scholarly journals Changes in the expression of substance P in nerve fibres of the colonic mucosa in dogs suffering from inflammatory bowel disease

2020 ◽  
Vol 68 (2) ◽  
pp. 154-159
Author(s):  
Andrzej Rychlik ◽  
Slawomir Gonkowski ◽  
Krystyna Makowska ◽  
Ewa Kaczmar ◽  
Jaroslaw Calka
Keyword(s):  
Inflammatory Bowel Disease ◽  
Substance P ◽  
Bowel Disease ◽  
Disease Process ◽  
Nerve Fibres ◽  
Mucosal Layer ◽  
Inflammatory Bowel ◽  
Healthy Dogs ◽  
Pain Stimuli

AbstractDue to its difficult diagnosis and complicated treatment, inflammatory bowel disease (IBD) in dogs is a challenge for the veterinarian. Several aspects connected with pathological changes during IBD still remain unknown. Since one of these aspects is the participation of intestinal innervation in the evolution of the disease, the aim of this study was to demonstrate changes in the number and distribution of intramucosal colonic nerve fibres immunoreactive to substance P (SP) arising as the disease progresses. SP is one of the most important neuronal factors in intestinal innervation which, among other tasks, takes part in the conduction of pain stimuli. Using routine immunofluorescence technique, the density of nerve fibres containing SP was evaluated within mucosal biopsy specimens collected from the descending colon of healthy dogs and animals suffering from IBD of varying severity. The results of the study indicate that during severe IBD the number of nerve fibres containing SP located in the colonic mucosal layer increases in comparison to control animals. The number of SP-positive intramucosal nerves amounted to 10.99 ± 2.11 nerves per observation field in healthy dogs, 14.62 ± 2.86 in dogs with mild IBD, 14.80 ± 0.91 in dogs with moderate IBD and 19.03 ± 6.11 in animals with severe IBD. The observed changes were directly proportional to the intensity of the disease process. These observations may suggest a role of this neuronal substance in pathological processes occurring during IBD. Although the exact mechanism of the observed changes has not been completely explained, the results obtained in this investigation may contribute to improving the diagnosis and treatment of this disease, as well as the staging of canine IBD in veterinary practice.

Serum IgG4 Subclass Deficiency Defines a Distinct, Commonly Encountered, Severe Inflammatory Bowel Disease Subtype

2020 ◽  
Author(s):  
Filippos Koutroumpakis ◽  
Anna Evans Phillips ◽  
Dhiraj Yadav ◽  
Jorge D Machicado ◽  
Maaz Ahsan ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Disease Severity ◽  
Bowel Disease ◽  
Disease Process ◽  
Serum Igg4 ◽  
Tertiary Center ◽  
Inflammatory Bowel ◽  
Subclass Deficiency ◽  
Igg4 Deficiency

Abstract Background Immunoglobulin G subclass 4 (IgG4) is hypothesized to play an immunomodulatory role, downregulating humoral immune responses. The role of this anti-inflammatory molecule in inflammatory bowel disease (IBD) has not been fully characterized. We sought to define alterations in serum IgG4 in patients with IBD and their association with multiyear disease severity. Methods We analyzed metadata derived from curated electronic health records from consented patients with IBD prospectively followed at a tertiary center over a 10-year time period. Patients with IBD with IgG4 serum levels available formed the study population. Demographics and multiyear clinical data were collected and analyzed. We stratified patients with IBD with low, normal, or high serum IgG4 levels. Results We found IgG4 characterized in 1193 patients with IBD and low IgG4 levels in 233 patients (20%) and elevated IgG4 levels in 61 patients (5%). An IgG4 deficiency did not significantly correlate with other antibody deficiencies. In a multiple Poisson regression analysis, low IgG4 was associated with more years on biologic agents (P = 0.002) and steroids (P = 0.049) and more hospital admissions (P < 0.001), clinic visits (P = 0.010), outpatient antibiotic prescriptions (P < 0.001), and CD-related surgeries (P = 0.011) during the study period after controlling for certain confounders. Elevated IgG4 was only associated with primary sclerosing cholangitis (P = 0.011). A cohort of patients with IgG4-deficient severe IBD received intravenous Ig replacement therapy, which benefited and was continued in 10 out of 11 individuals. Conclusions An IgG4 subclass deficiency, distinct from other antibody deficiencies, occurred commonly in a referral IBD population and was associated with multiple markers of disease severity. This is the first association of IgG4 subclass deficiency with an inflammatory disease process. Further work is needed to define the mechanistic role of IgG4 deficiency in this severe IBD subgroup.

scholarly journals Galanin - Immunoreactive Nerve Fibers in the Mucosal Layer of the Canine Gastrointestinal Tract During Inflammatory Bowel Disease

2015 ◽  
Vol 59 (1) ◽  
pp. 143-148 ◽  
Author(s):  
Andrzej Rychlik ◽  
Sławomir Gonkowski ◽  
Marcin Nowicki ◽  
Jarosław Całka ◽  
Marta Szweda
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Nerve Fibers ◽  
Immunofluorescence Method ◽  
Fiber Density ◽  
Biopsy Specimens ◽  
Mucosal Layer ◽  
Inflammatory Bowel ◽  
Healthy Dogs ◽  
Severity Of The Disease

Abstract The effect of inflammatory bowel disease (IBD) on the density of galanin - immunoreactive (GAL-IR) nerve fibers was determined in the mucosa of canine duodenum, jejunum, and descending colon. Fiber density was evaluated by a single immunofluorescence method in biopsy specimens obtained from healthy dogs and patients with variable severity of the disease. The density of GAL-IR nerve fibers was determined by the semi-quantitative method by counting fibers in the field of view (0.l mm2). Fiber density was higher in dogs with moderate and severe IBD than in healthy animals. The results of the study suggest that GAL present in intestinal nerve fibers could play a role in the pathogenesis and development of canine IBD.

scholarly journals Role of Substance P in the Pathophysiology of Inflammatory Bowel Disease and Its Correlation With the Degree of Inflammation

Cureus ◽  
2020 ◽  
Author(s):  
Mauli Patel ◽  
Sharathshiva Valaiyaduppu Subas ◽  
Mohammad R Ghani ◽  
Vishal Busa ◽  
Ahmed Dardeir ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Substance P ◽  
Bowel Disease ◽  
Inflammatory Bowel

scholarly journals The Role of Citrullination in Inflammatory Bowel Disease: A Neglected Player in Triggering Inflammation and Fibrosis?

2020 ◽  
Vol 27 (1) ◽  
pp. 134-144 ◽  
Author(s):  
Gabriele Dragoni ◽  
Gert De Hertogh ◽  
Séverine Vermeire
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Posttranslational Modification ◽  
Disease Process ◽  
Special Focus ◽  
Extracellular Traps ◽  
Fundamental Process ◽  
Gene Expression Analyses ◽  
Inflammatory Bowel

Abstract Citrullination is a posttranslational modification of proteins mediated by a specific family of enzymes called peptidylarginine deiminases (PAD). Dysregulation of these enzymes is involved in the etiology of various diseases, from cancer to autoimmune disorders. In inflammatory bowel disease (IBD), data for a role of citrullination in the disease process are starting to accumulate at different experimental levels including gene expression analyses, RNA, and protein quantifications. Most data have been generated in ulcerative colitis, but data in Crohn disease are lacking so far. In addition, the citrullination of histones is the fundamental process promoting inflammation through the formation of neutrophil extracellular traps (NETs). Interestingly, NETs have also been shown to activate fibroblasts into myofibroblasts in fibrotic interstitial lung disease. Therefore, citrullination merits more thorough study in the bowel to determine its role in driving disease complications such as fibrosis. In this review we describe the process of citrullination and the different players in this pathway, the role of citrullination in autoimmunity with a special focus on IBD, the emerging role for citrullination and NETs in triggering fibrosis, and, finally, how this process could be therapeutically targeted.

scholarly journals Vasoactive Intestinal Polypeptide (VIP) in the Intestinal Mucosal Nerve Fibers in Dogs with Inflammatory Bowel Disease

Animals ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 1759
Author(s):  
Andrzej Rychlik ◽  
Sławomir Gonkowski ◽  
Jarosław Całka ◽  
Krystyna Makowska
Keyword(s):  
Inflammatory Bowel Disease ◽  
Nervous System ◽  
Vasoactive Intestinal Polypeptide ◽  
Bowel Disease ◽  
Disease Process ◽  
Nerve Fibers ◽  
Inflammatory Bowel ◽  
Healthy Dogs ◽  
Adaptive Reactions ◽  
Intestinal Polypeptide

Canine inflammatory bowel disease (IBD) is a group of enteropathies with nonspecific chronic symptoms and poorly understood etiology. Many aspects connected with IBD are not understood. One of them is the participation of the intestinal nervous system in the development of pathological processes. Thus, this study aimed to demonstrate changes in the density of intramucosal nerve fibers containing vasoactive intestinal polypeptide (VIP)—one of the most important intestinal nervous factors caused by the various stages of IBD development. Mucosal biopsy specimens collected from the duodenum, jejunum and descending colon of healthy dogs and dogs with varied severity of IBD were included in the experiment. The density of VIP-like immunoreactive (VIP-LI) nerves was determined by a single immunofluorescence technique and a semi-quantitative method consisting in VIP-LI fiber counts in the field of view (0.1 mm2). The obtained results indicate that IBD induces changes in the density of mucosal VIP-LI nerve fibers in the canine gastrointestinal tract. The initial decrease is followed by an increase in VIP-like immunoreactivity in successive stages of the disease. These observations show that VIP is a neuronal factor that participates in the pathological processes connected with canine IBD. The observed changes probably result from the neuroprotective and/or adaptive properties of VIP. Protective and adaptive reactions induced by inflammation aim to protect the GI tract against damage by proinflammatory factors and ensure the homeostasis in the enteric nervous system (ENS) under the conditions changed by the disease process.

Role of perivascular nerve and sensory neurotransmitter dysfunction in inflammatory bowel disease

2021 ◽  
Author(s):  
Charles E. Norton ◽  
Elizabeth A. Grunz-Borgmann ◽  
Marcia L. Hart ◽  
Benjamin W. Jones ◽  
Craig L. Franklin ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Blood Flow ◽  
Substance P ◽  
Bowel Disease ◽  
Vascular Dysfunction ◽  
Receptor Expression ◽  
Mesenteric Arteries ◽  
Increased Risk ◽  
Inflammatory Bowel

Inflammatory Bowel Disease (IBD) is associated with both impaired intestinal blood flow and increased risk of cardiovascular disease, but the functional role of perivascular nerves that control vasomotor function of mesenteric arteries (MAs) perfusing the intestine during IBD is unknown. Because perivascular sensory nerves and their transmitters calcitonin gene-related peptide (CGRP) and substance P (SP) are important mediators of both vasodilation and inflammatory responses, our objective was to identify IBD-related deficits in perivascular sensory nerve function and vascular neurotransmitter signaling. In MAs from an IL-10-/- mouse model, IBD significantly impairs electrical field stimulation (EFS)-mediated sensory vasodilation and inhibition of sympathetic vasoconstriction, despite decreased sympathetic nerve density and vasoconstriction. The MA content and EFS-mediated release of both CGRP and SP are decreased with IBD, but IBD has unique effects on each transmitter. CGRP nerve density, receptor expression, hyperpolarization and vasodilation are preserved with IBD. In contrast, SP nerve density and receptor expression are increased, and SP hyperpolarization and vasodilation are impaired with IBD. A key finding is that blockade of SP receptors restores EFS-mediated sensory vasodilation and enhanced CGRP-mediated vasodilation in MAs from IBD but not Control mice. Together, these data suggest that an aberrant role for the perivascular sensory neurotransmitter SP and its downstream signaling in MAs underlies vascular dysfunction with IBD. We propose that with IBD, SP signaling impedes CGRP-mediated sensory vasodilation, contributing to impaired blood flow. Thus, substance P and NK1 receptors may represent an important target for treating vascular dysfunction in IBD.

Clinical Aspects of Idiopathic Inflammatory Bowel Disease: A Review for Pathologists

2016 ◽  
Vol 140 (5) ◽  
pp. 413-428 ◽  
Author(s):  
Hwajeong Lee ◽  
Maria Westerhoff ◽  
Bo Shen ◽  
Xiuli Liu
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Disease Process ◽  
Clinical Aspects ◽  
Team Approach ◽  
Pathologic Features ◽  
Inflammatory Bowel ◽  
Surgical Aspects ◽  
Idiopathic Inflammatory Bowel Disease

Context.—Idiopathic inflammatory bowel disease manifests with different clinical phenotypes showing varying behavior and risk for neoplasia. The clinical questions that are posed to pathologists differ depending on phase of the disease and the clinical circumstances. Understanding the clinical aspects of the dynamic disease process will enhance the role of pathology in optimizing the care of patients with inflammatory bowel disease. Objective.—To review clinical and surgical aspects of inflammatory bowel disease that are relevant to practicing pathologists. Data Sources.—The literature was reviewed. Conclusions.—Diagnosis and management of inflammatory bowel disease require an integrated evaluation of clinical, endoscopic, radiologic, and pathologic features. Therefore, close interaction between clinicians and pathologists is crucial. Having this team approach improves understanding of the pertinent clinical and surgical aspects of the disease and assists in the recognition of unusual presentation of variants, as well as mimics of idiopathic inflammatory bowel disease, by pathologists.

scholarly journals Treatment with Neurokinin-1 Receptor Antagonist Reduces Severity of Inflammatory Bowel Disease Induced by Cryptosporidium parvum

2002 ◽  
Vol 9 (2) ◽  
pp. 333-340 ◽  
Author(s):  
Ioana M. Sonea ◽  
Mitchell V. Palmer ◽  
Dhuha Akili ◽  
James A. Harp
Keyword(s):  
Inflammatory Bowel Disease ◽  
Substance P ◽  
Receptor Antagonist ◽  
Bowel Disease ◽  
Neurokinin 1 Receptor ◽  
Intestinal Lesions ◽  
Inflammatory Bowel ◽  
Neurokinin 1 ◽  
Neurotransmitter Substance

ABSTRACT Inflammatory bowel disease (IBD) is a chronic, debilitating disorder of uncertain and perhaps multiple etiologies. It is believed to be due in part to disregulation of the immune system. Neuroimmune interactions may be involved in induction or maintenance of IBD. In the present study, we examined the potential role of a neurotransmitter, substance P, in a mouse model of IBD. We found that binding sites for substance P, and more specifically, neurokinin-1 receptors, were upregulated in intestinal tissue of mice with IBD-like syndrome. Dosing of mice with LY303870, a neurokinin-1 receptor antagonist, reduced the severity of IBD, and treatment of mice with preexisting IBD allowed partial healing of lesions. We hypothesize that blocking the binding of substance P to the neurokinin-1 receptor interrupts the inflammatory cascade that triggers and maintains intestinal lesions of IBD.

Sign in / Sign up

Export Citation Format

Share Document