Isoproterenol Disrupts Intestinal Barriers Activating Gut-Liver-Axis: Effects on Intestinal Mucus and Vascular Barrier as Entry Sites

Digestion ◽  
2019 ◽  
Vol 101 (6) ◽  
pp. 717-729 ◽  
Author(s):  
Marcel Sorribas ◽  
Andrea de Gottardi ◽  
Sheida Moghadamrad ◽  
Mohsin Hassan ◽  
I. Spadoni ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Confocal Laser Endomicroscopy ◽  
Confocal Laser ◽  
Adrenergic Stimulation ◽  
Barrier Dysfunction ◽  
Mesenteric Lymph Nodes ◽  
Ileal Loop ◽  
Mesenteric Lymph ◽  
Mucin Expression

<b><i>Background:</i></b> The gut-liver-axis presents the pathophysiological hallmark for multiple liver diseases and has been proposed to be modulated during stress and shock. Access to the gut-liver-axis needs crossing of the mucus and gut-vascular barrier. The role of β-adrenoreceptor-activation for both barriers has not been defined and is characterized here. <b><i>Methods:</i></b> Splanchnic β-adrenergic stimulation was achieved by chronic intraperitoneal application of isoproterenol via alzet-pump in vivo. The intestinal permeability and gut-vascular barrier function was assessed in ileal loop experiments. The extravasation of predefined sizes of fluorescence isothiocyanate (FITC)-dextran molecules in ileal microcirculation was evaluated by intravital confocal laser endomicroscopy in vivo. Mucus parameters thickness, goblet cell count and mucin-expression were assessed by stereomicroscopy, immunostaining and RNA-sequencing respectively. Ileal lamina propria (LP) as well as mesenteric lymph node mononuclear cells was assessed by FACS. <b><i>Results:</i></b> Healthy mice lack translocation of 4 kDa-FITC-dextran from the small intestine to the liver, whereas isoproterenol-treated mice demonstrate pathological translocation (PBT). Mucus layer is reduced in thickness with loss of goblet-cells and mucin-2-staining and -expression in isoproterenol-treated animals under standardized gnotobiotic conditions. Isoproterenol disrupts the gut vascular barrier displaying Ileal extravasation of large-sized 70- and 150 kDa-FITC-dextran. This pathological endothelial permeability and accessibility induced by isoproterenol associates with an augmented expression of plasmalemmal-vesicle-associated-protein-1 in intestinal vessel. Ileal LP after isoproterenol treatment contains more CD11c+-dendritic cells (DC) with increased appearance of CCR7+ DC in mesenteric lymph nodes. <b><i>Conclusions:</i></b> Isoproterenol impairs the intestinal muco-epithelial and endothelial-vascular barrier promoting PBT to the liver. This barrier dysfunction on multiple levels potentially can contribute to liver injury induced by catecholamines during states of increased β-adrenergic drive.

scholarly journals Cross-sectional imaging of intestinal barrier dysfunction by confocal laser endomicroscopy can identify patients with food allergy in vivo with high sensitivity

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Timo Rath ◽  
Walburga Dieterich ◽  
Christiane Kätscher-Murad ◽  
Markus F. Neurath ◽  
Yurdagül Zopf
Keyword(s):  
Food Allergy ◽  
Intestinal Barrier ◽  
Confocal Laser Endomicroscopy ◽  
Confocal Laser ◽  
Epithelial Barrier ◽  
Barrier Dysfunction ◽  
Diagnostic Work ◽  
Work Up ◽  
Diagnostic Work Up

AbstractFood allergy (FA) affects approximately 3 to 4% of the adult population in westernized countries. Suspected FA is even more prevalent and requires extensive diagnostic work-up. Within this study, we evaluated whether assessment of the integrity of the epithelial barrier by confocal laser endomicroscopy (CLE) during colonoscopy can be used as a screening tool to identify patients with FA. 60 patients with suspected FA were prospectively included. Serology with total and food-specific IgE, anti-tissue transglutaminase, skin prick testing, food intolerance tests, food intake registration and assessment of clinical complaints were performed. During colonocopy, standardized CLE was performed in the terminal ileum and at two colorectal sites. Analysis of CLE images included functional (i.e. presence of epithelial barrier dysfunction) and quantitative parameters of intestinal architecture. 27 of 60 patients (45%) were diagnosed with FA. Barrier dysfunction was analyzed on 65.837 ileal and on 93.251 colonic images. 96% of patients with FA exhibited functional and structural barrier defects while barrier dysfunction was found in only 33% of patients without FA (p < 0.0001). Visualizing barrier dysfunction with CLE for in vivo diagnosis of FA had a sensitivity and specificity of 96% and 67%, respectively, with a positive and negative prediction of 70% and 96%, respectively. Parameters intrinsic to the crypt architecture including crypt diameter, intercrypt distance, crypt lumen diameter and colonic vasculature were not different between patients with and without FA. CLE-based imaging of the intestinal barrier during colonoscopy might help in stratifying patients with suspected FA for further diagnostic work-up.

scholarly journals Expert-led didactic versus self-directed audiovisual training of confocal laser endomicroscopy in evaluation of mucosal barrier defects

2018 ◽  
Vol 06 (01) ◽  
pp. E115-E122 ◽  
Author(s):  
Roy Huynh ◽  
Matthew Ip ◽  
Jeff Chang ◽  
Craig Haifer ◽  
Rupert Leong
Keyword(s):  
The Self ◽  
Mucosal Barrier ◽  
Confocal Laser Endomicroscopy ◽  
Controlled Study ◽  
Confocal Laser ◽  
Barrier Dysfunction ◽  
Self Directed Learning ◽  
Directed Group ◽  
Endoscopy Training

Abstract Background and study aims Confocal laser endomicroscopy (CLE) allows mucosal barrier defects along the intestinal epithelium to be visualized in vivo during endoscopy. Training in CLE interpretation can be achieved didactically or through self-directed learning. This study aimed to compare the effectiveness of expert-led didactic with self-directed audiovisual teaching for training inexperienced analysts on how to recognize mucosal barrier defects on endoscope-based CLE (eCLE). Materials and methods This randomized controlled study involved trainee analysts who were taught how to recognize mucosal barrier defects on eCLE either didactically or through an audiovisual clip. After being trained, they evaluated 6 sets of 30 images. Image evaluation required the trainees to determine whether specific features of barrier dysfunction were present or not. Trainees in the didactic group engaged in peer discussion and received feedback after each set while this did not happen in the self-directed group. Accuracy, sensitivity, and specificity of both groups were compared. Results Trainees in the didactic group achieved a higher overall accuracy (87.5 % vs 85.0 %, P = 0.002) and sensitivity (84.5 % vs 80.4 %, P = 0.002) compared to trainees in the self-directed group. Interobserver agreement was higher in the didactic group (k = 0.686, 95 % CI 0.680 – 0.691, P < 0.001) than in the self-directed group (k = 0.566, 95 % CI 0.559 – 0.573, P < 0.001). Confidence (OR 6.48, 95 % CI 5.35 – 7.84, P < 0.001) and good image quality (OR 2.58, 95 % CI 2.17 – 2.82, P < 0.001) were positive predictors of accuracy. Conclusion Expert-led didactic training is more effective than self-directed audiovisual training for teaching inexperienced analysts how to recognize mucosal barrier defects on eCLE.

scholarly journals Tryptophan, glutamine, leucine, and micronutrient supplementation improves environmental enteropathy in Zambian adults: a randomized controlled trial

2019 ◽  
Vol 110 (5) ◽  
pp. 1240-1252 ◽  
Author(s):  
John Louis-Auguste ◽  
Ellen Besa ◽  
Kanekwa Zyambo ◽  
Derick Munkombwe ◽  
Rosemary Banda ◽  
...  
Keyword(s):  
Randomized Controlled Trial ◽  
Controlled Trial ◽  
Microbial Translocation ◽  
Confocal Laser Endomicroscopy ◽  
Confocal Laser ◽  
Residential Areas ◽  
Barrier Dysfunction ◽  
Randomized Controlled ◽  
Environmental Enteropathy

ABSTRACT Background Environmental enteropathy (EE) refers to villus blunting, reduced absorption, and microbial translocation in children and adults in tropical or deprived residential areas. In previous work we observed an effect of micronutrients on villus height (VH). Objective We aimed to determine, in a randomized controlled trial, if amino acid (AA) or multiple micronutrient (MM) supplementation can improve intestinal structure or barrier dysfunction in Zambian adults with EE. Methods AA (tryptophan, leucine, and glutamine) and/or MM supplements were given for 16 wk in a 2 × 2 factorial comparison against placebo. Primary outcomes were changes in VH, in vivo small intestinal barrier dysfunction assessed by confocal laser endomicroscopy (CLE), and mechanistic (or mammalian) target of rapamycin complex 1 (MTORC1) nutrient responsiveness in lamina propria CD4+ lymphocytes. Results Over 16 wk AA, but not MM, supplementation increased VH by 16% (34.5 μm) compared with placebo (P = 0.04). Fluorescein leak, measured by CLE, improved only in those allocated to both AA and MM supplementation. No effect was seen on MTORC1 activation, but posttreatment MTORC1 and VH were correlated (ρ = 0.51; P = 0.001), and change in MTORC1 was correlated with change in VH in the placebo group (ρ = 0.63; P = 0.03). In secondary analyses no effect was observed on biomarkers of microbial translocation. Metabolomic analyses suggest alterations in a number of microbial- and host-derived metabolites including the leucine metabolite β-hydroxy-β-methylbutyrate, which was increased by AA supplementation and correlated with VH. Conclusions In this phase 2 trial, AA supplementation protected against a decline in VH over the supplementation period, and improved barrier function when combined with micronutrients. Leucine and MTORC1 metabolism may be involved in the mechanism of effect. This trial was registered at www.pactr.org as PACTR201505001104412.

Visualization of brain microvasculature and blood flow in vivo: Feasibility study using confocal laser endomicroscopy

2021 ◽  
Author(s):  
Evgenii Belykh ◽  
Xiaochun Zhao ◽  
Brandon Ngo ◽  
Dara S. Farhadi ◽  
Adam Kindelin ◽  
...  
Keyword(s):  
Blood Flow ◽  
Feasibility Study ◽  
Confocal Laser Endomicroscopy ◽  
Confocal Laser ◽  
Brain Microvasculature

S1426: High-Definition In-Vivo Probe-Based Confocal Laser Endomicroscopy of the Common Bile Duct

2010 ◽  
Vol 71 (5) ◽  
pp. AB158-AB159 ◽  
Author(s):  
Frederick K. Shieh ◽  
Michael H. Nathanson ◽  
Hillary Drumm ◽  
Priya A. Jamidar
Keyword(s):  
Bile Duct ◽  
Common Bile Duct ◽  
Confocal Laser Endomicroscopy ◽  
Confocal Laser ◽  
High Definition ◽  
The Common

Immunomodulatory role of thyroid hormones: in vivo effect of thyroid hormones on the blastogenic response of lymphoid tissues

1983 ◽  
Vol 103 (1) ◽  
pp. 95-100 ◽  
Author(s):  
Sadhana Chatterjee ◽  
Amar Singh Chandel
Keyword(s):  
Thyroid Hormones ◽  
Pokeweed Mitogen ◽  
Lymphoid Tissues ◽  
Mesenteric Lymph Nodes ◽  
Mesenteric Lymph ◽  
Hormone Administration ◽  
Blastogenic Response ◽  
Significant Depression

Abstract. In an attempt to find out the mechanism of immunomodulation by thyroid hormones (T3 and T4), their in vivo effect on the blastogenic response of lymphocytes from various lymphoid tissues of hormonetreated and thyroidectomized rats were studied. The blastogenic response of lymphocytes from thymus, peripheral blood and mesenteric lymph nodes to pokeweed mitogen (PWM) was found to be increased significantly following T3 or T4 administration for 15 days or 30 days. However, the response to phytohaemagglutinin (PHA) increased only after 1 month of T3 or T4 administration. The blastogenic response of spleen cells to both PHA and PWM was, on the other hand, found to be depressed following 15 days of hormone administration. Thyroidectomy invariably induced significant depression in the blastogenic response to both PHA and PWM in lymphocytes of all the lymphoid tissues. Thyroid hormone (T3) administration was found to restore the blastogenic response of the lymphocytes of thyroidectomized animals.

scholarly journals Endomicroscopy and Cancer: A New Approach to the Visualization of Neoangiogenesis

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Renato Cannizzaro ◽  
Maurizio Mongiat ◽  
Vincenzo Canzonieri ◽  
Mara Fornasarig ◽  
Stefania Maiero ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Confocal Laser Endomicroscopy ◽  
Molecular Profile ◽  
Confocal Laser ◽  
Antiangiogenic Treatment ◽  
New Approach ◽  
Angiogenic Therapy ◽  
Imaging Tool ◽  
Subcellular Resolution

Probe-based Confocal Laser Endomicroscopy (pCLE) is a novel imaging technique for gastrointestinal endoscopy providingin vivomicroscopy at subcellular resolution. It offers the possibility to analyze neoangiogenesis and vessel densityin vivo. Angiogenetic switch is essential in cancer progression. Aim of the paper was to review the use of this imaging tool to analyze colorectal and gastric cancers vascularizationin vivo. The aim is to provide the possibility of combining diagnostic evidences with vascularization and molecular profile to evaluate the efficacy of an antiangiogenic treatment in association with conventional therapy. pCLE can be considered a revolutionary method for real-time assessment of changes in vascularization pattern in this tumors and it may open the possibility to address the use of anti-angiogenic therapy in order to improve the outcome of the treatment.

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