Skip to main content
Erschienen in: Current Bladder Dysfunction Reports 4/2020

04.11.2020 | Voiding Dysfunction Evaluation (B Brucker and B Peyronnet, Section Editors)

Assessing In Vivo Bladder Urothelial Hyper-Permeability: Preclinical and Clinical Implications

verfasst von: Rheal A. Towner, Debra Saunders, Nataliya Smith

Erschienen in: Current Bladder Dysfunction Reports | Ausgabe 4/2020

Einloggen, um Zugang zu erhalten

Abstract

Purpose of Review

To provide an update on the detection and evaluation of bladder hyper-permeability related to interstitial cystitis/painful bladder syndrome (IC/PBS) and inflammatory bowel disorders (e.g., inflammatory bowel syndrome).

Recent Findings

We developed a contrast-enhanced magnetic resonance imaging (CE-MRI) approach to assess in vivo bladder hyper-permeability by instilling a MRI contrast agent, Gd-DTPA (gadolinium diethylenetriamine pentaacetic acid), by intravesical injection through a catheter into the bladder. Molecular-targeted MRI (mt-MRI) was also used to assess in vivo bladder hyper-permeability-associated biomarker expressions (e.g., claudin-2, vascular endothelial growth factor receptor-1, and decorin) in preclinical models. An example of evaluating the effect of a therapy against bladder hyper-permeability is also discussed.

Summary

The CE-MRI approach to detect in vivo bladder hyper-permeability not only serves as a measure of disease severity for IC/PBS and cross-talk complications associated with IBS but also be used to monitor therapeutic response.
Literatur
1.
Zurück zum Zitat • Daniels AM, Schulte AR, Herndon CM. Interstitial cystitis: an update on the disease process and treatment. J Pain Palliat Care Pharmacother. 2018;32(1):49–58 Recent review regarding interstitial cystitis.CrossRef • Daniels AM, Schulte AR, Herndon CM. Interstitial cystitis: an update on the disease process and treatment. J Pain Palliat Care Pharmacother. 2018;32(1):49–58 Recent review regarding interstitial cystitis.CrossRef
2.
Zurück zum Zitat Patnaik SS, Laganà AS, Vitale SG, Butticè S, Noventa M, Gizzo S, et al. Etiology, pathophysiology and biomarkers of interstitial cystitis/painful bladder syndrome. Arch Gynecol Obstet. 2017;295(6):1341–59.CrossRef Patnaik SS, Laganà AS, Vitale SG, Butticè S, Noventa M, Gizzo S, et al. Etiology, pathophysiology and biomarkers of interstitial cystitis/painful bladder syndrome. Arch Gynecol Obstet. 2017;295(6):1341–59.CrossRef
3.
Zurück zum Zitat Belknap S, Blalock E, Erickson D. The challenges of interstitial cystitis: current status and future prospects. Drugs. 2015;75(18):2057–63.CrossRef Belknap S, Blalock E, Erickson D. The challenges of interstitial cystitis: current status and future prospects. Drugs. 2015;75(18):2057–63.CrossRef
4.
Zurück zum Zitat Hurst RE, Greenwood-Van Meerveld B, Wisniewski AB, VanGordon S, Lin H, Kropp BP, et al. Increased bladder permeability in interstitial cystitis/painful bladder syndrome. Transl Androl Urol. 2015;4(5):563–71.PubMedPubMedCentral Hurst RE, Greenwood-Van Meerveld B, Wisniewski AB, VanGordon S, Lin H, Kropp BP, et al. Increased bladder permeability in interstitial cystitis/painful bladder syndrome. Transl Androl Urol. 2015;4(5):563–71.PubMedPubMedCentral
5.
Zurück zum Zitat Rooney P, Srivastava A, Watson L, Quinlan LR, Pandit A. Hyaluronic acid decreases IL-6 and IL-8 secretion and permeability in an inflammatory model of interstitial cystitis. Acta Biomater. 2015;19:66–75.CrossRef Rooney P, Srivastava A, Watson L, Quinlan LR, Pandit A. Hyaluronic acid decreases IL-6 and IL-8 secretion and permeability in an inflammatory model of interstitial cystitis. Acta Biomater. 2015;19:66–75.CrossRef
6.
Zurück zum Zitat Montalbetti N, Rued AC, Clayton DR, Ruiz WG, Bastacky SI, Prakasam HS, et al. Increased urothelial paracellular transport promotes cystitis. Am J Physiol Ren Physiol. 2015;309(12):F1070–81.CrossRef Montalbetti N, Rued AC, Clayton DR, Ruiz WG, Bastacky SI, Prakasam HS, et al. Increased urothelial paracellular transport promotes cystitis. Am J Physiol Ren Physiol. 2015;309(12):F1070–81.CrossRef
7.
Zurück zum Zitat Towner RA, Smith N, Saunders D, Van Gordon SB, Wisniewski AB, Tyler KR, et al. Contrast enhanced magnetic resonance imaging as a diagnostic tool to assess bladder permeability and associated colon cross talk: preclinical studies in a rat model. J Urol. 2015;193(4):1394–400.CrossRef Towner RA, Smith N, Saunders D, Van Gordon SB, Wisniewski AB, Tyler KR, et al. Contrast enhanced magnetic resonance imaging as a diagnostic tool to assess bladder permeability and associated colon cross talk: preclinical studies in a rat model. J Urol. 2015;193(4):1394–400.CrossRef
8.
Zurück zum Zitat Towner RA, Smith N, Saunders D, Van Gordon SB, Tyler KR, Wisniewski AB, et al. Assessment of colon and bladder crosstalk in an experimental colitis model using contrast-enhanced magnetic resonance imaging. Neurogastroenterol Motil. 2015;27(11):1571–9.CrossRef Towner RA, Smith N, Saunders D, Van Gordon SB, Tyler KR, Wisniewski AB, et al. Assessment of colon and bladder crosstalk in an experimental colitis model using contrast-enhanced magnetic resonance imaging. Neurogastroenterol Motil. 2015;27(11):1571–9.CrossRef
9.
Zurück zum Zitat • Daniele P, Cesare R, Bright OH, Nicolo F, Barbara G, Federica M, et al. Role of diffusion-weighted magnetic resonance imaging in the diagnosis of bladder pain syndrome/interstitial cystitis. Urology. 2020;141:55–9 This article indicates the importance of using diffusion-weighted imaging (DWeI) as an additional diagnostic tool for interstitial cystitis.CrossRef • Daniele P, Cesare R, Bright OH, Nicolo F, Barbara G, Federica M, et al. Role of diffusion-weighted magnetic resonance imaging in the diagnosis of bladder pain syndrome/interstitial cystitis. Urology. 2020;141:55–9 This article indicates the importance of using diffusion-weighted imaging (DWeI) as an additional diagnostic tool for interstitial cystitis.CrossRef
10.
Zurück zum Zitat • Charlanes A, Boudghene F, Chesnel C, Ciofu C, Le Breton F, Jousse M, et al. Diffusion-weighted magnetic resonance imaging: a new tool for the diagnosis of bladder pain syndrome/interstitial cystitis. Urol Int. 2019;102(1):109–12 This article indicates the importance of using diffusion-weighted imaging (DWI) as an additional diagnostic tool for interstitial cystitis.CrossRef • Charlanes A, Boudghene F, Chesnel C, Ciofu C, Le Breton F, Jousse M, et al. Diffusion-weighted magnetic resonance imaging: a new tool for the diagnosis of bladder pain syndrome/interstitial cystitis. Urol Int. 2019;102(1):109–12 This article indicates the importance of using diffusion-weighted imaging (DWI) as an additional diagnostic tool for interstitial cystitis.CrossRef
11.
Zurück zum Zitat Towner RA, Wisniewski AB, Wu DH, Van Gordon SB, Smith N, North JC, et al. A feasibility study to determine whether clinical contrast enhanced magnetic resonance imaging can detect increased bladder permeability in patients with interstitial cystitis. J Urol. 2016;195(3):631–8.CrossRef Towner RA, Wisniewski AB, Wu DH, Van Gordon SB, Smith N, North JC, et al. A feasibility study to determine whether clinical contrast enhanced magnetic resonance imaging can detect increased bladder permeability in patients with interstitial cystitis. J Urol. 2016;195(3):631–8.CrossRef
12.
Zurück zum Zitat •• Towner RA, Smith N, Saunders D, Lerner M, Greenwood-Van Meerveld B. Hurst RE. Assessing bladder hyper-permeability biomarkers in vivo using molecularly-targeted MRI. Am J Nuc Med Mol Imaging. 2020;10(1):57–65 This article provides in-depth description of a molecular-targeted approach to visualize bladder hyper-permeability markers in vivo with MRI. •• Towner RA, Smith N, Saunders D, Lerner M, Greenwood-Van Meerveld B. Hurst RE. Assessing bladder hyper-permeability biomarkers in vivo using molecularly-targeted MRI. Am J Nuc Med Mol Imaging. 2020;10(1):57–65 This article provides in-depth description of a molecular-targeted approach to visualize bladder hyper-permeability markers in vivo with MRI.
13.
Zurück zum Zitat Hauser PJ, Van Gordon SB, Seavey J, Sofinowski TM, Ramadan M, Abdullah S, et al. Abnormalities in expression of structural, barrier and differentiation related proteins, and chondroitin sulfate in feline and human interstitial cystitis. J Urol. 2015;194:571–7.CrossRef Hauser PJ, Van Gordon SB, Seavey J, Sofinowski TM, Ramadan M, Abdullah S, et al. Abnormalities in expression of structural, barrier and differentiation related proteins, and chondroitin sulfate in feline and human interstitial cystitis. J Urol. 2015;194:571–7.CrossRef
14.
Zurück zum Zitat Lucon M, Martins JR, Leite KR, Soler R, Nader HB, Srougi M, et al. Evaluation of the metabolism of glycosaminoglycans in patients with interstitial cystitis. Int Braz J Urol. 2014;40:72–9.CrossRef Lucon M, Martins JR, Leite KR, Soler R, Nader HB, Srougi M, et al. Evaluation of the metabolism of glycosaminoglycans in patients with interstitial cystitis. Int Braz J Urol. 2014;40:72–9.CrossRef
15.
Zurück zum Zitat Saban R, Saban MR, Maier J, Fowler B, Tengowski M, Davis CA, et al. Urothelial expression of neuropilins and VEGF receptors in control and interstitial cystitis patients. Am J Physiol Ren Physiol. 2008;295:F1613–23.CrossRef Saban R, Saban MR, Maier J, Fowler B, Tengowski M, Davis CA, et al. Urothelial expression of neuropilins and VEGF receptors in control and interstitial cystitis patients. Am J Physiol Ren Physiol. 2008;295:F1613–23.CrossRef
16.
Zurück zum Zitat Saban MR, Davis CA, Avelino A, Cruz F, Maier J, Bjorling DE, et al. VEGF signaling mediates bladder neuroplasticity and inflammation in response to BCG. BMC Physiol. 2011;11:16.CrossRef Saban MR, Davis CA, Avelino A, Cruz F, Maier J, Bjorling DE, et al. VEGF signaling mediates bladder neuroplasticity and inflammation in response to BCG. BMC Physiol. 2011;11:16.CrossRef
17.
Zurück zum Zitat Hurst RE, Moldwin RM, Mulholland SG. Bladder defense molecules, urothelial differentiation, urinary biomarkers, and interstitial cystitis. Urology. 2007;69:17–23.CrossRef Hurst RE, Moldwin RM, Mulholland SG. Bladder defense molecules, urothelial differentiation, urinary biomarkers, and interstitial cystitis. Urology. 2007;69:17–23.CrossRef
18.
Zurück zum Zitat Slobodov G, Feloney M, Gran C, Kyker KD, Hurst RE, Culkin DJ. Abnormal expression of molecular markers for bladder impermeability and differentiation in the urothelium of patients with interstitial cystitis. J Urol. 2004;171:1554–8.CrossRef Slobodov G, Feloney M, Gran C, Kyker KD, Hurst RE, Culkin DJ. Abnormal expression of molecular markers for bladder impermeability and differentiation in the urothelium of patients with interstitial cystitis. J Urol. 2004;171:1554–8.CrossRef
19.
Zurück zum Zitat Burgu B, McCarthy LS, Shah V, Long DA, Wilcox DT, Woolf AS. Vascular endothelial growth factor stimulates embryonic urinary bladder development in organ culture. BJU Int. 2006;98:217–25.CrossRef Burgu B, McCarthy LS, Shah V, Long DA, Wilcox DT, Woolf AS. Vascular endothelial growth factor stimulates embryonic urinary bladder development in organ culture. BJU Int. 2006;98:217–25.CrossRef
20.
Zurück zum Zitat Saban R. Angiogenic factors, bladder neuroplasticity and interstitial cystitis-new pathobiological insights. Transl Androl Urol. 2015;4(5):555–62.PubMedPubMedCentral Saban R. Angiogenic factors, bladder neuroplasticity and interstitial cystitis-new pathobiological insights. Transl Androl Urol. 2015;4(5):555–62.PubMedPubMedCentral
21.
Zurück zum Zitat • Montalbetti N, Rooney JG, Rued AC, Carattino MD. Molecular determinants of afferent sensitization in a rat model of cystitis with urotelial barrier dysfunction. J Neurophysiol. 2019;122:1136–46 This article describes the role of claudin-2 in bladder hyper-permeability.CrossRef • Montalbetti N, Rooney JG, Rued AC, Carattino MD. Molecular determinants of afferent sensitization in a rat model of cystitis with urotelial barrier dysfunction. J Neurophysiol. 2019;122:1136–46 This article describes the role of claudin-2 in bladder hyper-permeability.CrossRef
22.
Zurück zum Zitat • Montalbetti N, Stocker SD, Apodaca G, Bastacky SI, Carattino MD. Urinary K+ promotes irritative voiding symptoms and pain in the face of urothelial barrier dysfunction. Sci Rep. 2019;9:5509 This article describes the role of claudin-2 in bladder hyper-permeability.CrossRef • Montalbetti N, Stocker SD, Apodaca G, Bastacky SI, Carattino MD. Urinary K+ promotes irritative voiding symptoms and pain in the face of urothelial barrier dysfunction. Sci Rep. 2019;9:5509 This article describes the role of claudin-2 in bladder hyper-permeability.CrossRef
23.
Zurück zum Zitat Montalbetti N, Rued AC, Taiclet SN, Birder LA, Kullmann FA, Carattino MD. Urothelial tight junction barrier dysfunction sensitizes bladder afferents. eNeuro. 2017;4:ENEURO.0381–16.2017.CrossRef Montalbetti N, Rued AC, Taiclet SN, Birder LA, Kullmann FA, Carattino MD. Urothelial tight junction barrier dysfunction sensitizes bladder afferents. eNeuro. 2017;4:ENEURO.0381–16.2017.CrossRef
24.
Zurück zum Zitat •• Greenwood-Van Meerveld B, Mohammadi E, Latorre R, Truitt ER 3rd, Jay GD, Sullivan BD, et al. Preclinical animal studies of Intravesical recombinant human proteoglycan 4 as a novel potential therapy for diseases resulting from increased bladder permeability. Urology. 2018;116:230.e1–7 This article describes the use of contrast-enhanced MRI as an approach to assess a therapy for bladder hyper-permeability.CrossRef •• Greenwood-Van Meerveld B, Mohammadi E, Latorre R, Truitt ER 3rd, Jay GD, Sullivan BD, et al. Preclinical animal studies of Intravesical recombinant human proteoglycan 4 as a novel potential therapy for diseases resulting from increased bladder permeability. Urology. 2018;116:230.e1–7 This article describes the use of contrast-enhanced MRI as an approach to assess a therapy for bladder hyper-permeability.CrossRef
Metadaten
Titel
Assessing In Vivo Bladder Urothelial Hyper-Permeability: Preclinical and Clinical Implications
verfasst von
Rheal A. Towner
Debra Saunders
Nataliya Smith
Publikationsdatum
04.11.2020
Verlag
Springer US
Erschienen in
Current Bladder Dysfunction Reports / Ausgabe 4/2020
Print ISSN: 1931-7212
Elektronische ISSN: 1931-7220
DOI
https://doi.org/10.1007/s11884-020-00616-x

Weitere Artikel der Ausgabe 4/2020

Current Bladder Dysfunction Reports 4/2020 Zur Ausgabe

Inflammatory/Infectious Bladder Disorders (MS Mourad, Section Editor)

Vaginal Yeast Infection

Reconstructed Bladder Function & Dysfunction (M Kaufman, Section Editor)

Management of Pelvic Floor Disorders in Young Women

Reconstructed Bladder Function & Dysfunction (M Kaufman, Section Editor)

Antibiotic Prophylaxis in Pelvic Floor Surgery

Adjuvante Immuntherapie verlängert Leben bei RCC

25.04.2024 Nierenkarzinom Nachrichten

Nun gibt es auch Resultate zum Gesamtüberleben: Eine adjuvante Pembrolizumab-Therapie konnte in einer Phase-3-Studie das Leben von Menschen mit Nierenzellkarzinom deutlich verlängern. Die Sterberate war im Vergleich zu Placebo um 38% geringer.

Bei Senioren mit Prostatakarzinom auf Anämie achten!

24.04.2024 DGIM 2024 Nachrichten

Patienten, die zur Behandlung ihres Prostatakarzinoms eine Androgendeprivationstherapie erhalten, entwickeln nicht selten eine Anämie. Wer ältere Patienten internistisch mitbetreut, sollte auf diese Nebenwirkung achten.

Stufenschema weist Prostatakarzinom zuverlässig nach

22.04.2024 Prostatakarzinom Nachrichten

Erst PSA-Test, dann Kallikrein-Score, schließlich MRT und Biopsie – ein vierstufiges Screening-Schema kann die Zahl der unnötigen Prostatabiopsien erheblich reduzieren: Die Hälfte der Männer, die in einer finnischen Studie eine Biopsie benötigten, hatte einen hochgradigen Tumor.

Harnwegsinfektprophylaxe: Es geht auch ohne Antibiotika

20.04.2024 EAU 2024 Kongressbericht

Beim chronischen Harnwegsinfekt bei Frauen wird bisher meist eine Antibiotikaprophylaxe eingesetzt. Angesichts der zunehmenden Antibiotikaresistenz erweist sich das Antiseptikum Methenamin-Hippurat als vielversprechende Alternative, so die Auswertung einer randomisierten kontrollierten Studie.

Update Urologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.