Myenteric Research Articles

Schaumann bodies deposited along myenteric plexus of the muscularis propria is a unique histopathological feature of Crohn's disease.

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. 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. 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. Schaumann bodies are common in resected CD specimens, and their characteristic deposition pattern may serve as a diagnostic indication for CD.

Our Mental Health Is Determined by an Intrinsic Interplay between the Central Nervous System, Enteric Nerves, and Gut Microbiota.

Bacteria in the gut microbiome play an intrinsic part in immune activation, intestinal permeability, enteric reflex, and entero-endocrine signaling. The gut microbiota communicates with the central nervous system (CNS) through the production of bile acids, short-chain fatty acids (SCFAs), glutamate (Glu), γ-aminobutyric acid (GABA), dopamine (DA), norepinephrine (NE), serotonin (5-HT), and histamine. A vast number of signals generated in the gastrointestinal tract (GIT) reach the brain via afferent fibers of the vagus nerve (VN). Signals from the CNS are returned to entero-epithelial cells (EES) via efferent VN fibers and communicate with 100 to 500 million neurons in the submucosa and myenteric plexus of the gut wall, which is referred to as the enteric nervous system (ENS). Intercommunications between the gut and CNS regulate mood, cognitive behavior, and neuropsychiatric disorders such as autism, depression, and schizophrenia. The modulation, development, and renewal of nerves in the ENS and changes in the gut microbiome alter the synthesis and degradation of neurotransmitters, ultimately influencing our mental health. The more we decipher the gut microbiome and understand its effect on neurotransmission, the closer we may get to developing novel therapeutic and psychobiotic compounds to improve cognitive functions and prevent mental disorders. In this review, the intricate control of entero-endocrine signaling and immune responses that keep the gut microbiome in a balanced state, and the influence that changing gut bacteria have on neuropsychiatric disorders, are discussed.

Evaluation of Calretinin and enumeration of mast cells in rectum tissue biopsies of Hirschsprung and non-Hirschsprung disease in neonate and infant

The Hirschsprung disease (HD) is a complex genetic congenital condition characterized by the absence of ganglion cells in the myenteric and submucosal plexuses of the colon and rectum, leading to functional intestinal obstruction. A study was conducted from July 2022 to December 2022. The Toluidine blue stain and calretinin immunohistochemistry were applied to 36 cases of neonates and infants who clinically presented with symptoms suspicious of having HD, And the hematological study of cell blood counts test and compared the result of the HD group with the non-HD group and control group. The study showed an increase in mast cell numbers in the rectal biopsy tissue of HD patients compared with non-HD patients using Toluidine blue stain. The Immunohistochemistry for calretinin result displayed 27 (75%) cases as HD, while the remaining 9 (25%) cases were confirmed as non-HD and showed hypertrophied nerve fiber in HD cases. at the same time, the complete blood count result was unrelated to HD. Some worrying maternal risk factors were highlighted during pregnancy were the age of the mother at conception, maternal illness, intake of drugs, type of Childbirth, and number of previous maternal abortions; all of them show a non-significant difference between the HD group and non-HD group, also consanguineous marriage was detected and shows a significant difference between the HD group and non-HD group. Keywords: Hirschsprung, Calretinin, Toluidine blue, CBC count

Immunoexpression of Spexin in Selected Segments of the Bovine (Bos taurus taurus) Gastrointestinal Tract.

In the expansive domain of neuropeptide investigation, spexin (SPX) has emerged as a captivating subject, exerting a significant impact on diverse physiological processes. Initially identified in mice, SPX's distribution transcends various organs, suggesting its potential regulatory roles. Despite extensive research in smaller species, a notable gap exists in our comprehension of SPX in larger mammals, particularly ruminants. Our study meticulously explores the immunolocalization of SPX within the gastrointestinal organs of bovines, with a specific focus on the abomasum, jejunum, and colon. Tissue samples from Holstein-Friesian cattle underwent careful processing, and gene mRNA expression levels, particularly GALR2 and SPX, were assessed. Intriguingly, our findings revealed that GALR2 expression was highest in the jejunum, signifying a potentially critical role in this digestive segment. Immunohistochemistry further unveiled distinct patterns of SPX immunoreactivity in each examined region-abomasum, jejunum, and colon-highlighting nuanced, region-specific responses. Notably, the abomasum and jejunum predominantly exhibited positive immunoreactivity in the submucosal plexus, while the colon, in contrast, demonstrated a higher degree of immunoreactivity in myenteric plexus neurons. Our investigation, grounded in the hypothesis of ubiquitous SPX distribution in ruminants, delves deeper into the intricate role of SPX within the enteric nervous system. This study meticulously explores the spatial distribution of SPX within the myenteric and submucosal plexuses, integral components of the enteric nervous system. These findings significantly enhance our understanding of SPX's potential roles in gastrointestinal regulation in bovines, providing a unique perspective on larger mammals and enriching our comprehension of this intriguing neuropeptide's significance in various physiological processes.

β3 Adrenoceptor Agonism Prevents Hyperoxia-Induced Colonic Alterations.

Oxygen level is a key regulator of organogenesis and its modification in postnatal life alters the maturation process of organs, including the intestine, which do not completely develop in utero. The β3-adrenoreceptor (β3-AR) is expressed in the colon and has an oxygen-dependent regulatory mechanism. This study shows the effects of the β3-AR agonist BRL37344 in a neonatal model of hyperoxia-driven colonic injury. For the first 14 days after birth, Sprague-Dawley rat pups were exposed to ambient oxygen levels (21%) or hyperoxia (85%) and treated daily with BRL37344 at 1, 3, 6 mg/kg or untreated. At the end of day 14, proximal colon samples were collected for analysis. Hyperoxia deeply influences the proximal colon development by reducing β3-AR-expressing cells (27%), colonic length (26%) and mucin production (47%), and altering the neuronal chemical coding in the myenteric plexus without changes in the neuron number. The administration of BRL37344 at 3 mg/kg, but not at 1 mg/kg, significantly prevented these alterations. Conversely, it was ineffective in preventing hyperoxia-induced body weight loss. BRL37344 at 6 mg/kg was toxic. These findings pave the way for β3-AR pharmacological targeting as a therapeutic option for diseases caused by hyperoxia-impaired development, typical prematurity disorders.

Comparison between Whole-Mount Preparations and Paraffin-Embedded Sections in the Study of the Myenteric Plexus

Comparison between Whole-Mount Preparations and Paraffin-Embedded Sections in the Study of the Myenteric Plexus

Changes in the Phenotype of Intramural Inhibitory Neurons of the Porcine Descending Colon Resulting from Glyphosate Administration

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.

Immunohistochemical characterisation of the adult Nothobranchius furzeri intestine.

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.

Perioperative Histologically Controlled Fistula Resection in Patients with Imperforate Anus and Perineal Fistula.

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). 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. 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. PHCFR diminished PC to 6.5% of patients.

Three-Dimensional Fractal Analysis of the Interstitial Cells of Cajal Networks of Gastrointestinal Tissue Specimens.

Several functional gastrointestinaldisorders (FGIDs) have been associated with the degradation or remodeling of the network of interstitial cells of Cajal (ICC). Introducing fractal analysis to the field of gastroenterology as a promising data analytics approach to extract key structural characteristics that may provide insightful features for machine learning applications in disease diagnostics. Fractal geometry has advantages over several physically based parameters (or classical metrics) for analysis of intricate and complex microstructures that could be applied to ICC networks. In this study, three fractal structural parameters: Fractal Dimension, Lacunarity, and Succolarity were employed to characterize scale-invariant complexity, heterogeneity, and anisotropy; respectively of three types of gastric ICC network structures from a flat-mount transgenic mouse stomach. The Fractal Dimension of ICC in the longitudinal muscle layer was found to be significantly lower than ICC in the myenteric plexus and circumferential muscle in the proximal, and distal antrum, respectively (both p < 0.0001). Conversely, the Lacunarity parameters for ICC-LM and ICC-CM were found to be significantly higher than ICC-MP in the proximal and in the distal antrum, respectively (both p < 0.0001). The Succolarity measures of ICC-LM network in the aboral direction were found to be consistently higher in the proximal than in the distal antrum (p < 0.05). The fractal parameters presented here could go beyond the limitation of classical metrics to provide better understanding of the structural-functional relationship between ICC networks and the conduction of gastric bioelectrical slow waves.

Histological Image-based Ensemble Model to Identify Myenteric Plexitis and Predict Endoscopic Postoperative Recurrence in Crohn's Disease: A Multicentre, Retrospective Study.

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. 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. 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. 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.

Distribution, quantification, and characterization of substance P enteric neurons in the submucosal and myenteric plexuses of the porcine colon

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/mm2 in the AC, 166/mm2 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.

OGBN P30 Post-operative and symptomatic outcomes following Laparoscopic Hellers Cardiomyotomy- single centre experience

Abstract Background Esophageal achalasia represents a uncommon primary oesophageal motility disorder secondary to loss of inhibitory neurons in the oesophageal myenteric plexus level. The main goal of treating oesophageal achalasia is to relieve dysphagia secondary to the functional obstruction of the distal oesophagus by the inability of the Lower Oesophageal Sphincter (LOS) to relax appropriately after deglutition. The Eckardt score (ES) was developed to objectively assess the symptom severity and continues to be widely used. Aim of this study was to assess the post-operative outcomes and symptomatic improvement using ES in consecutive patients undergoing laparoscopic Hellers cardiomyotomy for achalasia in our unit. Methods Data of consecutive patients who underwent LHCM between January 2016 and December 2021 was collected. Patient demographics, surgical details, perioperative course, ES, and manometric data including Integrated Relaxation Pressure (IRP), were retrieved from a prospectively maintained database. Primary outcomes assessed were peri-operative morbidity assessed using Clavien-Dindo grade. Secondary outcomes assessed were improvement in symptoms using ES (pre- and post-operative). ES of ≤3 was considered as symptomatic improvement. Data was analysed using Microsoft Excel. Comparison of pre-operative and post-operative means was performed using paired t test. Fishers exact test was used for categorical variables. A p-value &amp;lt;0.05 was considered statistically significant. Results 41 patients underwent LHCM. Twenty-one were males. Median age was 56 years (20-77). 95.12% patients had dysphagia for a median duration of 24 months (2-180). Type II achalasia was most common in 87.80%. Median IRP was 22.3 mm Hg (11-78). Oesophageal dilation was performed in 2 while, 10 patients received botulin injection pre-operatively. Median hospital stay was 1 day (1-12). 92.68% had no post operative complications. None of the patients had significant complications (Clavien-Dindo &amp;gt;grade 2). At a median follow-up of 60 months, there was significant improvement in ES 8±1.97 to 1.82±1.16, p&amp;lt;0.001 and dysphagia score (p&amp;lt;0.001). Conclusions LHCM with fundoplication leads to significant symptomatic improvement with excellent short and medium term outcomes with low morbidity and complication rates. A detailed pre-operative discussion with patients is essential to provide tailored treatment as per individual patient symptoms.

Anti-Gephyrin Antibodies: A Novel Specificity in Patients With Systemic Sclerosis and Lower Bowel Dysfunction.

Autoantibodies are clinically useful in phenotyping patients with systemic sclerosis (SSc). Gastrointestinal (GI) function is regulated by the enteric nervous system (ENS) and commonly impaired in SSc, suggesting that the SSc autoimmune response may target ENS antigens. We sought to identify novel anti-ENS autoantibodies with an aim to clinically phenotype SSc GI dysfunction. Serum from a patient with SSc with GI dysfunction but without defined SSc-associated autoantibodies was used for autoantibody discovery. Immunoprecipitations performed with murine myenteric plexus lysates were on-bead digested, and autoantigens were identified by mass spectrometry. Prevalence was determined, and clinical features associated with novel autoantibodies were evaluated in a SSc cohort using regression analyses. The expression of gephyrin in human GI tract tissue was examined by immunohistochemistry. We identified gephyrin as a novel SSc autoantigen. Anti-gephyrin antibodies were present in 9% of patients with SSc (16/188) and absent in healthy controls (0/46). Anti-gephyrin antibody-positive patients had higher constipation scores (1.00 vs 0.50, P = 0.02) and were more likely to have severe constipation and severe distention/bloating (46% vs 15%, P = 0.005; 54% vs 25%, P = 0.023, respectively). Anti-gephyrin antibody levels were significantly higher among patients with severe constipation (0.04 vs 0.00; P = 0.001) and severe distention and bloating (0.03 vs 0.004; P = 0.010). Severe constipation was associated with anti-gephyrin antibodies even in the adjusted model. Importantly, gephyrin was expressed in the ENS, which regulates gut motility. Gephyrin is a novel ENS autoantigen that is expressed in human myenteric ganglia. Anti-gephyrin autoantibodies are associated with the presence and severity of constipation in patients with SSc.

Morphological features of basal laminas of enteral nervous system structures in chronic slow transit constipation

BACKGROUND: Studies on basal laminas in the tissues of the enteric nervous system are few and are carried out on experimental models in vivo and in vitro, performed on animals. The morphological features of the structure and localization of BL, their cellular sources of origin in various tissues of the gastrointestinal tract in normal and pathological conditions remain poorly studied.&#x0D; AIM: Study of morphological features and distribution of basal laminas in human colon tissues and their changes in pathology.&#x0D; MATERIALS AND METHODS: Fragments of the large intestine, obtained as a result of surgery for chronic slow-transit constipation, performed in S. M. Kirov Military Medical Academy were studied. The selective marker of basal laminas, type IV collagen, as well as neuronal and glial immunohistochemical markers (PGP 9.5, GFAP, S100 proteins) were used in the work&#x0D; RESULTS: It has been shown that the greatest immunoreactivity within the intestinal wall is observed in the myenteric membrane, weak in the vessels of the submucosa, locally expressed in the subepithelial region of the mucous membrane (in the upper sections of the crypts). In smooth muscle, basal laminas were found around the smooth muscle cells of the longitudinal and concentric layers of the muscular membrane, mucous membrane, veins and arteries, as well as in the endothelium. It has been shown that the ganglionic Auerbachs plexus is delimited from closely adjacent muscle layers of a continuous basal lamina, similar to the basal plate (glia limitans) of the brain and spinal cord of the CNS. It is clearly defined by its appearance it has the form of a continuous hollow tubular structure. The sources of the formation of the basal plate around the ganglia of Auerbach and Meissners plexuses are various glial elements: in the first plexus, astrocyte-like and non-myelinated Schwann cells (both types located in the neuropil), and in the second plexus, glia of the autonomic nervous system (satellite cells of neurons and neurolemmocytes of postganglionic nerve fibers).&#x0D; CONCLUSIONS: For the first time, the transition of basal lamina from the Auerbachs plexus to numerous basal plates of neurolemmocytes of the Remakov fibers of the main terminal nerve plexus, which are involved in the innervation of the smooth muscle cells of the muscular membrane, is shown. Signs of dystrophic changes in the basal lamina structure associated with pathological changes in chronic slow transit constipation (tissue edema, inflammatory reactions, manifestations of agangliosis, gliosis, focal denervation of muscle cells, degeneration of nerve endings of neuromuscular and ganglionic plexuses) are shown in the work.

Comparison of wholemount dissection methods for neuronal subtype marker expression in the mouse myenteric plexus.

Accurately reporting the identity and representation of enteric nervous system (ENS) neuronal subtypes along the length of the gastrointestinal (GI) tract is critical to advancing our understanding of ENS control of GI function. Reports of varying proportions of subtype marker expression have employed different dissection techniques to achieve wholemount muscularis preparations of myenteric plexus. In this study, we asked whether differences in GI dissection methods could introduce variability into the quantification of marker expression. We compared three commonly used methods of ENS wholemount dissection: two flat-sheet preparations that differed in the order of microdissection and fixation and a third rod-mounted peeling technique. We also tested a reversed orientation variation of flat-sheet peeling, two step-by-step variations of the rod peeling technique, and whole-gut fixation as a tube. We assessed marker expression using immunohistochemistry, genetic reporter lines, confocal microscopy, and automated image analysis. We found no significant differences between the two flat-sheet preparation methods in the expression of calretinin or neuronal nitric oxide synthase (nNOS) as a proportion of total neurons in ileum myenteric plexus. However, the rod-mounted peeling method resulted in decreased proportion of neurons labeled for both calretinin and nNOS. This method also resulted in decreased transgenic reporter fluorescent protein (tdTomato) for substance P in distal colon and choline acetyltransferase (ChAT) in both ileum and distal colon. These results suggest that labeling among some markers, both native protein and transgenic fluorescent reporters, is decreased by the rod-mounted mechanical method of peeling. The step-by-step variations of this method point to mechanical manipulation of the tissue as the likely cause of decreased labeling. Our study thereby demonstrates a critical variability in wholemount muscularis dissection methods.

Historical Cohort Study of Congenital Isolated Hypoganglionosis of the Intestine: Determining the Best Surgical Interventions.

No standard diagnostic method or surgical treatment for congenital isolated hypoganglionosis (CIHG) has been established. This study aimed to analyze the clinical outcomes of patients with CIHG and identify the best surgical interventions provided thus far. Data on surgical interventions in 19 patients were collected between 1992 and 2020, including the type of enterostomy, type of revision, and length of the intestines. Ganglion cells in the myenteric plexus were enumerated using Hu C/D staining. The ratio of the length of the small intestine to its height was defined as the intestinal ratio (IR). The outcomes were assessed using the stoma output, growth parameters including the body mass index (BMI), and parenteral nutrition (PN) dependency. All patients required a diverting enterostomy. The IR ranged from 0.51 to 1.75 after multiple non-transplant surgeries. The stoma types were tube-stoma, end-stoma, Santulli-type, and Bishop-Koop (BK)-type. Patients with Santulli- or BK-type stomas had better BMIs and less PN dependency in terms of volume than those with end-stomas or tube-stomas. Two patients with BK-type stomas were off PN, and three who underwent an intestinal transplantation (Itx) achieved enteral autonomy. The management of CIHG involves a precise diagnosis using Hu C/D staining, neonatal enterostomy, and stoma revision using the adjusted IR and Itx if other treatments do not enable enteral autonomy.

Protective effect of alpha-ketoglutarate against water-immersion restraint stress-induced gastric mucosal damage in mice

Gastric lesions have several aetiologies, among which stress is the most prominent. Therefore, identification of new therapies to prevent stress is of considerable importance. Alpha-ketoglutarate (α-kg) several beneficial effects and has shown promise in combating oxidative stress, inflammation, and premature aging. Thus, this study aimed to evaluate the protective effect of α-kg in a gastric damage model by water-immersion restraint stress (WIRS). Pretreatment with α-kg decreased stress-related histopathological scores of tissue oedema, cell loss, and inflammatory infiltration. The α-kg restored the percentage of type III collagen fibres. Mucin levels were preserved as well as the structure and area of the myenteric plexus ganglia were preserved after pretreatment with α-kg. Myeloperoxidase (MPO) levels and the expression of pro-inflammatory cytokines (TNF-α and IL-1β) were also reduced following α-kg pretreatment. Decreased levels of glutathione (GSH) in the stress group were restored by α-kg. The omeprazole group was used as standard drug e also demonstrated improve on some parameters after the exposition to WIRS as inflammatory indexes, GSH and mucin. Through this, was possible to observe that α-kg can protect the gastric mucosa exposed to WIRS, preserve tissue architecture, reduce direct damage to the mucosa and inflammatory factors, stimulate the production of type III collagen and mucin, preserve the myenteric plexus ganglia, and maintain antioxidant potential. Due to, we indicate that α-kg has protective activity of the gastric mucosa, demonstrating its ability to prevent damage associated with gastric lesions caused by stress.

L-glutathione 1% promotes neuroprotection of nitrergic neurons and reduces the oxidative stress in the jejunum of rats with Walker-256-bearing tumor.

Our main goals were to investigate the effects of L-glutathione (1%) treatment in Walker-256 tumor-bearing rats by analyzing immunoreactive neurons (IR), responsive to the nNOS enzyme and 3-Nitrotyrosine, in their jejunum myenteric plexus. Moreover, the oxidative state and inflammatory process in these animals were investigated. Four experimental groups were utilized: control (C), control treated with L-glutathione (CGT), Walker-256 tumor-bearing rats (TW), and Walker-256 tumor-bearing rats treated with L-glutathione (TWGT). After 14 days of tumor inoculation, the jejunum was collected for immunohistochemical techniques and assessment of oxidative status. Plasma was collected to evaluate oxidative status and measure cytokines. The TW group exhibited a decrease of reduced glutathione in their jejunum, which was prevented in the L-glutathione treated TWGT group. TW animals presented pronounced oxidative stress by increasing levels of lipoperoxidation in their jejunum and malondialdehyde in their plasma; however, the L-glutathione treatment in TWGT group was not able to avoid it. The total antioxidant capacity was altered in groups TW and TWGT, yet the last one had a better index in their plasma. The IL-10, and TNF-α levels increased in TWGT animals. The nNOS-IR neuron density decreased in the jejunum myenteric plexus of the TW group, which was avoided in the TWGT group. The nNOS +3-Nitrotyrosine neurons quantification did not show significative alterations. The treatment with L-glutathione (1%) imposed an important defense to some parameters of oxidative stress induced by TW-256, leading to neuroprotection to the loss in the nNOS-IR neuron density.

Hirschsprung disease.

Hirschsprung disease (HSCR) is a rare congenital intestinal disease that occurs in 1 in 5,000 live births. HSCR is characterized by the absence of ganglion cells in the myenteric and submucosal plexuses of the intestine. Most patients present during the neonatal period with the first meconium passage delayed beyond 24 h, abdominal distension and vomiting. Syndromes associated with HSCR include trisomy 21, Mowat-Wilson syndrome, congenital central hypoventilation syndrome, Shah-Waardenburg syndrome and cartilage-hair hypoplasia. Multiple putative genes are involved in familial and isolated HSCR, of which the most common are the RET proto-oncogene and EDNRB. Diagnosis consists of visualization of a transition zone on contrast enema and confirmation via rectal biopsy. HSCR is typically managed by surgical removal of the aganglionic bowel and reconstruction of the intestinal tract by connecting the normally innervated bowel down to the anus while preserving normal sphincter function. Several procedures, namely Swenson, Soave and Duhamel procedures, can be undertaken and may include a laparoscopically assisted approach. Short-term and long-term comorbidities include persistent obstructive symptoms, enterocolitis and soiling. Continued research and innovation to better understand disease mechanisms holds promise for developing novel techniques for diagnosis and therapy, and improving outcomes inpatients.