To study the effect of intravesical instillation of botulinum neurotoxin-A (BoNT-A) combined with low energy shock wave (LESW) for treatment of overactive bladder (OAB) in a rat model and to investigate its effect on the associated inflammatory and oxidative stress process. Material and Methods: Forty rats were subdivided into four equal groups: normal control group, OAB group, LESW group, and BoNT-A plus LESW group. Cystometrogram (CMG) changes and histopathological changes in the bladder mucosa were assessed in the different groups. Oxidative stress markers (malondialdehyde [MDA] and superoxide dismutase [SOD]) and proinflammatory cytokines (tumor necrotic factor-α [TNF-α] and interleukin-6 [IL-6]) were compared among groups. Results: BoNT-A plus LESW group showed statistically significant lower amplitude (p = .001) and lower frequency of detrusor contractions (p = .01) compared to LESW, which showed no statistically significant difference in comparison to the OAB group. Also, the combined group significantly reduced submucosal edema and inflammatory cell infiltrate scores compared to all groups (p < .05). LESW was associated with 42% reduction of MDA expression while, LESW plus BoNT-A decreased it by 68% (p < .001). Also, LESW and LESW plus BoNT-A increased SOD expression by 43% and 75%, respectively (p < .001). LESW plus BoNT-A was associated with statistically significant lower expression of TNF-α and IL-6 expression by 37% and 66% in comparison to LESW group (p = .001). Conclusion: Intravesical instillation of BoNT-A plus LESW is an effective method for increasing the urothelial permeability to BoNT-A and enhancing its therapeutic effect against OAB in rat model through the expression of a substantial anti-inflammatory and antioxidative stress effect.
PurposeThis is an experimental preclinical study testing the applicability of autologous skeletal muscle-derived cells as a treatment of SUI in a canine model.MethodsTen mongrel dogs were included in this study. Skeletal muscle was harvested for biopsy in 4 dogs. One month later, incontinence was induced in 8 dogs through urethrolysis. Biopsied muscle cells were incubated and expanded for 8 weeks. Muscle-derived cells were collected and covered with a polyglycolic acid (PGA) scaffold immersed in culture medium and coated with Matrigel to be used as a sling, which was placed suburethrally in 8 dogs; 4 had cell seeding, and 4 had scaffolds only. Urethral pressure (UP) measurements were performed at baseline and 2 & 6 weeks after sling insertion. The urethra was harvested 4 weeks after sling insertion for histopathology.ResultsOne month, a statistically significant increase of mean urethral pressure values compared to baseline was observed in all dogs with a scaffold inserted. The increase ranged from 5 to 40 cmH2O. Histopathology showed significant periurethral proliferation of skeletal muscles in 4 dogs with cell-seeded scaffolds. These levels were the maximum levels in dogs # 1 & 2. This was not the case in the 4 dogs that had slings only.ConclusionBased on the outcome of this preliminary experience, the use of skeletal muscle-seeded PGA scaffolds seems to be an easy and reproducible procedure which preserves histological differentiation and integrity in a canine model
Introduction:This is an experimental pre-clinical study, testing the applicability of autologous skeletal muscle derived cells as a treatment of SUI in canine modelMethods:10 Mongrel dogs included. Skeletal muscle biopsy was harvested in 4. 1 month later, incontinence was induced in 8 dogs through urethrolysis. Muscle biopsy was incubated and expanded for 8 weeks. Muscle derived cells were collected and covered a Polyglycolic acid (PGA) scaffold immersed in culture medium and coated with matrigel to be used as a sling. Placed suburethral in 8 dogs; 4 had cell- seeded and 4 had scaffold only. Urethral pressure (UP) measurement was done at baseline 2 &6 weeks after sling insertion. The urethra was harvested 4 weeks after sling insertion for histopathology.Results:UP shows increase of maximum urethral pressure during static measurement in all dogs with a scaffold inserted. The increase ranged from 5-40 cmH20 Histopathology shows significant periurethral proliferation of skeletal muscles in 4 dogs with cell-seeded scaffold. This was maximum in dogs # 1& 2. This was not the case in the 4 dogs that had sling only.Conclusion: Use of skeletal muscle –seeded PGA scaffold is a practical technique with preserved integrity of histological differentiation in canine model.
Introduction & hypothesis: This is an experimental pre-clinical study testing for the applicability of autologous skeletal muscle derived cells as a seeded sling for the treatment of Stress urinary incontinence in canine model. Methods: 10 Mongrel dogs: In 4, skeletal muscle biopsy was harvested from Biceps Femoris. 1 month later, incontinence was induced in 8 dogs through surgical disruption of the pubourethral ligaments. Muscle biopsy was incubated in medium and after expansion for 8 weeks, Muscle derived cells were collected. Polyglycolic acid scaffold was immersed in culture medium, coated with matrigel and cells were seeded. The sling was placed suburethral in 8 dogs; 2 of which were cell-seeded and 4 had the scaffold only. Urethral pressure measurement was done at baseline and 2 weeks after insertion of the sling. The urethra with its surrounding was harvested 4 weeks after sling insertion for histopathology. 2 dogs were considered as control, in which no urethrolysis or insertion of slings was carried out. Results: Urethral pressure shows increase of maximum urethral pressure during static measurement in all dogs with a scaffold inserted. The increase ranged from 5-40 centimeter water (Median: 23 cmH20). Histopathology shows significant periurethral proliferation of skeletal muscles in 4 dogs with cell-seeded scaffold, as demonstrated by Desmin. This was maximum in dogs numbers 1and 2. This was not the case in the 4 dogs that had Polyglycolic acid sling only. Conclusion: The use of skeletal muscle-seeded scaffold is a practical technique with preserved integrity of histological differentiation in canine model at short term.
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