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Michael B Chancellor - One of the best experts on this subject based on the ideXlab platform.
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strain history and tgf β1 induce urinary Bladder Wall smooth muscle remodeling and elastogenesis
Biomechanics and Modeling in Mechanobiology, 2012Co-Authors: Rebecca L Heise, Michael B Chancellor, Aron Parekh, Erinn M Joyce, Michael S SacksAbstract:Mechanical cues that trigger pathological remodeling in smooth muscle tissues remain largely unknown and are thought to be pivotal triggers for strain-induced remodeling. Thus, an understanding of the effects mechanical stimulation is important to elucidate underlying mechanisms of disease states and in the development of methods for smooth muscle tissue regeneration. For example, the urinary Bladder Wall (UBW) adaptation to spinal cord injury (SCI) includes extensive hypertrophy as well as increased collagen and elastin, all of which profoundly alter its mechanical response. In addition, the pro-fibrotic growth factor TGF-β1 is upregulated in pathologies of other smooth muscle tissues and may contribute to pathological remodeling outcomes. In the present study, we utilized an ex vivo organ culture system to investigate the response of UBW tissue under various strain-based mechanical stimuli and exogenous TGF-β1 to assess extracellular matrix (ECM) synthesis, mechanical responses, and Bladder smooth muscle cell (BSMC) phenotype. Results indicated that a 0.5-Hz strain frequency triangular waveform stimulation at 15% strain resulted in fibrillar elastin production, collagen turnover, and a more compliant ECM. Further, this stretch regime induced changes in cell phenotype while the addition of TGF-β1 altered this phenotype. This phenotypic shift was further confirmed by passive strip biomechanical testing, whereby the Bladder groups treated with TGF-β1 were more compliant than all other groups. TGF-β1 increased soluble collagen production in the cultured Bladders. Overall, the 0.5-Hz strain-induced remodeling caused increased compliance due to elastogenesis, similar to that seen in early SCI Bladders. Thus, organ culture of Bladder strips can be used as an experimental model to examine ECM remodeling and cellular phenotypic shift and potentially elucidate BMSCs ability to produce fibrillar elastin using mechanical stretch either alone or in combination with growth factors.
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diabetes induced alternations in biomechanical properties of urinary Bladder Wall in rats
Urology, 2009Co-Authors: Naoki Yoshimura, Michael B Chancellor, Chung Cheng Wang, Jiro Nagatomi, Khashayar K Toosi, Jui Hsiang Hsieh, Michael S SacksAbstract:Objectives To determine whether diabetes mellitus and the associated changes in Bladder function will trigger Bladder Wall tissue remodeling and concomitant alterations in the mechanical properties. We investigated the time course of changes in function and mechanical properties of diabetic and diuretic rat Bladders using both in vivo and in vitro techniques Methods Cystometry was performed at 2, 4, and 8 weeks on female Sprague-Dawley rats that had received either a single injection of streptozotocin (65 mg/kg intraperitoneally) or 5% sucrose in drinking water for the duration of the experiments. At each point, the biaxial mechanical properties of 10 × 10-mm tissue specimens obtained from the posterior part of Bladder Wall were quantified. The changes in overall tissue compliance and mechanical anisotropy as a function of time were examined Results Both diabetic and diuretic conditions led to increases in Bladder weight, Bladder capacity, and in vivo compliance compared with the controls at all points tested. Under biaxial loading, all Bladder Wall tissues exhibited a nonlinear stress-strain relationship and mechanical anisotropy, with greater tissue compliance in the circumferential direction than in the longitudinal direction. Although the compliance of the Bladder Wall increased progressively and synchronously in both diabetic and diuretic Bladders for ≤4 weeks, only the diabetic Bladders continued to increase the compliance for ≤8 weeks (diabetic 0.64 ± 0.04 vs diuretic 0.48 ± 0.05, P = .03) Conclusions The results of our study have shown that diuresis mainly contributes to the “early” changes of mechanical properties of the Bladder, with diabetes inducing additional “late” changes of mechanical properties of the rat Bladders after 4 weeks.
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biaxial mechanical properties of muscle derived cell seeded small intestinal submucosa for Bladder Wall reconstitution
Biomaterials, 2005Co-Authors: Michael S Sacks, Johnny Huard, Claire D Gloeckner, William C De Groat, Steve Y Chung, Ryan Pruchnic, Michael B ChancellorAbstract:Abstract Bladder Wall replacement remains a challenging problem for urological surgery due to leakage, infection, stone formation, and extensive time needed for tissue regeneration. To explore the feasibility of producing a more functional biomaterial for Bladder reconstitution, we incorporated muscle-derived cells (MDC) into small intestinal submucosa (SIS) scaffolds. MDC were harvested from mice hindleg muscle, transfected with a plasmid encoding for β -galactosidase, and placed into single-layer SIS cell culture inserts. Twenty-five MDC and/or SIS specimens were incubated at 37°C for either 10 or 20 days. After harvesting, mechanical properties were characterized using biaxial testing, and the areal strain under 1 MPa peak stress used to quantify tissue compliance. Histological results indicated that MDC migrated throughout the SIS after 20 days. The mean (±SE) areal strain of the 0 day control group was 0.182±0.027 ( n =5). After 10 days incubation, the mean (±SE) areal strain in MDC/SIS was 0.247±0.014 ( n =5) compared to 10 day control SIS 0.200±0.024 ( n =6). After 20 days incubation, the mean areal strain of MDC/SIS was 0.255±0.019 ( n =5) compared to control SIS 0.170±0.025 ( n =5). Both 10 and 20 days seeded groups were significantly different ( p =0.027) than that of incubated SIS alone, but were not different from each other. These results suggest that MDC growth was supported by SIS and that initial remodeling of the SIS ECM had occurred within the first 10 days of incubation, but may have slowed once the MDC had grown to confluence within the SIS.
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passive biaxial mechanical properties of the rat Bladder Wall after spinal cord injury
The Journal of Urology, 2002Co-Authors: Claire D Gloeckner, Michael S Sacks, Matthew O Fraser, George T Somogyi, William C De Groat, Michael B ChancellorAbstract:Purpose: Changes in the mechanical properties of the Bladder Wall after spinal cord injury can alter Bladder compliance and Wall tension, leading to changes in afferent nerve activity and to abnormal reflex mechanisms. To our knowledge we report the first application of biaxial mechanical testing to the normal Bladder Wall and demonstrate how these properties change after spinal cord injury.Materials and Methods: Whole Bladders were harvested from mature female Sprague-Dawley rats weighing 250 to 300 gm. Test group animals underwent complete spinal cord transection at the T9 to T10 level and normal animals comprised the control group. The Bladders were cut open longitudinally, the trigone and apex were removed and the remaining tissue was trimmed to a square of 9 to 13 mm. per side. Mechanical properties of the tissue sample were tested using planar biaxial testing, in which a stress was applied in the circumferential and longitudinal (base-apex) directions, and resulting axial strains were measured.Resul...
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preliminary results of myoblast injection into the urethra and Bladder Wall a possible method for the treatment of stress urinary incontinence and impaired detrusor contractility
Neurourology and Urodynamics, 2000Co-Authors: Michael B Chancellor, Teruhiko Yokoyama, Sean Tirney, Carol E Mattes, Hideo Ozawa, Naoki Yoshimura, Johnny HuardAbstract:The purpose of this study is to explore the feasibility of myoblasts, the precursors of muscle fibers, injected periurethrally as a potential treatment of stress urinary incontinence. We also studied myoblast injection into the Bladder Wall to potentially improve detrusor contractility. A myoblast cell line was transduced with adenovirus carrying the expression of the β-galactosidase reporter gene while in culture. The cells were incubated with fluorescent latex microspheres (FLMs) to follow the outcome of the injected cells. The tissue was harvested 3–4 days after injection; sectioned, fixed, assayed for β-galactosidase expression, and counterstained with H+E. Photographs of the slides were taken under light and fluorescence microscopy. We have noted a large number of cells expressing β-galactosidase and containing FLMs in the urethral and Bladder Walls under fluorescent microscopy (8 animals). Many regenerative myofibers expressing β-galactosidase were also seen in the urethral and Bladder Walls. The fusion of injected myoblasts to form myotubes was seen in both the urethral and Bladder Walls. The introduction of myoblasts into the urethral and Bladder Wall is feasible and results in formation of myotubes and myofibers in the smooth muscle layers of the lower urinary tract. We hypothesize that myoblast injections can be used as a non-allergenic agent to enhance urethral closure and Bladder function. Neurourol. Urodynam. 19:279–287, 2000. © 2000 Wiley-Liss, Inc.
Michael S Sacks - One of the best experts on this subject based on the ideXlab platform.
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strain history and tgf β1 induce urinary Bladder Wall smooth muscle remodeling and elastogenesis
Biomechanics and Modeling in Mechanobiology, 2012Co-Authors: Rebecca L Heise, Michael B Chancellor, Aron Parekh, Erinn M Joyce, Michael S SacksAbstract:Mechanical cues that trigger pathological remodeling in smooth muscle tissues remain largely unknown and are thought to be pivotal triggers for strain-induced remodeling. Thus, an understanding of the effects mechanical stimulation is important to elucidate underlying mechanisms of disease states and in the development of methods for smooth muscle tissue regeneration. For example, the urinary Bladder Wall (UBW) adaptation to spinal cord injury (SCI) includes extensive hypertrophy as well as increased collagen and elastin, all of which profoundly alter its mechanical response. In addition, the pro-fibrotic growth factor TGF-β1 is upregulated in pathologies of other smooth muscle tissues and may contribute to pathological remodeling outcomes. In the present study, we utilized an ex vivo organ culture system to investigate the response of UBW tissue under various strain-based mechanical stimuli and exogenous TGF-β1 to assess extracellular matrix (ECM) synthesis, mechanical responses, and Bladder smooth muscle cell (BSMC) phenotype. Results indicated that a 0.5-Hz strain frequency triangular waveform stimulation at 15% strain resulted in fibrillar elastin production, collagen turnover, and a more compliant ECM. Further, this stretch regime induced changes in cell phenotype while the addition of TGF-β1 altered this phenotype. This phenotypic shift was further confirmed by passive strip biomechanical testing, whereby the Bladder groups treated with TGF-β1 were more compliant than all other groups. TGF-β1 increased soluble collagen production in the cultured Bladders. Overall, the 0.5-Hz strain-induced remodeling caused increased compliance due to elastogenesis, similar to that seen in early SCI Bladders. Thus, organ culture of Bladder strips can be used as an experimental model to examine ECM remodeling and cellular phenotypic shift and potentially elucidate BMSCs ability to produce fibrillar elastin using mechanical stretch either alone or in combination with growth factors.
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diabetes induced alternations in biomechanical properties of urinary Bladder Wall in rats
Urology, 2009Co-Authors: Naoki Yoshimura, Michael B Chancellor, Chung Cheng Wang, Jiro Nagatomi, Khashayar K Toosi, Jui Hsiang Hsieh, Michael S SacksAbstract:Objectives To determine whether diabetes mellitus and the associated changes in Bladder function will trigger Bladder Wall tissue remodeling and concomitant alterations in the mechanical properties. We investigated the time course of changes in function and mechanical properties of diabetic and diuretic rat Bladders using both in vivo and in vitro techniques Methods Cystometry was performed at 2, 4, and 8 weeks on female Sprague-Dawley rats that had received either a single injection of streptozotocin (65 mg/kg intraperitoneally) or 5% sucrose in drinking water for the duration of the experiments. At each point, the biaxial mechanical properties of 10 × 10-mm tissue specimens obtained from the posterior part of Bladder Wall were quantified. The changes in overall tissue compliance and mechanical anisotropy as a function of time were examined Results Both diabetic and diuretic conditions led to increases in Bladder weight, Bladder capacity, and in vivo compliance compared with the controls at all points tested. Under biaxial loading, all Bladder Wall tissues exhibited a nonlinear stress-strain relationship and mechanical anisotropy, with greater tissue compliance in the circumferential direction than in the longitudinal direction. Although the compliance of the Bladder Wall increased progressively and synchronously in both diabetic and diuretic Bladders for ≤4 weeks, only the diabetic Bladders continued to increase the compliance for ≤8 weeks (diabetic 0.64 ± 0.04 vs diuretic 0.48 ± 0.05, P = .03) Conclusions The results of our study have shown that diuresis mainly contributes to the “early” changes of mechanical properties of the Bladder, with diabetes inducing additional “late” changes of mechanical properties of the rat Bladders after 4 weeks.
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biaxial mechanical properties of muscle derived cell seeded small intestinal submucosa for Bladder Wall reconstitution
Biomaterials, 2005Co-Authors: Michael S Sacks, Johnny Huard, Claire D Gloeckner, William C De Groat, Steve Y Chung, Ryan Pruchnic, Michael B ChancellorAbstract:Abstract Bladder Wall replacement remains a challenging problem for urological surgery due to leakage, infection, stone formation, and extensive time needed for tissue regeneration. To explore the feasibility of producing a more functional biomaterial for Bladder reconstitution, we incorporated muscle-derived cells (MDC) into small intestinal submucosa (SIS) scaffolds. MDC were harvested from mice hindleg muscle, transfected with a plasmid encoding for β -galactosidase, and placed into single-layer SIS cell culture inserts. Twenty-five MDC and/or SIS specimens were incubated at 37°C for either 10 or 20 days. After harvesting, mechanical properties were characterized using biaxial testing, and the areal strain under 1 MPa peak stress used to quantify tissue compliance. Histological results indicated that MDC migrated throughout the SIS after 20 days. The mean (±SE) areal strain of the 0 day control group was 0.182±0.027 ( n =5). After 10 days incubation, the mean (±SE) areal strain in MDC/SIS was 0.247±0.014 ( n =5) compared to 10 day control SIS 0.200±0.024 ( n =6). After 20 days incubation, the mean areal strain of MDC/SIS was 0.255±0.019 ( n =5) compared to control SIS 0.170±0.025 ( n =5). Both 10 and 20 days seeded groups were significantly different ( p =0.027) than that of incubated SIS alone, but were not different from each other. These results suggest that MDC growth was supported by SIS and that initial remodeling of the SIS ECM had occurred within the first 10 days of incubation, but may have slowed once the MDC had grown to confluence within the SIS.
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passive biaxial mechanical properties of the rat Bladder Wall after spinal cord injury
The Journal of Urology, 2002Co-Authors: Claire D Gloeckner, Michael S Sacks, Matthew O Fraser, George T Somogyi, William C De Groat, Michael B ChancellorAbstract:Purpose: Changes in the mechanical properties of the Bladder Wall after spinal cord injury can alter Bladder compliance and Wall tension, leading to changes in afferent nerve activity and to abnormal reflex mechanisms. To our knowledge we report the first application of biaxial mechanical testing to the normal Bladder Wall and demonstrate how these properties change after spinal cord injury.Materials and Methods: Whole Bladders were harvested from mature female Sprague-Dawley rats weighing 250 to 300 gm. Test group animals underwent complete spinal cord transection at the T9 to T10 level and normal animals comprised the control group. The Bladders were cut open longitudinally, the trigone and apex were removed and the remaining tissue was trimmed to a square of 9 to 13 mm. per side. Mechanical properties of the tissue sample were tested using planar biaxial testing, in which a stress was applied in the circumferential and longitudinal (base-apex) directions, and resulting axial strains were measured.Resul...
Andrea Tubaro - One of the best experts on this subject based on the ideXlab platform.
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ultrasound estimated Bladder weight and measurement of Bladder Wall thickness useful noninvasive methods for assessing the lower urinary tract
The Journal of Urology, 2010Co-Authors: Elizabeth Bright, Andrea Tubaro, Matthias Oelke, Paul AbramsAbstract:Purpose: In the last decade interest has arisen in the use of ultrasound derived measurements of Bladder Wall thickness, detrusor Wall thickness and ultrasound estimated Bladder weight as potential diagnostic tools for conditions known to induce detrusor hypertrophy. However, to date such measurements have not been adopted into clinical practice. We performed a comprehensive review of the literature to assess the potential clinical usefulness of these measurements.Materials and Methods: A MEDLINE® search was conducted to identify all published literature up to June 2009, investigating measurements of Bladder Wall thickness, detrusor Wall thickness and ultrasound estimated Bladder weight.Results: Measurements of Bladder and detrusor Wall thickness, and ultrasound estimated Bladder weight have been studied in men, women and children. A convincing trend has been shown in the ability of these measurements to differentiate men with from those without Bladder outlet obstruction. In addition, measurements of bla...
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the diagnosis of Bladder outlet obstruction in men by ultrasound measurement of Bladder Wall thickness
The Journal of Urology, 1998Co-Authors: Carlo Manieri, Simon Carter, Gianfranco Romano, Alberto Trucchi, Marco Valenti, Andrea TubaroAbstract:AbstractPurpose: The objective of the study was to investigate specificity and sensitivity of Bladder Wall thickness in the diagnosis of Bladder outlet obstruction.Materials and Methods: The study included 174 patients referred to our prostate centers for lower urinary tract symptoms. Free uroflowmetry and pressure-flow studies were performed in duplicate as part of the diagnostic evaluation. After the 2 voiding studies were done the Bladder was filled to 150 ml. and Wall thickness was measured via suprapubic ultrasound. Bladder outlet obstruction was diagnosed and graded according to the Abrams-Griffiths and Schafer nomogram as well as to the group specific urethral resistance algorithm.Results: A significant correlation (r>0.6, p
Daniel S Engeler - One of the best experts on this subject based on the ideXlab platform.
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transurethral resection of Bladder cancer on the lateral Bladder Wall without obturator nerve block extent of adductor spasms using the monopolar versus bipolar technique a prospective randomised study
World Journal of Urology, 2018Co-Authors: Tobias Gramann, Christoph Schwab, Valentin Zumstein, Patrick Betschart, M Meier, Hans Schmid, Daniel S EngelerAbstract:To establish whether bipolar transurethral resection of tumours (bTURB) on the lateral Bladder Wall is superior to monopolar transurethral resection (mTURB) of such tumours. To our knowledge, this is the first prospective randomised study, which defines complete resection depending on obturator jerk as primary endpoint. In a prospective, randomised, single centre study, 52 patients with newly diagnosed or recurrent Bladder tumour on the lateral Bladder Wall were enrolled and randomised to undergo mTURB or bTURB; 44 patients were eligible for analysis, of whom 21 underwent mTURB and 23 bTURB. Any differences between the two techniques related to the incidence of unwanted stimulation of the obturator nerve and subsequent adductor spasms were evaluated. All procedures were carried out under laryngeal mask anaesthesia without obturator nerve block (ONB) and without drug-induced relaxation. Baseline characteristics of the two study groups did not differ statistically significantly. The success rate defined as complete resection of the Bladder tumour without any clinically relevant adductor spasm was 61.9% in the monopolar group and 82.6% in the bipolar group (p = 0.18). Complete, undisturbed resection of tumours of the lateral Bladder Wall is feasible with mTURB and bTURB. Adductor spasms due to obturator jerk can occur suddenly with the risk of Bladder perforation. We therefore support ONB when using spinal anaesthesia and drug-induced relaxation when using general anaesthesia when performing TURB on the lateral Bladder Wall.
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transurethral resection of Bladder cancer on the lateral Bladder Wall without obturator nerve block extent of adductor spasms using the monopolar versus bipolar technique a prospective randomised study
World Journal of Urology, 2018Co-Authors: Tobias Gramann, Christoph Schwab, Valentin Zumstein, Patrick Betschart, M Meier, Hanspeter Schmid, Daniel S EngelerAbstract:Purpose To establish whether bipolar transurethral resection of tumours (bTURB) on the lateral Bladder Wall is superior to monopolar transurethral resection (mTURB) of such tumours. To our knowledge, this is the first prospective randomised study, which defines complete resection depending on obturator jerk as primary endpoint.
Aleš Mrhar - One of the best experts on this subject based on the ideXlab platform.
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effect of polymer charge on permeability of urinary Bladder Wall
Scientia Pharmaceutica, 2010Co-Authors: Kerec M Kos, Marija Bogataj, Aleš MrharAbstract:The scope of the present work was to establish the role of the polymer charge on its ability to enhance the permeability of the urinary Bladder Wall. [...]
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enhanced permeability of the urinary Bladder Wall the role of polymer charge
Die Pharmazie, 2009Co-Authors: Kerec Kos M, Marija Bogataj, Aleš MrharAbstract:The urothelium is usually impermeable to substances present in the urine. In the current work the possibility of using different absorption enhancers in the development of intravesical drug delivery systems was explored. To establish the role of the polymer charge on its ability to improve Bladder Wall permeability, cationic poly-L-arginine, anionic NaCMC and alginate as well as nonionic HPC and HPMC were tested. The permeability experiments were performed on isolated pig urinary Bladders. We established that the charge of the polymer affects its ability to enhance the permeability of the urinary Bladder Wall, but to a limited extent. Positively charged polymers were the most promising absorption enhancers for the urinary Bladder Wall. In order to significantly enhance the permeability of the Bladder Wall, higher concentrations of poly-L-arginine were needed compared to chitosan. Moreover, chitosan reached the plateau of its absorption enhancement effect after 60 min, while poly-L-arginine increased the permeability continuously over 90 min. In contrast to polycarbophil, two other anionic polymers, NaCMC and alginate, did not significantly enhance the permeation of pipemidic acid into the tissue. Interactions between the polymers and the drug might prevail over the potential effect of NaCMC and alginate on tissue permeability. Furthermore, for the nonionic polymers HPMC and HPC an insignificant influence on Bladder Wall permeability was determined. Therefore, the selection of absorption enhancers for intravesical drug delivery systems is limited and cannot be done only on the basis of polymer charge.
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heparin decreases permeability of pig urinary Bladder Wall preliminarily enhanced by chitosan
Drug Development and Industrial Pharmacy, 2008Co-Authors: Mojca Kerec Kos, Marija Bogataj, Aleš MrharAbstract:Chitosan significantly increases the permeability of the isolated pig urinary Bladder Wall by causing urothelial desquamation, the extent of which depends also on the concentration of the polymer. By desquamation permeability barriers of the urothelium are removed. To gain additional insight into the mechanism by which chitosan acts an absorption enhancer into urinary Bladder mucosa, we evaluated the influence of a polysaccharide heparin on the permeability of isolated pig urinary Bladder Wall preliminarily treated with chitosan. Moreover, we aimed to establish whether the effect of heparin depends on its concentration and on the degree of urothelial desquamation caused by chitosan. In the permeability studies performed by the use of diffusion cells, transport of a model drug, pipemidic acid, into the isolated pig urinary Bladder Wall was determined. Heparin did not have a significant effect on the permeability of the intact urothelium. When applied to the urinary Bladder Wall, whose permeability was preliminarily enhanced by 0.005% or 0.001% w/v chitosan, heparin decreased the permeation of pipemidic acid into the Bladder Wall to a level not significantly different from the intact tissue. However, the effect of heparin was not significant at the highest concentration of chitosan tested, where the damage to the urothelium was much more intense compared with that found at lower concentrations of the polymer. The formation of complexes between pipemidic acid and heparin cannot be excluded completely, but it seems that they are not the main reason for the decreased permeation of pipemidic acid in the presence of heparin. By application on the urothelium, damaged by chitosan, heparin is supposed to form a layer on the surface of the urothelium that prevents the transport of the model drug into the Bladder Wall. In this way heparin probably restores the impermeability properties of the urinary Bladder Wall to a degree dependent on the urothelial damage.
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permeability of pig urinary Bladder Wall time and concentration dependent effect of chitosan
Biological & Pharmaceutical Bulletin, 2006Co-Authors: Mojca Kerec Kos, Marija Bogataj, Peter Veranic, Aleš MrharAbstract:Chitosan in 0.5% w/v concentration enhanced the permeability of the isolated pig urinary Bladder Wall by desquamation of the urothelium as ascertained in our previous study. The aim of the present work was to determine the time and concentration dependence of chitosan's effect on the permeation of a model drug into the Bladder Wall and to establish if the mechanism of permeation enhancement depends on the concentration of chitosan used. In the permeability studies performed by the use of diffusion cells, transport of a model drug moxifloxacin into the isolated pig urinary Bladder Wall was determined. For morphological observations of the urothelium in response to chitosan treatment scanning and transmission electron microscopy were applied. Within 90 min the effect of chitosan on the tissue amounts of moxifloxacin gradually increased and approached its plateau. In one hour even 0.0005% w/v dispersion of chitosan significantly enhanced the permeability of the pig urinary Bladder Wall for the model drug and at 0.001% w/v concentration the maximal effect on the tissue permeability was achieved. All concentrations of chitosan that significantly enhanced the permeability of the Bladder Wall triggered necrosis of superficial cells or desquamation of the urothelium. However, at lower concentrations and shorter exposure times the damage of the urothelium was limited to the changes in tight junctions. Chitosan was ascertained to increase the permeation of moxifloxacin into the urinary Bladder Wall in a time and concentration dependent manner.
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permeability of pig urinary Bladder Wall the effect of chitosan and the role of calcium
European Journal of Pharmaceutical Sciences, 2005Co-Authors: Mojca Kerec, Marija Bogataj, Peter Veranic, Aleš MrharAbstract:Chitosan is a cationic polysaccharide widely employed as an absorption enhancer. The aim of this work was to examine the effect of chitosan on the permeability of isolated pig urinary Bladder Wall as well as to determine the role of calcium ions in this process. Besides permeability studies, scanning electron microscopy and fluorescent microscopy were applied to get an insight into the mechanism by which chitosan increases the permeability of urinary Bladder Wall. Additionally, the obtained findings were compared to the mechanism proposed for Caco-2 cells. The results show that 0.5% (w/v) chitosan increases the permeability of urinary Bladder Wall by causing the desquamation of the urothelium. Calcium ions, when applied to the luminal surface of the urinary Bladder at the same time as chitosan, decreases the effect of chitosan on permeation of the model drug moxifloxacin into the Bladder Wall in concentration dependent way. The desquamation of urothelium cells caused by chitosan was reduced in the presence of calcium, but not to such extent as it would be expected from the permeability studies. When present, calcium obviously interferes directly in the interactions between chitosan and the surface of urothelium.