Flibanserin and 8‐OH‐DPAT Implicate Serotonin in Association between Female Marmoset Monkey Sexual Behavior and Changes in Pair‐Bond Quality

IntroductionPsychopathological origins of personally distressing, hypoactive sexual desire disorder (HSDD) in women are unknown, but are generally attributed to an inhibitory neural regulator, serotonin (5‐HT). Flibanserin, a 5‐HT_1A agonist and 5‐HT_2A antagonist, shows promise as a treatment for HSDD.AimTo test the hypothesis that female marmoset sexual behavior is enhanced by flibanserin and diminished by 8‐OH‐DPAT, in order to evaluate the efficacy of serotonergic modulation of female sexual behavior in a pairmate social setting comparable to humans.MethodsSexual and social behavior were examined in eight female marmoset monkeys receiving daily flibanserin (15 mg/kg), 8‐OH‐DPAT (0.1 mg/kg), or corresponding vehicle for 15–16 weeks in a counterbalanced, within‐subject design, while housed in long‐term, stable male–female pairs.Main Outcome MeasuresMarmoset pairmate interactions, including sexual and social behavior, were scored during weeks 5–6 of daily flibanserin, 8‐OH‐DPAT or vehicle treatment. 24‐hour pharmacokinetic profiles of the drugs and their metabolites, as well as drug‐induced acute symptoms of the 5‐HT behavioral syndrome were also assessed.ResultsTwo‐way analysis of variance reveals that flibanserin‐treated females attract more male sexual interest (P = 0.020) and trigger increased grooming (P = 0.001) between partners. In contrast, 8‐OH‐DPAT‐treated females show increased rejection of male sexual advances (P = 0.024), a tendency for decreased male sexual interest (P = 0.080), and increased aggression with their male pairmates (P = 0.049).ConclusionsWhile 8‐OH‐DPAT‐treated female marmosets display decreased sexual receptivity and increased aggressive interactions with their male pairmates, flibanserin‐treated female marmosets demonstrate increased affiliative behavior with their male pairmates. Such pro‐affiliation attributes may underlie flibanserin's effectiveness in treating HSDD in women. Aubert Y, Gustison ML, Gardner LA, Bohl MA, Lange JR, Allers KA, Sommer B, Datson NA, and Abbott DH. Flibanserin and 8‐OH‐DPAT implicate serotonin in association between female marmoset monkey sexual behavior and changes in pair‐bond quality. J Sex Med 2012;9:694–707.     

Improving greater trochanteric reattachment with a novel cable plate system

Cable-grip systems are commonly used for greater trochanteric reattachment because they have provided the best fixation performance to date, even though they have a rather high complication rate. A novel reattachment system is proposed with the aim of improving fixation stability. It consists of a Y-shaped fixation plate combined with locking screws and superelastic cables to reduce cable loosening and limit greater trochanter movement.The novel system is compared with a commercially available reattachment system in terms of greater trochanter movement and cable tensions under different greater trochanteric abductor application angles.A factorial design of experiments was used including four independent variables: plate system, cable type, abductor application angle, and femur model. The test procedure included 50 cycles of simultaneous application of an abductor force on the greater trochanter and a hip force on the femoral head.The novel plate reduces the movements of a greater trochanter fragment within a single loading cycle up to 26%. Permanent degradation of the fixation (accumulated movement based on 50-cycle testing) is reduced up to 46%. The use of superelastic cables reduces tension loosening up to 24%. However this last improvement did not result in a significant reduction of the grater trochanter movement.The novel plate and cables present advantages over the commercially available greater trochanter reattachment system. The plate reduces movements generated by the hip abductor. The superelastic cables reduce cable loosening during cycling. Both of these positive effects could decrease the risks related to grater trochanter non-union.     

Combination of Doxazosin and Sildenafil Exerts an Additive Relaxing Effect Compared with Each Compound Alone on Human Cavernosal and Prostatic Tissue

IntroductionPhosphodiesterase 5 inhibitors (PDE5) such as sildenafil are first-line treatment for erectile dysfunction (ED). Alpha1 (α1)-adrenoceptor antagonists such as doxazosin are indicated for the treatment of patients with lower urinary tract symptoms (LUTS)/benign prostatic hyperplasia (BPH). ED and LUTS/BPH are conditions that are often associated. Accordingly, α1-adrenoceptor antagonists and PDE5 inhibitors will be often prescribed in real life setting together.AimTo evaluate the effects of the combination of sildenafil and doxazosin on human cavernosal and prostatic tissue.MethodsProstatic and erectile tissues were obtained from nine to 12 patients, respectively. Patients underwent cystoprostatectomy for infiltrating bladder cancer or penile surgery for penile implant, congenital curvature or Peyronie's disease.Main Outcome MeasuresIn organ baths, prostatic and cavernosal strips were submitted to either concentration-response curves (CRC) to phenylephrine (Phe) or norepinephrine (NE), respectively, in presence of vehicle, sildenafil (10^?6 M, 10^?5 M), doxazosin (10^?8 M, 3.10^?8 M, or 10^?7 M), or a combination of both. Continuous electrical field stimulation (EFS; 32 Hz, 5 ms, 5 seconds, 300 mA) was performed on prostatic strips which were incubated with sildenafil 10^?6 M or vehicle before the successive addition of doxazosin (10^?7 M, 10^?6 M) or vehicle. Cavernosal strips were pre-incubated with doxazosin (10^?9 M, 10^?8 M) or vehicle, then CRC to sildenafil were constructed on NE (3.10^?6 M) precontracted cavernosal strips.ResultsCombination of sildenafil and doxazosin exerted a greater relaxing effect on CRC to Phe or NE compared with each compound alone in both tissues. Sildenafil significantly enhanced the relaxing effect of doxazosin on EFS-induced contractions in prostatic strips. Doxazosin significantly increased the ability of sildenafil to inhibit NE-induced contractions in cavernosal strips.ConclusionsSildenafil and doxazosin reduced adrenergic tone of prostatic and cavernosal smooth muscle and their combination provided a significant benefit when targeting relaxation of both tissues. These experiments provide support for further clinical evaluation of the sildenafil and doxazosin combination in ED patients with LUTS/BPH. Oger S, Behr-Roussel D, Gorny D, Lecoz O, Lebret T, Denoux Y, Faix A, Leriche A, Wayman C, Alexandre L, and Giuliano F. Combination of doxazosin and sildenafil exerts an additive relaxing effect compared with each compound alone on human cavernosal and prostatic tissue. J Sex Med 2009;6:836–847.