Alejandro J. Miranda-Sousa

Effects of two atypical neuroleptics, olanzapine and risperidone, on the function of the urinary bladder and the external urethral sphincter in anesthetized rats

BackgroundA previous report showed that the atypical neuroleptic clozapine resulted in marked changes in urodynamic parameters and greatly inhibited the activity of the external urethral sphincter in anesthetized rats. Such findings may help explain the high incidence of urinary disturbances reported during clozapine therapy. In an effort to extend our observations to other atypical neuroleptic agents, the present study investigated the effects of two newer atypical antipsychotics, olanzapine and risperidone, on the bladder and external urethral sphincter during cystometry in anesthetized rats.ResultsAt a dose of 0.1 mg/kg (i.v.), olanzapine decreased the micturition volume and increased the residual volume. In addition, olanzapine decreased the expulsion time and the amplitude of the high frequency oscillations observed during the expulsion phase. Larger doses (1 mg/kg) had a greater effect. Olanzapine also reduced the activity recorded from the external urethral sphincter, and the bursting observed during the expulsion phase was abolished by 1.0 mg/kg. Risperidone had similar effects although the maximal effects were smaller than those observed with olanzapine. The amplitude of bladder contractions elicited by electrical stimulation of the pelvic nerve was reduced by olanzapine but not risperidone suggesting a possible anti-muscarinic peripheral effect of olanzapine.ConclusionsOlanzapine and risperidone significantly altered several voiding parameters and decreased the activity of the external urethral sphincter in the anesthetized rat. We propose that these effects are due to the central action of these drugs and not to peripheral effects. These findings may explain some of the clinical reports of urinary incontinence with risperidone and may predict similar occurrences with olanzapine therapy.

Sexual Function After Surgery for Prostate or Bladder Cancer

BACKGROUND Compromised sexual function is often a side effect for patients following radical surgical procedures for bladder or prostate cancer. METHODS The authors review the classification and physiology of sexual function and dysfunction. Moreover, they explain the possible pathophysiology directly resulting from surgery, and they discuss several approaches available to address these problems. RESULTS Options for male sexual dysfunction, primarily erectile dysfunction resulting from radical prostatectomy or surgery for bladder cancer, range from patient education to penile prosthesis implantation. Female sexual dysfunction caused by surgical intervention for bladder cancer includes problems with libido, arousal, orgasm, and dyspareunia. Treatment options for women can include sex therapy, hormonal therapy, and preventive strategies. However, no consensus has been established on the most effective agents and time points to treat male or female sexual dysfunction following radical cystectomies or prostatectomies. The chronic intermittent treatment of erectile dysfunction following radical prostatectomy has been commonly referred to as penile rehabilitation. CONCLUSIONS Additional research is needed to obtain further data concerning sexual dysfunction in both men and women following radical pelvic surgeries. Modification of surgical techniques, the use of various treatment modalities for sexual dysfunction, and the development of new agents will help to successfully minimize or prevent damage and restore normal sexual function after local surgical therapy for prostate or bladder cancer in the future.

Separate urinary bladder and prostate neurons in the central nervous system of the rat: simultaneous labeling with two immunohistochemically distinguishable pseudorabies viruses

BackgroundThis work examines the central nervous system distribution of virus-labeled neurons from the rat urinary bladder and the prostate simultaneously within the same tissue sections. Two immunohistochemically distinct pseudorabies virus strains were simultaneously injected into male Sprague Dawley rats (~280 gm). One virus was injected into the bladder and the other into the prostate. After incubation intervals of 2.25, 2.5, 2.75, 3 and 4 days, sections from the spinal cord and brain were processed immunohistochemically to detect cells, within a single section, which were labeled separately by each virus or were labeled by both viruses.ResultsEach strain of virus labeled a separate population of neurons and some neurons were labeled by both strains. The majority of neurons labeled by virus from the urinary bladder were found in the L6-S1 spinal cord segments within the dorsal gray commissure, the intermediolateral area and the superficial dorsal horn. Neurons labeled by virus from the prostate were mainly found in the L1-L2 spinal cord segments in the dorsal gray commissure and the intermediolateral areas. Double-labeled interneurons in L1-L2 were mainly located in the intermediolateral area. In L6-S1 they were divided between the dorsal gray commissure and the intermediolateral area.ConclusionsSpinal neurons innervating the bladder are clearly separate and different from those innervating the prostate. This difference also persists in the brain. In disagreement with previous reports, no direct anatomical evidence of parasympathetic innervation of the prostate was observed.

Central effects of clozapine in regulating micturition in anesthetized rats

BackgroundWe previously showed that systemic administration of the atypical neuroleptic clozapine in the rat altered a number of urodynamic variables and inhibited the external urethral sphincter. Since clozapine acts at several receptor types both at the periphery and the central nervous system, the site of action remained uncertain. Therefore, the purpose of this study was to determine the effects of central administration of clozapine on the bladder and the external urethral sphincter during cystometry and to examine differences in spinal versus supraspinal administration. We extended our observations by delivering clozapine centrally in anesthetized rats instrumented with either an intrathecal (L6-S1 spinal segment) or an intracerebroventricular (lateral ventricle) catheter.ResultsClozapine decreased micturition volume and increased residual volume possibly by acting at a supraspinal site. Expulsion time and amplitude of the high frequency oscillations were reduced by clozapine possibly by acting at a spinal site. Bladder capacity was increased after central clozapine but probably due to a peripheral effect. Clozapine acting at spinal and supraspinal sites increased pressure threshold. Contraction time and peak pressure were not affected by clozapine. The EMG from the external urethral sphincter was also reduced following clozapine centrally and suggests a spinal and a supraspinal site of action.ConclusionsThe results from the present study suggest that spinal and supraspinal central sites mediate clozapines action in inhibiting expulsion parameters and the external urethral sphincter of the rat. Therefore, the reduction in the voiding efficiency observed after clozapine appears to be mediated by spinal and supraspinal sites.