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Arquivos de Gastroenterologia 2024Chagas disease causes digestive anatomic and functional changes, including the loss of the myenteric plexus and abnormal esophageal radiologic and manometric findings.
BACKGROUND
Chagas disease causes digestive anatomic and functional changes, including the loss of the myenteric plexus and abnormal esophageal radiologic and manometric findings.
OBJECTIVE
To evaluate the association of abnormal esophageal radiologic findings, cardiac changes, distal esophageal contractions, and complaints of dysphagia and constipation in upper (UES) and lower (LES) esophageal sphincter basal pressure in Chagas disease patients.
METHODS
The study evaluated 99 patients with Chagas disease and 40 asymptomatic normal volunteers. The patients had normal esophageal radiologic examination (n=61) or esophageal retention without an increase in esophageal diameter (n=38). UES and LES pressure was measured with the rapid pull-through method in a 4-channel water-perfused round catheter. Before manometry, the patients were asked about dysphagia and constipation and submitted to electrocardiography and chest radiography.
RESULTS
The amplitude of esophageal distal contraction decreased from controls to chagasic patients with esophageal retention. The proportion of failed and simultaneous contractions increased in patients with abnormal radiologic examination (P<0.01). There were no significant differences in UES and LES pressure between the groups. UES pressure was similar between Chagas disease patients with cardiomegaly (n=27, 126.5±62.7 mmHg) and those without it (n=72, 144.2±51.6 mmHg, P=0.26). Patients with constipation had lower LES pressure (n=23, 34.7±20.3 mmHg) than those without it (n=76, 42.9±20.5 mmHg, P<0.03).
CONCLUSION
Chagas disease patients with absent or mild esophageal radiologic involvement had no significant changes in UES and LES basal pressure. Constipation complaints are associated with decreased LES basal pressure.
Topics: Humans; Male; Female; Manometry; Middle Aged; Chagas Disease; Esophageal Sphincter, Lower; Case-Control Studies; Esophageal Motility Disorders; Adult; Esophageal Sphincter, Upper; Constipation; Aged; Deglutition Disorders; Pressure
PubMed: 38896574
DOI: 10.1590/S0004-2803.24612023-174 -
Cureus May 2024Hirschsprung disease, a rare genetic disorder affecting the enteric nervous system, is characterized by the absence of ganglion cells in the myenteric plexus. Typically...
Hirschsprung disease, a rare genetic disorder affecting the enteric nervous system, is characterized by the absence of ganglion cells in the myenteric plexus. Typically identified in neonates due to the failure to pass meconium, diagnosis beyond the first year of life is considered delayed. Common clinical manifestations in children with late-onset Hirschsprung disease include abdominal distension, abdominal pain, vomiting, fever, and abnormal bowel sounds. Sigmoid volvulus, though uncommon, can complicate Hirschsprung disease, potentially leading to misdiagnosis and severe complications such as intestinal perforation, hemorrhage, sepsis, and even mortality. Non-surgical interventions such as antibiotic therapy, intestinal decompression, and fluid resuscitation are preferred initial treatments to stabilize the patient. This case involves a 9-year-old boy who has presented with abdominal distension since birth and a lengthy history of irregular bowel habits. The diagnosis of Hirschsprung disease was confirmed at our institution, and the patient underwent a two-stage repair procedure, which was completed without any intraoperative or postoperative complications. The patient experienced an uneventful recovery, was discharged with stable vital signs, and regained normal bowel function. This case highlights the challenges of delayed diagnosis at nine years and underscores the importance of prompt management.
PubMed: 38883048
DOI: 10.7759/cureus.60315 -
Cureus Apr 2024Gastric schwannomas are an exceedingly rare tumor arising from the myenteric plexus of the gastrointestinal enteric nervous system. These schwannomas are most commonly...
Gastric schwannomas are an exceedingly rare tumor arising from the myenteric plexus of the gastrointestinal enteric nervous system. These schwannomas are most commonly benign and reported to occur in female patients with a mean age of 58 at presentation. They are most often discovered incidentally, but can occasionally present with abdominal discomfort, obstructive symptoms, or GI bleeding. Frequently, the initial clinical consideration is for a gastrointestinal stromal tumor, which is much more common. A definitive diagnosis is made with microscopic imaging and immunohistochemical staining. Complete surgical resection, typically performed laparoscopically, is the most definitive and usually curative treatment, requiring no further follow-up. Herein, we present the first and only case of gastric schwannoma in an octogenarian and discuss an update on current diagnostic and therapeutic options.
PubMed: 38800239
DOI: 10.7759/cureus.58857 -
Cells May 2024Intestinal homeostasis results from the proper interplay among epithelial cells, the enteric nervous system (ENS), interstitial cells of Cajal (ICCs), smooth muscle...
Intestinal homeostasis results from the proper interplay among epithelial cells, the enteric nervous system (ENS), interstitial cells of Cajal (ICCs), smooth muscle cells, the immune system, and the microbiota. The disruption of this balance underpins the onset of gastrointestinal-related diseases. The scarcity of models replicating the intricate interplay between the ENS and the intestinal epithelium highlights the imperative for developing novel methods. We have pioneered a sophisticated tridimensional in vitro technique, coculturing small intestinal organoids with myenteric and submucosal neurons. Notably, we have made significant advances in (1) refining the isolation technique for culturing the myenteric plexus, (2) enhancing the isolation of the submucosal plexus-both yielding mixed cultures of enteric neurons and glial cells from both plexuses, and (3) subsequently co-culturing myenteric and submucosal neurons with small intestinal organoids. This co-culture system establishes neural innervations with intestinal organoids, allowing for the investigation of regulatory interactions in the context of gastrointestinal diseases. Furthermore, we have developed a method for microinjecting the luminal space of small intestinal organoids with fluorescently labeled compounds. This technique possesses broad applicability such as the assessment of intestinal permeability, transcytosis, and immunocytochemical and immunofluorescence applications. This microinjection method could be extended to alternative experimental setups, incorporating bacterial species, or applying treatments to study ENS-small intestinal epithelium interactions. Therefore, this technique serves as a valuable tool for evaluating the intricate interplay between neuronal and intestinal epithelial cells (IECs) and shows great potential for drug screening, gene editing, the development of novel therapies, the modeling of infectious diseases, and significant advances in regenerative medicine. The co-culture establishment process spans twelve days, making it a powerful asset for comprehensive research in this critical field.
Topics: Animals; Mice; Coculture Techniques; Gastrointestinal Tract; Intestine, Small; Myenteric Plexus; Neurons; Organoids; Submucous Plexus
PubMed: 38786037
DOI: 10.3390/cells13100815 -
Nature Communications May 2024Digestive Chagas disease (DCD) is an enteric neuropathy caused by Trypanosoma cruzi infection. There is a lack of evidence on the mechanism of pathogenesis and...
Digestive Chagas disease (DCD) is an enteric neuropathy caused by Trypanosoma cruzi infection. There is a lack of evidence on the mechanism of pathogenesis and rationales for treatment. We used a female C3H/HeN mouse model that recapitulates key clinical manifestations to study how infection dynamics shape DCD pathology and the impact of treatment with the front-line, anti-parasitic drug benznidazole. Curative treatment 6 weeks post-infection resulted in sustained recovery of gastrointestinal transit function, whereas treatment failure led to infection relapse and gradual return of DCD symptoms. Neuro/immune gene expression patterns shifted from chronic inflammation to a tissue repair profile after cure, accompanied by increased cellular proliferation, glial cell marker expression and recovery of neuronal density in the myenteric plexus. Delaying treatment until 24 weeks post-infection led to partial reversal of DCD, suggesting the accumulation of permanent tissue damage over the course of chronic infection. Our study shows that murine DCD pathogenesis is sustained by chronic T. cruzi infection and is not an inevitable consequence of acute stage denervation. The risk of irreversible enteric neuromuscular tissue damage and dysfunction developing highlights the importance of prompt diagnosis and treatment. These findings support the concept of treating asymptomatic, T. cruzi-infected individuals with benznidazole to prevent DCD development.
Topics: Animals; Chagas Disease; Female; Trypanocidal Agents; Nitroimidazoles; Trypanosoma cruzi; Mice; Mice, Inbred C3H; Enteric Nervous System; Disease Models, Animal; Nerve Regeneration
PubMed: 38782898
DOI: 10.1038/s41467-024-48749-5 -
Journal of Inflammation Research 2024Allied disorders of Hirschsprung's disease (ADHD) exhibit symptoms akin to those of Hirschsprung's disease, primarily characterized by intestinal obstruction, bowel...
BACKGROUND
Allied disorders of Hirschsprung's disease (ADHD) exhibit symptoms akin to those of Hirschsprung's disease, primarily characterized by intestinal obstruction, bowel dilatation, and chronic constipation. The occurrence of amyloid complications in patients with ADHD is infrequent. In this report, we present a case of ADHD with intestinal ulcers as the initial gastrointestinal manifestation, and subsequent pathological examination revealed the presence of amyloid deposits in the colonic mucosa.
CASE REPORT
A male patient, aged 20, exhibited recurring abdominal distension and intestinal obstruction for a duration of three years. Multiple colonoscopies revealed the presence of recurrent colonic ulcers, with pathological examination indicating the existence of amyloid deposits within the mucosal layer of the colon. Abdominal CT scans suggested colonic dilatation. Following a multidisciplinary consultation, a subtotal resection of the colon was performed, and subsequent postoperative pathology confirmed a decrease and absence of myenteric plexus ganglion cells. Considering the patient's symptoms and the findings from the postoperative pathology, a diagnosis of ADHD was made. The patient's symptoms resolved postoperatively and he was discharged from the hospital and followed up for 1 year in stable condition.
CONCLUSION
Our study highlights the potential association between ADHD and the initial presentation of recurrent colonic ulcers, accompanied by amyloid deposition in the intestinal mucosa. This finding suggests a possible pathogenic mechanism for ADHD and offers a novel perspective on its diagnosis.
PubMed: 38779428
DOI: 10.2147/JIR.S459548 -
STAR Protocols Jun 2024Here, we present our protocol to culture enteric glial cells from the submucosal and myenteric plexus of neonatal and juvenile pig colons. We describe steps for colon...
Here, we present our protocol to culture enteric glial cells from the submucosal and myenteric plexus of neonatal and juvenile pig colons. We describe steps for colon isolation, microdissection, and enzymatic and mechanical dissociation. We include procedures for passaging and analyzing cell yield, freeze/thaw efficiency, and purity. This protocol allows for the generation of primary cultures of enteric glial cells from single-cell suspensions of microdissected layers of the colon wall and can be used to culture enteric glia from human colon specimens. For complete details on the use and execution of this protocol, please refer to Ziegler et al..
Topics: Animals; Neuroglia; Swine; Myenteric Plexus; Colon; Cell Culture Techniques; Animals, Newborn; Submucous Plexus; Cells, Cultured
PubMed: 38762883
DOI: 10.1016/j.xpro.2024.103057 -
Journal of Neuroscience Methods Jul 2024The enteric nervous system (ENS) is comprised of neurons, glia, and neural progenitor cells that regulate essential gastrointestinal functions. Advances in...
BACKGROUND
The enteric nervous system (ENS) is comprised of neurons, glia, and neural progenitor cells that regulate essential gastrointestinal functions. Advances in high-efficiency enteric neuron culture would facilitate discoveries surrounding ENS regulatory processes, pathophysiology, and therapeutics.
NEW METHOD
Development of a simple, robust, one-step method to culture murine enteric neurospheres in a 3D matrix that supports neural growth and differentiation.
RESULTS
Myenteric plexus cells isolated from the entire length of adult murine small intestine formed ≥3000 neurospheres within 7 days. Matrigel-embedded neurospheres exhibited abundant neural stem and progenitor cells expressing Sox2, Sox10 and Msi1 by day 4. By day 5, neural progenitor cell marker Nestin appeared in the periphery of neurospheres prior to differentiation. Neurospheres produced extensive neurons and neurites, confirmed by Tubulin beta III, PGP9.5, HuD/C, and NeuN immunofluorescence, including neural subtypes Calretinin, ChAT, and nNOS following 8 days of differentiation. Individual neurons within and external to neurospheres generated depolarization induced action potentials which were inhibited in the presence of sodium channel blocker, Tetrodotoxin. Differentiated neurospheres also contained a limited number of glia and endothelial cells.
COMPARISON WITH EXISTING METHODS
This novel one-step neurosphere growth and differentiation culture system, in 3D format (in the presence of GDNF, EGF, and FGF2), allows for ∼2-fold increase in neurosphere count in the derivation of enteric neurons with measurable action potentials.
CONCLUSION
Our method describes a novel, robust 3D culture of electrophysiologically active enteric neurons from adult myenteric neural stem and progenitor cells.
Topics: Animals; Myenteric Plexus; Neurons; Cell Culture Techniques; Neural Stem Cells; Cell Differentiation; Mice; Mice, Inbred C57BL; Cells, Cultured; Action Potentials; Laminin; Drug Combinations; Proteoglycans; Male; Neurogenesis; Collagen
PubMed: 38670535
DOI: 10.1016/j.jneumeth.2024.110144 -
Frontiers in Pharmacology 2024Vincristine (VCR), an antineoplastic drug, induces peripheral neuropathy characterized by nerve damage, limiting its use and reducing the quality of life of patients....
Vincristine (VCR), an antineoplastic drug, induces peripheral neuropathy characterized by nerve damage, limiting its use and reducing the quality of life of patients. VCR causes myenteric neuron damage, inhibits gastrointestinal motility, and results in constipation or paralytic ileus in patients. Oxytocin (OT) is an endogenous neuropeptide produced by the enteric nerve system, which regulates gastrointestinal motility and exerts neuroprotective effects. This study aimed to investigate whether OT can improve VCR-induced gastrointestinal dysmotility and evaluate the underlying mechanism. Mice were injected either with saline or VCR (0.1 mg/kg/d, i. p.) for 14 days, and OT (0.1 mg/kg/d, i.p.) was applied 1 h before each VCR injection. Gastrointestinal transit and the contractile activity of the isolated colonic segments were assessed. The concentration of OT in plasma was measured using ELISA. Immunofluorescence staining was performed to analyze myenteric neurons and reactive oxygen species (ROS) levels. Furthermore, the indicators of oxidative stress were detected. The protein expressions of Nrf2, ERK1/2, P-ERK1/2, p38, and P-p38 in the colon were tested using Western blot. VCR reduced gastrointestinal transit and the responses of isolated colonic segments to electrical field stimulation and decreased the amount of neurons. Furthermore, VCR reduced neuronal nitric oxide synthase and choline acetyltransferase immunopositive neurons in the colonic myenteric nerve plexus. VCR increased the concentration of OT in plasma. Exogenous OT pretreatment ameliorated the inhibition of gastrointestinal motility and the injury of myenteric neurons caused by VCR. OT pretreatment also prevented the decrease of superoxide dismutase activity, glutathione content, total antioxidative capacity, and Nrf2 expression, the increase of ROS levels, and the phosphorylation of ERK1/2 and p38 MAPK following VCR treatment. Our results suggest that OT pretreatment can protect enteric neurons from VCR-induced injury by inhibiting oxidative stress and MAPK pathways (ERK1/2, p38). This may be the underlying mechanism by which it alleviates gastrointestinal dysmotility.
PubMed: 38655179
DOI: 10.3389/fphar.2024.1270612 -
BioRxiv : the Preprint Server For... Apr 2024The enteric nervous system (ENS) is contained within two layers of the gut wall and is made up of neurons, immune cells, and enteric glia cells (EGCs) that regulate...
The enteric nervous system (ENS) is contained within two layers of the gut wall and is made up of neurons, immune cells, and enteric glia cells (EGCs) that regulate gastrointestinal (GI) function. EGCs in both inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) change in response to inflammation, referred to as reactive gliosis. Whether EGCs restricted to a specific layer or region within the GI tract alone can influence intestinal immune response is unknown. Using bulk RNA-sequencing and hybridization, we identify G-protein coupled receptor , as a gene expressed only in EGCs of the myenteric plexus, one of the two layers of the ENS. We show that Gpr37 contributes to key components of LPS-induced reactive gliosis including activation of NF-kB and IFN-y signaling and response genes, lymphocyte recruitment, and inflammation-induced GI dysmotility. Targeting Gpr37 in EGCs presents a potential avenue for modifying inflammatory processes in the ENS.
PubMed: 38645163
DOI: 10.1101/2024.04.09.588619