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American Journal of Physiology.... May 2021Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare autosomal recessive disease caused by thymidine phosphorylase (TP) enzyme defect. As...
Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare autosomal recessive disease caused by thymidine phosphorylase (TP) enzyme defect. As gastrointestinal changes do not revert in patients undergone TP replacement therapy, one can postulate that other unexplored mechanisms contribute to MNGIE pathophysiology. Hence, we focused on the local TP angiogenic potential that has never been considered in MNGIE. In this study, we investigated the enteric submucosal microvasculature and the effect of hypoxia on fibrosis and enteric neurons density in jejunal full-thickness biopsies collected from patients with MNGIE. Orcein staining was used to count blood vessels based on their size. Fibrosis was assessed using the Sirius Red and Fast Green method. Hypoxia and neoangiogenesis were determined via hypoxia-inducible-factor-1α (HIF-1α) and vascular endothelial cell growth factor (VEGF) protein expression, respectively. Neuron-specific enolase was used to label enteric neurons. Compared with controls, patients with MNGIE showed a decreased area of vascular tissue, but a twofold increase of submucosal vessels/mm with increased small size and decreased medium and large size vessels. VEGF positive vessels, fibrosis index, and HIF-1α protein expression were increased, whereas there was a diminished thickness of the longitudinal muscle layer with an increased interganglionic distance and reduced number of myenteric neurons. We demonstrated the occurrence of an angiopathy in the GI tract of patients with MNGIE. Neoangiogenetic changes, as detected by the abundance of small size vessels in the jejunal submucosa, along with hypoxia provide a morphological basis to explain neuromuscular alterations, vasculature breakdown, and ischemic abnormalities in MNGIE. Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is characterized by a genetically driven defect of thymidine phosphorylase, a multitask enzyme playing a role also in angiogenesis. Indeed, major gastrointestinal bleedings are life-threatening complications of MNGIE. Thus, we focused on jejunal submucosal vasculature and showed intestinal microangiopathy as a novel feature occurring in this disease. Notably, vascular changes were associated with neuromuscular abnormalities, which may explain gut dysfunction and help to develop future therapeutic approaches in MNGIE.
Topics: Gastrointestinal Tract; Humans; Intestinal Pseudo-Obstruction; Mitochondrial Encephalomyopathies; Muscular Dystrophy, Oculopharyngeal; Neovascularization, Pathologic; Ophthalmoplegia; Thymidine Phosphorylase
PubMed: 33655764
DOI: 10.1152/ajpgi.00047.2021 -
BMC Microbiology Feb 2024Pediatric chronic intestinal pseudo-obstruction (PIPO) is a rare disease characterized by symptoms and radiological signs suggestive of intestinal obstruction, in the...
BACKGROUND
Pediatric chronic intestinal pseudo-obstruction (PIPO) is a rare disease characterized by symptoms and radiological signs suggestive of intestinal obstruction, in the absence of lumen-occluding lesions. It results from an extremely severe impairment of propulsive motility. The intestinal endocrine system (IES) jointly with the enteric nervous system (ENS) regulates secreto-motor functions via different hormones and bioactive messengers/neurotransmitters. The neurotransmitter 5-hydroxytryptamine (5-HT) (or serotonin) is linked to intestinal peristalsis and secretory reflexes. Gut microbiota and its interplay with ENS affect 5-HT synthesis, release, and the subsequent serotonin receptor activation. To date, the interplay between 5-HT and gut microbiota in PIPO remains largely unclear. This study aimed to assess correlations between mucosa associated microbiota (MAM), intestinal serotonin-related genes expression in PIPO. To this purpose, biopsies of the colon, ileum and duodenum have been collected from 7 PIPO patients, and 7 age-/sex-matched healthy controls. After DNA extraction, the MAM was assessed by next generation sequencing (NGS) of the V3-V4 region of the bacterial RNA 16 S, on an Illumina Miseq platform. The expression of genes implicated in serotoninergic pathway (TPH1, SLC6A4, 5-HTR3 and 5-HTR4) was established by qPCR, and correlations with MAM and clinical parameters of PIPO have been evaluated.
RESULTS
Our results revealed that PIPO patients exhibit a MAM with a different composition and with dysbiosis, i.e. with a lower biodiversity and fewer less connected species with a greater number of non-synergistic relationships, compared to controls. qPCR results revealed modifications in the expression of serotonin-related intestinal genes in PIPO patients, when compared to controls. Correlation analysis do not reveal any kind of connection.
CONCLUSIONS
For the first time, we report in PIPO patients a specific MAM associated to underlying pathology and an altered intestinal serotonin pathway. A possible dysfunction of the serotonin pathway, possibly related to or triggered by an altered microbiota, may contribute to dysmotility in PIPO patients. The results of our pilot study provide the basis for new biomarkers and innovative therapies targeting the microbiota or serotonin pathways in PIPO patients.
Topics: Humans; Child; Serotonin; Gastrointestinal Microbiome; Pilot Projects; Intestines; Intestinal Pseudo-Obstruction; Serotonin Plasma Membrane Transport Proteins
PubMed: 38302874
DOI: 10.1186/s12866-024-03200-z -
Journal of the American Association For... May 2008Here we describe the epizootiology and pathology of spontaneous, fatal acute intestinal pseudoobstruction that occurred in a mouse colony of 1000 breeding pairs, mainly...
Here we describe the epizootiology and pathology of spontaneous, fatal acute intestinal pseudoobstruction that occurred in a mouse colony of 1000 breeding pairs, mainly of the C57Bl/6 strain and free from known pathogenic agents. Most of the mice affected were dams in the second week of lactation. At necropsy, segments of the small intestines were distended with fluid contents. Widespread apoptosis of the villus epithelium of the small intestine and superficial epithelial cells of the large intestine, associated with strong expression of active caspase 3, was a distinctive feature. Necrotic enterocytes, mucosal erosions, and acute mucosal inflammation were prominent in some mice, and morphologic signs of toxemia were generally present. No light microscopic neuronal changes were apparent in the gut, and no etiologic agents were identified. These results indicate that sudden activation of apoptosis in the trophically stimulated gut epithelium during peak lactation was instrumental for the fatal outcome of the condition, but the primary cause of the motility dysfunction of the bowel was not established.
Topics: Animals; Apoptosis; Caspase 3; Enterocytes; Female; Gastrointestinal Motility; Immunohistochemistry; Intestinal Pseudo-Obstruction; Intestine, Small; Lactation; Male; Mice; Mice, Inbred C57BL; Necrosis; Sweden
PubMed: 18459715
DOI: No ID Found -
ARP Rheumatology 2024
Topics: Humans; Hydronephrosis; Intestinal Pseudo-Obstruction
PubMed: 38558066
DOI: 10.63032/HIIJ8275 -
Hinyokika Kiyo. Acta Urologica Japonica Oct 2011To identify the incidence and risk factors for developing early postoperative paralytic ileus (POPI) after radical cystectomy and cutaneous ureterostomy with a...
To identify the incidence and risk factors for developing early postoperative paralytic ileus (POPI) after radical cystectomy and cutaneous ureterostomy with a unilateral and parallel stoma, we retrospectively reviewed 21 patients (mean age 73.0, 19 males and 2 females) with a minimum of 3 months of follow-up. POPI occurred in 4 patients (19.0%), who did not need surgical treatment and the insertion of a nasogastric tube. Age and past history of abdominal surgery influenced the occurrence of POPI. The patients with and without POPI had a mean age of 82.3±7.4 and 70.8±6.3 years old, respectively (p=0.0025), and 75.0% (3/4) and 11.8% (2/17) of the patients, respectively, had a past history of abdominal surgery (p= 0.0276). There were no significant differences between patients with and without POPI in any of the following factors examined : sex, body mass index, American Society of Anesthesiologists score, pT-category, neoadjuvant chemotherapy, preoperative serum levels of hemoglobin, creatinine, total protein, and albumin, operative time, blood loss, transfusion volume, stomal side, postoperative day of ambulation, and removal of epidural anesthesia tube. In conclusion, our results showed that increasing age and a past history of abdominal surgery were significantly associated with the occurrence of POPI after radical cystectomy and cutaneous ureterostomy.
Topics: Aged; Aged, 80 and over; Cystectomy; Female; Humans; Intestinal Pseudo-Obstruction; Male; Middle Aged; Postoperative Complications; Risk Factors; Ureterostomy; Urinary Bladder Neoplasms
PubMed: 22089149
DOI: No ID Found -
World Journal of Gastroenterology Jul 2010Interstitial cells of Cajal (ICC) are important players in the symphony of gut motility. They have a very significant physiological role orchestrating the normal... (Review)
Review
Interstitial cells of Cajal (ICC) are important players in the symphony of gut motility. They have a very significant physiological role orchestrating the normal peristaltic activity of the digestive system. They are the pacemaker cells in gastrointestinal (GI) muscles. Absence, reduction in number or altered integrity of the ICC network may have a dramatic effect on GI system motility. More understanding of ICC physiology will foster advances in physiology of gut motility which will help in a future breakthrough in the pharmacological interventions to restore normal motor function of GI tract. This mini review describes what is known about the physiologic function and role of ICCs in GI system motility and in a variety of GI system motility disorders.
Topics: Animals; Constipation; Esophageal Achalasia; Gastroesophageal Reflux; Gastrointestinal Diseases; Gastrointestinal Motility; Gastrointestinal Stromal Tumors; Gastrointestinal Tract; Gastroparesis; Hirschsprung Disease; Humans; Interstitial Cells of Cajal; Intestinal Pseudo-Obstruction
PubMed: 20614479
DOI: 10.3748/wjg.v16.i26.3239 -
The Cochrane Database of Systematic... Dec 2014This is an updated version of the original Cochrane review published in 2007. Traditionally, after major abdominal gynaecologic surgery postoperative oral intake is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This is an updated version of the original Cochrane review published in 2007. Traditionally, after major abdominal gynaecologic surgery postoperative oral intake is withheld until the return of bowel function. There has been concern that early oral intake would result in vomiting and severe paralytic ileus with subsequent aspiration pneumonia, wound dehiscence, and anastomotic leakage. However, evidence-based clinical studies suggest that there may be benefits from early postoperative oral intake.
OBJECTIVES
To assess the effects of early versus delayed (traditional) initiation of oral intake of food and fluids after major abdominal gynaecologic surgery.
SEARCH METHODS
We searched the Menstrual Disorders and Subfertility Group's Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), electronic databases (MEDLINE, EMBASE, CINAHL), and the citation lists of relevant publications. The most recent search was conducted 1 April 2014. We also searched a registry for ongoing trials (www.clinicaltrials.gov) on 13 May 2014.
SELECTION CRITERIA
Randomised controlled trials (RCTs) were eligible that compared the effect of early versus delayed initiation of oral intake of food and fluids after major abdominal gynaecologic surgery. Early feeding was defined as oral intake of fluids or food within 24 hours post-surgery regardless of the return of bowel function. Delayed feeding was defined as oral intake after 24 hours post-surgery and only after signs of postoperative ileus resolution.
DATA COLLECTION AND ANALYSIS
Two review authors selected studies, assessed study quality and extracted the data. For dichotomous data, we calculated the risk ratio (RR) with a 95% confidence interval (CI). We examined continuous data using the mean difference (MD) and a 95% CI. We tested for heterogeneity between the results of different studies using a forest plot of the meta-analysis, the statistical tests of homogeneity of 2 x 2 tables and the I² value. We assessed the quality of the evidence using GRADE methods.
MAIN RESULTS
Rates of developing postoperative ileus were comparable between study groups (RR 0.47, 95% CI 0.17 to 1.29, P = 0.14, 3 RCTs, 279 women, I² = 0%, moderate-quality evidence). When we considered the rates of nausea or vomiting or both, there was no evidence of a difference between the study groups (RR 1.03, 95% CI 0.64 to 1.67, P = 0.90, 4 RCTs, 484 women, I² = 73%, moderate-quality evidence). There was no evidence of a difference between the study groups in abdominal distension (RR 1.07, 95% CI 0.77 to 1.47, 2 RCTs, 301 women, I² = 0%) or a need for postoperative nasogastric tube placement (RR 0.48, 95% CI 0.13 to 1.80, 1 RCT, 195 women).Early feeding was associated with shorter time to the presence of bowel sound (MD -0.32 days, 95% CI -0.61 to -0.03, P = 0.03, 2 RCTs, 338 women, I² = 52%, moderate-quality evidence) and faster onset of flatus (MD -0.21 days, 95% CI -0.40 to -0.01, P = 0.04, 3 RCTs, 444 women, I² = 23%, moderate-quality evidence). In addition, women in the early feeding group resumed a solid diet sooner (MD -1.47 days, 95% CI -2.26 to -0.68, P = 0.0003, 2 RCTs, 301 women, I² = 92%, moderate-quality evidence). There was no evidence of a difference in time to the first passage of stool between the two study groups (MD -0.25 days, 95% CI -0.58 to 0.09, P = 0.15, 2 RCTs, 249 women, I² = 0%, moderate-quality evidence). Hospital stay was shorter in the early feeding group (MD -0.92 days, 95% CI -1.53 to -0.31, P = 0.003, 4 RCTs, 484 women, I² = 68%, moderate-quality evidence). Infectious complications were less common in the early feeding group (RR 0.20, 95% CI 0.05 to 0.73, P = 0.02, 2 RCTs, 183 women, I² = 0%, high-quality evidence). In one study, the satisfaction score was significantly higher in the early feeding group (MD 11.10, 95% CI 6.68 to 15.52, P < 0.00001, 143 women, moderate-quality evidence).
AUTHORS' CONCLUSIONS
Early postoperative feeding after major abdominal gynaecologic surgery for either benign or malignant conditions appeared to be safe without increased gastrointestinal morbidities or other postoperative complications. The benefits of this approach include faster recovery of bowel function, lower rates of infectious complications, shorter hospital stay, and higher satisfaction.
Topics: Drinking; Eating; Female; Food; Genital Neoplasms, Female; Gynecologic Surgical Procedures; Humans; Hysterectomy; Intestinal Pseudo-Obstruction; Nausea; Ovariectomy; Postoperative Care; Postoperative Complications; Randomized Controlled Trials as Topic; Recovery of Function; Time Factors
PubMed: 25502897
DOI: 10.1002/14651858.CD004508.pub4 -
Indian Journal of Psychological Medicine Jan 2013A 32-year-old man, diagnosed with catatonic schizophrenia, was treated with risperidone and lorazepam in the general hospital psychiatry setup. He developed signs of...
A 32-year-old man, diagnosed with catatonic schizophrenia, was treated with risperidone and lorazepam in the general hospital psychiatry setup. He developed signs of intestinal obstruction, which was diagnosed as paralytic ileus and was treated conservatively along with stopping the offending drug. Risperidone is said to be devoid of anticholinergic side effects, but prevalence of these varies from 7% to 13% in patients receiving treatment for schizophrenia. Constipation has been reported but fatal adverse effect like paralytic ileus with risperidone is rarely reported. Timely diagnosis can save the need for surgical interventions and fatal complications. This predisposition in schizophrenia could be due to neurodevelopmentally shared abnormality of brain and gut nervous system.
PubMed: 23833349
DOI: 10.4103/0253-7176.112214 -
The Journal of Medical Investigation :... 2017A 78-year-old female was referred to our hospital with a diagnosis of type A acute aortic dissection. There was a history of thrombosed aortic dissection six months...
A 78-year-old female was referred to our hospital with a diagnosis of type A acute aortic dissection. There was a history of thrombosed aortic dissection six months prior and conservative management has been performed. Enhanced computed tomography showed type A acute aortic dissection with patent false lumen limited to the ascending aorta and ileus of the small intestine. Emergency hemiarch replacement was performed under mild hypothermic circulatory arrest and selective antegrade cerebral perfusion. Due to preoperative paralytic ileus, oral intake was initiated postoperative day four. Postoperative computed tomography revealed improvement of paralytic ileus. J. Med. Invest. 64: 286-287, August, 2017.
Topics: Acute Disease; Aged; Aortic Dissection; Female; Humans; Intestinal Pseudo-Obstruction; Tomography, X-Ray Computed
PubMed: 28954997
DOI: 10.2152/jmi.64.286 -
Medicine Jul 2019Intestinal pseudo-obstruction (IPO) is a rare and life-threatening complication of lupus.
INTRODUCTION
Intestinal pseudo-obstruction (IPO) is a rare and life-threatening complication of lupus.
PATIENT CONCERNS
A patient with long-standing lupus developed recurrent abdominal pain and distension as well as nausea and emesis.
DIAGNOSIS
Imaging showed dilated small bowel loops with air-fluid levels and bowel wall thickening. She also had bilateral hydronephrosis.
INTERVENTIONS
She was given high-doses of intravenous steroids and cyclophosphamide.
OUTCOMES
Her symptoms resolved within a week of starting immunosuppression. She was eventually transitioned to mycophenolate mofetil. She remained in remission and immunosuppression was successfully stopped after 1 year.
CONCLUSIONS
Intestinal pseudo-obstruction is a rare complication of lupus that is often seen in association with ureterohydronephrosis and interstitial cystitis. This clinical syndrome is thought to be because of smooth muscle dysmotility of the gastrointestinal and genitourinary tracts, although the exact mechanism of dysmotility remains unknown. This condition is often responsive to immunosuppression if recognized and treated promptly.
Topics: Adult; Diagnosis, Differential; Female; Humans; Hydronephrosis; Immunosuppression Therapy; Intestinal Pseudo-Obstruction; Lupus Erythematosus, Systemic
PubMed: 31305400
DOI: 10.1097/MD.0000000000016178