Cystitis Research Today is a free monthly online journal that collates and summarizes the latest research about Cystitis, including details on urinary tract infections, causes, treatment, prevention.

Sesquiterpene lactone parthenolide ameliorates bladder inflammation and bladder overactivity in cyclophosphamide induced rat cystitis model by inhibiting nuclear factor-kappaB phosphorylation.

Kiuchi H, Takao T, Yamamoto K, Nakayama J, Miyagawa Y, Tsujimura A, Nonomura N, Okuyama A

Department of Urology, Osaka University Graduate School of Medicine, Suita, Japan.

PURPOSE: Cyclophosphamide (Sigma) is associated with urological complications, including irritative voiding symptoms and hemorrhagic cystitis. Evidence suggests that tumor necrosis factor-alpha (R&D Systems), interleukin-1beta and cyclooxygenase-2 are directly involved in the pathogenesis of cyclophosphamide induced cystitis and these molecules depend on transcription factor NF-kappaB for maximal secretion. Additionally, sesquiterpene lactone parthenolide has been shown to be a potent nuclear factor-kappaB inhibitor. We hypothesized that enhanced nuclear factor-kappaB activity contributes to cyclophosphamide induced cystitis and, therefore, it may be an attractive target for preventing cyclophosphamide cystitis. We determined whether parthenolide could be used as a preventive agent for hemorrhagic cystitis and bladder overactivity. Moreover, we determined the molecular mechanisms of parthenolide on the inhibitory action of nuclear factor-kappaB in inflammatory human benign urothelial cells. MATERIALS AND METHODS: Rats were pretreated with parthenolide or vehicle solution and administered cyclophosphamide. Histological analysis and cystometry were performed 24 hours after cyclophosphamide administration. Human urothelial cells were pretreated with parthenolide and stimulated with tumor necrosis factor-alpha. Western blotting and immunofluorescence were performed to determine activation of the cyclooxygenase-2 and nuclear factor-kappaB pathway. RESULTS: Parthenolide pretreatment inhibited bladder inflammation as well as bladder overactivity and it was also associated with nuclear factor-kappaB activation in the bladder. Parthenolide dose dependently suppressed tumor necrosis factor-alpha induced cyclooxygenase-2 expression and prevented nuclear factor-kappaB phosphorylation as well as nuclear factor-kappaB nuclear translocation and IkappaBalpha phosphorylation/degradation. CONCLUSIONS: Nuclear factor-kappaB may have a crucial role in the pathogenesis of cyclophosphamide induced cystitis models. Parthenolide ameliorates bladder inflammation and bladder overactivity, and it might be a promising agent for preventing cyclophosphamide induced complications.

Published 13 April 2009 in J Urol, 181(5): 2339-48.
Full-text of this article is available online (may require subscription).

Articles on Cystitis published 13 April 2009:

Tamm-horsfall protein protects against urinary tract infection by proteus mirabilis.   J Urol, 181(5): 2332-8.

PURPOSE: Proteus mirabilis is a common cause of urinary tract infection. We determined the role of Tamm-Horsfall protein as a host defense factor against the cystitis and pyelonephritis caused by P. mirabilis. MATERIALS AND METHODS: We generated Tamm-Horsfall protein gene knockout mice using homologous recombination. We introduced P. mirabilis transurethrally into the bladder of Tamm-Horsfall protein deficient (THP(-/-)) and genetically similar WT (THP(+/+)) mice. We cultured urine to ... [Abstract] [Full-text]

Complications in women undergoing Burch colposuspension versus autologous rectus fascial sling for stress urinary incontinence.   J Urol, 181(5): 2192-7.

PURPOSE: We determined the clinicodemographic factors associated with complications of continence procedures, the impact of concomitant surgery on the complication rate and the relationship between the incidence of cystitis and the method of postoperative bladder drainage. MATERIALS AND METHODS: We reviewed serious adverse events and adverse events in the Stress Incontinence Surgical Efficacy Trial, a randomized trial comparing Burch colposuspension to the autologous rectus fascial sling. ... [Abstract] [Full-text]

Increased startle responses in interstitial cystitis: evidence for central hyperresponsiveness to visceral related threat.   J Urol, 181(5): 2127-33.

PURPOSE: Hypersensitivity to visceral stimuli in interstitial cystitis/painful bladder syndrome may result from enhanced responsiveness of affective circuits (including the amygdala complex) and associated central pain amplification. Potentiation of the eyeblink startle reflex under threat is mediated by output from the amygdala complex and, therefore, represents a noninvasive marker to study group differences in responsiveness in this brain circuit. MATERIALS AND METHODS: Acoustic startle ... [Abstract] [Full-text]

Articles on Cystitis published 6 April 2009:

Is it safe to use aluminum in the treatment of pediatric hemorrhagic cystitis? A case discussion of aluminum intoxication and review of the literature.   J Pediatr Hematol Oncol, 31(4): 285-8.

In pediatric oncology patients, hemorrhagic cystitis can be a life-threatening complication of bone marrow transplantation, chemotherapy, and radiation therapy. The treatment of this condition is often challenging and includes intravesical irrigation with aluminum, embolization, endoscopic laser coagulation, hydrostatic pressure, use of hyperbaric oxygen, instillation of formalin, prostaglandins, and oral sodium pentosan polysulfate. Although the efficacy of aluminum irrigation is well ... [Abstract] [Full-text]

Decreased viral load and symptoms of polyomavirus-associated chronic interstitial cystitis after intravesical cidofovir treatment.   Clin Infect Dis, 48(9): e86-8.

Interstitial cystitis causes disabling bladder pain and is usually diagnosed in the absence of infection. We describe a patient with interstitial cystitis who had high urinary levels of polyomavirus that decreased dramatically after initiation of intravesical cidofovir treatment; the patient also showed substantial improvement in symptoms. Another patient had milder symptoms of cystitis and intermittent polyomavirus shedding. Polyomaviruses, particularly BK virus, may cause some cases of ... [Abstract] [Full-text]

Articles on Cystitis published 2 April 2009:

Abnormal glycosylation of Tamm-Horsfall protein in patients with interstitial cystitis.   BJU Int, 103(8): 1085-9.

OBJECTIVE: To confirm abnormal glycosylation of Tamm-Horsfall protein (THP) in patients with interstitial cystitis (IC). PATIENTS, SUBJECTS AND METHODS: The sialic acid content of THP, a critical component of its biological activity, is reduced in patients with IC. N-glycan shows reduced levels of high molecular weight tri- and tetra-antennary sialylated oligosaccharides. These results are supported by quantitative monosaccharide analysis of neutral and amino sugars in patients vs control ... [Abstract] [Full-text]

Articles on Cystitis published 23 March 2009:

Intravesical alkalinized lidocaine (PSD597) offers sustained relief from symptoms of interstitial cystitis and painful bladder syndrome.   BJU Int, 103(7): 910-8.

OBJECTIVE: To assess the immediate and sustained relief of the symptoms of interstitial cystitis/painful bladder syndrome (IC/PBlS) after a consecutive 5-day course of treatment with intravesical alkalinized lidocaine (PSD597), and to characterize the pharmacokinetics of single and multiple doses of intravesical PSD597 in a subgroup of patients. PATIENTS AND METHODS: In all, 102 adult patients (99 women) with a clinical diagnosis of IC/PBlS were randomized from 19 centres in the USA and Canada ... [Abstract] [Full-text]

Articles on Cystitis published 4 March 2009:

Genetic profiles of fluoroquinolone-resistant Escherichia coli isolates obtained from patients with cystitis: phylogeny, virulence factors, PAIusp subtypes, and mutation patterns.   J Clin Microbiol, 47(3): 791-5.

The low virulence of quinolone- and fluoroquinolone-resistant Escherichia coli strains is known, although the reasons for this remain unclear. We surveyed the mutation patterns of quinolone resistance determining regions (QRDRs), phylogenetic distribution, prevalence of 18 urovirulence genes, and PAIusp subtypes in 89 fluoroquinolone-resistant E. coli (FQREC) isolates obtained from patients with cystitis and compared them with those of their fluoroquinolone-susceptible counterparts (FQSEC). ... [Abstract] [Full-text]

© 2004-2009 Cystitis Research Today. All Rights Reserved.