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Journal of Clinical Pathology Dec 2023Schaumann bodies were first identified in sarcoidosis by Dr Schaumann in 1941. They were also detected in 10% of Crohn's disease (CD) cases in a study involving patients...
AIMS
Schaumann bodies were first identified in sarcoidosis by Dr Schaumann in 1941. They were also detected in 10% of Crohn's disease (CD) cases in a study involving patients with surgically resected CD. However, the characteristics and significance of Schaumann bodies in CD have yet to be fully elucidated. This study aimed to determine the pathological features and diagnostic significance of Schaumann bodies in various bowel diseases.
METHODS
Overall, 278 bowel specimens were collected from patients with CD, intestinal tuberculosis, ulcerative colitis, intestinal schistosomiasis, diverticulosis and idiopathic mesenteric vasculopathy. The frequency, pathology and clinical features of patients with Schaumann bodies were studied.
RESULTS
Schaumann bodies were present exclusively in CD (27.0%, 38 of 141) and were not detected in other intestinal diseases within the series. In CD, Schaumann bodies were deposited along the myenteric plexus of the muscularis propria (84.2%, 32 of 38). These bodies were small (diameter: 60.3±32.7 µm) and exhibited a low density in the intestinal wall (1.1±0.4 per low-power field). The majority were located within the cytoplasm of multinucleated giant cells (84.2%, 32 of 38) and were not found within or adjacent to granulomas. Notably, the number of female patients with CD and Schaumann bodies was higher than that of males.
CONCLUSION
Schaumann bodies are common in resected CD specimens, and their characteristic deposition pattern may serve as a diagnostic indication for CD.
PubMed: 38123350
DOI: 10.1136/jcp-2023-209271 -
Scientific Reports Dec 2023Previously, the presence of a blood-myenteric plexus barrier and its disruption was reported in experimentally induced colitis via a macrophage-dependent process. The...
Previously, the presence of a blood-myenteric plexus barrier and its disruption was reported in experimentally induced colitis via a macrophage-dependent process. The aim of this study is to reveal how myenteric barrier disruption and subsequent neuronal injury affects gut motility in vivo in a murine colitis model. We induced colitis with dextran sulfate sodium (DSS), with the co-administration of liposome-encapsulated clodronate (L-clodronate) to simultaneously deplete blood monocytes contributing to macrophage infiltration in the inflamed muscularis of experimental mice. DSS-treated animals receiving concurrent L-clodronate injection showed significantly decreased blood monocyte numbers and colon muscularis macrophage (MM) density compared to DSS-treated control (DSS-vehicle). DSS-clodronate-treated mice exhibited significantly slower whole gut transit time than DSS-vehicle-treated animals and comparable to that of controls. Experiments with oral gavage-fed Evans-blue dye showed similar whole gut transit times in DSS-clodronate-treated mice as in control animals. Furthermore, qPCR-analysis and immunofluorescence on colon muscularis samples revealed that factors associated with neuroinflammation and neurodegeneration, including Bax1, Hdac4, IL-18, Casp8 and Hif1a are overexpressed after DSS-treatment, but not in the case of concurrent L-clodronate administration. Our findings highlight that MM-infiltration in the muscularis layer is responsible for colitis-associated dysmotility and enteric neuronal dysfunction along with the release of mediators associated with neurodegeneration in a murine experimental model.
Topics: Mice; Animals; Clodronic Acid; Colitis; Inflammation; Macrophages; Colon; Dextran Sulfate; Mice, Inbred C57BL; Disease Models, Animal
PubMed: 38105266
DOI: 10.1038/s41598-023-50059-7 -
Folia Morphologica Dec 2023Neurons of the enteric nervous system are characterised by high neuronal plasticity, with their number likely to change in response to various endogenous and exogenous...
BACKGROUND
Neurons of the enteric nervous system are characterised by high neuronal plasticity, with their number likely to change in response to various endogenous and exogenous substances.
MATERIALS AND METHODS
Fifteen sexually immature gilts divided into 3 groups were used: control - animals receiving empty gelatin capsules; G1 - animals receiving a low dose of glyphosate - 0.05 mg/kg bw/day; G2 - animals receiving a higher dose of glyphosate-0.5 mg/kg/day in gelatin capsules orally for 28 days. Frozen sections were then subjected to the procedure of double immunofluorescent staining.
RESULTS
With low-dose supplementation, no effect on the SP- and CART-positive neuron population was observed. However, a reduction in the number of VAChT-positive neurons in the internal submucosal plexus was described, while the number of CGRP-positive neurons increased in all enteric plexuses. In response to a high glyphosate dose, the quantitative variability of the neurons was significantly more pronounced than that for a low dose. There was an increase in the number of SP- and CGRP-positive neurons and a decrease in the number of VAChT-positive neurons in both the myenteric plexus and the submucosal plexuses. The response of CART-positive neurons was the weakest, as a high dose of glyphosate led to an increase in the number of neurons only in the myenteric plexus.
CONCLUSIONS
The above data show that glyphosate is an exogenous substance that affects neuronal populations of the enteric nervous system, in this case, the descending colon.
PubMed: 38078736
DOI: 10.5603/fm.97761 -
International Journal of Molecular... Nov 2023Environmental contamination and the resulting food contamination represent a serious problem and pose a major threat to animal and human health. The gastrointestinal...
Environmental contamination and the resulting food contamination represent a serious problem and pose a major threat to animal and human health. The gastrointestinal tract is directly exposed to a variety of substances. One is glyphosate, whose presence in the soil is commonly observed. This study demonstrates the effects of low and high glyphosate doses on the populations of intramural neurons of the porcine descending colon. An analysis was performed on neurons ex-pressing the vasoactive intestinal peptide, pituitary adenylate cyclase-activating peptide, a neuronal isoform of nitrogen oxide synthase, and galanin. Even a low dose of glyphosate increased the number of neurons immunoreactive against the studied substances. However, the changes depended on both the plexus analysed and the substance tested. Meanwhile, a high glyphosate dose resulted in quantitative changes (an increase in the number) within neurons immunoreactive against all the studied neuropeptides/enzymes in the myenteric plexus and both submucosal plexuses. The response of the enteric nervous system in the form of an increase in the number of neurons immunoreactive against neuroprotective substances may suggest that glyphosate has a toxic effect on enteric neurons which attempt to increase their survivability through the released neuroprotective substances.
Topics: Humans; Swine; Animals; Colon, Descending; Enteric Nervous System; Vasoactive Intestinal Peptide; Pituitary Adenylate Cyclase-Activating Polypeptide; Neurons; Phenotype
PubMed: 38069321
DOI: 10.3390/ijms242316998 -
European Journal of Pediatric Surgery :... Nov 2023Postoperative constipation (PC) in patients with imperforate anus and perineal fistula (PF) has been reported in up to 60%. Histological studies of PF revealed...
INTRODUCTION
Postoperative constipation (PC) in patients with imperforate anus and perineal fistula (PF) has been reported in up to 60%. Histological studies of PF revealed innervation anomalies which seem to be one of the reasons for PC. Perioperative histologically controlled fistula resection (PHCFR) allows appropriate resection of PF and pull-down normoganglionic rectum at the time of posterior sagittal anorectoplasty (PSARP).
MATERIALS AND METHODS
A total of 665 patients with anorectal malformations underwent surgery between 1991 and 2021. Of these, 364 presented PF; 92 out of them (41 F) were studied. Patients with sacral and spinal cord anomalies, neurological disorders, and cut-back anoplasty were excluded. PSARP was done on all patients. Hematoxylin-eosin staining and NADH Tetrazolium-reductase histochemical method were used. Four and more ganglion cells in the myenteric plexus represented a sufficient length of the resection. The continence was scored according to the modified Krickenbeck scoring system. Final scores ranged from 1 to 7 points. Values are given as median.
RESULTS
A total of 65 (70.7%) patients presented an aganglionic segment in PF, and 27 patients presented hypoganglionosis. The median length of the resected fistula was 25 mm (interquartile range [IQR]: 20-30). The median total continence score was 7 (IQR: 6-7). Post-op constipation was observed in 6/92 (6.5%) patients.
CONCLUSION
PHCFR diminished PC to 6.5% of patients.
PubMed: 38016642
DOI: 10.1055/s-0043-1777101 -
Cell and Tissue Research Jan 2024Nothobranchius furzeri is emerging as an exciting vertebrate organism in the field of biomedicine, developmental biology and ecotoxicology research. Its short generation...
Nothobranchius furzeri is emerging as an exciting vertebrate organism in the field of biomedicine, developmental biology and ecotoxicology research. Its short generation time, compressed lifespan and accelerated ageing make it a versatile model for longitudinal studies with high traceability. Although in recent years the use of this model has increased enormously, there is still little information on the anatomy, morphology and histology of its main organs. In this paper, we present a description of the digestive system of N. furzeri, with emphasis on the intestine. We note that the general architecture of the intestinal tissue is shared with other vertebrates, and includes a folding mucosa, an outer muscle layer and a myenteric plexus. By immunohistochemical analysis, we reveal that the mucosa harbours the same type of epithelial cells observed in mammals, including enterocytes, goblet cells and enteroendocrine cells, and that the myenteric neurons express neurotransmitters common to other species, such as serotonin, substance P and tyrosine hydroxylase. In addition, we detect the presence of a proliferative compartment at the base of the intestinal folds. The description of the normal intestinal morphology provided here constitutes a baseline information to contrast with tissue alterations in future lines of research assessing pathologies, ageing-related diseases or damage caused by toxic agents.
Topics: Animals; Aging; Intestines; Mammals
PubMed: 38015266
DOI: 10.1007/s00441-023-03845-8 -
Journal of Crohn's & Colitis May 2024Myenteric plexitis is correlated with postoperative recurrence of Crohn's disease when relying on traditional statistical methods. However, comprehensive assessment of...
Histological Image-based Ensemble Model to Identify Myenteric Plexitis and Predict Endoscopic Postoperative Recurrence in Crohn's Disease: A Multicentre, Retrospective Study.
BACKGROUND AND AIMS
Myenteric plexitis is correlated with postoperative recurrence of Crohn's disease when relying on traditional statistical methods. However, comprehensive assessment of myenteric plexus remains challenging. This study aimed to develop and validate a deep learning system to predict postoperative recurrence through automatic screening and identification of features of the muscular layer and myenteric plexus.
METHODS
We retrospectively reviewed 205 patients who underwent bowel resection surgery from two hospitals. Patients were divided into a training cohort [n = 108], an internal validation cohort [n = 47], and an external validation cohort [n = 50]. A total of 190 960 patches from 278 whole-slide images of surgical specimens were analysed using the ResNet50 encoder, and 6144 features were extracted after transfer learning. We used five robust algorithms to construct classification models. The performances of the models were evaluated based on the area under the receiver operating characteristic curve [AUC] in three cohorts.
RESULTS
The stacking model achieved satisfactory accuracy in predicting postoperative recurrence of CD in the training cohort (AUC: 0.980; 95% confidence interval [CI] 0.960-0.999), internal validation cohort [AUC: 0.908; 95% CI 0.823-0.992], and external validation cohort [AUC: 0.868; 95% CI 0.761-0.975]. The accuracy for identifying the severity of myenteric plexitis was 0.833, 0.745, and 0.694 in the training, internal validation and external validation cohorts, respectively.
CONCLUSIONS
Our work initially established an interpretable stacking model based on features of the muscular layer and myenteric plexus extracted from histological images to identify the severity of myenteric plexitis and predict postoperative recurrence of CD.
Topics: Humans; Myenteric Plexus; Crohn Disease; Retrospective Studies; Recurrence; Female; Male; Adult; Deep Learning; Middle Aged; Algorithms
PubMed: 38001024
DOI: 10.1093/ecco-jcc/jjad196 -
Pediatric Surgery International Nov 2023It has long been established that the failure of enteric neural crest cells (ENCCs) to colonize the entire gut results in aganglionosis at the distal colon in...
PURPOSE
It has long been established that the failure of enteric neural crest cells (ENCCs) to colonize the entire gut results in aganglionosis at the distal colon in Hirschsprung disease (HD). However, it is still unclear how the intestinal microenvironment of the distal aganglionic gut differs from that of the proximal ganglionic gut in HD versus normal gut. We have recently succeeded in transplanting ENCC into aganglionic gut in endothelin receptor B (Ednrb) knockout (KO) mice. to advance the development of cell therapy for HD, it is essential to determine if the transplanted ENCCs differentiate normally in aganglionic gut. Therefore, we designed this study to investigate the impact of the environment of the recipient intestinal tract, at various sites of aganglionic gut, on the differentiation of transplanted ENCCs.
METHODS
ENCCs were isolated from Sox10 Venus transgenic (Tg) mouse gut on embryonic day 18.5 (E18.5) and neurospheres (NS) were generated. Then, NS were transplanted into aganglionic KO and wildtype (WT) gut that had been transected just distal to the ENCC wavefront (KO-wf: n = 6, WT: n = 7), and into distal KO gut transected at a site equivalent to that of the WT (KO-d: n = 6) on E12.5. ENCC differentiation was evaluated using whole-mount immunohistochemistry with Tuj-1 (neuronal marker) and GFAP (glial marker) antibodies.
RESULTS
The transplanted ENCCs migrated to form the myenteric and submucosal plexus in all groups. The ratio of the area of Tuj-1-positive cells/GFAP-positive cells in migrated cells in the recipient gut was found to be significantly lower in KO-d compared to KO-wf and WT, while there was no significant difference between KO-wf and WT groups. This suggests that neuronal/glial differentiation was decreased in KO-d compared to that in KO-wf and WT groups.
CONCLUSION
Our study highlights the differences in ENCC differentiation depending on the site of transplantation. To further develop cell therapy for HD, it is important to consider the impact of the recipient intestinal environment on transplanted ENCCs.
Topics: Mice; Animals; Neural Crest; Cell Differentiation; Hirschsprung Disease; Mice, Transgenic; Mice, Knockout; Enteric Nervous System; Cell Movement
PubMed: 37982909
DOI: 10.1007/s00383-023-05587-8 -
Cell and Tissue Research Jan 2024The pig is an important translational model for studying intestinal physiology and disorders for its many homologies with humans, including the organization of the...
The pig is an important translational model for studying intestinal physiology and disorders for its many homologies with humans, including the organization of the enteric nervous system (ENS), the major regulator of gastrointestinal functions. This study focused on the quantification and neurochemical characterization of substance P (SP) neurons in the pig ascending (AC) and descending colon (DC) in wholemount preparations of the inner submucosal plexus (ISP), outer submucosal plexus (OSP), and myenteric plexus (MP). We used antibodies for the pan-neuronal marker HuCD, and choline acetyltransferase (ChAT) and neuronal nitric oxide synthase (nNOS), markers for excitatory and inhibitory transmitters, for multiple labeling immunofluorescence and high-resolution confocal microscopy. The highest density of SP immunoreactive (IR) neurons was in the ISP (222/mm in the AC, 166/mm in the DC), where they make up about a third of HuCD-IR neurons, compared to the OSP and MP (19-22% and 13-17%, respectively, P < 0.001-0.0001). HuCD/SP/ChAT-IR neurons (up to 23%) were overall more abundant than HuCD/SP/nNOS-IR neurons (< 10%). Most SP-IR neurons contained ChAT-IR (62-85%), whereas 18-38% contained nNOS-IR with the highest peak in the OSP. A subpopulation of SP-IR neurons contains both ChAT- and nNOS-IR with the highest peak in the OSP and ISP of DC (33-36%) and the lowest in the ISP of AC (< 10%, P < 0.001). SP-IR varicose fibers were abundant in the ganglia. This study shows that SP-IR neurons are functionally distinct with variable proportions in different plexuses in the AC and DC reflecting diverse functions of specific colonic regions.
Topics: Humans; Swine; Animals; Myenteric Plexus; Submucous Plexus; Substance P; Neurons; Colon; Choline O-Acetyltransferase
PubMed: 37982872
DOI: 10.1007/s00441-023-03842-x -
Science (New York, N.Y.) Nov 2023Glial cells in the gut are specialized to fine-tune intestinal function.
Glial cells in the gut are specialized to fine-tune intestinal function.
Topics: Neuroglia; Intestines; Animals; Mice; Myenteric Plexus
PubMed: 37917691
DOI: 10.1126/science.adk3883