ABSTRACT
The incidence and mortality rate of pancreatic cancer are increasing worldwide. Regional lymph nodes, liver, lung, and peritoneum are common sites of metastasis from pancreatic cancer, but the gastrointestinal tract is rare as a metastatic organ from pancreatic cancer. An 80-year-old man was referred to our department for a hypovascular pancreatic mass on contrast-enhanced computed tomography (CECT). Endoscopic ultrasound-guided fine needle aspiration revealed adenocarcinoma, and he was diagnosed with pancreatic cancer. No lymph nodes or distant metastases were detected by either CECT or gadolinium-enhanced magnetic resonance imaging, and we evaluated this case as borderline resectable. However, total colonoscopy for positive fecal occult blood tests revealed a reddish and hemorrhagic mucosal thickening in the ascending and sigmoid colon and rectum, which was inconsistent with primary colorectal cancer. Biopsy specimens from these sites revealed cytokeratin (CK)7-positive and CK20- and CDX2-negative adenocarcinoma, consistent with cancer of pancreatic origin. The patient underwent palliative chemotherapy with gemcitabine but died from COVID-19 infection eight months after diagnosis. Performing total colonoscopy as a preoperative screening is important for accurate cancer staging of patients with possible resectable pancreatic cancer.
Subject(s)
Adenocarcinoma , Pancreatic Neoplasms , Male , Humans , Aged, 80 and over , Pancreatic Neoplasms/pathology , Endoscopic Ultrasound-Guided Fine Needle Aspiration , Lymph Nodes/pathology , Adenocarcinoma/pathology , Intestine, Large/pathologyABSTRACT
BACKGROUND: Diffusion-weighted MRI (DWI) is routinely used in abdominal imaging. In addition to neoplastic diseases, inflammatory changes can be delineated and diagnosed based on diffusion restriction in DWI. DWI is also increasingly used in the context of MRI of the small and large intestine. OBJECTIVE: This article focuses on the technical aspects of DWI and its role in the diagnosis of Crohn's disease (CD) as well as in the grading of disease severity and in treatment monitoring. MATERIALS AND METHODS: Guidelines, basic research papers, and review articles were analyzed. RESULTS: Diffusion-weighted MRI is a specialized MRI technique that visualizes the diffusion of water molecules in biological tissues. In the context of MRI of the small and large intestine, DWI facilitates the diagnosis of inflammatory bowel disease and assessment of treatment response. DWI enables detection of not only intra- and transmural changes, but also extramural pathologies and complications. However, DWI also has its limitations and challenges. CONCLUSION: This article provides a comprehensive overview of the use of DWI for diagnostic evaluation of bowel wall changes and extramural complications in the setting of CD. It also summarizes the relevant evidence available in the literature.
Subject(s)
Crohn Disease , Humans , Crohn Disease/diagnostic imaging , Crohn Disease/pathology , Diffusion Magnetic Resonance Imaging/methods , Magnetic Resonance Imaging , Intestines/pathology , Intestine, Large/pathologyABSTRACT
The range of lesions with a serrated appearance within the large intestine has expanded and become more complex over the last 30 years. The majority of these were previously known as metaplastic polyps but are today called hyperplastic polyps (HPs). HPs show two main growth patterns: microvesicular and goblet cell-rich. The former type shows morphological and molecular similarities (eg, BRAF mutations) to the more recently described sessile serrated lesion (SSL). In this review, we debate whether these lesions represent a biological spectrum or separate entities. Whichever view is held, microvesicular HPs and SSLs are distinct from the goblet cell-rich HP and the traditional serrated adenoma (TSA), which may themselves share molecular changes (eg, KRAS mutations), with the goblet cell-rich HP representing a precursor to the TSA. Both SSLs and the goblet cell-rich HP-TSA pathway are routes to colorectal cancer within the serrated pathway and overlaps between them can occur, for example, a (BRAF-mutated) TSA may arise from an SSL.
Subject(s)
Adenoma , Colonic Polyps , Colorectal Neoplasms , Humans , Colonic Polyps/genetics , Colonic Polyps/pathology , Colorectal Neoplasms/pathology , Proto-Oncogene Proteins B-raf/genetics , Adenoma/pathology , Intestine, Large/metabolism , Intestine, Large/pathologyABSTRACT
BACKGROUND: MODUL is an adaptable, signal-seeking trial designed to test novel agents in predefined patient subgroups in first-line metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: Patients with measurable, unresectable, previously untreated mCRC received induction with ≤8 cycles of FOLFOX + bevacizumab followed by randomization to maintenance treatment comprising control [fluoropyrimidine (FP)/bevacizumab: 5-fluorouracil 1600-2400 mg/m2 46-h intravenous (i.v.) infusion day 1 q2 weeks plus leucovorin 400 mg/m2 2-h infusion i.v. day 1 q2 weeks or capecitabine 1000 mg/m2 b.i.d. orally days 1-14 every 21 days; bevacizumab 5 mg/kg 15-30-min i.v. infusion q2 weeks] or experimental treatment in one of four biomarker-driven cohorts. In patients with BRAF wild-type (BRAFwt) tumors (cohort 2), experimental treatment was FP/bevacizumab + atezolizumab (800 mg 60-min i.v. infusion q2 weeks). Primary efficacy endpoint was progression-free survival (PFS; intent-to-treat population). Enrollment is complete; efficacy and safety findings from cohort 2 are presented. RESULTS: Four hundred and forty-five patients with BRAFwt mCRC were randomized (2 : 1) to maintenance in cohort 2. At a median follow-up of 10.5 months, PFS outcome hypothesis was not met [hazard ratio (HR) 0.92; 95% confidence interval (CI) 0.72-1.17; P = 0.48]; overall survival (OS) was immature. At a median follow-up of 20.3 months (2-year survival follow-up), PFS benefit was also not met (HR 0.95; 95% CI 0.77-1.18; P = 0.666); OS HR with nearly two-thirds of patients with events was 0.83 (95% CI 0.65-1.05; P = 0.117). No new safety signals were identified. The most common grade ≥3 treatment-emergent adverse events (TEAEs) for experimental versus control arms were hypertension (6.1% versus 4.2%), diarrhea (3.1% versus 2.1%), and palmar-plantar erythrodysesthesia syndrome (1.0% versus 2.5%). Four patients experienced TEAEs with fatal outcome, two were study treatment-related: hepatic failure (experimental arm) and large intestine perforation (control arm; bevacizumab-related). CONCLUSIONS: Adding atezolizumab to FP/bevacizumab as first-line maintenance treatment after FOLFOX + bevacizumab induction for BRAFwt mCRC did not improve efficacy outcomes.
Subject(s)
Colonic Neoplasms , Colorectal Neoplasms , Humans , Bevacizumab/pharmacology , Bevacizumab/therapeutic use , Leucovorin/pharmacology , Leucovorin/therapeutic use , Capecitabine/pharmacology , Capecitabine/therapeutic use , Proto-Oncogene Proteins B-raf , Colorectal Neoplasms/pathology , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Fluorouracil/adverse effects , Intestine, Large/pathologyABSTRACT
The main purpose of the study is to determine peculiar morphological characteristics of structural changes of alimentary system organs in the case of experimental undifferentiated dysplasia of connective tissue (UDCT). Intranatal antigen introduction was conducted as an experimental model of UDCT. Objects of investigation - pharynx, duodenum, ileum, caecum, ascendant colon of white rats from the first up to the 60th day of postnatal life. Animals were contained in standard conditions of vivarium according to Law of Ukraine â 1759-VI (15.12.2009) On the Protection of Animals from Cruelty. Morphological structure of organs were examined at days 1st, 7th, 14th, 21th, 45th, 60th after birth. Morphometric, histological, histochemical, lectinistochemical, immunehistochemic and statistic methods were used. Analysis of the obtained results was conducted by means of statistical methods with the use of computer license program «Statistica for Windows 13¼ (StatSoft Inc., â JPZ804I382130ARCN10-J). The compared results considered such, that for certain differ at Ñ<0,05 that is generally accepted for biological and medical researches. On the background of experimental syndrome of UDCT, developed by intranatal antigen loading, it is settled that the number of intraepithelial lymphocytes, number of lymphocytes of submucose layer of alimentary tract increases. Ratio between cells of mucosa (including epithelial layer and submucosal layer) changes. Interrelation between layers of alimentary tube changes resulting in the thickening of mucosa (including epithelial layer and submucosal layer) and thinning of muscular layer. These inflections result in elongation of duodenum, small and large intestines. Throughout the first month after birth in rats with experimental syndrome of UDCT lymphocyte/epitheliocyte, lymphocyte/ fibroblast and lymphocyte/mitosis indexes change in proximal and distal parts of digestive tract.
Subject(s)
Connective Tissue , Duodenum , Intestine, Large , Animals , Colon , Connective Tissue/pathology , Duodenum/pathology , Ileum , Intestinal Mucosa/pathology , Intestine, Large/pathologyABSTRACT
The colorectal cancer remains one of leading problems of modern coloproctology and oncology. The polyps are one of pathology of colon widespread in population and predictor of colorectal cancer. Their timely detection and removal is considered as only effective measure of prevention of colon malignant neoplasms. The morbidity of colon malignant neoplasms in the Perm Kray was monitored in 2004-2018. Its structure and dynamics were evaluated. The software is described that allows both physicians and patients to evaluate probability of detecting colon neoplasms that contributes to expansion of the research database of coloproctologic studies. The ways of increasing effectiveness of predicting incidence of colorectal cancer and colon polyps were proposed on the basis of neural networks, that permit to increase detection of corresponding pathology by personalizing screening.
Subject(s)
Colonic Polyps , Colorectal Neoplasms , Colonic Polyps/diagnosis , Colonic Polyps/epidemiology , Colonic Polyps/pathology , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/epidemiology , Humans , Incidence , Intestine, Large/pathology , Mass ScreeningABSTRACT
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the causative agent of the newly emerging lung disease pandemic COVID-19. This viral infection causes a series of respiratory disorders, and although this virus mainly infects respiratory cells, the small intestine can also be an important site of entry or interaction, as enterocytes highly express in angiotensin-2 converting enzyme (ACE) receptors. There are countless reports pointing to the importance of interferons (IFNs) with regard to the mediation of the immune system in viral infection by SARS-CoV-2. Thus, this review will focus on the main cells that make up the large intestine, their specific immunology, as well as the function of IFNs in the intestinal mucosa after the invasion of coronavirus-2.
Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , COVID-19/metabolism , Intestinal Mucosa/metabolism , Intestine, Large/metabolism , SARS-CoV-2/metabolism , COVID-19/pathology , Humans , Intestinal Mucosa/injuries , Intestinal Mucosa/pathology , Intestinal Mucosa/virology , Intestine, Large/injuries , Intestine, Large/pathology , Intestine, Large/virologyABSTRACT
Environmental enteric dysfunction is associated with malnutrition as well as infant growth stunting and has been classically defined by villous blunting, decreased crypt-to-villus ratio, and inflammation in the small intestine. Here, we characterized environmental enteric dysfunction among infant rhesus macaques that are naturally exposed to enteric pathogens commonly linked to human growth stunting. Remarkably, despite villous atrophy and histological abnormalities observed in the small intestine, poor growth trajectories and low serum tryptophan levels were correlated with increased histopathology in the large intestine. This work provides insight into the mechanisms underlying this disease and indicates that the large intestine may be an important target for therapeutic intervention.
Subject(s)
Intestine, Large/pathology , Intestine, Small/pathology , Macaca mulatta/growth & development , Animals , Duodenum/pathology , Female , Gastrointestinal Tract , Gene Expression , Growth Disorders/pathology , Humans , Ileum/pathology , Inflammation , Intestinal Diseases , Intestinal Mucosa , Jejunum/pathology , Male , MalnutritionABSTRACT
OBJECTIVE: Effective medical therapy and validated trial outcomes are lacking for small bowel Crohn's disease (CD) strictures. Histopathology of surgically resected specimens is the gold standard for correlation with imaging techniques. However, no validated histopathological scoring systems are currently available for small bowel stricturing disease. We convened an expert panel to evaluate the appropriateness of histopathology scoring systems and items generated based on panel opinion. DESIGN: Modified RAND/University of California Los Angeles methodology was used to determine the appropriateness of 313 candidate items related to assessment of CD small bowel strictures. RESULTS: In this exercise, diagnosis of naïve and anastomotic strictures required increased bowel wall thickness, decreased luminal diameter or internal circumference, and fibrosis of the submucosa. Specific definitions for stricture features and technical sampling parameters were also identified. Histopathologically, a stricture was defined as increased thickness of all layers of the bowel wall, fibrosis of the submucosa and bowel wall, and muscularisation of the submucosa. Active mucosal inflammatory disease was defined as neutrophilic inflammation in the lamina propria and any crypt or intact surface epithelium, erosion, ulcer and fistula. Chronic mucosal inflammatory disease was defined as crypt architectural distortion and loss, pyloric gland metaplasia, Paneth cell hyperplasia, basal lymphoplasmacytosis, plasmacytosis and fibrosis, or prominent lymphoid aggregates at the mucosa/submucosa interface. None of the scoring systems used to assess CD strictures were considered appropriate for clinical trials. CONCLUSION: Standardised assessment of gross pathology and histopathology of CD small bowel strictures will improve clinical trial efficiency and aid drug development.
Subject(s)
Crohn Disease/pathology , Intestinal Obstruction/pathology , Intestine, Large/pathology , Consensus , Constriction, Pathologic , Crohn Disease/complications , Humans , Intestinal Obstruction/etiology , Severity of Illness Index , Surveys and QuestionnairesABSTRACT
The public has gradually begun to regard inflammatory bowel disease (IBD) as a crucial health issue; however, its mode of action has not been fully elucidated. Sophorolipid (SPL), a glycolipid-type biosurfactant, could be used as a potential treatment in physical intestinal dystrophy. We conducted a 2 × 2 factorial experiment to investigate the protective effect of SPL in a dextran sulfate sodium (DSS)-induced colitis mouse model (first factor, presence of SPL in feed; second factor, presence of DSS in water). Forty C57BL/6 mice (8-week-old) were used, and they were allocated to treatments according to their initial body weight. After a 7 d adjustment period, the DSS treatment was initiated in specific groups. At day 14, DSS was withdrawn from mice, and half of the mice were randomly selected and euthanized to collect colon and colon content samples. Three days after the end of DSS treatment, the rest of the mice were euthanized to investigate the therapeutic effect of SPL. Dietary SPL improved the growth performance in 3 d after DSS treatment, and the histopathological score was lower in the DSS-treated SPL group than in the DSS-treated control group. Mucosal thickness and goblet cell numbers significantly increased in the SPL-supplemented groups compared to in the control group. Similarly, SPL supplementation upregulated the gene expression levels of mucin-2, interleukin-10, and transforming growth factor-ß, and increased the concentration of short chain fatty acid compared to the control groups. In conclusion, dietary supplementation with SPL attenuated the pathological response against acute and chronic inflammation by the maintenance of the mucosal barrier and wound healing capacity.
Subject(s)
Colitis/metabolism , Intestine, Large/drug effects , Oleic Acids/pharmacology , Protective Agents/pharmacology , Animals , Colitis/chemically induced , Cytokines/metabolism , Dextran Sulfate/adverse effects , Disease Models, Animal , Intestinal Mucosa/cytology , Intestinal Mucosa/drug effects , Intestinal Mucosa/pathology , Intestine, Large/cytology , Intestine, Large/pathology , Mice , Mice, Inbred C57BLABSTRACT
BACKGROUND: Asymptomatic patients with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) can develop hypercoagulable conditions and acute vascular events. The objective of this study is to determine whether SARS-CoV-2 was present in resected specimens from patients with acute bowel ischemia, but asymptomatic for Coronavirus Disease 2019 (COVID-19) and with persistently real-time polymerase chain reaction negative pharyngeal swab. METHODS: Three consecutive patients presented severe abdominal symptoms due to extensive ischemia and necrosis of the bowel, with co-existent thrombosis of abdominal blood vessels. None had the usual manifestations of COVID-19, and repeated pharyngeal swabs tested negative. They underwent emergency surgery with intestinal resection. Immunohistochemical testing for SARS-CoV-2 on resected tissue was performed. RESULTS: All tested samples were strongly positive for SARS-CoV-2. CONCLUSIONS: This is the first case report in which patients with severe intestinal symptoms presented a marked SARS-CoV-2 positivity in the resected tissues, without any usual clinical manifestations of COVID-19. These results suggest that the patients might be infected with SARS-CoV-2 presenting acute abdominal distress but without respiratory or constitutional symptoms.
Subject(s)
COVID-19 , Intestine, Large/pathology , Ischemia , COVID-19/pathology , Humans , Ischemia/diagnosis , Ischemia/virology , Necrosis , Real-Time Polymerase Chain Reaction , SARS-CoV-2 , ThrombosisABSTRACT
Malignant peripheral nerve sheath tumor (MPNST) contains properties and histologic markers of both neural crest cells and mesenchymal cells. It is a rare diagnosis, with an incidence of 1:100,000/year or 4%-10% of soft-tissue sarcomas. There are very few cases reported and studied. Therefore, establishing a proper diagnosis and treatment of MPNST provides a challenge. We present this unique and rare case of metastatic MPNST of the small and large bowel with bone, pulmonary, liver, and splenic metastases. The patient subsequently developed hemorrhagic brain metastases and died 6 months after THE initial diagnosis.
Résumé La tumeur maligne de la gaine nerveuse périphérique (MPNST) contient des propriétés et des marqueurs histologiques des cellules de la crête neurale et du mésenchyme cellules. Il s'agit d'un diagnostic rare, avec une incidence de 1: 100 000 / an ou 4 à 10% des sarcomes des tissus mous. Il y a très peu de cas signalés et étudié. Par conséquent, l'établissement d'un diagnostic et d'un traitement appropriés de la MPNST constitue un défi. Nous présentons ce cas unique et rare de MPNST métastatique du petit et du gros intestin avec métastases osseuses, pulmonaires, hépatiques et spléniques. Le patient a ensuite développé métastases cérébrales hémorragiques et est décédé 6 mois après LE diagnostic initial.
Subject(s)
Intestinal Neoplasms/secondary , Intestine, Large/pathology , Intestine, Small/pathology , Nerve Sheath Neoplasms/secondary , Neurofibrosarcoma/pathology , Soft Tissue Neoplasms/pathology , Aged , Antibiotics, Antineoplastic/therapeutic use , Bone Neoplasms/secondary , Bone Neoplasms/surgery , Chemotherapy, Adjuvant , Doxorubicin/therapeutic use , Humans , Intestinal Neoplasms/drug therapy , Intestinal Neoplasms/pathology , Male , Neoplasm Metastasis , Neoplasms, Second Primary , Nerve Sheath Neoplasms/surgery , Neurofibrosarcoma/drug therapy , Neurofibrosarcoma/surgery , Soft Tissue Neoplasms/drug therapy , Soft Tissue Neoplasms/surgery , Treatment OutcomeABSTRACT
Plasmodium falciparum is a protozoan parasite which causes malarial disease in humans. Infections commonly occur in sub-Saharan Africa, a region with high rates of inadequate nutrient consumption resulting in malnutrition. The complex relationship between malaria and malnutrition and their effects on gut immunity and physiology are poorly understood. Here, we investigated the effect of malaria infection in the guts of moderately malnourished mice. We utilized a well-established low protein diet that is deficient in zinc and iron to induce moderate malnutrition and investigated mucosal tissue phenotype, permeability, and innate immune response in the gut. We observed that the infected moderately malnourished mice had lower parasite burden at the peak of infection, but damaged mucosal epithelial cells and high levels of FITC-Dextran concentration in the blood serum, indicating increased intestinal permeability. The small intestine in the moderately malnourished mice were also shorter after infection with malaria. This was accompanied with lower numbers of CD11b+ macrophages, CD11b+CD11c+ myeloid cells, and CD11c+ dendritic cells in large intestine. Despite the lower number of innate immune cells, macrophages in the moderately malnourished mice were highly activated as determined by MHCII expression and increased IFNγ production in the small intestine. Thus, our data suggest that malaria infection may exacerbate some of the abnormalities in the gut induced by moderate malnutrition.
Subject(s)
Immunity, Innate , Immunity, Mucosal , Intestinal Mucosa/pathology , Malaria/complications , Malnutrition/complications , Plasmodium chabaudi , Animals , Cytokines/biosynthesis , Intestinal Mucosa/immunology , Intestine, Large/immunology , Intestine, Large/pathology , Intestine, Small/immunology , Intestine, Small/pathology , Macrophages/immunology , Malaria/immunology , Malaria/pathology , Male , Malnutrition/immunology , Malnutrition/pathology , Mice , Mice, Inbred C57BLABSTRACT
BACKGROUND: Patients with Crohn's disease suffer from a higher rate of anastomotic leakages after ileocecal resection than patients without Crohn's disease. Our hypothesis was that microscopic inflammation at the resection margins of ileocecal resections in Crohn's disease increases the rate of anastomotic leakages. PATIENTS AND METHODS: In a retrospective cohort study, 130 patients with Crohn's disease that underwent ileocecal resection between 2015 and 2019, were analyzed. Anastomotic leakage was the primary outcome parameter. Inflammation at the resection margin was characterized as "inflammation at proximal resection margin", "inflammation at distal resection margin" or "inflammation at both ends". RESULTS: 46 patients (35.4%) showed microscopic inflammation at the resection margins. 17 patients (13.1%) developed anastomotic leakage. No difference in the rate of anastomotic leakages was found for proximally affected resection margins (no anastomotic leakage vs. anastomotic leakage: 20.3 vs. 35.3%, p = 0.17), distally affected resection margins (2.7 vs. 5.9%, p = 0.47) or inflammation at both ends (9.7 vs. 11.8%, p = 0.80). No effect on the anastomotic leakage rate was found for preoperative hemoglobin concentration (no anastomotic leakage vs. anastomotic leakage: 12.3 vs. 13.5 g/dl, p = 0.26), perioperative immunosuppressive medication (62.8 vs. 52.9%, p = 0.30), BMI (21.8 vs. 22.4 m2/kg, p = 0.82), emergency operation (21.2 vs. 11.8%, p = 0.29), laparoscopic vs. open procedure (p = 0.58), diverting ileostomy (31.9 vs. 57.1%, p = 0.35) or the level of surgical training (staff surgeon: 80.5 vs. 76.5%, p = 0.45). CONCLUSION: Microscopic inflammation at the resection margins after ileocecal resection in Crohn's disease is common. Histologically inflamed resection margins do not appear to affect the rate of anastomotic leakages. Our data suggest that there is no need for extensive resections or frozen section to achieve microscopically inflammation-free resection margins.
Subject(s)
Anastomosis, Surgical/adverse effects , Anastomotic Leak/pathology , Crohn Disease/surgery , Inflammation/pathology , Intestine, Large/pathology , Intestine, Small/pathology , Adolescent , Adult , Aged , Anastomotic Leak/etiology , Crohn Disease/immunology , Crohn Disease/pathology , Female , Humans , Inflammation/etiology , Intestine, Large/surgery , Intestine, Small/surgery , Male , Margins of Excision , Middle Aged , Retrospective Studies , Young AdultABSTRACT
Many infants on an exclusive breastfeeding regimen are often fed inadequate amounts, and this creates an imbalance between the overall effects of breast milk and commercial infant formulas. We comparatively analyzed the impact of human milk and two infant formulas in modulating the intestinal microbiota and the immune systems of mice colonized by healthy infant feces. The results showed that compared to infant formula, human milk decreased the levels of alanine transaminase, alkaline phosphatase, and total protein. Also, it improved the immune system through the level of cytokines (CD4+ lymphocytes, Th1, Th2, Th17, and Treg cells) and immunity indicators (IL-2, IL-4, IL-9, and sIgA). Human milk decreased intestinal mucosal permeability compared to infant formula. Bacterial 16S rRNA gene sequence analysis revealed that human milk increased the abundance of Akkermansia and Bacteroides, while infant formula increased the abundance of Lactobacillus and Escherichia_Shigella. Collectively, our results showed that human milk is more suitable for infants than the two commercial infant formulas based on intestinal microbiota and immune system analyses. These findings thus support a theoretical basis for the development of infant formulas.
Subject(s)
Gastrointestinal Microbiome , Infant Formula , Milk, Human , Adult , Animals , Cytokines/metabolism , Feces/microbiology , Gastrointestinal Microbiome/drug effects , Gastrointestinal Microbiome/physiology , Humans , Infant, Newborn , Intestinal Absorption , Intestine, Large/drug effects , Intestine, Large/pathology , Male , Mice , Mice, Inbred C57BLABSTRACT
BACKGROUND AND AIM: Paralytic ileus is a common intestinal dysfunction in critically ill patients, which results in complications and poor hospital outcomes. There are still no established effective medications, except correcting the primary causes and prokinetics trial, which have limited efficacy and potential adverse events. This study aims to evaluate the efficacy of prucalopride on paralytic ileus in critically ill patients. METHODS: A randomized, double-blind, placebo-controlled trial of five consecutive days treatment periods was conducted. Critically ill patients with paralytic ileus were included. The primary endpoint was the improvement of bowel dilatation on plain abdominal radiography. The secondary endpoint was the change of abdominal circumference. RESULTS: Twenty patients were consecutively enrolled in the study. There was no significant difference in baseline characteristics of patients. The common causes of hospitalization were infection and respiratory problems. The maximum large bowel diameters dramatically decreased in prucalopride group and reached maximum point on the third day after intervention when compared with placebo (-2.1 [± 1.8] vs 0.3 [± 1.5] cm, P = 0.01). The maximum small bowel diameters were noticeably less decreased and were not significantly different when compared with placebo. The abdominal circumferences notably decreased and significantly diverged from placebo on the third day. CONCLUSIONS: Prucalopride was an effective enterokinetic agent to improve non-severe inflammatory/ischemic bowel conditions related paralytic ileus in critically ill patients. Its effect was predominant on large intestine but could not be well demonstrated on small bowel in this study. Future study or concomitant other prokinetics for upper gut motility should be further evaluated.
Subject(s)
Benzofurans/therapeutic use , Critical Illness , Intestinal Pseudo-Obstruction/drug therapy , Double-Blind Method , Female , Humans , Intestinal Pseudo-Obstruction/pathology , Intestine, Large/pathology , Intestine, Small/pathology , Male , Middle Aged , Pilot Projects , Serotonin 5-HT4 Receptor Agonists/therapeutic use , Treatment OutcomeABSTRACT
The mechanisms of cellular energy sensing and AMPK-mediated mTORC1 inhibition are not fully delineated. Here, we discover that RIPK1 promotes mTORC1 inhibition during energetic stress. RIPK1 is involved in mediating the interaction between AMPK and TSC2 and facilitate TSC2 phosphorylation at Ser1387. RIPK1 loss results in a high basal mTORC1 activity that drives defective lysosomes in cells and mice, leading to accumulation of RIPK3 and CASP8 and sensitization to cell death. RIPK1-deficient cells are unable to cope with energetic stress and are vulnerable to low glucose levels and metformin. Inhibition of mTORC1 rescues the lysosomal defects and vulnerability to energetic stress and prolongs the survival of RIPK1-deficient neonatal mice. Thus, RIPK1 plays an important role in the cellular response to low energy levels and mediates AMPK-mTORC1 signaling. These findings shed light on the regulation of mTORC1 during energetic stress and unveil a point of crosstalk between pro-survival and pro-death pathways.
Subject(s)
Autophagy-Related Protein 5/genetics , Fas-Associated Death Domain Protein/genetics , Intestine, Large/metabolism , Mechanistic Target of Rapamycin Complex 1/genetics , Receptor-Interacting Protein Serine-Threonine Kinases/genetics , AMP-Activated Protein Kinases/genetics , AMP-Activated Protein Kinases/metabolism , Animals , Animals, Newborn , Autophagy-Related Protein 5/deficiency , Caspase 8/genetics , Caspase 8/metabolism , Cell Death/genetics , Fas-Associated Death Domain Protein/deficiency , Gene Expression Regulation , Glucose/antagonists & inhibitors , Glucose/pharmacology , HEK293 Cells , HT29 Cells , Humans , Intestine, Large/drug effects , Intestine, Large/pathology , Jurkat Cells , Lysosomes/drug effects , Lysosomes/metabolism , Lysosomes/pathology , Mechanistic Target of Rapamycin Complex 1/metabolism , Metformin/antagonists & inhibitors , Metformin/pharmacology , Mice , Mice, Inbred C57BL , Mice, Knockout , Phosphorylation , Receptor-Interacting Protein Serine-Threonine Kinases/deficiency , Signal Transduction , Sirolimus/pharmacology , Tuberous Sclerosis Complex 2 Protein/genetics , Tuberous Sclerosis Complex 2 Protein/metabolismABSTRACT
No disponible
Subject(s)
Humans , Male , Middle Aged , Failure to Thrive/etiology , Torsion Abnormality/diagnostic imaging , Intestinal Diseases/diagnostic imaging , Intestines/abnormalities , Failure to Thrive/pathology , Intestine, Small/abnormalities , Tomography, X-Ray Computed , Intestine, Large/diagnostic imaging , Intestine, Large/pathology , Rifaximin/administration & dosage , Intestine, Small/diagnostic imagingABSTRACT
The enteric nervous system (ENS), located in the wall of the gastrointestinal (GI) tract, is characterized by complex organization and a high degree of neurochemical diversity of neurons. One of the less known active neuronal substances found in the enteric neurons is neuregulin 1 (NRG1), a factor known to be involved in the assurance of normal development of the nervous system. During the study, made up using the double immunofluorescence technique, the presence of NRG1 in the ENS of the selected segment of porcine large intestine (caecum, ascending and descending colon) was observed in physiological conditions, as well as under the impact of low and high doses of bisphenol A (BPA) which is commonly used in the production of plastics. In control animals in all types of the enteric plexuses, the percentage of NRG1-positive neurons oscillated around 20% of all neurons. The administration of BPA caused an increase in the number of NRG1-positive neurons in all types of the enteric plexuses and in all segments of the large intestine studied. The most visible changes were noted in the inner submucous plexus of the ascending colon, where in animals treated with high doses of BPA, the percentage of NRG1-positive neurons amounted to above 45% of all neuronal cells. The mechanisms of observed changes are not entirely clear, but probably result from neurotoxic, neurodegenerative and/or proinflammatory activity of BPA and are protective and adaptive in nature.
Subject(s)
Benzhydryl Compounds/toxicity , Endocrine Disruptors/toxicity , Enteric Nervous System/drug effects , Intestine, Large/drug effects , Neuregulin-1/genetics , Phenols/toxicity , Administration, Oral , Animals , Drug Administration Schedule , Enteric Nervous System/metabolism , Enteric Nervous System/pathology , Female , Gene Expression/drug effects , Intestine, Large/innervation , Intestine, Large/metabolism , Intestine, Large/pathology , Neuregulin-1/agonists , Neuregulin-1/metabolism , Neurons/drug effects , Neurons/metabolism , Neurons/pathology , Submucous Plexus/drug effects , Submucous Plexus/metabolism , Submucous Plexus/pathology , SwineABSTRACT
A 24-year-old horse was presented with a clinical history of anaemia, large intestine impaction and hind limb weakness. Loss of body weight was also reported. Hematocrit and hemoglobin levels were low and piroplasmosis test was negative. Nasogastric intubation with laxative agents was performed and 50 ml of a red blood-cell-supplement was given daily during a month. An assessment following Traditional Chinese Veterinary Medicine (TCVM) principles was performed after the last episode of large intestine impaction. A swollen, pale and wet tongue was observed. A superficial, weak pulse combined punctually with a slippery pulse was detected on the right side. The pulse on the left side was very thin. BL18, BL20 and BL23 were the most sensitive acupoints on the right side. BL18 and BL23 were the most sensitive on the left. TCVM diagnosis was Qi/Yang Kidney Deficiency, Spleen Qi Deficiency with Stagnation and Blood Deficiency. It received acupuncture at Bai-Hui, KI3, KI7, KI10, BL23, GB39, ST36, BL17 and acupressure at SP10. The client reported a significant improvement after treatment and hematocrit and hemoglobin levels were normal. KI3, ST36, BL39 acupoints were treated 14 days later. The outcome was favourable and one acupuncture session per month was recommended. No previous case reports in equines have been documented with a combination of blood, gastrointestinal and musculoskeletal problems in the same episode. This case is an example of an integrative approach to investigate the origin and the interdependent relation between body systems.