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Neuroscience Letters Aug 2023Enteric glial cells are emerging as critical players in the regulation of intestinal motility, secretion, epithelial barrier function, and gut homeostasis in health and...
Enteric glial cells are emerging as critical players in the regulation of intestinal motility, secretion, epithelial barrier function, and gut homeostasis in health and disease. Enteric glia react to intestinal inflammation by converting to a 'reactive glial phenotype' and enteric gliosis, contributing to neuroinflammation, enteric neuropathy, bowel motor dysfunction and dysmotility, diarrhea or constipation, 'leaky gut', and visceral pain. The focus of the minireview is on the impact of inflammation on enteric glia reactivity in response to diverse insults such as intestinal surgery, ischemia, infections (C. difficile infection, HIV-Tat-induced diarrhea, endotoxemia and paralytic ileus), GI diseases (inflammatory bowel diseases, diverticular disease, necrotizing enterocolitis, colorectal cancer) and functional GI disorders (postoperative ileus, chronic intestinal pseudo-obstruction, constipation, irritable bowel syndrome). Significant progress has been made in recent years on molecular pathogenic mechanisms of glial reactivity and enteric gliosis, resulting in enteric neuropathy, disruption of motility, diarrhea, visceral hypersensitivity and abdominal pain. There is a growing number of glial molecular targets with therapeutic implications that includes receptors for interleukin-1 (IL-1R), purines (P2X2R, A2BR), PPARα, lysophosphatidic acid (LPAR1), Toll-like receptor 4 (TLR4R), estrogen-β receptor (ERβ) adrenergic α- (α-R) and endothelin B (ETBR), connexin-43 / Colony-stimulating factor 1 signaling (Cx43/CSF1) and the S100β/RAGE signaling pathway. These exciting new developments are the subject of the minireview. Some of the findings in pre-clinical models may be translatable to humans, raising the possibility of designing future clinical trials to test therapeutic application(s). Overall, research on enteric glia has resulted in significant advances in our understanding of GI pathophysiology.
Topics: Humans; Infant, Newborn; Gliosis; Clostridioides difficile; Enteric Nervous System; Gastrointestinal Diseases; Neuroglia; Inflammation; Abdominal Pain; Gastrointestinal Motility; Diarrhea; Constipation; Intestinal Pseudo-Obstruction
PubMed: 37451357
DOI: 10.1016/j.neulet.2023.137395 -
Gastroenterologie Clinique Et Biologique 2006Chronic intestinal pseudo-obstruction (CIPO) is a disease characterized by episodes resembling mechanical obstruction in the absence of organic, systemic, or metabolic... (Review)
Review
Chronic intestinal pseudo-obstruction (CIPO) is a disease characterized by episodes resembling mechanical obstruction in the absence of organic, systemic, or metabolic disorders. Pseudo-obstruction is an uncommon condition and can result from primary (40%) or secondary (60%) causes. The most common symptoms are nausea, vomiting, abdominal distension, abdominal pain and constipation or diarrhea. These symptoms are usually present many years before CIPO diagnosis. They can lead to severe electrolyte disorders and malnutrition. Principles for management of patients with CIPO are: to establish a correct clinical diagnosis in excluding mechanical obstruction; to perform a symptomatic and physiologic assessment of the gastrointestinal tract involved; to look for extra-intestinal manifestations, especially for myopathy and neuropathy; to discuss in some cases a surgery for full-thickness intestinal biopsies, and/or a neuromuscular biopsy in case of mitochondrial cytopathy suspicion. The management is primarily focused on symptom control and nutritional support to prevent weight loss and malnutrition. Treatment of CIPO includes prokinetic agents which may help to reduce gastrointestinal symptoms Courses of antibiotics may be needed in patients with symptoms suggestive of bacterial overgrowth. When necessary, enteral nutrition is preferred. In carefully selected patients, feeding jejunostomy with or without decompression gastrostomy may be tried. Long term parenteral nutrition should be reserved for patients who can not tolerate enteral nutrition. Intestinal transplantation can be discussed in selected patients.
Topics: Chronic Disease; Dopamine Antagonists; Gastrointestinal Agents; Humans; Intestinal Pseudo-Obstruction; Nutritional Support
PubMed: 17075444
DOI: 10.1016/s0399-8320(06)73359-0 -
Archives of Iranian Medicine Dec 2022
Topics: Humans; Muscular Dystrophy, Oculopharyngeal; Intestinal Pseudo-Obstruction; Ophthalmoplegia; Brain Diseases
PubMed: 37543914
DOI: 10.34172/aim.2022.132 -
Nutrients Feb 2021Intestinal failure (IF) is defined as reduction in functioning gut mass below the minimal amount necessary for adequate digestion and absorption. In most cases, IF... (Review)
Review
BACKGROUND
Intestinal failure (IF) is defined as reduction in functioning gut mass below the minimal amount necessary for adequate digestion and absorption. In most cases, IF results from intrinsic diseases of the gastrointestinal tract (digestive IF) (DIF); few cases arise from digestive vascular components, gut annexed (liver and pancreas) and extra-digestive organs or from systemic diseases (non-digestive IF) (NDIF). The present review revised etiology and treatments of DIF and NDIF, with special focus on the pathophysiological mechanisms, whereby NDIF develops.
METHODS
We performed a comprehensive search of published literature from January 2010 to the present by selecting the following search strings: "intestinal failure" OR "home parenteral nutrition" OR "short bowel syndrome" OR "chronic pseudo-obstruction" OR "chronic intestinal pseudo-obstruction" OR "autoimmune enteropathy" OR "long-term parenteral nutrition".
RESULTS
We collected overall 1656 patients with well-documented etiology of IF: 1419 with DIF (86%) and 237 with NDIF (14%), 55% males and 45% females. Among DIF cases, 66% had SBS and among NDIF cases 90% had malabsorption/maldigestion.
CONCLUSIONS
The improved availability of diagnostic and therapeutic tools has increased prevalence and life expectancy of rare and severe diseases responsible for IF. The present review greatly expands the spectrum of knowledge on the pathophysiological mechanisms through which the diseases not strictly affecting the intestine can cause IF. In view of the rarity of the majority of pediatric IF diseases, the development of IF Registries is strongly required; in fact, through information flow within the network, the Registries could improve IF knowledge and management.
Topics: Child; Humans; Intestinal Pseudo-Obstruction; Malabsorption Syndromes; Nutritional Support; Short Bowel Syndrome
PubMed: 33673586
DOI: 10.3390/nu13030786 -
Developmental Biology Sep 2016The enteric nervous system (ENS) is involved in the regulation of virtually all gut functions. Conditions referred to as enteric neuropathies are the result of various... (Review)
Review
The enteric nervous system (ENS) is involved in the regulation of virtually all gut functions. Conditions referred to as enteric neuropathies are the result of various mechanisms including abnormal development, degeneration or loss of enteric neurons that affect the structure and functional integrity of the ENS. In the past decade, clinical and molecular research has led to important conceptual advances in our knowledge of the pathogenetic mechanisms of these disorders. In this review we consider ENS disorders from a clinical perspective and highlight the advancing knowledge regarding their pathophysiology. We also review current therapies for these diseases and present potential novel reparative approaches for their treatment.
Topics: Chagas Disease; Constipation; Enteric Nervous System; Esophageal Achalasia; Gastrointestinal Tract; Hirschsprung Disease; Humans; Intestinal Pseudo-Obstruction
PubMed: 27059882
DOI: 10.1016/j.ydbio.2016.03.032 -
Revista Espanola de Enfermedades... Feb 2021MELAS syndrome with chronic intestinal pseudo-obstruction and neurological symptoms in a patient with a fatal evolution despite medical and surgical treatment.
MELAS syndrome with chronic intestinal pseudo-obstruction and neurological symptoms in a patient with a fatal evolution despite medical and surgical treatment.
Topics: Chronic Disease; Humans; Intestinal Pseudo-Obstruction; MELAS Syndrome
PubMed: 33226257
DOI: 10.17235/reed.2020.7099/2020 -
Nutrients Nov 2020Gastrointestinal dysmotility is a common problem in a subgroup of children with intestinal failure (IF), including short bowel syndrome (SBS) and pediatric intestinal... (Review)
Review
Gastrointestinal dysmotility is a common problem in a subgroup of children with intestinal failure (IF), including short bowel syndrome (SBS) and pediatric intestinal pseudo-obstruction (PIPO). It contributes significantly to the increased morbidity and decreased quality of life in this patient population. Impaired gastrointestinal (GI) motility in IF arises from either loss of GI function due to the primary disorder (e.g., neuropathic or myopathic disorder in the PIPO syndrome) and/or a critical reduction in gut mass. Abnormalities of the anatomy, enteric hormone secretion and neural supply in IF can result in rapid transit, ineffective antegrade peristalsis, delayed gastric emptying or gastroesophageal reflux. Understanding the underlying pathophysiologic mechanism(s) of the enteric dysmotility in IF helps us to plan an appropriate diagnostic workup and apply individually tailored nutritional and pharmacological management, which might ultimately lead to an overall improvement in the quality of life and increase in enteral tolerance. In this review, we have focused on the pathogenesis of GI dysmotility in children with IF, as well as the management and treatment options.
Topics: Child; Gastroesophageal Reflux; Gastrointestinal Motility; Gastrointestinal Tract; Humans; Intestinal Pseudo-Obstruction; Short Bowel Syndrome
PubMed: 33217928
DOI: 10.3390/nu12113536 -
The American Journal of Tropical... Oct 2020The COVID-19 pandemic has recently spread worldwide, presenting primarily in the form of pneumonia or other respiratory disease. In addition, gastrointestinal...
The COVID-19 pandemic has recently spread worldwide, presenting primarily in the form of pneumonia or other respiratory disease. In addition, gastrointestinal manifestations have increasingly been reported as one of the extrapulmonary features of the virus. We report two cases of SARS-CoV-2 infection complicated by paralytic ileus. The first patient was a 33-year-old man who was hospitalized with severe COVID-19 pneumonia requiring ventilator support and intensive care. He developed large bowel dilatation and perforation of the mid-transverse colon, and underwent laparotomy and colonic resection. Histopathology of the resected bowel specimen showed acute inflammation, necrosis, and hemorrhage, supporting a role for COVID-19-induced micro-thrombosis leading to perforation. The second patient was a 33-year-old man who had severe COVID-19 pneumonia, renal failure, and acute pancreatitis. His hospital course was complicated with paralytic ileus, and he improved with conservative management. Both cases were observed to have elevated liver transaminases, which is consistent with other studies. Several authors have postulated that the angiotensin-converting enzyme 2 receptors, the host receptors for COVID-19, that are present on enterocytes in both the small and large bowel might mediate viral entry and resultant inflammation. This is a potential mechanism of paralytic ileus in cases of severe COVID-19 infection. Recognizing paralytic ileus as a possible complication necessitates timely diagnosis and management.
Topics: Adult; Betacoronavirus; Biomarkers; COVID-19; Coronavirus Infections; Humans; Intestinal Perforation; Intestinal Pseudo-Obstruction; Liver; Male; Pancreatitis; Pandemics; Pneumonia, Viral; Positive-Pressure Respiration; Renal Dialysis; Renal Insufficiency; SARS-CoV-2; Tomography, X-Ray Computed; Transaminases
PubMed: 32876011
DOI: 10.4269/ajtmh.20-0894 -
International Journal of Molecular... Mar 2023The immunoglobulin-like cell adhesion molecule CLMP is a member of the CAR family of cell adhesion proteins and is implicated in human congenital short-bowel syndrome... (Review)
Review
The immunoglobulin-like cell adhesion molecule CLMP is a member of the CAR family of cell adhesion proteins and is implicated in human congenital short-bowel syndrome (CSBS). CSBS is a rare but very severe disease for which no cure is currently available. In this review, we compare data from human CSBS patients and a mouse knockout model. These data indicate that CSBS is characterized by a defect in intestinal elongation during embryonic development and impaired peristalsis. The latter is driven by uncoordinated calcium signaling via gap junctions, which is linked to a reduction in connexin43 and 45 levels in the circumferential smooth muscle layer of the intestine. Furthermore, we discuss how mutations in the gene affect other organs and tissues, including the ureter. Here, the absence of CLMP produces a severe bilateral hydronephrosis-also caused by a reduced level of connexin43 and associated uncoordinated calcium signaling via gap junctions.
Topics: Animals; Mice; Humans; Connexin 43; Cell Adhesion; Coxsackie and Adenovirus Receptor-Like Membrane Protein; Cell Adhesion Molecules; Intestinal Pseudo-Obstruction
PubMed: 36982793
DOI: 10.3390/ijms24065719 -
Journal of Medical Radiation Sciences Dec 2018There is discord on the value of the erect abdominal radiograph for diagnosing acute abdominal pathologies. The erect radiograph can be uncomfortable for patients in...
INTRODUCTION
There is discord on the value of the erect abdominal radiograph for diagnosing acute abdominal pathologies. The erect radiograph can be uncomfortable for patients in pain and increases patient radiation dose.
AIM
To determine if including the erect abdominal radiograph in plain abdominal radiography (PAR) improved diagnostic accuracy for identifying mechanical bowel obstruction and/or paralytic ileus in adults presenting with acute abdominal pain.
METHODS
PAR of 40 consecutive adults presenting with suspected bowel obstruction or paralytic ileus was retrospectively sampled and independently reviewed by two emergency department (ED) consultants and two radiology consultants for bowel obstruction and paralytic ileus across two sessions. In session 1, the assessors assessed the supine abdominal radiographs (PAR 1) and clinical details in a randomised order, and session 2, at least 6 weeks later, they assessed the supine and erect radiographs (PAR 2) and clinical details of the randomly re-ordered cases. Computed tomography was the reference standard. Pair-wise comparisons of receiver operating characteristic curves were calculated to assess for significant differences in participants' diagnostic accuracy using MedCalc 16.4.3.
RESULTS
Average sensitivity, specificity and area under the receiver operating characteristic curves (AUROC) were 69.7%, 61.0% and 0.642 for PAR 1, respectively, and 80.0%, 53.4% and 0.632 for PAR 2 respectively. For AUROC there were no significant differences (P > 0.05) between PAR 1 and PAR 2. Intra-rater and inter-rater agreement improved in PAR 2.
CONCLUSION
There was no statistically significant improvement in diagnostic accuracy when including the erect radiograph in PAR for the acute abdomen.
Topics: Abdominal Pain; Adolescent; Adult; Female; Humans; Image Interpretation, Computer-Assisted; Intestinal Obstruction; Intestinal Pseudo-Obstruction; Male; Middle Aged; Observer Variation; Radiography, Abdominal; Retrospective Studies; Sensitivity and Specificity; Supine Position; Young Adult
PubMed: 30039624
DOI: 10.1002/jmrs.299