB1R by taranabant leads to weight loss by reducing food intake and increasing energy expenditure and fat oxidation.

Ultrasound use in suspected testicular torsion: an association with delay to theatre and increased intraoperative finding of non-viable testicle.

AIM: Testicular torsion is a surgical emergency and delayed operative management can negatively impact fertility. The aims of this study were to establish patterns of ultrasound use, correlate ultrasound and intraoperative findings and determine the impact of ultrasound on admission-to-operation time in patients undergoing scrotal exploration for suspected torsion. METHOD: All adult patients who underwent acute scrotal exploration for suspected torsion between 2007 and 2017 at Auckland City Hospital were included (n=316). Clinical notes were reviewed for demographic and clinical data. Admission-to-operation time was compared between patients who had a formal ultrasound and those who did not. RESULTS: Ultrasound was performed in 153/316 (48.4%) patients. Ultrasound sensitivity and specificity for torsion was 97.8% and 52.9% respectively. Median admission-to-operation time was 106 minutes for patients who did not have an ultrasound and 225 minutes for those who did (excluding those with missed torsion on ultrasound) (p=<0.0001). Non-viable testicle was identified intraoperatively in 11/163 patients (6.7%) who did not have an ultrasound, and in 42/122 (34.4%) of those who did (excluding those with missed torsion on ultrasound) (p=<0.0001). CONCLUSION: Ultrasound is a sensitive test for testicular torsion but associated with an average two-hour delay to theatre and a higher rate of intraoperative finding of non-viable testicle in this centre.