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Mechanical and chemical trauma are a widely accepted theories to explain the pathogenesis of meatalstenosis after newborn circumcision. The aim of the present study was to explore the theory that an exposed glans is prone to meatal stenosis. This was done by a novel investigation of boys who were born with "hooded prepuce", a condition in which the glans is completely exposed. Physical examination, lower urinary tract symptoms, urethral meatus configuration, and surgical procedures of 18 children admitted for routine circumcision, who had congenital hooded prepuce with normally located urethral meatus, were analyzed. The study period was 2013 and 2018. All the cases have been seen because of neonatal circumcision request, but was postponed due to hooded prepuce. The only presenting complaint in children was a cosmetically unattractive appearance. There were no symptoms associated with meatal stenosis, they circumcised in an average of 6 years and non of them required any additional procedure.Conclusion: Meatal stenosis did not occur in cases whose glans penis are naked with hooded prepuce. These findings do not support the default chemical and mechanical trauma theories. Hooded prepuce without any penile anomalies is only a cosmetically unattractive appearance and circumcision can correct this. What is known: ⢠The common theory of meatal stenosis etiology is that the meatus undergoes irritation with chemical/mechanical trauma in the absence of a prepuce after newborn circumcision. ⢠Circumcision is usually postponed in newborns with hooded prepuce. What is new: ⢠We did not notice meatal stenosis in cases whose urethral meatus were not covered with a prepuce congenitally. Ammoniacal dermatitis or mechanical trauma theories may not explain the cause of meatal stenosis. ⢠Hooded prepuce is not a handicap to newborn circumcision. It is just a cosmetic problem and circumcision can solve it.
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Circuncisão Masculina/efeitos adversos , Doenças do Pênis/complicações , Pênis/anormalidades , Estreitamento Uretral/etiologia , Criança , Humanos , Recém-Nascido , Masculino , Doenças do Pênis/cirurgia , Pênis/lesões , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Uretra/lesões , Uretra/patologia , Estreitamento Uretral/epidemiologiaRESUMO
Congenital nephrotic syndrome is a term used to describe a condition in babies who develop severe proteinuria and hypoalbuminaemia within their first three months of life. They generally have oedema and ascites from birth which, because of increased intra-abdominal pressure, can result in an umbilical hernia. The report presents a five-month old infant with congenital nephrotic syndrome who had spontaneous umbilical hernia rupture with evisceration. The approach to umbilical hernias is usually conservative, but in selected cases elective surgery may be indicated.
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Hérnia Umbilical/cirurgia , Síndrome Nefrótica/complicações , Ruptura Espontânea/cirurgia , Colo , Edema/etiologia , Feminino , Hérnia Umbilical/etiologia , Humanos , Lactente , Intestino DelgadoRESUMO
Although necrotizing enterocolitis (NEC) is a frequently encountered entity in premature infants in the neonatal intensive care unit, intussusception is extremely rare. Abdominal distension, bilious/non-bilious gastric residuals and bloody stool are the common clinical findings of both entities. Here we present three cases of intussusception misdiagnosed as NEC, two of which were complicated with intestinal perforation. Similar clinical findings of NEC and intussusception leads to misdiagnosis and delay in treatment, particularly in premature infants with intussusception.
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Doenças do Prematuro/diagnóstico , Intussuscepção/diagnóstico , Síndrome de Stevens-Johnson/diagnóstico , Erros de Diagnóstico , Feminino , Humanos , Recém-Nascido , MasculinoRESUMO
BACKGROUND: Autologous tissues derived from bowel, buccal mucosa and skin are primarily used to repair or replace diseased vaginal segments as well as create neovaginas for male-to-female transgenders. These grafts are often limited by scarce tissue supply, donor site morbidity and post-operative complications. Bi-layer silk fibroin (BLSF) biomaterials represent potential alternatives for vaginoplasty given their structural strength and elasticity, low immunogenicity, and processing flexibility. The goals of the current study were to assess the potential of acellular BLSF scaffolds for vaginal tissue regeneration in respect to conventional small intestinal submucosal (SIS) matrices in a rat model of vaginoplasty. METHODS: Inlay vaginoplasty was performed with BLSF and SIS scaffolds (N = 21 per graft) in adult female rats for up to 2 months of implantation. Nonsurgical controls (N = 4) were investigated in parallel. Outcome analyses included histologic, immunohistochemical and histomorphometric evaluations of wound healing patterns; µ-computed tomography (CT) of vaginal continuity; and breeding assessments. RESULTS: Animals in both scaffold cohorts exhibited 100% survival rates with no severe post-operative complications. At 2 months post-op, µ-CT analysis revealed normal vaginal anatomy and continuity in both graft groups similar to controls. In parallel, BLSF and SIS grafts also induced comparable constructive remodeling patterns and were histologically equivalent in their ability to support formation of vascularized vaginal neotissues with native tissue architecture, however with significantly less smooth muscle content. Vaginal tissues reconstructed with both implants were capable of supporting copulation, pregnancy and similar amounts of live births. CONCLUSIONS: BLSF biomaterials represent potential "off-the-shelf" candidates for vaginoplasty.
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PURPOSE: Ureteral reimplantation via pneumovesicum is a new aspect of vesicoureteral reflux management. We aimed to determine the effects of carbon dioxide (CO2) insufflation on the upper urinary tract in an experimental model. MATERIALS AND METHODS: Thirty New Zealand rabbits were allocated into five groups of six rabbits each. Right ureters were cannulated for CO2 insufflation in four groups. The pressures and durations of CO2 insufflation in the respective groups were as follows: Group A (10 mm Hg, 2 h); B (12 mm Hg, 2 h); C (10 mm Hg, 4 h); and D (12 mm Hg, 4 h) and control (E). Blood gas analysis, urea and creatinine levels were measured from renal veins and aorta. Histopathological evaluation of the renal parenchyma and ureters was scored. RESULTS: Significant histopathological changes were detected in the ipsilateral ureter and renal parenchyma exposed to CO2 insufflation, predominantly observed in groups insufflated for longer durations, p < 0.05. Blood gases drawn separately from renal veins were significantly more acidotic, and serum urea and creatinine levels were increased in all the groups, p < 0.05. CONCLUSIONS: CO2 causes significant histopathological and biochemical changes in the early period. Long-term results are required to determine whether permanent renal injury occurs.
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Dióxido de Carbono/administração & dosagem , Dióxido de Carbono/efeitos adversos , Insuflação/efeitos adversos , Sistema Urinário/lesões , Refluxo Vesicoureteral/fisiopatologia , Animais , Gasometria/métodos , Dióxido de Carbono/sangue , Creatinina/sangue , Modelos Animais de Doenças , Insuflação/métodos , Coelhos , Fatores de Tempo , Ureia/sangueRESUMO
Peyronie's disease (PD) is a debilitating pathology which is associated with penile curvature and erectile dysfunction due to the formation of fibrotic plaques in the penile tunica albuginea. In the present study, we developed a novel rabbit model of PD via subtunical injection of recombinant transforming growth factor (TGF)-ß1 protein and characterized erectile function and histopathological endpoints following plaque formation. Ten adult male, New Zealand white rabbits were randomized into 3 experimental groups including nonsurgical controls (NSC, N = 3) and those receiving subtunical injections of vehicle (N = 3) or TGF-ß1 protein (0.5 µg/50 µl; N = 4). Following 1 month post-op, focal fibrous plaques composed of disorganized collagen type I and III bundles as well as fragmented elastin fibers at TGF-ß1 injection sites were observed in contrast to control groups. Cavernosometric and cavernosographic evaluations revealed no significant differences in maximum intracorporal pressures or substantial curvature during papaverine-induced erection in either the vehicle or TGF-ß1 cohorts. Immunohistochemical and histomorphometric analyses demonstrated significant increases in elastase 2B expression in TGF-ß1-induced plaques as well as significant declines in matrix metalloproteinase (MMP)-2 and -9 expression relative to control levels. Our results demonstrate that PD-like fibrotic plaques can be created in the rabbit penile tunica albuginea following TGF-ß1 injection.
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Background: Preclinical animal models which mimic the dimensions of long urethral strictures (>2 cm in length) encountered in the clinic are necessary to evaluate prospective graft designs for urethroplasty. The purpose of this study was to develop both male and female porcine models of long urethral strictures (â¼4 cm in length) and characterize histological and functional outcomes of iatrogenic stricture formation between genders. Methods: Focal, partial thickness urethral injuries were created over 5-6 cm long segments in male and female swine (N = 4 per gender) via electrocoagulation and the degree of stricture formation was monitored for up to 6 weeks by urethroscopy and retrograde urethrography. Animals were sacrificed following stricture confirmation and histological, immunohistochemical, and histomorphometric analyses were performed on strictured and uninjured control urethral segments to profile wound healing responses. Results: Urethral stricture formation was detected in all female swine by 2 weeks and 100 % of male swine at 3.2 ± 1.8 weeks, post-operatively. The mean length of urethral strictures in both male and female swine was â¼4 cm. Substantial variations in the degree of stricture severity between sexes were observed with males exhibiting significant urethral stenosis and loss of α-smooth muscle actin+ smooth muscle bundles in comparison to controls, while females primarily displayed defects in pan-cytokeratin+ epithelia as well as functional urethral obstruction. Conclusions: Electrocoagulation injury is sufficient to produce long urethral strictures in male and female swine and the degree of stricture severity and nature of urethral obstruction was observed to be dependent on gender. Animal Protocol: AUP-19-150. Key message: Novel male and female models of long urethral strictures in swine were created to characterize histological and functional outcomes of iatrogenic stricture formation between genders.
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Esophageal pathologies such as atresia and benign strictures often require surgical reconstruction with autologous tissues to restore organ continuity. Complications such as donor site morbidity and limited tissue availability have spurred the development of acellular grafts for esophageal tissue replacement. Acellular biomaterials for esophageal repair rely on the activation of intrinsic regenerative mechanisms to mediate de novo tissue formation at implantation sites. Previous research has identified signaling cascades involved in neoepithelial formation in a rat model of onlay esophagoplasty with acellular silk fibroin grafts, including phosphoinositide 3-kinase (PI3K), and protein kinase B (Akt) signaling. However, it is currently unknown how these mechanisms are governed by DNA methylation (DNAme) during esophageal wound healing processes. Reduced-representation bisulfite sequencing is performed to characterize temporal DNAme dynamics in host and regenerated tissues up to 1 week postimplantation. Overall, global hypermethylation is observed at postreconstruction timepoints and an inverse correlation between promoter DNAme and the expression levels of differentially expressed proteins during regeneration. Site-specific hypomethylation targets genes associated with immune activation, while hypermethylation occurs within gene bodies encoding PI3K-Akt signaling components during the tissue remodeling period. The data provide insight into the epigenetic mechanisms during esophageal regeneration following surgical repair with acellular grafts.
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Fibroínas , Ratos , Animais , Alicerces Teciduais , Proteínas Proto-Oncogênicas c-akt , Fosfatidilinositol 3-Quinases/genética , Metilação de DNA , Regeneração/genéticaRESUMO
Background: The primary strategy for urinary diversion in radical cystectomy patients involves incorporation of autologous gastrointestinal conduits into the urinary tract which leads to deleterious consequences including chronic infections and metabolic abnormalities. This report investigates the efficacy of an acellular, tubular bi-layer silk fibroin (BLSF) graft to function as an alternative urinary conduit in a porcine model of urinary diversion. Materials and methods: Unilateral urinary diversion with stented BLSF conduits was executed in five adult female, Yucatan mini-swine over a 3 month period. Longitudinal imaging analyses including ultrasonography, retrograde ureteropyelography and video-endoscopy were carried out monthly. Histological, immunohistochemical (IHC), and histomorphometric assessments were performed on neoconduits at harvest. Results: All animals survived until scheduled euthanasia and displayed moderate hydronephrosis (Grades 1-3) in reconstructed collecting systems over the course of the study period. Stented BLSF constructs supported formation of vascularized, retroperitoneal tubes capable of facilitating external urinary drainage. By 3 months post-operative, neoconduits contained α-smooth muscle actin+ and SM22α+ smooth muscle as well as uroplakin 3A+ and pan-cytokeratin + urothelium. However, the degree of tissue regeneration in neotissues was significantly lower in comparison to ureteral controls as determined by histomorphometry. In addition, neoconduit stenting was necessary to prevent stomal occlusion. Conclusion: BLSF biomaterials represent emerging platforms for urinary conduit construction and may offer a functional replacement for conventional urinary diversion techniques following further optimization of mechanical properties and regenerative responses.
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Introduction: The creation of synthetic reservoirs for bladder replacement has been limited by challenges of interfacing synthetic materials and native tissue. We sought to overcome this challenge by utilizing a novel bilayer silk fibroin scaffold (BLSF) as an intermediary toward the development of an acellular prosthetic reservoir. Methods: Under institutionally approved protocols, 3D-printed reservoirs were implanted in six juvenile female pigs after cystectomy. BLSF was attached to the in situ prosthetic reservoir serving as an intermediary to native ureteral and urethral tissue anastomoses. Our first protocol allowed four pigs to be survived up to 7 days, and the second protocol allowed two pigs to be survived for up to 1 year. At the first sign of functional decline or the end of the study period, the animals were euthanized, and kidneys, ureters, prosthetic bladder, and urethra were harvested en bloc for histopathology analysis. Results: The first two pigs had anastomotic urine leaks because of design flaws resulting in early termination. The third pig had acute renal failure resulting in early termination. The artificial bladder design was modified in subsequent iterations. The fourth pig survived for 7 days and, upon autopsy, had intact urethral and ureteral anastomoses. The fifth and sixth pigs survived for 11 and 12 weeks, respectively, before they were sacrificed because of failure to thrive. One animal developed an enteric fistula. The other animal had an intact anastomosis, and the BLFS was identified at the ureteral and urethral anastomoses on histopathologic analysis. Conclusions: Replacing the porcine bladder with a prosthetic bladder was achieved for up to 3 months, the second longest survival period for a nonbiologic bladder alternative. BLSF was used for the first time to create an interface between synthetic material and biologic tissue by allowing ingrowth of urothelium onto the acellular alloplastic bladder.
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Fibroínas , Ureter , Suínos , Feminino , Animais , Bexiga Urinária/cirurgia , Bexiga Urinária/patologia , Estudos de Viabilidade , Ureter/cirurgia , Cistectomia/métodosRESUMO
OBJECTIVE: In a cystometry procedure in a child with myelomeningocele (MMC), a pressure increase in the abdominal pressure (P (abd)) tracing was detected during filling. This pressure alteration was not related to other known events (straining, talking, rectal contractions). This study was conducted to investigate this phenomenon. MATERIAL AND METHODS: Forty-three children with MMC were enrolled in the study. A slow and gradual pressure increase associated with the bladder filling was sought in the P (abd) tracings. End filling and initial P (abd) gradient more than 3 cm H(2)O were considered as increased P (abd). If the defined pressure event occurs, the bladder was evacuated for verifying the filling-pressure relation. Age, gender, study position, pelvic floor tonicity and cystometric capacity were correlated with the pressure alteration. RESULTS: P (abd) increase was noted in 18 (41.8%) children. The mean P (abd) gradient between end and initial filling was 4.78 ± 1.63 cm H(2)O in these children. No statistically significant difference was noted for age, gender and study position. Statistically significant differences were noted with decreased pelvic floor tonicity and high values of cystometric capacity (p = 0.003 and p < 0.001, respectively). CONCLUSIONS: The pressure increase is thought to be a consequence of a posterior positional change in the bladder during filling die to decreased pelvic floor support in MMC. This pressure alteration was more obvious with increased bladder capacity. Urodynamic studies of children with MMC should be carefully evaluated for the presence of this phenomenon to prevent low measurement of the detrusor pressure, compliance and detrusor leak point pressure values.
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Meningomielocele/fisiopatologia , Tono Muscular , Diafragma da Pelve/fisiopatologia , Urodinâmica/fisiologia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Estudos ProspectivosRESUMO
Ureteral reconstruction with autologous tissue grafts is often limited by tissue availability and donor site morbidity. This study investigates the performance of acellular, bi-layer silk fibroin (BLSF) scaffolds in a porcine model of ureteroplasty. Tubular ureteroplasty with BLSF grafts in combination with transient stenting for 8 weeks was performed in adult female, Yucatan, mini-swine (N = 5). Animals were maintained for 12 weeks post-op with imaging of neoconduits using ultrasonography and retrograde ureteropyelography carried out at 2 and 4 weeks intervals. End-point analyses of ureteral neotissues and unoperated controls included histological, immunohistochemical (IHC), histomorphometric evaluations as well as ex vivo functional assessments of contraction/relaxation. All animals survived until scheduled euthanasia and displayed mild hydronephrosis (Grades 1-2) in reconstructed collecting systems during the 8 weeks stenting period with one animal presenting with a persistent subcutaneous fistula at 2 weeks post-op. By 12 weeks of scaffold implantation, unstented neoconduits led to severe hydronephrosis (Grade 4) and stricture formation in the interior of graft sites in 80% of swine. Bulk scaffold extrusion into the distal ureter was also apparent in 60% of swine contributing to ureteral obstruction. However, histological and IHC analyses revealed the formation of innervated, vascularized neotissues with a-smooth muscle actin+ and SM22α+ smooth muscle bundles as well as uroplakin 3A+ and pan-cytokeratin + urothelium. Ex vivo contractility and relaxation responses of neotissues were similar to unoperated control segments. BLSF biomaterials represent emerging platforms for tubular ureteroplasty, however further optimization is needed to improve in vivo degradation kinetics and mitigate stricture formation.
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The use of autologous tissue grafts for tunica albuginea repair in Peyronie's disease and congenital chordee is often restricted by limited tissue availability and donor site morbidity, therefore new biomaterial options are needed. In this study, bi-layer silk fibroin (BLSF) scaffolds were investigated to support functional tissue regeneration of tunica albuginea in a rabbit corporoplasty model. Eighteen adult male, New Zealand white rabbits were randomized to nonsurgical controls (NSC, N = 3), or subjected to corporoplasty with BLSF grafts (N = 5); decellularized small intestinal submucosa (SIS) matrices (N = 5); or autologous tunica vaginalis (TV) flaps (N = 5). End-point evaluations were cavernosography, cavernosometry, histological, immunohistochemical, and histomorphometric assessments. Maximum intracorporal pressures (ICP) following papaverine-induced erection were similar between all groups. Eighty percent of rabbits repaired with BLSF scaffolds or TV flaps achieved full rigid erections, compared to 40% of SIS reconstructed animals. Five-minute peak erections were maintained in 60% of BLSF rabbits, compared to 20% of SIS and TV flap reconstructed rabbits. Graft perforation occurred in 60% of TV group at maximum ICP compared to 20% of BLSF cohort. Neotissues supported by SIS and BLSF scaffolds were composed of collagen type I and elastin fibers similar to NSC. SIS and TV flaps showed significantly elevated levels of corporal fibrosis relative to NSC with a corresponding decrease in corporal smooth muscle cells expressing contractile proteins. BLSF biomaterials represent emerging platforms for corporoplasty and produce superior functional and histological outcomes in comparison to TV flaps and SIS matrices for tunica albuginea repair.
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Surgical reconstruction of tubular esophageal defects with autologous gastrointestinal segments is the gold standard treatment to replace damaged or diseased esophageal tissues. Unfortunately, this approach is associated with adverse complications, including dysphagia, donor-site morbidity, and in some cases patient death. Bilayer silk fibroin (BLSF) scaffolds were investigated as alternative, acellular grafts for tubular esophagoplasty in a porcine defect model for 3 months of implantation. Adult Yucatan mini-swine (n = 5) were subjected to esophageal reconstruction with tubular BLSF grafts (2 cm in length) in combination with transient esophageal stenting for 2 months followed by a 1-month period, where the graft site was unstented. All animals receiving BLSF grafts survived and were capable of solid food consumption, however strictures were noted at graft regions in 60% of the experimental cohort between 2 and 3 months postop and required balloon dilation. In addition, fluoroscopic analysis showed peristaltic function in only 1/5 neotissues. Following swine harvest at 3 months, ex vivo tissue bath evaluations revealed that neoconduits exhibited contractile responses to carbachol, electric field stimulation, and KCl, whereas sodium nitroprusside and isoproterenol induced relaxation effects. Histological (Masson's Trichrome) and immunohistochemical analyses of regenerated tissue conduits showed a stratified, squamous epithelium expressing pan-cytokeratins buttressed by a vascularized lamina propria containing a smooth muscle-rich muscularis mucosa surrounded by a muscularis externa. Neuronal density, characterized by the presence of synaptophysin-positive boutons, was significantly lower in neotissues in comparison to nonsurgical controls. BLSF scaffolds represent a promising platform for the repair of tubular esophageal defects, however improvements in scaffold design are needed to reduce the rate of complications and improve the extent of constructive tissue remodeling. Impact statement The search for a superior "off-the-shelf" scaffold capable of repairing tubularesophageal defects as well as overcoming limitations associated with conventional autologous gastrointestinal segments remains elusive. The purpose of this study was to investigate the performance of an acellular, bilayer silk fibroin graft (BLSF) for tubular esophagoplasty in a porcine model. Our results demonstrated that BLSF scaffolds supported the formation of tubular neotissues with innervated, vascularized epithelial and muscular components capable of contractile and relaxation responses. BLSF scaffolds represent a promising platform for esophageal tissue engineering.
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Esofagoplastia , Fibroínas , Animais , Fibroínas/farmacologia , Regeneração , Seda , Suínos , Engenharia Tecidual , Alicerces TeciduaisRESUMO
Constructive remodeling of focal esophageal defects with biodegradable acellular grafts relies on the ability of host progenitor cell populations to repopulate implant regions and facilitate growth of de novo functional tissue. Intrinsic molecular mechanisms governing esophageal repair processes following biomaterial-based, surgical reconstruction is largely unknown. In the present study, we utilized mass spectrometry-based quantitative proteomics and in silico pathway evaluations to identify signaling cascades which were significantly activated during neoepithelial formation in a Sprague Dawley rat model of onlay esophagoplasty with acellular silk fibroin scaffolds. Pharmacologic inhibitor and rescue experiments revealed that epithelialization of neotissues is significantly dependent in part on pro-survival stimuli capable of suppressing caspase activity in epithelial progenitors via activation of hepatocyte growth factor receptor (c-MET), tropomyosin receptor kinase A (TrkA), phosphoinositide 3-kinase (PI3K), and protein kinase B (Akt) signaling mechanisms. These data highlight the molecular machinery involved in esophageal epithelial regeneration following surgical repair with acellular implants.
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Esôfago/citologia , Fibroínas/administração & dosagem , Procedimentos de Cirurgia Plástica/métodos , Animais , Células Epiteliais/citologia , Esôfago/cirurgia , Humanos , Ratos Sprague-Dawley , Regeneração , Transdução de SinaisRESUMO
OBJECTIVE: Acute intestinal ischemia reperfusion (I/R) injury affects not only the intestines but also remote organs due to pro-inflammatory and tissue injurious factors. Thus, we aimed to investigate the roles of melatonin (a powerful antioxidant) and 1400W (a strong inhibitor of inducible nitric oxide) in a rat intestinal I/R injury model, since oxidative and nitrosative injury are believed to be the major causes. METHODS: A total of 56 Wistar albino rats were used, with seven rats in each group. After I/R induction in the intestines by clamping/unclamping the superior mesenteric artery, we measured malondialdehyde, superoxide dismutase, glutathione peroxidase, nitric oxide, and 3-nitrotyrosine levels in lung, kidney, and liver tissues (to evaluate remote organ injury) as well as in the intestines. Study groups received melatonin, 1400W or both to examine the roles of these molecules in the pathogenesis of injury following I/R. RESULTS: Melatonin and 1400W had an ameliorating effect on both oxidative and nitrosative stress in the intestine and the lung against mesenteric I/R injury in rats. Moreover, each of these two agents had an inhibitory effect on oxidative injury and histopathological changes in the intestine and the lung. Furthermore, the combination of both agents (melatonin and 1400W) was more effective than either of the agents alone (P < 0.05). CONCLUSION: Melatonin and 1400W, either alone or in combination, were efficient in ameliorating experimental I/R injury of the intestines.
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Amidinas/farmacologia , Antioxidantes/farmacologia , Benzilaminas/farmacologia , Inibidores Enzimáticos/farmacologia , Melatonina/farmacologia , Oclusão Vascular Mesentérica/tratamento farmacológico , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Glutationa Peroxidase/metabolismo , Mucosa Intestinal/metabolismo , Intestinos/irrigação sanguínea , Intestinos/patologia , Rim/metabolismo , Rim/patologia , Fígado/metabolismo , Fígado/patologia , Pulmão/metabolismo , Pulmão/patologia , Masculino , Malondialdeído/metabolismo , Oclusão Vascular Mesentérica/metabolismo , Oclusão Vascular Mesentérica/patologia , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Óxido Nítrico Sintase Tipo II/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Superóxido Dismutase/metabolismo , Taxa de Sobrevida , Tirosina/análogos & derivados , Tirosina/metabolismo , Glutationa Peroxidase GPX1RESUMO
OBJECTIVE: To assess the efficacy of acellular bilayer silk fibroin (BLSF) grafts to repair full-thickness tracheal defects and to compare the performance with conventional porcine small intestinal submucosa (SIS) implants. STUDY DESIGN: A prospective controlled animal trial in a rat model of onlay tracheoplasty. SETTING: Pediatric medical center. SUBJECTS AND METHODS: Tracheal reconstruction of adult Sprague-Dawley rats was performed with BLSF (n = 38) or SIS (n = 32) matrices for up to 3 months of implantation. Functional evaluations of repaired conduits as well as histologic, immunohistochemical, and histomorphometric analyses of neotissues were assessed. RESULTS: Prior to scheduled euthanasia, survival rates of rats receiving BLSF or SIS grafts were ≥94%, with no clinical signs of airway obstruction observed over the course of the study. Micro-computed tomography analysis revealed that the mean percentage of stenosis was <20% in both implant groups. BLSF and SIS grafts supported formation of pseudostratified ciliated columnar epithelium by 1 week postoperatively; however, each matrix failed to promote de novo chondrogenesis by 3 months following repair. CONCLUSIONS: BLSF scaffolds can be used for reconstruction of rat tracheal patch defects with functional outcomes comparable to those of SIS matrices.
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Fibroínas/uso terapêutico , Procedimentos de Cirurgia Plástica/métodos , Regeneração , Engenharia Tecidual/métodos , Traqueostomia/métodos , Animais , Materiais Biocompatíveis , Biópsia por Agulha , Modelos Animais de Doenças , Sobrevivência de Enxerto , Imuno-Histoquímica , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Alicerces TeciduaisRESUMO
INTRODUCTION: Delayed presentation of posterior urethral valves (PUVs) is a rare condition. Presentation and diagnosis of the patients with late PUVs are challenging. Voiding cystourethrogram (VCUG) is mainly practiced. In this study, we aimed to evaluate the children with late-presented PUVs, and the reliability of VCUG in this group. MATERIALS AND METHODS: Between January 2003 and December 2017 records of patients who were diagnosed with late-presented PUVs were analyzed. Delayed presentation of PUV was defined as patients who were diagnosed and treated after infancy. Cases were examined in terms of age at diagnosis, presenting symptoms, urinalysis, urinary ultrasound, urodynamic studies, VCUG, and dimercaptosuccinic acid scintigraphy findings. Postoperative follow-up conditions were also assessed. RESULTS: Seventeen boys were diagnosed with late-presented PUVs (mean age was 7.35 years). The most common symptoms at presentation were frequency (58.8%), day and nighttime incontinence (47%), and febrile urinary infection (41%). PUV was noted by VCUG in 10 patients alone. The classical sign of dilated posterior urethra was detected in 9 patients. The 10th patient had posterior urethral irregularity. Urethra could not be evaluated due to unsuccessful voiding in one patient. Six patients had normally appearing urethra on VCUG. Reflux was detected in nine (52.9%) patients. CONCLUSION: Late-presented PUVs may be missed on VCUG. Whether a PUV might be present is crucial in boys with a history of recurrent urinary infection, persistent reflux, and repetitive daytime incontinence. Based on our results, we conclude that cystoscopic examination should be preferred for those cases to diagnose PUVs regardless of VCUG results.
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Cistografia/métodos , Uretra/anormalidades , Uretra/diagnóstico por imagem , Adolescente , Humanos , Masculino , Recidiva , Reprodutibilidade dos Testes , Estudos Retrospectivos , Uretra/cirurgia , Estreitamento Uretral/diagnóstico por imagem , Estreitamento Uretral/etiologia , Estreitamento Uretral/cirurgia , Infecções Urinárias/etiologia , Micção , Transtornos Urinários/etiologiaRESUMO
IMPACT STATEMENT: The search for an ideal "off-the-shelf" biomaterial for augmentation cystoplasty remains elusive and current scaffold configurations are hampered by mechanical and biocompatibility restrictions. In addition, preclinical evaluations of potential scaffold designs for bladder repair are limited by the lack of tractable large animal models of obstructive bladder disease that can mimic clinical pathology. The results of this study describe a novel, minimally invasive, porcine model of partial bladder outlet obstruction that simulates clinically relevant phenotypes. Utilizing this model, we demonstrate that acellular, bi-layer silk fibroin grafts can support the formation of vascularized, innervated bladder tissues with functional properties.
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Fibroínas/química , Regeneração , Alicerces Teciduais/química , Doenças da Bexiga Urinária , Animais , Modelos Animais de Doenças , Feminino , Suínos , Doenças da Bexiga Urinária/fisiopatologia , Doenças da Bexiga Urinária/psicologia , Doenças da Bexiga Urinária/terapia , UrodinâmicaRESUMO
INTRODUCTION: Nitric oxide (NO) and peroxynitrite (OONO-) are implicated in the pathophysiology of renal ischemia/reperfusion (I/R). The aim of this study was to investigate and compare the efficiency of S-methylisothiourea (SMT), an iNOS inhibitor, and mercaptoethylguanidine (MEG), a scavenger of peroxynitrite, on renal dysfunction and injury induced by I/R of rat kidney. MATERIALS AND METHODS: Thirty-two male Sprague-Dawley rats were divided into four groups: sham-operated, I/R, I/R+SMT, and I/R+MEG. Rats were given SMT (10 mg/kg i.p.) or MEG (10 mg/kg i.p.) 6 h prior to I/R and at the beginning of reperfusion. All rats except sham-operated underwent 60 min of bilateral renal ischemia followed by 6 h of reperfusion. After reperfusion, kidneys and blood were obtained for evaluation. Superoxide dismutase, glutathione peroxidase, malondialdehide, protein carbonyl content, and nitrite/nitrate level (NO(x)) were determined in the renal tissue. Serum creatinine (S(Cr)), blood urea nitrogen (BUN), and aspartate aminotransferase (AST) were determined in the blood. Additionally, renal sections were used for histological grade of renal injury. RESULTS: SMT and MEG significantly reduced the I/R-induced increases in S(Cr), BUN, and AST. Both SMT and MEG attenuated the tissue NO(x) levels, indicating reduced NO production. In addition, SMT and MEG markedly reduced elevated oxidative stress product, restored decreased antioxidant enzymes, and attenuated histological alterations. Interestingly, MEG exerted a greater renoprotective effect than SMT. CONCLUSIONS: These data support the finding that iNOS and peroxynitrite are involved in the renal I/R injury, and suggest that a scavenger of peroxynitrite might be more effective than iNOS inhibitors as a therapeutic intervention.