Pharmacokinetic characterisation of a valproate Autism Spectrum Disorder rat model in a context of co-exposure to α-Hexabromocyclododecane.

Assessing the role of α-hexabromocyclododecane α-HBCDD as a factor of susceptibility for Autism Spectrum disorders by using valproic acid-exposed rat model (VPA) required characterizing VPA pharmacokinetic in the context of α-HBCDD-co-exposure in non-pregnant and pregnant rats. The animals were exposed to α-HBCDD by gavage (100 ng/kg/day) for 12 days. This was followed by a single intraperitoneal dose of VPA (500 mg/kg) or a daily oral dose of VPA (500 mg/kg) for 3 days. Exposure to α-HBCDD did not affect the pharmacokinetics of VPA in pregnant or non-pregnant rats. Surprisingly, VPA administration altered the pharmacokinetics of α-HBCDD. VPA also triggered higher foetal toxicity and lethality with the PO than IP route. α-HBCDD did not aggravate the embryotoxicity observed with VPA, regardless of the route of exposure. Based on this evidence, a single administration of 500 mg/kg IP is the most suitable VPA model to investigate α-HBCDD co-exposure.

Effects of alpha1-blockers on urodynamic parameters of bladder outlet obstruction in patients with lower urinary tract symptoms suggestive of benign prostatic enlargement: a review.

α1-adrenergic receptors blockers (ABs) are recommended as first-line medical therapy in men with Lower Urinary Tract Symptoms suggestive of Benign Prostatic Enlargement (LUTS/BPE). Available ABs include: terazosin, doxazosin, tamsulosin, naftopidil, alfuzosin and silodosin. These agents have different profiles of selectivity for α1-adrenergic receptors subtypes. All these agents are efficacious in improving both storage and voiding LUTS. In recent years the efficacy of ABs in improving urodynamic parameters of bladder outlet obstruction (BOO) has been questioned. We reviewed literature evidences about the effects of available ABs on invasive urodynamic parameters of BOO in men with LUTS/BPE. The impact of ABs therapy on urodynamic parameters indicative of BOO has been evaluated for all currently approved drugs. Available data demonstrate improvements in terms of both free uroflowmetry and pressure-flow parameters. While the impact of ABs on maximum urinary flow is clinically modest, the improvement of detrusor pressure at maximum urinary flow is more robust. Only few studies exist that directly compare the urodynamic effects of a small number of ABs. According to these studies there are no differences among ABs in terms of urodynamic efficacy. Indirect comparison of ABs suggests greater effectiveness of silodosin in terms of detrusor pressure at maximum urinary flow reduction. Studies that stratified populations based upon the degree of obstruction at baseline demonstrated greater urodynamic changes in patients with baseline BOO with respect to the unobstructed patients. Globally, the quality of studies available is low and there is considerable heterogeneity among studies.

Tadalafil once daily and extracorporeal shock wave therapy in the management of patients with Peyronie's disease and erectile dysfunction: results from a prospective randomized trial.

Extracorporeal shock wave therapy improves erectile function in patients with Peyronie's disease. However, erectile dysfunction still persists in many cases. We aimed to investigate the effects of extracorporeal shock wave therapy plus tadalafil 5 mg once daily in the management of patients with Peyronie's disease and erectile dysfunction not previously treated. One hundred patients were enrolled in a prospective, randomized, controlled study. Patients were randomly allocated to receive either extracorporeal shock wave therapy alone for 4 weeks (n = 50) or extracorporeal shock wave therapy plus tadalafil 5 mg once daily for 4 weeks (n = 50). Main outcome measures were: erectile function (evaluated through the shortened version of the International Index of Erectile Function), pain during erection (evaluated through a Visual Analog Scale), plaque size, penile curvature and quality of life (evaluated through an internal questionnaire). Follow-up evaluations were performed after 12 and 24 weeks. In both groups, at 12 weeks follow-up, mean Visual Analog Scale score, mean International Index of Erectile Function score and mean quality of life score ameliorated significantly while mean plaque size and mean curvature degree were unchanged. Intergroup analysis revealed a significantly higher mean International Index of Erectile Function score and quality of life score in patients receiving the combination. After 24 weeks, intergroup analysis revealed a significantly higher mean International Index of Erectile Function score and mean quality of life score in patients that received extracorporeal shock wave therapy plus tadalafil. In conclusion extracorporeal shock wave therapy plus tadalafil 5 mg once daily may represent a valid conservative strategy for the management of patients with Peyronie's disease and erectile dysfunction.