Androgens are essential for the expression of normal libido in the male, but their role in the maintenance of the erectile response in humans is controversial. It has been shown previously in the rat that castration induces 1) loss of penile reflexes; and 2) considerable reduction in the erectile response to electric field stimulation (EFS) of the cavernosal nerve. Both of these effects can be reversed by testosterone replacement. The current study was performed to determine whether these testosterone effects are mediated via its conversion to dihydrotestosterone (DHT), and to what extent the synthesis of the mediator of penile erection, nitric oxide, is affected by castration and androgen replacement. Five-month-old rats were either castrated or left intact. The orchiectomized rats were implanted with SILASTIC brand silicon tubing (Dow Corning) containing testosterone or DHT with or without daily injections of the 5 alpha-reductase inhibitor finasteride. After 7 days, rats were submitted to EFS and the intracavernosal pressure was recorded. Castration reduced the EFS-induced erectile response by 50% in comparison with intact rats and testosterone restored this decrease to normal. When finasteride was given to these testosterone-treated castrate rats, erectile response was not restored. DHT was as effective as testosterone in restoring response to EFS in castrates and this effect was not decreased by finasteride. Nitric oxide synthase activity in the penile cytosol was measured by the arginine-citrulline conversion and was found to correlate with the EFS determinations. These results show that DHT is the active androgen in the prevention of erectile failure seen in castrated rats, and suggest that this effect may be mediated, at least partially, by changes in nitric oxide synthase levels in the penis.
After a followup of 1 year 3rd generation cryosurgery appears to be well tolerated and minimally invasive. The use of ultrathin needles through a brachytherapy template allows for a simple percutaneous procedure and a relatively short learning curve. A prospective multicenter trial is ongoing to determine the long-term efficacy of this technique.
Androgens are essential for the expression of normal libido in the male, but their role in the maintenance of the erectile response in humans is controversial. It has been shown previously in the rat that castration induces 1) loss of penile reflexes; and 2) considerable reduction in the erectile response to electric field stimulation (EFS) of the cavernosal nerve. Both of these effects can be reversed by testosterone replacement. The current study was performed to determine whether these testosterone effects are mediated via its conversion to dihydrotestosterone (DHT), and to what extent the synthesis of the mediator of penile erection, nitric oxide, is affected by castration and androgen replacement. Five-month-old rats were either castrated or left intact. The orchiectomized rats were implanted with SILASTIC brand silicon tubing (Dow Corning) containing testosterone or DHT with or without daily injections of the 5 alpha-reductase inhibitor finasteride. After 7 days, rats were submitted to EFS and the intracavernosal pressure was recorded. Castration reduced the EFS-induced erectile response by 50% in comparison with intact rats and testosterone restored this decrease to normal. When finasteride was given to these testosterone-treated castrate rats, erectile response was not restored. DHT was as effective as testosterone in restoring response to EFS in castrates and this effect was not decreased by finasteride. Nitric oxide synthase activity in the penile cytosol was measured by the arginine-citrulline conversion and was found to correlate with the EFS determinations. These results show that DHT is the active androgen in the prevention of erectile failure seen in castrated rats, and suggest that this effect may be mediated, at least partially, by changes in nitric oxide synthase levels in the penis.
Castration in the rat reduces both the erectile response and penile nitric oxide synthase (NOS) activity, and these effects are prevented by androgen administration. In this study we determined that the decrease of penile NOS in the castrated rat is due to NOS enzyme inhibition rather than to a reduction of its content and that this inhibition may be reversed. Adult rats were either castrated or left intact, and, after 1 wk, electrical field stimulation (EFS) was applied to the cavernosal nerve and the penises were excised either at the peak of erection or after detumescence. Penile NOS activity in the non-EFS castrates decreased by 70% as compared with the intact non-EFS-treated controls, but neuronal NOS content remained unaffected despite changes in regional distribution. NOS activity in the castrated penis was restored to normal values by EFS at the peak of stimulation, and then decreased on detumescence. This was in contrast to the intact controls in which EFS did not stimulate penile NOS activity. These data indicate that androgen depletion in the rat reduces penile NOS activity rather than NOS content and that this enzyme inhibition is reversed by cavernosal nerve stimulation.
Extended-release ciprofloxacin is well tolerated and penetrates effectively into prostate tissue. Tissue levels of ciprofloxacin are similar whether the extended-release ciprofloxacin is administered 1 hour or 3 hours before TRNBP, indicating that tissue levels are maintained for several hours after administration. PK modelling as used in this trial is suitable to prospectively outline clinical designs. Further investigation of single-dose, extended-release ciprofloxacin as prophylaxis for TRNBP is warranted.
Since histological changes seen in this animal model occur after the time of testicular descent (day 28 of age), we hypothesize that these changes are due to an abnormal anatomical position of the testis as opposed to an inherent testicular defect in the LE/ORL rat. This hypothesis is supported by the fact that no histological differences were noted between the scrotal testes of unilaterally cryptorchid animals and bilaterally descended control animals.
15574 Background: Currently the potential for over- and under-treatment using radical and watchful waiting options respectively constitutes a challenge in the management of patients with early organ-confined prostate cancer. Target focal therapy (TFT) is emerging as an intermediary alternative option for such men. The goal is to provide ablative treatment with minimal impact on morbidity. Methods: As part of an IRB approved study protocol a total of 24 patients initially underwent a 3 dimensional transperineal mapping biopsy under TRUS guidance to confirm the extent of tumor burden and localize the cancer foci within the prostate. Only 12 men qualified to undergo target focal cryotherapy. The remaining patients did not qualify due to upgrading or downgrading of their stage and opted for other treatment options. Follow- up consisted of serial PSA measurements at 3 months interval, disease specific QOL questionnaires, IPSS, and SHIM scores. Results: The mean age was 62.4 years. The mean (SD) prostate size at the time of mapping biopsy was 39 ±14.8g. After mapping biopsy all patients reported time limited hematuria and 2 patients developed urinary retention and were managed successfully with Foley’s catheter for 5 days. Mean PSA before treatment was 5.2 ± 4.1 ng/dl. 10/12 patients had Gleason score (GS) of 3+3, the remaining 2 patients had GS of 3+4. At 3 months follow-up. A median drop of PSA of 1.9 (0, 9.5) ng/dl. All patients reported full urinary continence post operatively. IPSS median drop of 0 (2, -16). Sexual health as assessed by SHIM score showed a median drop of 6 (1, -15) points. In general 4 patients reported a significant change in sexual performance. 2 of which opted for PDE inhibitor with successful regaining of erection at 6 months follow-up. Overall EPIC QOL scores showed no change in rectal, urinary and hormonal components. Sexual component registered a drop of 5 points. Conclusions: The current initial early results appear to be encouraging for future implementation of TFT on select patients with organ confined early stage cancer. Future larger randomized studies are needed to better understand the value of this alternative option in the management of prostate cancer. No significant financial relationships to disclose.
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