dinoprost and Cystitis

The cyclophosphamide-induced hemorrhagic cystitis (CP-HC) is a common consequence of cyclophosphamide treatment with complex pathophysiology involving several inflammatory mechanisms and autonomic nervous system dysregulation.. To determine effects of prostaglandin PGE1 and PGF2alpha analogues on the activity of the autonomic nervous system (ANS), estimatedindirectly on the basis of heart rate variability (HRV), in an experimental model of cyclophosphamide-induced hemorrhagic cystitis (CP-HC). Moreover we verified if potential changes in autonomic regulation can contribute to uroprotective role of prostaglandins.. The study included three groups of rats with experimentally induced CP-HC. The animals from group 2 and 3 were administered PGE1 and PGF2a analogues, respectively, and the rats from group 1 (controls) did not receive any treatment. The HRV of animals from all the groups was analyzed after seven days of the experiment.. Administration of both PGF2alpha and PGE1 was associated with an increase in the power of VLF component and total power on frequency-domain analysis. Moreover, a significant increase in the power of non-normalized components, LH and HF, and two parameters of time-domain analysis, SDN-N and rMSSD, was documented in PGF2alpha-administered animals. Both prostaglandin-treated groups did not differ significantly from the controls in terms of the values of normalized parameters, nLF and nHF.. The analyzed prostaglandin analogues increased total autonomic activity but did not induced preferential changes in sympathetic or parasympathetic activity. Nevertheless, the VLF changes documented on HRV analysis may reflect a decrease in the level of certain pro-inflammatory mediators, thus pointing to, previously postulated in literature, potential beneficial uroprotective effect of prostaglandins in CP-HC.

Topics: Alprostadil; Animals; Autonomic Nervous System; Cyclophosphamide; Cystitis; Dinoprost; Female; Heart Rate; Hemorrhage; Rats; Rats, Wistar

To investigate the release of inflammatory mediators by the urinary bladder in response to exposure to pro-inflammatory peptides.. Isolated guinea pig urinary bladder was incubated with 10 mumol/L each of substance P (SP), neurokinin A (NKA), calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP), octreotide acetate (a long-acting analogue of somatostatin, SOM), or bradykinin (BK), and the release of histamine, prostaglandin (PG) E2, PGF2 alpha and leukotriene B4 (LTB4) was determined during 0-5, 5-30 and 30-120 min after addition.. Substance P, NKA, VIP and BK stimulated the release of histamine, while CGRP and SOM suppressed the release to below the spontaneous rates. All peptides, except CGRP and SOM, stimulated the release of PGE2 between 0 and 30 min, and only VIP failed to stimulate the release of PGF2 alpha within 5 min of exposure. Substance P, NKA, VIP and BK stimulated the release of LTB4 and this required > 5 min of exposure.. These results indicate that the peptides evaluated induce an immediate and transient release of histamine and activation of cyclooxygenase and delayed activation of 5-lipoxygenase. These actions may directly regulate the participation of these peptides in the pathogenesis of cystitis.

Topics: Animals; Bradykinin; Cystitis; Dinoprost; Dinoprostone; Female; Guinea Pigs; Histamine; Inflammation Mediators; Leukotriene B4; Peptides; Somatostatin; Substance P

The treatment of cyclophosphamide-induced hemorrhagic cystitis is difficult. We report a successful case of severe cyclophosphamide-induced hemorrhagic cystitis treated with intravesical instillation of prostaglandin F2 alpha. A 32-year-old woman underwent high-dose cyclophosphamide conditioning before the autologous bone marrow transplantation. She developed clot retention which required continuous irrigation with normal saline. The patient had failed to respond to continuous bladder irrigation with saline and intravesical administration of 1% alum. Fifty ml of prostaglandin F2 alpha solution (1 mg in 100 ml normal saline) was instilled into the bladder, with a dwelling time of 60 minutes, three times a day for 5 days. The hematuria cleared completely 3 days after therapy. The only adverse effect was bladder spasm which was controlled with oxybutynin chloride. The success of this therapy suggests that prostaglandin F2 alpha is a safe and useful therapy for hemorrhagic cystitis secondary to cyclophosphamide chemotherapy.

Topics: Administration, Intravesical; Adult; Cyclophosphamide; Cystitis; Dinoprost; Female; Hemorrhage; Humans

It is well-established that cystitis is a significant cause of morbidity after cyclophosphamide administration in clinical populations. We induced hemorrhagic cystitis in rats using cyclophosphamide and compared controls to those pretreated with prostaglandin F2 alpha. Rats were then evaluated for differences in bladder weights, gross edema, gross bleeding, and histologic changes. The weights of the bladders which had been treated with cyclophosphamide were 94% greater than the controls. The weights of the bladders which were pretreated with prostaglandin F2 alpha before cyclophosphamide were only 19% greater than controls. Significant differences were found between cyclophosphamide controls and prostaglandin F2 alpha pretreated groups for gross weight (p less than .0005), gross edema (p less than .0005), and histology (.0005 less than p less than .005). We conclude that prostaglandin F2 alpha may be helpful in preventing cyclophosphamide induced cystitis.

Topics: Animals; Cyclophosphamide; Cystitis; Dinoprost; Female; Pilot Projects; Premedication; Rats; Rats, Inbred Strains; Urinary Bladder

Topics: Cystitis; Dinoprost; Hemorrhage; Humans

We report a case of intractable cyclophosphamide-induced hemorrhagic cystitis. Conservative therapy, including suprapubic cystostomy with through-and-through bladder irrigation, failed to slow the bleeding. We then instilled 200 cc of a 0.7 mg. per cent solution of prostaglandin F2-alpha into the bladder for 4 hours daily. The bleeding ceased completely by the end of treatment 5 and the patient remains free of hematuria. There were no side effects noted during the 5 days of treatment. This form of therapy offers an effective, safe and easy alternative to more caustic bladder irrigants and methods of treatment.

Topics: Administration, Intravesical; Cryoglobulinemia; Cyclophosphamide; Cystitis; Dinoprost; Humans; Male; Middle Aged; Prostaglandins F; Therapeutic Irrigation