Submucosal Tissue Research Articles

Endoscopic treatment of complete stripping of esophageal mucosal and submucosal tissue layers.

Endoscopic treatment of complete stripping of esophageal mucosal and submucosal tissue layers.

Rectifying disorder of extracellular matrix to suppress urethral stricture by protein nanofilm-controlled drug delivery from urinary catheter

Urethral stricture secondary to urethral injury, afflicting both patients and urologists, is initiated by excessive deposition of extracellular matrix in the submucosal and periurethral tissues. Although various anti-fibrotic drugs have been applied to urethral stricture by irrigation or submucosal injection, their clinical feasibility and effectiveness are limited. Here, to target the pathological state of the extracellular matrix, we design a protein-based nanofilm-controlled drug delivery system and assemble it on the catheter. This approach, which integrates excellent anti-biofilm properties with stable and controlled drug delivery for tens of days in one step, ensures optimal efficacy and negligible side effects while preventing biofilm-related infections. In a rabbit model of urethral injury, the anti-fibrotic catheter maintains extracellular matrix homeostasis by reducing fibroblast-derived collagen production and enhancing metalloproteinase 1-induced collagen degradation, resulting in a greater improvement in lumen stenosis than other topical therapies for urethral stricture prevention. Such facilely fabricated biocompatible coating with antibacterial contamination and sustained-drug-release functionality could not only benefit populations at high risk of urethral stricture but also serve as an advanced paradigm for a range of biomedical applications.

Comparative study of optical coherence tomograph and histological images of eustachian tube nasopharyngeal region and adjacent structures in vivo and ex-vivo miniature pigs

ObjectivesOptical Coherence Tomograph (OCT) imaging technology can be used to examine, in vivo, the human ET. At present, it is impossible to achieve the OCT scanning vivo and ex vivo in the same individual human body, or study the consistency between OCT images and histological images of the eustachian tube nasopharyngeal region and adjacent structures. The aim of this study was to determine the consistency between OCT images and histological sections in vivo and ex vivo in miniature pigs.MethodsOCT imaging was performed on five adult miniature pigs in vivo and ex vivo. The images of the eustachian tube OCT (ET-OCT), nasopharynx OCT (NP-OCT) and histological cross sections were further studied.ResultsAll five miniature pigs achieved the OCT scan successfully, acquiring ET-OCT and NP-OCT images in vivo and ex vivo on both sides. The acquired ET OCT images closely matched the histological images, revealing details of the cartilage, submucosa, glands, and mucosa. The lower segment of the ET wall mucosa had an abundance of glands and submucosal tissues, with more low-signal areas appearing in the ex vivo images. The NP-OCT images of the nasopharynx matched the details of the mucosa and submucosal tissues. The ex-vivo OCT images showed thicker mucosa and more scattered slightly lower signal areas compared to the vivo OCT images.ConclusionsET-OCT images and NP-OCT images matched the histological structure of eustachian tube nasopharyngeal region structures in miniature pigs both in vivo and ex vivo. OCT images may be sensitive to changes in edema and ischemia status. There is a great potential for morphological assessment of inflammation, edema, injure, mucus gland status.

Enhanced neuron-glia network in the submucosa and increased neuron outgrowth into the mucosa are associated with distinctive expressions of neuronal factors in the colon of rat IBS model.

Neuronal attraction and repulsion factors regulate neuron network formation. In the colon of irritable bowel syndrome (IBS), neuron network and enteric glial cells (EGCs) in the submucosa, neuronal outgrowth in the mucosa, and expressions of neuronal factors remain unknown. IBS models were prepared by intracolonic injections of acetic acid to Wistar Kyoto (WKY) rats. Using whole-mount submucosal plexus tissue stripped from the distal colon, we examined neuron network, EGC morphology, and localization of both attraction factor (nerve growth factor: NGF) and repulsion factor (semaphorin3A: Sema3A). We evaluated mRNA expressions of NGF and Sema3A in the mucosa and submucosa and neuron outgrowth into the mucosa. In IBS models, nerve fibers were thickened and densely increased in the submucosa remarkably from the outer toward the inner plexus. Submucosal EGCs exhibited process hyperplasia and bulbous swelling of terminals. NGF was predominantly expressed in EGCs than neurons in the submucosa. NGF mRNA expressions were increased in the submucosa in WKY, and their expressions were increased in the mucosa after the injection. Sema3A mRNA expressions were increased in both layers of WKY but tended to be decreased in the mucosa alone after the injection. Neuron outgrowth was increased into the mucosa. NGF was localized at EGCs in the lamina propria mucosae but not mucosal mast cells. Neuron network enhancement in the submucosa and neuron outgrowth into the mucosa may be associated with axon guidance factors expressed in hyperplastic EGCs in the colonic submucosa of IBS models.

Editorial: Optimizing the success of cold snare polypectomy in colonoscopy practice

Editorial: Optimizing the success of cold snare polypectomy in colonoscopy practice

Preliminary results of absorbable magnesium stent for treating eustachian tube dysfunction in a porcine model.

Absorbable magnesium (Mg) stents have an attractive biocompatibility and rapid degradation rate, but their degradable behavior and efficacy in the Eustachian tube (ET) have not yet been investigated. In this study, the degradable behavior of the Mg stent in artificial nasal mucus was evaluated. The Mg stents in the porcine ET model were also investigated to evaluate their safety and efficacy. Four Mg stents were placed into the four ETs of two pigs. The mass loss rate of the Mg stents gradually decreased over time. The decrease rates were 30.96% at one week, 49.00% at two weeks, and 71.80% at four weeks. On the basis of histological findings, the thickness of submucosal tissue hyperplasia and the degree of inflammatory cell infiltration significantly decreased at four weeks compared with two weeks. Biodegradation of the Mg stent occurred before tissue proliferative reactions, and the ET patency was successfully maintained without stent-induced tissue hyperplasia at four weeks. The Mg stent that biodegrades rapidly seems to be effective and safe in porcine ET. Further investigation is required to verify the optimal stent shape and indwell period in the ET.

Pediatric Angioedema without Wheals: How to Guide the Diagnosis.

Angioedema (AE) is a vascular reaction of subcutaneous and submucosal tissues that identifies various clinical pictures and often is associated with wheals. AE without wheals (AEwW) is infrequent. The ability to distinguish between AEwW mediated by mast cells and bradykinin-mediated or leukotriene-mediated pathways is often crucial for a correct diagnostic-therapeutic and follow-up approach. AEwW can be hereditary or acquired. Factors typically correlated with hereditary angioedema (HAE) are a recurrence of episodes, familiarity, association with abdominal pain, onset after trauma or invasive procedures, refractoriness to antiallergic therapy, and lack of pruritus. The acquired forms of AE can present a definite cause based on the anamnesis and diagnostic tests. Still, they can also have an undetermined cause (idiopathic AE), distinguished according to the response to antihistamine in histamine-mediated and non-histamine-mediated forms. Usually, in childhood, AE responds to antihistamines. If AEwW is not responsive to commonly used treatments, it is necessary to consider alternative diagnoses, even for pediatric patients. In general, a correct diagnostic classification allows, in most cases, optimal management of the patient with the prescription of appropriate therapy and the planning of an adequate follow-up.

Managing Diagnosis, Treatment, and Burden of Disease in Hereditary Angioedema Patients with Normal C1-Esterase Inhibitor.

Hereditary angioedema (HAE) is a rare, chronic, and debilitating genetic disorder characterized by recurrent and unpredictable swelling episodes that primarily affect the subcutaneous and/or submucosal tissues of the extremities, larynx, face, abdomen, and genitals. Most cases of HAE are caused by mutations in the serpin family G member 1 gene (SERPING1), which encodes C1-esterase inhibitor (C1-INH) protein. Mutations in SERPING1 lead to deficient (type I HAE-C1-INH) or dysfunctional (type II HAE-C1-INH) C1-INH protein and subsequent dysregulation of the kallikrein-bradykinin cascade. However, some patients present with a third type of HAE (HAE-nI-C1-INH), which was first described in the year 2000 and is characterized by an absence of mutations in SERPING1. Although mutations in the coagulation factor XII, angiopoietin-1, plasminogen, kininogen-1, myoferlin, and heparan sulfate-glucosamine 3-O-sulfotransferase-6 genes have been identified in some patients with HAE-nI-C1-INH, genetic cause is still unknown in many cases, hindering full elucidation of the pathology of this HAE subtype. Diagnosis of HAE-nI-C1-INH is also further complicated by the fact that patients typically demonstrate normal plasma levels of C1-INH and complement component 4 protein and normal C1-INH functionality during laboratory analysis. Therefore, we review the challenges associated with diagnosing, treating, and living with HAE-nI-C1-INH. We conclude that raising awareness of the presenting features of HAE-nI-C1-INH within the clinical setting and among the general public is critical to aid earlier suspicion and diagnosis of the disease. Furthermore, adopting an individualized approach to HAE-nI-C1-INH treatment is essential to help address the current and significant unmet needs in this patient population.

Top Ten Lymphoproliferative Lesions Not to Miss When Evaluating Oral Ulcer Biopsies.

Oral ulcers represent afull thickness lossof the mucosal epithelium leading to exposure of the submucosal connective tissue. These are common and usually self-limited lesions, although they may sometimes result from neoplasms, most commonly squamous cell carcinoma. Lymphoproliferative disorders may be difficult to diagnose in apthous ulcers since they mimic reactive inflammation. This review presents ten rare oral lymphoid proliferations which should not be missed when assessing oral ulcer biopsies. The ten lesions include several with diagnostic cells which look similar to the histiocytes of a reactive inflammatory ulcer, including Rosai-Dorfman disease, reticulohistiocytoma, Langerhans cell histiocytosis, and traumatic ulcerative granuloma. Other lesions, such as EBV-positive mucocutaneous ulcer, extranodal marginal zone lymphoma of mucosal-associated lymphoid tissue, and plasmablastic lymphoma have lymphoid and/or plasma cell differentiation that mimic the reactive lymphocytes and plasma cells foundin reactive ulcers. Two dendritic cell lesions, follicular dendritic cell sarcoma and blastic plasmacytoid dendritic cell neoplasm, both have distinct phenotypes which are required to make an accurate diagnosis. Each of these lesions are diagnosed by evaluating their histology, along with their phenotypic profile, which is sometimes enhanced by pertinent molecular findings.

Molecular Docking Investigation of Dioscorea alata Compounds Binding to CCKBR, CHRM3, CHRM5, and H2R for Gastric Ulcer Treatment

Gastric ulcer is a pathological condition characterized by damage to the mucosal and submucosal tissue layers of the stomach. The main proteins targeted in the treatment of gastric ulcers are CCKBR, CHRM3, CHRM5, and H2R because of their roles in the regulation of gastric acid secretion. Dioscorea alata (DA) is known to contain various active compounds with high sapogenin, diosgenin, and dioscorin content, in addition to its carbohydrate content. We investigated the potential of DA compounds to bind to these proteins in silico. Compound and protein structures were retrieved from PubChem (https://pubchem.ncbi.nlm.nih.gov), ChemSpider (http://www.chemspider.com), and the RCSB PDB (https://rcsb.org). Proteins and compounds are prepared first, and then docked to obtain the interactions that might form, and finally visualized to observe the interactions that have been constructed. The results showed that diosgenin and prosapogenin have potential as inhibitors of CCKBR and CHRM5, and diosgenin and dimethyl batatasin IV have potential as inhibitors of CHRM3 and H2R. We conclude that diosgenin, prosapogenin, and dimethyl batatasin IV in DA compounds have the potential to inhibit CCKBR, CHRM3, CHRM5, and H2R for gastric ulcer treatment. It is necessary to further study the effect of Dioscorea alata in vitro through a gastric ulcer model study. HIGHLIGHTS Dioscorea alata (DA) is known to contain various active compounds with high sapogenin, diosgenin, and dioscorin content in addition to its carbohydrate content Gastritis (gastric ulcer) is a pathological condition characterized by damage to the mucosal and sub-mucosal tissue layers of the stomach. The main proteins targeted in the treatment of gastric ulcers are CCKBR, CHRM3, CHRM5, and H2R because of their roles in the regulation of gastric acid secretion We performed an in-silico study to investigate the potential of DA compounds to inhibit these proteins. Compound and protein structures were retrieved from PubChem, ChemSpider, and the RCSB PDB. Proteins were prepared with Swiss PDB viewer v. 4.10. Compounds were prepared with Open Babel in Cytoscape v.3.9.1. Docking was done with AutoDock Vina in PyRx v.0.9.7. Visualization was done with Discovery Studio v. 19.1 We determined that several DA compounds have the potential to act as inhibitors of CCKBR, CHRM3, CHRM5, and H2R by reviewing the predicted binding energy, competitive properties based on literature studies and the bioactivity and molecular docking analysis. The results of this study are expected to be the basis for further gastric ulcer treatment research GRAPHICAL ABSTRACT

Comparison of Selected Health and Well Being Characteristics in Seniors with Hereditary Angioedema (HAE) and a Non-HAE Patient Matched Cohort

Hereditary angioedema (HAE) is a rare, chronic, genetic disease associated with recurrent, unpredictable episodes of localized swelling of cutaneous and submucosal tissue and can be life-threatening. Although HAE requires lifelong treatment, disease course, management, and outcomes are rarely reported in older populations.

Tumor de células granulares de partes blandas: hallazgos en resonancia magnética

Granular cell tumors are histologically unique neoplasms that often manifest as painless solitary nodules located in the dermis or submucosal tissue. In this article we analyze the radiologic features of this type of tumor in five patients by magnetic resonance imaging (MRI), analyzing morphologic and signal characteristics. MR imaging findings were similar to other publications and we demonstrate low ADC values in our series.

Bleeding Post Radiofrequency Ablation of Inferior Turbinate

Nasal obstruction is a troublesome condition and negatively impacts the quality of life. One of the most important causes is inferior turbinate hypertrophy. Radiofrequency submucosal tissue ablation is an effective technique used to reduce inferior turbinate volume. It is considered a safe, minimally invasive procedure with a low risk of complications. Most of the complications reported were minor such as pain, edema, sneezing, crustation, and bleeding. This study demonstrates a case of major bleeding as a complication of radiofrequency ablation of inferior turbinate aiming to reduce the incidence of such complication. The patient had major bleeding resulting in a drop in hemoglobin level, however, no surgical intervention was required, and he was managed conservatively.

Association of Actinomyces Israelii with Pyogenic Granuloma - A RT-QPCR Study

Background Pyogenic granuloma is a benign vascular non-neoplastic inflammatory lesion that may be re-active to trauma hormonal changes and chronic local irritation. Occasionally they occur as a result of the invasion of microorganisms secondary to minor trauma. Actinomyces species are one of the normal habitants of the oral cavity that tend to penetrate submucosal tissues when there is a disruption in the mucosal barrier and cause pathology. Actinomyces israelii a gram-positive rod-shaped bacterium is an opportunistic pathogen that is difficult to culture. Molecular analyses a polymerase chain reaction and DNA sequencing will identify bacterial species and strains that are difficult or impossible to grow in artificial culture media.Methodology A total of 15 paraffin-embedded pyogenic granuloma samples were taken. All samples were subjected to molecular analysis using real-time polymerase chain reaction with forward and reverse primers of Actinomyces israelii.Result Out of 15 samples 13 samples 86.7 had expressed Actinomyces israelii gene sequence with good mean CT value suggesting that Actinomyces israelii have an association with pyogenic granuloma. There was a weak negative correlation r - 0.022 between age and CT value and the correlation was found to be statistically insignificant p0.943.Conclusion The anterior region of the oral cavity is more prone to trauma and thereby might act as a source for breaking the mucosal barrier which can be a route for microorganisms to establish their association with pyogenic granuloma. These microorganisms may play a role in recurrence. Identification of the causative organisms of irritation could serve as a tool for the radical treatment of pyogenic granulomas.

Idiopathic gingival enlargement: A brief review and case report

Idiopathic gingival enlargement is a heterogenous group of disorders characterized by progressive enlargement of the gingiva caused by an increase in submucosal connective tissue elements. Many cases are iatrogenic and some are inherited or idiopathic. We present a case of idiopathic gingival enlargement to highlight the etiological factors, radiographic and histological features

The Antioxidant Effects of Sesamol on Bleomycin-Induced Oral Submucous Fibrosis

Objective: Oral submucous fibrosis (OSF) is a disease characterized by abnormal collagen deposition that causes inflammation and malignancy in oral mucosal tissue. Fibroblasts and myofibroblasts, are the cells that show significant activation in the development of OSF. Bleomycin (BL) is a chemotherapeutic agent commonly used in cancer treatment that also causes inflammatory changes in the oral mucosa, initiating fibrosis in the oral submucosal tissue. Sesamol (SE) has antioxidative and anti-inflammatory properties which are abundant in sesame seeds and sesame oil, and SE has a beneficial effect on the mucosal layer. This experimental study aimed to investigate SE’s effects on BL-induced OSF. Materials and Methods: The study obtained 18 healthy adult male albino rats aged 3-4 months and weighing 200-250g from Bolu Abant Izzet Baysal University’s Experimental Animal Application and Research Center. The rats were divided randomly into control, BL, and BL + SE groups (n = 6 in each group). A model of OSF was established in the rats by administering 0.5 mg/mL of BL and 50 mg\kg of SE to the BL+SE group each day. The hematoxylin and eosin stain and Masson’s trichrome stain were used to assess histopathological changes in the oral mucosa. Results: The results revealed SE to have beneficial effects on BL-induced OSF through its antioxidant and anti-inflammatory properties. Histopathological evaluations and biochemical analysis of oral submucosal tissue samples also revealed SE to provide statistically significant protection against fibrosis in the oral mucosa (p < 0.01). Conclusion: This study has demonstrated oral submucous fibrosis that develops due to BL as well as SE to have an antioxidant effect on OSF regarding BL-induced reactive oxygen species (ROS) activation and collagen synthesis.

Compression Optical Coherence Elastography for Assessing Elasticity of the Vaginal Wall under Prolapse after Neodymium Laser Treatment

Early stages of pelvic organ prolapses are mainly associated with the pelvic floor disfunction as a result of elasticity changes in the connective tissues including the vaginal wall. In this study, for the first time we used a compression optical coherence elastography (C-OCE) method for assessing elasticity of the vaginal wall under prolapse conditions after intravaginal neodymium (Nd:YAG) laser treatment. C-OCE was used for a comparative ex vivo study of vaginal wall average values of stiffness (elastic Young’s modulus) in patients with age norm (n = 6), stage I–II prolapse (n = 5) without treatment and stage I–II prolapse post 1–2 months Nd:YAG laser treatment (n = 10). To verify the C-OCE data, the structural features of the submucosal connective tissue were identified morphometrically by Van Gieson staining using quantitative textural analysis of the state of collagen bundles. The results of a comparative evaluation of C-OCE and histological images demonstrate a statistically significant tissue stiffness decrease in vaginal wall prolapse compared to the age norm (73.5 ± 18.9 kPa vs. 233.5 ± 48.3 kPa; p < 0.05). This agrees with the histologically revealed increase in the space between the bundles of collagen fibers, which leads to a decrease in the uniformity of their arrangement. After Nd:YAG laser treatment, we observed statistically significant connective tissue stiffness increase compared to vaginal wall prolapse without treatment (152.1 ± 19.2 kPa vs. 73.5 ± 18.9 kPa; p < 0.05), which was associated with an increase in the local thickness of the collagen bundles, a change in their orientation, and an increase in the uniformity of their arrangement. The obtained results indicate that the C-OCE can be a robust method for detecting the early stages of vaginal wall prolapse and assessing the elastic modulus increase in the vaginal wall after laser treatment.

Effects of Sprayable, Highly Adhesive Hydrophobized Gelatin Microparticles on Endoscopic Submucosal Dissection: A Swine Model

Introduction: Sprayable wound dressings containing hydrophobized microparticles (hMPs) are characterized by strong adhesiveness. We examined the effect of hMPs derived from Alaska pollock gelatin on endoscopic submucosal dissection (ESD) ulcers. Methods: (1) In an in vivo model of miniature swine gastric ESD, gastric ulcers were created by ESD and then sprayed with hMPs or untreated followed by microscopic examination. (2) In an ex vivo ESD model of resected stomach, a pinhole-shaped perforation was created on the ESD ulcer of resected stomach; hMPs were then sprayed on the perforation; and air leakage and intragastric pressure were measured. (3) In an in vivo duodenal ESD model of miniature swine, duodenal artificial ESD ulcers with pinhole-shaped perforation were examined; ulcers were classified into hMPs-sprayed and nonsprayed groups, and inflammation in the intrinsic muscle layer and serosa were compared between the groups. Results: (1) Histological observation of submucosal tissues showed a decreased number of invading inflammatory cells in hMP-sprayed tissues compared with the control in miniature swine gastric ESD (p < 0.05). In addition, the rates of anti-alpha smooth muscle actin and type I collagen positivity were significantly lower in the hMPs group than in the control group (p < 0.05). (2) Intragastric pressure could not be measured in the nonsprayed group, whereas no air leakage was observed in the sprayed group when pressurized up to 26 mm Hg in the resected stomach model. (3) The sprayed group showed suppressed inflammation of the intrinsic muscular layer and serosa in both cases compared with the nonsprayed group in miniature swine duodenal ESD (p < 0.05). Conclusions: Sprayable, tissue-adhesive hMPs are a promising medical material for intraoperative and postoperative treatment of ESD-induced wound via anti-inflammation and strong adhesiveness.

Hereditary Angioedema: The Clinical Picture of Excessive Contact Activation.

Hereditary angioedema is a rare, genetic disorder characterized by painful, debilitating and potentially life-threatening angioedema attacks in subcutaneous and submucosal tissue. While usually unpredictable, attacks can be provoked by a variety of triggers including physical injury and certain medication and are often preceded by prodromal symptoms. Hereditary angioedema has a profound influence on the patients' lives. The fundamental cause of hereditary angioedema in almost all patients is a mutation in the SERPING1 gene leading to a deficiency in C1-inhibitor. Subsequently, the contact activation cascade and kallikrein-kinin pathway are insufficiently inhibited, resulting in excessive bradykinin production triggering vascular leakage. While C1-inhibitor is an important regulator of the intrinsic coagulation pathway, fibrinolytic system and complement cascade, patients do not have an increased risk of coagulopathy, autoimmune conditions or immunodeficiency disorders. Hereditary angioedema is diagnosed based on C1-inhibitor level and function. Genetic analysis is only required in rare cases where hereditary angioedema with normal C1-inhibitor is found. In recent years, new, highly specific therapies have greatly improved disease control and angioedema-related quality of life. This article reviews the clinical picture of hereditary angioedema, the underlying pathophysiology, diagnostic process and currently available as well as investigational therapeutic options.

Comparative Pharmacokinetics and Tissue Distribution of M10 and Its Metabolite Myricetin in Normal and Dextran-Sodium-Sulfate-Induced Colitis Mice

M10, a novel myricetin derivative, is an anti-inflammatory agent designed for treatment of colitis. Here, we aim to investigate its pharmacokinetic behavior and tissue distribution in a mouse model with colitis. Pharmacokinetics and tissue distribution of M10 and its metabolite myricetin were compared in normal mice and in dextran-sodium-sulfate (DSS)-induced colitis mice. The role of fecal microbiota was also analyzed during metabolism of M10 in vitro. After oral administration, M10 was very low in the plasma of both normal and diseased mice. However, both M10 and myricetin were mainly distributed in the gastrointestinal tract, including the stomach, colon and small intestine, in physiological and pathological conditions. Significantly, M10 and myricetin were found in higher levels in gastrointestinal tracts with inflamed tissues than in normal tissues of mice. An in vitro assay revealed that 80% of M10 was metabolized to myricetin via fecal microbiota. After oral administration, M10 was not absorbed into circulation but mainly distributed in the inflamed submucosal tissues of colitic mice, where it was metabolized into myricetin to prevent colitis development.