Advances in Therapeutic Development for Radiation Cystitis

Radiation treatment for pelvic malignancies is typically associated with radiation injury to urinary bladder that can ultimately lead to radiation cystitis (RC). The late sequelae of radiation therapy may take many years to develop and include bothersome storage symptoms such as hematuria, which may be life‐threatening in severe cases of hemorrhagic cystitis. Although no definitive treatment is currently available, various interventions are used for radiation and hemorrhagic cystitis including blood transfusion, bladder irrigation, intravesical instillation of substances such as alum, silver nitrate, prostaglandins or formalin, and fulguration of intravesical bleeding sites and surgery options such as supravesical urinary diversions and cystectomy. Effects of non‐surgical treatments for radiation and hemorrhagic cystitis are of modest success and studies are lacking to control the effects caused by RC. When such measures have proven ineffective, use of bladder botulinum toxin injection has been reported. New therapy, such as intravesical immunosuppression with local tacrolimus formulation is being developed for the treatment of radiation hemorrhagic cystitis.     

Foetal remnants in the uterus and their relation to other uterine heterotopia

Foetal remnants were found in uterine curettings obtained from three women complaining of irregular vaginal bleeding. These findings are discussed in relation to other cases in the literature in which heterotopic tissues have been found in curettings and also for the light they throw on the origin of the so-called uterine teratomas.     

Effects of long-term treatment with testosterone enanthate in rhesus monkeys: I. Pharmacokinetics of testosterone, testicular volume and liver metabolism of testosterone

The effects of long-term administration of testosterone enanthate on the pharmacokinetics and bioavailability of testosterone were studied in adult male rhesus monkeys (n = 9), injected with 50 mg of testosterone enanthate (TE) once every 14 days for a total of 32 months. Control animals were injected with 0.2 mL olive oil. Serum testosterone levels increased sharply within 24 h of the first injection of TE and reached a peak on day 3 followed by a sharp decline, but baseline values were not reached even by day 14. Subsequent injections of TE caused a similar pharmacokinetic profile until the 55th injection; testosterone levels on day 3 declined from the 56 to 58th injection and remained in a lower range until the last injection. Repeated injections of TE increased the bioavailability of testosterone as shown by the Area Under the Curve. The nocturnal (22.00 h) surge in testosterone levels during the pretreatment phase was abolished by TE injections. TE injections altered the metabolism of testosterone by the liver, as studied in vitro; while liver from control animals converted testosterone to androstenedione as the major metabolite, androsterone was the major metabolite in chronically TE-treated animals. Spermatogenesis and the associated increase in testicular volume observed in control animals in winter were suppressed in TE-treated animals. The results indicate that repeated TE injections elevate serum testosterone to supra-physiological levels with marked fluctuations in circulating testosterone levels after each injection. Possibly in response to these elevated levels, there was a change in the metabolism of testosterone by the liver as observed in vitro.     

Promise of Urinary Nerve Growth Factor for Assessment of Overactive Bladder Syndrome

Overactive bladder syndrome (OAB) is highly prevalent bladder disorder in men and women. About 10–15% of the population suffers from urgency frequency with or without urgency urinary incontinence. It is estimated that 50–75% of patients with OAB may have urodynamic detrusor overactivity (DO). Urodynamic study invasive and most of the OAB patients might not accept it as a routine assessment. Therefore, a more objective and non‐invasive test for diagnosis and assessing DO from OAB patients is needed. Recently, urinary nerve growth factor (NGF) has gained great interest in detecting DO in patients with OAB. Urinary NGF level was found to increase in OAB and urodynamic DO. Urinary NGF levels correlated with severity of OAB symptoms. Patients with either idiopathic or neurogenic DO may have increased urinary NGF levels. Urinary NGF levels have been shown to decrease in patients with patients with OAB and DO who have been well treated with antimuscarinics or botulinum toxin injection, but not in those with persistent OAB after treatment. Not all patients with OAB can have an elevated urinary NGF level; it may also be increased in patients with interstitial cystitis/painful bladder syndrome and other lower urinary tract diseases, suggesting urinary NGF expression could be a product of bladder inflammation and a limited specificity of urinary NGF for diagnosing DO. The source of urinary NGF has not yet been fully explored yet. Nevertheless, urinary NGF level is likely to be a promising biomarker for diagnosis of DO from OAB patients, to monitor therapeutic outcome and predict disease progression.