Combined application of chondroitinase ABC and photobiomodulation with low-intensity laser on the anal sphincter repair in rabbit.
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ABSTRACT:
SUBMITTER: Sarveazad A
PROVIDER: S-EPMC8672605 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundAnal sphincter injury leads to fecal incontinence. Based on the regenerative capability of laser and human adipose-derived stem cells (hADSCs), this study was designed to assess the effects of co-application of these therapies on anal sphincter recovery after injury.DesignMale rabbits were assigned to equal groups (n?=?7) including control, sphincterotomy, sphincterotomy treated with laser (660?nm, 90 s, immediately after sphincterotomy, daily, 14?days), hADSCs (2?×?106 hADSCs injected into injured area of the sphincter immediately after sphincterotomy), and laser?+?hADSCs. Ninety?days after sphincterotomy, manometry and electromyography were performed, sphincter collagen content was evaluated, and Ki67, myosin heavy chain (MHC), skeletal muscle alpha-actin (ACTA1), vascular endothelial growth factor A (VEGFA), and vimentin mRNA gene expression were assessed.ResultsThe laser?+?hADSCs group had a higher resting pressure compared with the sphincterotomy (p?<?0.0001), laser (p?<?0.0001), and hADSCs (p?=?0.04) groups. Maximum squeeze pressure was improved in all treated animals compared with the sphincterotomized animals (p?<?0.0001), without a significant difference between treatments (p?>?0.05). In the laser?+?hADSCs group, motor unit numbers were higher than those in the laser group (p?<?0.0001) but did not differ from the hADSCs group (p?=?0.075). Sphincterotomy increased collagen content, but the muscle content (p?=?0.36) and collagen content (p?=?0.37) were not significantly different between the laser?+?hADSCs and control groups. Laser?+?hADSCs increased ACTA1 (p?=?0.001) and MHC (p?<?0.0001) gene expression compared with laser or hADSCs alone and was associated with increased VEGFA (p?=?0.009) and Ki67 mRNA expression (p?=?0.01) and decreased vimentin mRNA expression (p?<?0.0001) compared with laser.ConclusionThe combination of laser and hADSCs appears more effective than either treatment alone for promoting myogenesis, angiogenesis, and functional recovery after anal sphincterotomy.
| S-EPMC6889595 | biostudies-literature
Project description:BackgroundIncidence of complications following obstetrical anal sphincter injury (OASI) during vaginal delivery are poorly defined. They are only studied in high level maternities, small cohorts, all stages of perineal tear or in low-income countries. The aim of our study was to describe complications after primary OASI repair following a vaginal delivery in all French maternity wards at short and midterm and to assess factors associated with complication occurrence.MethodsWe conducted a historical cohort study using the French nationwide claim database (PMSI) from January 2013 to December 2021. All women who sustained an OASI repair following a vaginal delivery were included and virtually followed-up for 2 years. Then, we searched for OASIS complications. Finally, we evaluated factors associated with OASIS complication repaired or not and OASIS complication repairs.ResultsAmong the 61,833 included women, 2015 (2.8%) had an OASI complication and 842 (1.16%) underwent an OASI complication repair. Women were mainly primiparous (71.6%) and 44.3% underwent an instrumental delivery. During a follow-up of 2 years, 0.6% (n = 463), 0.3% (n = 240), 0.2% (n = 176), 0.1% (n = 84), 0.06% (n = 43) and 0.01% (n = 5) of patients underwent second surgery for a perineal repair, a fistula repair, a sphincteroplasty, a perineal infection, a colostomy and a sacral nervous anal stimulation, respectively. Only one case of artificial anal sphincter was noticed. Instrumental deliveries (OR = 1.56 CI95%[1.29;1.9]), private for-profit hospitals (OR = 1.42 [1.11;1.82], reference group "public hospital"), obesity (OR = 1.36 [1;1.84]), stage IV OASIS (OR = 2.98 [2.4;3.72]), perineal wound breakdown (OR = 2.8 [1.4;5.48]), ages between 25 and 29 years old (OR = 1.59 [1.17;2.18], refence group "age between 13 and 24 years old") and 30 and 34 years old (OR = 1.57 [1.14; 2.16], refence group "age between 13 and 24 years old") were factors associated with OASIS complication repairs.ConclusionsMaternal age, stage IV OASIS, obesity, instrumental deliveries and private for-profit hospitals seemed to predict OASIS complications. Understanding factors associated with OASIS complications could be beneficial for the patient to inform them and to influence the patient's follow-up in order to prevent complications, repairs and maternal distress.
| S-EPMC11325760 | biostudies-literature
Project description:BackgroundLong-term results after obstetric anal sphincter injury (OASI) are poor. We aimed to improve the long-term outcome after OASI by lessening symptoms of anal incontinence.MethodsIn a prospective study at Malmö University Hospital, twenty-six women with at least grade 3B OASI were classified and sutured in a systematic way, including separate suturing of the internal and external sphincter muscles with monofilament absorbable sutures. The principal outcome assessed by answers given to six questions, was a difference in anal incontinence score, between the study group and two control groups (women with prior OASI [n = 180] and primiparous women delivered vaginally without a diagnose of OASI [n = 100]).ResultsAn anal incontinence score of zero (i.e., no symptoms) was found in 74% of the study group, 47% of the OASI control group, and 66% of the vaginal control group (p = 0.02 and 0.5, as compared to the study group).ConclusionsA modified suturing technique was followed by significant improved one-year symptoms of anal incontinence as compared to historical cases.
| S-EPMC2949785 | biostudies-literature
Project description:BackgroundSpinal cord injury (SCI) presents a significant challenge for the field of neurotherapeutics. Stem cells have shown promise in replenishing the cells lost to the injury process, but the release of axon growth-inhibitory molecules such as chondroitin sulfate proteoglycans (CSPGs) by activated cells within the injury site hinders the integration of transplanted cells. We hypothesised that simultaneous application of enteric neural stem cells (ENSCs) isolated from the gastrointestinal tract, with a lentivirus (LV) containing the enzyme chondroitinase ABC (ChABC), would enhance the regenerative potential of ENSCs after transplantation into the injured spinal cord.MethodsENSCs were harvested from the GI tract of p7 rats, expanded in vitro and characterised. Adult rats bearing a contusion injury were randomly assigned to one of four groups: no treatment, LV-ChABC injection only, ENSC transplantation only or ENSC transplantation+LV-ChABC injection. After 16 weeks, rats were sacrificed and the harvested spinal cords examined for evidence of repair.ResultsENSC cultures contained a variety of neuronal subtypes suitable for replenishing cells lost through SCI. Following injury, transplanted ENSC-derived cells survived and ChABC successfully degraded CSPGs. We observed significant reductions in the injured tissue and cavity area, with the greatest improvements seen in the combined treatment group. ENSC-derived cells extended projections across the injury site into both the rostral and caudal host spinal cord, and ENSC transplantation significantly increased the number of cells extending axons across the injury site. Furthermore, the combined treatment resulted in a modest, but significant functional improvement by week 16, and we found no evidence of the spread of transplanted cells to ectopic locations or formation of tumours.ConclusionsRegenerative effects of a combined treatment with ENSCs and ChABC surpassed either treatment alone, highlighting the importance of further research into combinatorial therapies for SCI. Our work provides evidence that stem cells taken from the adult gastrointestinal tract, an easily accessible source for autologous transplantation, could be strongly considered for the repair of central nervous system disorders.
| S-EPMC7789480 | biostudies-literature
Project description:OBJECTIVE:To describe long-term quality of life (QOL) outcomes after rectourethral fistula (RUF) repair. RUF is a debilitating diagnosis and complex surgical dilemma with limited data regarding QOL after repair. METHODS:Patients at a tertiary referral center undergoing transperineal RUF repair 1/2009-5/2016 were analyzed. Patients were contacted by telephone to assess QOL following repair. Descriptive analysis performed of short-term surgical data (success and complications) and long-term QOL data (novel questionnaire). RESULTS:Twenty one men underwent RUF surgery with 95% success after initial repair. Fifty two percent had a history of radiation and/or ablation. Four individuals (19%) experienced a Clavien-Dindo complication within 30 days, with 3 of those being grade III+. Fifteen had postoperative urinary incontinence, of whom 73% underwent artificial urinary sphincter placement. Three previously radiated individuals underwent subsequent urethral stricture surgery. At long-term follow-up (mean 45.6 ± 27.1 months), 53% reported perineal pain, 43% reported problems related to the gracilis flap, and 80% reported urinary incontinence (primarily occasional mild leakage). Twenty one percent were unable to do the things they wanted in their daily lives, while 80% reported that surgery positively impacted their life. None would have opted for complete urinary diversion. CONCLUSION:RUF repair leads to patient satisfaction and improved QOL, despite possible residual issues such as perineal pain and urinary incontinence. Definitive RUF repair should be offered to suitable radiated and nonradiated patients.
| S-EPMC6289716 | biostudies-literature
Project description:Video-assisted anal fistula treatment (VAAFT) may have a recurrence rate comparable to that of fistulectomy and sphincter repair (FSR) in the treatment of high anal fistula and with potential advantages in wound healing, functional outcome and quality of life. The aim and objectives of the study are to compare the outcome of VAAFT with that of FSR for high cryptoglandular anal fistula. This was a single-centre randomized controlled trial of adults with high anal fistula comparing FSR with VAAFT. Primary outcome was fistula recurrence. Secondary outcomes were results of anal manometry, quality of life and faecal continence. A power calculation of 33 patients in each arm (1 : 1) was based on recurrence in the FSR and VAAFT groups of 5 per cent and 30 per cent respectively. Follow-up at 6 months after surgery included physical examination, MRI, anal manometry, quality-of-life assessment (RAND SF 36 questionnaire) and faecal-continence assessment (Wexner score). The study was terminated early due to high recurrence rates in both groups. A total of 45 patients were included. Recurrence rates were 65 per cent for VAAFT and 27 per cent for FSR, with hazard ratio 4.18 (P = 0.016). Length of the fistula was a risk factor with an association with recurrence (hazard ratio 1.8, P = 0.020). There were significant differences in quality of life in favour of FSR and in anal manometry in favour of VAAFT with a significant improvement in Wexner score in both groups. FSR was associated with a lower recurrence rate than VAAFT in the management of complex anal fistulae in this single-centre study but the study was terminated early due to higher than predicted recurrence rate in both groups. NCT02585167 (http://www.clinicaltrials.org).
| S-EPMC8493008 | biostudies-literature
Project description:Malignant gliomas (glioblastomas; GBMs) are extremely aggressive and have a median survival of approximately 15 months. Current treatment modalities, which include surgical resection, radiation and chemotherapy, have done little to prolong the lives of GBM patients. Chondroitin sulfate proteoglycans (CSPG) are critical for cell-cell and cell-extracellular matrix (ECM) interactions and are implicated in glioma growth and invasion. Chondroitinase (Chase) ABC is a bacterial enzyme that cleaves chondroitin sulfate disaccharide chains from CSPGs in the tumor ECM. Wild-type Chase ABC has limited stability and/or activity in mammalian cells; therefore, we created a mutant humanized version (Chase M) with enhanced function in mammalian cells. We hypothesized that disruption of cell-cell and cell-ECM interactions by ChaseM and temozolomide (TMZ) will enhance the chemotherapeutic availability and sensitivity of glioma cells. Utilizing primary patient-derived neurospheres, we found that ChaseM decreases glioma neurosphere aggregation in vitro. Furthermore, an oncolytic HSV-1 virus expressing secreted ChaseM (OV-ChaseM) enhanced viral spread and glioma cell killing compared to OV-Control, in vitro. OV-ChaseM plus TMZ combinatorial treatment resulted in a significant synergistic enhancement of glioma cell killing accompanied by an increase in apoptotic cell death. Intracellular flow cytometric analysis revealed a significant reduction in the phosphorylation of the pro-survival AKT protein following OV-ChaseM plus TMZ treatment. Lastly, in nude mice bearing intracranial GBM30 glioma xenografts, intratumoral OV-ChaseM plus TMZ (10 mg/kg by oral gavage) combination therapy resulted in a significant (p < 0.02) enhancement of survival compared to each individual treatment alone. These data reveal that OV-ChaseM enhances glioma cell viral susceptibility and sensitivity to TMZ.
| S-EPMC5382089 | biostudies-literature
Project description:Background & aimsThe anal sphincters and puborectalis are imaged routinely with an endoanal magnetic resonance imaging (MRI) coil, which does not assess co-aptation of the anal canal at rest. By using a MRI torso coil, we identified a patulous anal canal in some patients with anorectal disorders. We aimed to evaluate the relationship between anal sphincter and puborectalis injury, a patulous anal canal, and anal pressures.MethodsWe performed a retrospective analysis of data from 119 patients who underwent MRI and manometry analysis of anal anatomy and pressures, respectively, from February 2011 through March 2013 at the Mayo Clinic. Anal pressures were determined by high-resolution manometry, anal sphincter and puborectalis injury was determined by endoanal MRI, and anal canal integrity was determined by torso MRI. Associations between manometric and anatomic parameters were evaluated with univariate and multivariate analyses.ResultsFecal incontinence (55 patients; 46%) and constipation (36 patients; 30%) were the main indications for testing; 49 patients (41%) had a patulous anal canal, which was associated with injury to more than 1 muscle (all P ≤ .001), and internal sphincter (P < .01), but not puborectalis (P = .09) or external sphincter (P = .06), injury. Internal (P < .01) and external sphincter injury (P = .02) and a patulous canal (P < .001), but not puborectalis injury, predicted anal resting pressure. A patulous anal canal was the only significant predictor (P < .01) of the anal squeeze pressure increment.ConclusionsPatients with anorectal disorders commonly have a patulous anal canal, which is associated with more severe anal injury and independently predicted anal resting pressure and squeeze pressure increment. It therefore is important to identify a patulous anal canal because it appears to be a marker of not only anal sphincter injury but disturbances beyond sphincter injury, such as damage to the anal cushions or anal denervation.
| S-EPMC4575824 | biostudies-literature
Project description:BackgroundThere is currently no effective treatment for promoting regeneration of injured nerves in patients who have sustained injury to the central nervous system such as spinal cord injury. Chondroitinase ABC is an enzyme, which promotes neurite outgrowth and regeneration. It has shown considerable promise as a therapy for these conditions. The aim of the study is to determine if targeting chondroitinase ABC expression to the neuronal axon can further enhance its ability to promote axon outgrowth. Long-distance axon regeneration has not yet been achieved, and would be a significant step in attaining functional recovery following spinal cord injury.Methodology/principal findingsTo investigate this, neuronal cultures were transfected with constructs encoding axon-targeted chondroitinase, non-targeted chondroitinase or GFP, and the effects on neuron outgrowth and sprouting determined on substrates either permissive or inhibitory to neuron regeneration. The mechanisms underlying the observed effects were also explored. Targeting chondroitinase to the neuronal axon markedly enhances its ability to promote neurite outgrowth. The increase in neurite length is associated with an upregulation of β-integrin staining at the axonal cell surface. Staining for phosphofocal adhesion kinase, is also increased, indicating that the β-integrins are in an activated state. Expression of chondroitinase within the neurons also resulted in a decrease in expression of PTEN and RhoA, molecules which present a block to neurite outgrowth, thus identifying two of the pathways by which ChABC promotes neurite outgrowth.Conclusions / significanceThe novel finding that targeting ChABC to the axon significantly enhances its ability to promote neurite extension, suggests that this may be an effective way of promoting long-distance axon regeneration following spinal cord injury. It could also potentially improve its efficacy in the treatment of other pathologies, where it has been shown to promote recovery, such as myocardial infarction, stroke and Parkinson's disease.
| S-EPMC6974052 | biostudies-literature
Project description:This study aimed to describe the incidence of fecal incontinence (FI) at 6, 12, and 24 weeks postpartum; anal incontinence (AI) and fecal urgency at 24 weeks; and identify predictors of AI in women with obstetric anal sphincter injury (OASI).Primiparous women sustaining OASIs were identified at 8 clinical sites. Third-degree OASIs were characterized using World Health Organization criteria, 3a (<50%) or 3b (>50%) tear through the sphincter. Fecal incontinence was defined as leakage of liquid/solid stool and/or mucus in the past month; AI was defined as leakage of liquid/solid stool and/or mucus and/or gas in the past month and was assessed at 6, 12, and 24 weeks postpartum using the Fecal Incontinence Severity Index. Logistic regression identified variables associated with AI.Three hundred forty-three women participated: 297 subjects sustained a third-degree OASI, 168 type 3a, 98 type 3b and 31 indeterminant; 45 had a fourth-degree OASI. Overall FI incidence at 6, 12, and 24 weeks was 7% [23/326; 95% confidence interval (CI), 4%-10%], 4% (6/145; 95% CI, 2%-9%), and 9% (13/138; 95% CI, 5%-16%), respectively. At 24 weeks, AI incidence was 24% (95% CI, 17%-32%) and fecal urgency 21% (95% CI, 15%-29%). No significant differences in FI and AI rates were noted by third-degree type or between groups with third and fourth OASI. Flatal incontinence was greater in women sustaining a fourth-degree tear (35% vs 16%, P = 0.04). White race (adjusted odds ratio, 4.64; 95% CI, 1.35-16.02) and shorter duration of second stage (adjusted odds ratio, 1.47 per 30 minute decrease; 95% CI, 1.12-1.92) were associated with AI at 24 weeks.Overall 24-week incidence of FI is 9% (95% CI, 5%-16%) and AI is 24% (95% CI, 17%-32%). In women with OASI, white race and shorter second-stage labor were associated with postpartum AI.NCT01166399 (http://clinicaltrials.gov).
| S-EPMC4481184 | biostudies-literature