Rat Model Of Cystitis Research Articles

Effect of eviprostat on bladder overactivity in an experimental cystitis rat model

The purpose of this study was to investigate the effects of eviprostat, a phytotherapeutic drug, on bladder overactivity and inflammation in a cyclophosphamide (CYP)-induced cystitis rat model. Female Sprague-Dawley rats received a single intraperitoneal injection of CYP (200 mg/kg) or saline. After the CYP injection, eviprostat (9, 18 or 54 mg/kg per day) or a vehicle was orally given twice each day. Four days after the CYP injection, bladder function was evaluated by cystometrograms under urethane anesthesia. In a separate group, bladder inflammation was compared between the eviprostat- or vehicle-treated animals. Furthermore, the effects of eviprostat on carbachol-induced muscle contraction were evaluated by an in vitro experiment. The intercontraction interval (ICI) significantly decreased in the CYP-injected rats in comparison to the saline-injected rats. In the CYP-injected group, 18 and 54 mg/kg per day of eviprostat treatment significantly increased the ICI, but did not change the maximum voiding pressure in comparison to the vehicle treatment. In the saline-injected group, no significant changes of any parameters in the cystometrograms were observed between the eviprostat- and vehicle-treated groups. CYP-induced bladder inflammation tended to be lower in the eviprostat-treated group in comparison to the vehicle-treated group. An in vitro experiment revealed that eviprostat failed to inhibit carbachol-induced muscle contraction. The oral administration of eviprostat suppressed CYP-induced bladder overactivity. The effects of eviprostat on the micturition reflex may be irrespective of antimuscarinic action. The present findings raise the possibility that eviprostat could be an effective treatment for bladder overactivity associated with inflammation.

Induction of COX-2 expression by acrolein in the rat model of hemorrhagic cystitis

Aim Acrolein (ACR) is a urinary metabolite of cyclophosphamide (CPS) and ifosfamide (IFS), which has been demonstrated to be the causative agent of hemorrhagic cystitis (HC), induced by these compounds. In this study, we investigate the participation of cyclooxygenase-2 (COX-2) on ACR-induced HC. Methods Male Wistar rats (150–200 g; six rats per group) were treated with distilled water or intravesical ACR and analyzed by changes in bladder wet weight, macroscopic and microscopic parameters and COX-2 expression. Results COX-2 immunohistochemical expression was significant 12 h after ACR administration mainly in subepithelial cells. ACR injection also alters some macroscopic and microscopic parameters in bladder of rats analyzed by Gray's criteria. Conclusions COX-2 participates in the pathogenesis of ACR-induced HC first seen 12 h after initial contact between ACR and urothelium.

Beneficial effects of suplatast tosilate (IPD‐1151T) in a rat cystitis model induced by intravesical hydrochloric acid

To examine the effects of suplatast tosilate (IPD-1151T), a Th2 cytokine inhibitor recently recognized to improve the symptoms in patients with interstitial cystitis (IC), in a rat model of HCl-induced chronic cystitis, to elucidate the possible mechanisms by which the drug improves the symptoms of IC. Chronic cystitis was induced by intravesical instillation of 0.2 mL of 0.4 m HCl in female adult rats. After a once-daily oral administration of IPD-1151T (0.1-100 mg/kg) or prednisolone (5 mg/kg) for 7 days, cystometry was performed under urethane anaesthesia. The bladder from HCl-induced cystitis rats was also assessed histopathologically. On cystometrography there was frequent voiding in cystitis rats. Administration of IPD-1151T for 7 days after intravesical HCl instillation dose-dependently increased the micturition volume and intercontraction intervals. Treatment with prednisolone had similar therapeutic effects. Histological analyses in the bladder from cystitis rats revealed oedema and infiltration of inflammatory cells such as mast cells and eosinophils in the lamina propria and the transitional epithelial thickening. These histological changes and the number of mast cells and eosinophils were reduced by administration of IPD-1151T or prednisolone. The present results indicate that IPD-1151T improves bladder function and pathological changes in HCl-induced cystitis rats, as previously observed in patients with IC. The rat cystitis model induced by HCl could provide useful information for studying proposed therapies for IC which might involve T cell-dependent inflammatory responses as one of its potential pathophysiologies.

260: Dynamic Changes in Glutamate and Serotonin Levels in the Periaqueductal Gray Matter in Acetic Acid-Induced Rat Cystitis Model: An in vivo Microdialysis Study

You have accessJournal of UrologyModerated Poster 9, Sunday, May 20, 2007, 10:00 am - 12:00 pm1 Apr 2007260: Dynamic Changes in Glutamate and Serotonin Levels in the Periaqueductal Gray Matter in Acetic Acid-Induced Rat Cystitis Model: An in vivo Microdialysis Study Takeya Kitta, Hiroshi Tanaka, Hiroshi Sano, Tsuyoshi Furuno, Takahiko Mitsui, Kimihiko Moriya, Machiko Matsumoto, Mitsuhiro Yoshioka, and Katsuya Nonomura Takeya KittaTakeya Kitta More articles by this author , Hiroshi TanakaHiroshi Tanaka More articles by this author , Hiroshi SanoHiroshi Sano More articles by this author , Tsuyoshi FurunoTsuyoshi Furuno More articles by this author , Takahiko MitsuiTakahiko Mitsui More articles by this author , Kimihiko MoriyaKimihiko Moriya More articles by this author , Machiko MatsumotoMachiko Matsumoto More articles by this author , Mitsuhiro YoshiokaMitsuhiro Yoshioka More articles by this author , and Katsuya NonomuraKatsuya Nonomura More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(18)30525-1AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "260: Dynamic Changes in Glutamate and Serotonin Levels in the Periaqueductal Gray Matter in Acetic Acid-Induced Rat Cystitis Model: An in vivo Microdialysis Study." The Journal of Urology, 177(4S), p. 87 © 2016 by American Urological AssociationFiguresReferencesRelatedDetails Volume 177Issue 4SApril 2007Page: 87 Advertisement Copyright & Permissions© 2016 by American Urological AssociationMetricsAuthor Information Takeya Kitta More articles by this author Hiroshi Tanaka More articles by this author Hiroshi Sano More articles by this author Tsuyoshi Furuno More articles by this author Takahiko Mitsui More articles by this author Kimihiko Moriya More articles by this author Machiko Matsumoto More articles by this author Mitsuhiro Yoshioka More articles by this author Katsuya Nonomura More articles by this author Expand All Advertisement PDF DownloadLoading ...

Epinephrine promotes hemostasis in rats with cyclophosphamide-induced hemorrhagic cystitis

Objectives To evaluate the hypothesis that intravesical instillation of epinephrine would attenuate bladder hemorrhage in a rat model of cyclophosphamide (CYP)-induced hemorrhagic cystitis. Methods Female Sprague-Dawley rats were divided into seven treatment groups: positive control (CYP, 150 mg/kg), negative control (epinephrine, 10 μg/mL), intravesical instillation of normal saline (vehicle) and epinephrine (2.5, 5, and 10 μg/mL), and intraperitoneal administration of mesna (50 mg/kg). Rats were killed on days 1, 2, and 3, and the urinary bladders were removed, weighed, and evaluated by gross and histologic analysis. Vesical vascular permeability was determined by wet bladder weight and Evan’s blue dye absorbance. Results Cyclophosphamide administration induced severe hemorrhagic cystitis with marked edema, hemorrhage, and inflammation. All three epinephrine-treated groups had marked attenuation of hemorrhagic cystitis compared with the positive and negative control and mesna-treated groups. Epinephrine was also associated with significant inhibition of tissue edema, indicating decreased vesical vascular permeability. Conclusions In this rat model of CYP-induced hemorrhagic cystitis, intravesical instillation of epinephrine inhibited edema, hemorrhage, and inflammation.

L6‐S1 spinal nerve stimulation reduces micturition frequency in anaesthetized rats with cyclophosphamide‐induced cystitis

To further investigate the rationale for using spinal nerve stimulation (SNS) for treating bladder overactivity associated with cystitis in a rat model of cyclophosphamide-induced cystitis, as several studies suggested that symptoms associated with chronic cystitis could be treated using stimulation of sacral spinal nerves, but the mechanisms by which it works are unknown. Cystitis was induced by i.p. injection of cyclophosphamide 48 h before the experiments in anaesthetized male rats. Neurograms were taken by placing a recording electrode onto the pelvic nerve and a stimulating electrode on either the L6 or S1 ipsilateral spinal nerves. Two selected intensities were then evaluated for SNS in control and cyclophosphamide-treated rats during cystometry. Cyclophosphamide resulted in significant bladder overactivity. There was no apparent difference in the neurograms generated in response to SNS of the S1 and L6 spinal nerves, and between cyclophosphamide and control rats. Intensities of 200 microA (Adelta-fibre-specific) and 2 mA (Adelta+ C-fibres) were chosen for SNS. Continuous SNS at 200 microA significantly reduced the frequency of voiding and non-voiding contractions in cyclophosphamide-treated rats. SNS at 2 mA resulted in the abolition of voiding contractions, accompanied by continuous leakage of urine. SNS recruiting only Adelta-fibre produced fewer voiding contractions in cyclophosphamide-treated rats, to a level similar to that from the control rats. These results support the ability of SNS to decrease bladder overactivity in a pathophysiological model of chemical irritation of the bladder.

The Effect of Botulinum Toxin and Resiniferatoxin on the Detrusor Overactivity Induced by Cyclophosphamide in Rat Bladder

Purpose: The purpose of this study was to compare the effects of resiniferatoxin (RTX) and botulinum toxin (BTX) on the bladder detrusor function in a cyclophosphamide (CYP)-induced cystitis rat model. Materials and Methods: Sprague-Dawley rats were divided into 5 groups (1: saline treated, 2: CYP and BTX treated, 3: CYP and RTX treated, 4 and 5: CYP treated and sham operated as the counterpart of groups 2 and 3, respectively, with normal saline). 100mg/kg CYP was injected every third day for five weeks. Cystometrograms were performed after the BTX and RTX treatments. Results: 1. The normal control group and the CYP-treated only group. In the CYP-treated group, the time of micturition frequency, the maximal detrusor pressure on the cystometergram (Pvesmax at CMG), the maximal detrusor pressure on the pressure-flow study (Pvesmax at pr/flow) and the episodes of irregular contractions were increased. 2. The CYP-only group and the CYP/BTX or CYP/RTXtreated groups. In the CYP/BTX or CYP/RTX treated groups, the time of micturition frequency, the Pvesmax at CMG, the Pvesmax at pr/flow and the episode of irregular contractions were decreased. 3. The CYP/BTXtreated group and the CYP/ RTXtreated group. There was no statistically significant difference between the two groups regarding micturition frequency, the PvesMax at CMG and the PvesMax at pr/flow, the Dhfo and the episodes of involuntary contractions (p>0.05). Conclusions: Intravesical administration of BTX or RTX blocked the CYP-induced detrusor overactivity as was shown by the restoration of the micturition frequency, the intravesical pressure and the involuntary contraction episodes to a control level. There was no statistically significant difference between the two groups regarding the urodynamic parameters. (Korean J Urol 2006;47:47-54)

147: Intra Vesical Admininstration of Antisense Peptide Nucleic Acid Down Regulates Urothelial NGF Expression in Rat Model of Cystitis

You have accessJournal of UrologyDiscussed Poster, Sunday, May 22, 2005, 8:00 am - 12:00 pm1 Apr 2005147: Intra Vesical Admininstration of Antisense Peptide Nucleic Acid Down Regulates Urothelial NGF Expression in Rat Model of Cystitis Pradeep Tyagi, Michael B. Chancellor, Naoki Yoshimura, and Leaf Huang Pradeep TyagiPradeep Tyagi More articles by this author , Michael B. ChancellorMichael B. Chancellor More articles by this author , Naoki YoshimuraNaoki Yoshimura More articles by this author , and Leaf HuangLeaf Huang More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(18)34412-4AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "147: Intra Vesical Admininstration of Antisense Peptide Nucleic Acid Down Regulates Urothelial NGF Expression in Rat Model of Cystitis." The Journal of Urology, 173(4S), p. 40 © 2016 by American Urological AssociationFiguresReferencesRelatedDetails Volume 173Issue 4SApril 2005Page: 40 Advertisement Copyright & Permissions© 2016 by American Urological AssociationMetricsAuthor Information Pradeep Tyagi More articles by this author Michael B. Chancellor More articles by this author Naoki Yoshimura More articles by this author Leaf Huang More articles by this author Expand All Advertisement PDF downloadLoading ...

Sustained intravesical drug delivery using thermosensitive hydrogel.

Direct instillation of drug solutions into the bladder through a urethral catheter (i.e., intravesical therapy) evades systemic adverse effects of drugs used for bladder diseases. However, conventional vehicles for these drugs fail to extend duration of drug exposure in the bladder beyond the first voiding of urine postinstillation. The current study seeks to overcome the aforementioned inherent limitation of intravesical drug administration by using thermosensitive hydrogel as a matrix for sustained intravesical drug delivery. Under halothane anesthesia, normal adult female Sprague-Dawley rats were catheterized with PE-50 tubing to instill either 0.02% w/v solution of fluorescein isothiocyanate (FITC) or the same amount of FITC in a 30% w/v dispersion of thermosensitive [Poly(ethylene glycol)-Poly[lactic acid-co-glycolic acid]-Poly(ethylene glycol)) (PEG-PLGA-PEG) polymer in a 0.1 M phosphate buffer. After instillations, rats were kept in metabolic cages for urine collection. Fluorescence emanating from FITC was measured in the urine at various time points up to 24 h after instillation. A rat model of cyclophosphamide-induced cystitis was chosen for the efficacy study using misoprostol as a model drug entrapped in the thermosensitive hydrogel in place of FITC. Efficacy of hydrogel containing misoprostol was compared against rat groups instilled with saline, hydrogel, and misoprostol independently. Prolonged drug exposure to the bladder afforded by hydrogel was evident from the time course of FITC elimination in the urine and by the green fluorescence of FITC seen at the bladder surface when isolated 24 h after instillation. Rats instilled with free FITC voided almost all of the fluorescence in the urine within the first 8 h, whereas rats instilled with hydrogel encapsulated FITC showed sustained release up to 24 h after instillation. Using a cyclophosphamide-induced cystitis model, rats instilled with misoprostol, a synthetic PGE1 analog, showed significantly reduced frequency of urine voiding (p < 0.05) as compared to the rats instilled with saline. Histological examination of the urothelium showed near normal morphology in rats instilled with misoprostol in hydrogel, whereas extensive tissue damage was observed in rats instilled with saline. Our study showed that PEG-PLGA-PEG polymer could be used as a viable sustained drug delivery system for intravesical therapy of diseases of the bladder such as cystitis using misoprostol.

Targeting afferent hyperexcitability for therapy of the painful bladder syndrome

The involvement of C-fiber afferent pathways in urinary frequency and pain associated with painful bladder syndrome raises the possibility of multiple targets for the treatment of this disease. Using an in vivo measurement of bladder activity as well as whole-cell patch clamp recording techniques to examine the properties of bladder afferent neurons in animal models of chronic cystitis, we have documented that tetrodotoxin-resistant sodium channels encoded by the Na v 1.8 (PN3/SNS) gene and nitric oxide acting via a cyclic guanosine monophosphate (cGMP)-dependent mechanism are important in modulating bladder pain responses. Thus, suppression of C-fiber afferent nerve activity by blocking specific sodium channels, elevating nitric oxide levels, or activating cGMP-dependent pathways might represent novel strategies for the treatment of symptoms in patients with painful bladder syndrome. Another treatment strategy is suppression of release or activity of proinflammatory agents that can cause normally unexcitable C-fiber afferents to become hyperactive or hyperexcitable. This approach to management of bladder pain was tested in patients with painful bladder syndrome by examining the effectiveness of the antiallergic agent suplatast tosilate (IPD-1151T), which suppresses urinary frequency in a rat model of cystitis. IPD-1151T is an immunoregulator that suppresses cytokine production in T-helper 2 cells and inhibits immunoglobulin E antibody formation and antigen-induced histamine release from mast cells. Preliminary data from an open-label clinical trial showed that 16 of 23 (70%) patients responded to treatment with IPD-1151T (300 mg/day orally for 12 months). The finding that expression of platelet-derived endothelial cell growth factor, which can activate mast cells, was lower in the bladder of responders than nonresponders indicates that bladder levels of platelet-derived endothelial cell growth factor may be a useful marker for this disease.

EFFECTS OF THE NUCLEAR FACTOR-κB INHIBITORS 2-HYDROXY-4-TRIFLUOROMETHYLBENZOIC ACID AND ASPIRIN ON MICTURITION IN RATS WITH NORMAL AND INFLAMED BLADDER

We examined the effects of intravenous administration of the 2 nuclear factor-kappaB inhibitors aspirin and 2-hydroxy-4-trifluoromethylbenzoic acid (HTB) on bladder filling and voiding in anesthetized and conscious rats. Disappearance of isovolumic bladder contractions after intravenous administration of different doses of aspirin and HTB in anesthetized, transurethrally catheterized rats was evaluated. Cystometry was performed in conscious rats during bladder infusion with saline or diluted acetic acid as well as in those with cyclophosphamide induced cystitis. Changes in bladder capacity and voiding pressure were evaluated after intravenous administration of test compounds. Aspirin induced a dose dependent disappearance of isovolumic bladder contractions in anesthetized rats with an extrapolated dose of 2.1 mg./kg. inducing 10 minutes of bladder quiescence. HTB was practically inactive, inducing a dose independent block of 3 to 4 minutes after intravenous administration of 1 to 10 mg./kg. In conscious rats with a bladder infused with saline aspirin was poorly active on bladder capacity, inducing a 20% increase 60 minutes after intravenous administration of 30 and 100 mg./kg. In rats with a bladder infused with acetic acid aspirin was much more active when injected at the initiation of inflammation and after 1 hour of irritant infusion. In this latter situation aspirin increased bladder capacity up to 60% after intravenous administration of 30 and 100 mg./kg. Similar results were obtained in rats with cyclophosphamide induced cystitis in which the bladder was infused with saline. In these cystometrography models 30 mg./kg. HTB intravenously was completely inactive. The results show that HTB is devoid of significant effects on the micturition reflex in the absence or presence of bladder inflammation, suggesting that acute inhibition of nuclear factor-kappaB does not influence bladder urodynamics in rats. In contrast, aspirin, which is a cyclooxygenase and nuclear factor-kappaB inhibitor, was always effective, indicating the important role of cyclooxygenase enzymes.

Peripheral changes and neuropathic pain after chronic trigeminal nerve injuries

The involvement of C-fiber afferent pathways in urinary frequency and pain associated with painful bladder syndrome raises the possibility of multiple targets for the treatment of this disease. Using an in vivo measurement of bladder activity as well as whole-cell patch clamp recording techniques to examine the properties of bladder afferent neurons in animal models of chronic cystitis, we have documented that tetrodotoxin-resistant sodium channels encoded by the Nav 1.8 (PN3/SNS) gene and nitric oxide acting via a cyclic guanosine monophosphate (cGMP)-dependent mechanism are important in modulating bladder pain responses. Thus, suppression of C-fiber afferent nerve activity by blocking specific sodium channels, elevating nitric oxide levels, or activating cGMP-dependent pathways might represent novel strategies for the treatment of symptoms in patients with painful bladder syndrome. Another treatment strategy is suppression of release or activity of proinflammatory agents that can cause normally unexcitable C-fiber afferents to become hyperactive or hyperexcitable. This approach to management of bladder pain was tested in patients with painful bladder syndrome by examining the effectiveness of the antiallergic agent suplatast tosilate (IPD-1151T), which suppresses urinary frequency in a rat model of cystitis. IPD-1151T is an immunoregulator that suppresses cytokine production in T-helper 2 cells and inhibits immunoglobulin E antibody formation and antigen-induced histamine release from mast cells. Preliminary data from an open-label clinical trial showed that 16 of 23 (70%) patients responded to treatment with IPD-1151T (300 mg/day orally for 12 months). The finding that expression of platelet-derived endothelial cell growth factor, which can activate mast cells, was lower in the bladder of responders than nonresponders indicates that bladder levels of platelet-derived endothelial cell growth factor may be a useful marker for this disease.

The role of nerve growth factor in a model of visceral inflammation

There is growing evidence that nerve growth factor may be an important mediator of the sensory disorders associated with inflammation. This hypothesis was tested in a rat model of cystitis. In this model, an experimental inflammation is created in anaesthetized rats with an irritant chemical. Within 1 h, bladder reflexes, activated by the sensory innervation of this viscus, become exaggerated, mimicking the disorders seen in humans with chronic cystitis. The development of this hyper-reflexia following experimental inflammation was quantified using the technique of repeated cystometrograms. By several measures, bladder reflex excitability increased about three-fold after 5 h. Firstly, the study investigated whether inflammatory changes can be prevented by pharmacological antagonism of nerve growth factor. A synthetic fusion protein was used, consisting of the extracelluar domain of the high-affinity nerve growth factor receptor, trkA, coupled to the Fc portion of an immunoglobulin. Previous work has shown that this molecule can sequester nerve growth factor and reduce its bioavailability both in vitro and in vivo. Treatment of animals with the fusion molecule at 1 mg/kg, immediately before inflammation of the bladder, largely, and very significantly, prevented the expected increases in reflex excitability of this organ. Pretreatment with a related fusion protein, capable of sequestering neurotrophin brain-derived neurotrophic factor and neurotrophin-4/5, but not nerve growth factor, was without effect. Similarly, a control fusion molecule, without neurotrophin-sequestering capacity, did not reduce the inflammation-induced hyper-reflexia. Systemic treatment with the nerve growth factor-sequestering molecule, but not control molecules, partially and significantly reversed established inflammatory changes, by about 30–60%, depending on outcome measure. The nerve growth factor-sequestering protein had no significant effects on bladder reflex excitability in the uninflamed state. It was also without significant effect on capsaicin-induced contractions of the urinary bladder. Administration of exogenous nerve growth factor into the lumen of the urinary bladders of normal anaesthetized rats produced a rapid and marked bladder hyper-reflexia similar to that seen with experimental inflammation. These findings are consistent with other circumstantial evidence that nerve growth factor may interact with visceral sensory systems. Together, the data strongly suggest that nerve growth factor produced in inflamed tissues is a critical mediator of the sensory disorders associated with inflammation.

Effect of Bradykinin and Tachykinin Receptor Antagonist on Xylene-Induced Cystitis in Rats

The effects of the bradykinin receptor selective antagonist, Hoe 140, and of the tachykinin NK-1 receptor antagonist (±)CP 96,345 were investigated in a rat model of chemically-induced cystitis (intravesical instillation of xylene in female rats). Intravenous injection of bradykinin (1μmol./kg.) or substance P (3nmol./kg.) produced plasma protein extravasation (PPE) in the rat urinary bladder. Bradykinin response was prevented by Hoe 140 (100nmol./kg. intravenously) and unaffected by (±)CP 96,345 (10μmol./kg. intravenously). Plasma protein extravasation produced by substance P was inhibited by (±)CP 96,345 but unchanged by Hoe 140. Catheterization required for intravesical xylene instillation into the female rat bladder produced per se an inflammatory response which was abolished by either Hoe 140 or (±)CP 96,345. Intravesical instillation of xylene produced a large PPE response which was reduced by about 65% by Hoe 140 or (±)CP 96,345. Combined administration of the two antagonists produced an additive effect on the PPE response to xylene. We conclude that both bradykinin and tachykinins are involved in the inflammatory reaction of the rat urinary bladder to catheterization and xylene irritation.

Receptor-binding function of type 1 pili effects bladder colonization by a clinical isolate of Escherichia coli.

The role of type 1 pili in promoting bladder colonization was examined by constructing two mutant strains of a clinical Escherichia coli isolate. One mutant was isogenic to the parental strain save for a lesion in a gene required for pilus receptor binding; the other mutant was isogenic save for a lesion in the gene encoding the pilus structural subunit. Using mixed infections of the parental and mutant strains in an ascending rat cystitis model, we found that type 1-piliated mutants that lacked the receptor-binding function were as ineffective in bladder colonization as were mutants lacking the entire organelle.

Effect of piliation on Klebsiella pneumoniae infection in rat bladders.

The possible role of pili in the pathogenesis of urinary tract infection caused by Klebsiella pneumoniae was investigated in a rat model of cystitis by utilizing piliated- and nonpiliated-phase organisms derived from a single parent strain. Bladder surfaces were examined for evidence of infection by scanning electron microscopy. In animals infected with piliated-phase organisms, foci of infection were evident in the majority of bladders examined. Rat bladders associated with nonpiliated-phase bacteria showed little evidence of infection. The ability of methyl-D-mannoside, a known inhibitor of pilus-mediated adherence to mammalian cells, to protect the bladder surface from colonization was also tested. The results showed a significant decrease in the ability of piliated-phase K. pneumoniae to establish infection in bladders. These observations suggest that pili may play an integral role in the ability of K. pneumoniae to cause urinary tract infections by mediating the attachment of the bacteria to the uroepithelial surface.