Colonic Mucosa Barrier Defects in Collagenous and Ischemic Colitis

Abstract Aims The subepithelial myofibroblasts (SEMFs) and the subepithelial band of macrophages (SEBM) are major components of the colonic mucosa barrier. Although their role in homeostasis is widely recognized, their contribution to disease states is largely unknown. The aim of the study was to explore histological characteristics of SEMFs and SEBM in collagenous and ischemic colitis.Methods Ten colonic biopsies of collagenous colitis, 10 of ischemic colitis and 10 control biopsies of normal mucosa were examined. SEMFs, SEBM and lamina propria macrophages were identified immunohistochemically by aSMA and CD68 respectively.ResultsIn collagenous colitis, SEMFs were rarely detectable in the collagenous band while in the lower lamina propria cell processes were formed. SEBM was preserved in areas with a collagenous layer up to 20μm. In thicker layers, it was fragmented and gradually disappeared in parallel with engulfment of enlarged macrophages. In the lower lamina propria macrophages were usually increased.In ischemic colitis, rounding, disintegration and extinction of SEMFs constituted successive alterations coinciding with crypt shrinkage and denudation. SEBM displayed total or almost total abolishment in areas with crypt damage and stroma fibrosis but also in sights with minimal changes.ConclusionIn collagenous colitis, alterations of mucosa barrier are related to collagenous layer thickness. SEMFs changes probably reflect derangement of differentiation and migration while SEMB alterations seem to be compensated by macrophage activation and numerical increase in lamina propria. The striking damage of mucosa barrier in ischemic colitis is indicative of its high sensitivity to hypoxia and hypoperfusion. The histological differences between collagenous colitis and ischemic colitis may be proven of differential diagnostic significance.

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Case Report: Regulatory T Cell-Independent Induction of Remission in a Patient With Collagenous Colitis

Frontiers in Medicine ◽

10.3389/fmed.2021.678268 ◽

2021 ◽

Vol 8 ◽

Author(s):

Hajime Honjo ◽

Tomohiro Watanabe ◽

Mizuki Tomooka ◽

Takuya Matsubara ◽

Masashi Kono ◽

...

Keyword(s):

T Cells ◽

Lamina Propria ◽

Colonic Mucosa ◽

Inflammatory Responses ◽

Collagenous Colitis ◽

Pathological Examination ◽

Surface Epithelium ◽

Inflammatory Disorder ◽

Independent Manner ◽

Chronic Inflammatory Disorder

Collagenous colitis (CC), a prototypical microscopic colitis, is a chronic inflammatory disorder of the colon. The diagnosis of CC depends on the pathological examination. The colonic mucosa of patients with CC is characterized by the presence of a substantially thickened collagen band (>10μm) under the surface epithelium. In addition, intraepithelial and lamina propria lymphocytes are markedly increased in patients with CC. However, the roles played by the lymphocytes accumulating in the colonic mucosa of patients with CC are poorly defined. Recent studies indicate that T cells infiltrating the colonic mucosa of patients with CC are mainly represented by CD4+ T cells, CD8+ T cells, and forkhead box P3 (FOXP3)+ regulatory T cells (Tregs). Given that activation of CD4+/CD8+ T cells and FOXP3+ Tregs usually mediates pro-inflammatory and anti-inflammatory responses, respectively, alterations in the colonic numbers of these adaptive T cells might be related to the resolution of colitis in patients with CC. We determined alterations in the composition of colonic T cells by extensive immunohistochemical (IHC) analyses in a case of CC successfully treated with budesonide and metronidazole. Colonic lamina propria immune cells mainly comprised CD3+ T cells, CD4+ T cells, CD8+ T cells, CD68+ macrophages, and FOXP3+ Tregs, but not CD20+ B cells or myeloperoxidase (MPO)+ granulocytes in the active phase. During remission, the numbers of CD3+ T cells, CD4+ T cells, CD8+ T cells, and CD68+ macrophages did not change significantly in the colonic lamina propria, whereas FOXP3+ Tregs were markedly decreased, suggesting that induction of remission was achieved in a Treg-independent manner. Thus, our study indicates that accumulation of FOXP3+ Tregs in the colonic mucosa of patients with CC might be a counter-regulatory mechanism reflecting persistent inflammation and that induction of remission might be achieved without activation of Tregs.

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Microscopic colitis: A literature review

Revista da Associação Médica Brasileira ◽

10.1590/1806-9282.62.09.895 ◽

2016 ◽

Vol 62 (9) ◽

pp. 895-900 ◽

Cited By ~ 1

Author(s):

ANA PAULA HAMER SOUSA CLARA ◽

FLÁVIA DRAGO MAGNAGO ◽

JULIANA NEVES FERREIRA ◽

THAIS GAGNO GRILLO

Keyword(s):

Scientific Evidence ◽

Collagenous Colitis ◽

Gastrointestinal Disorder ◽

Normal Mucosa ◽

Term Treatment ◽

Diagnostic Methods ◽

Microscopic Colitis ◽

Older Individuals ◽

Short Term Treatment ◽

Pubmed Database

SUMMARY Microscopic colitis (MC) refers to chronic inflammation of the colon which is characterized by histologic changes at the level of a radiologically and endoscopically normal mucosa. It is a common cause of chronic non-bloody diarrhea that occurs primarily in older individuals; however, there are few studies in the literature with strong scientific evidence compared to other inflammatory bowel diseases (IBD), which limits the knowledge of physicians and pathologists. This article aims to review the information on MC, describing diagnostic methods and drugs available for treatment. We conducted a search of the Pubmed database and CAPES Portal using the keywords “microscopic colitis”, “collagenous colitis”, “lymphocytic colitis”, and “review” for selection of articles published between 1996 and 2015 related to the topic. Based on the studies discussed in this review, we conclude that MC is a relatively new gastrointestinal disorder, most studies are incipient particularly with respect to pathophysiology and immunology, and budesonide is the best documented short-term treatment. However, further studies are needed to elucidate the best strategy for treatment in the long term.

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Chemokine Ligand 13 (CXCL13) in Neuroborreliosis and Neurosyphilis as Selected Spirochetal Neurological Diseases: A Review of Its Diagnostic Significance

International Journal of Molecular Sciences ◽

10.3390/ijms21082927 ◽

2020 ◽

Vol 21 (8) ◽

pp. 2927

Author(s):

Monika Gudowska-Sawczuk ◽

Barbara Mroczko

Keyword(s):

Cerebrospinal Fluid ◽

Nervous System ◽

Neurological Diseases ◽

Treponema Pallidum ◽

High Sensitivity ◽

Borrelia Burgdorferi Sensu Lato ◽

Laboratory Diagnostics ◽

Diagnostic Significance ◽

Pubmed Database ◽

Chemokine Ligand

Neuroborreliosis (NB) and neurosyphilis (NS) are abnormal conditions caused by spirochetal bacteria which affect the nervous system. Diagnosis of neuroborreliosis and neurosyphilis is determined by clinical examination of visible symptoms, serum and cerebrospinal fluid (CSF) analysis, and serological detection of antibodies against Borrelia burgdorferi sensu lato and Treponema pallidum, respectively. Establishing a diagnosis may sometimes pose a number of diagnostic difficulties. A potential role of chemokine ligand 13 (CXCL13) as an accurate diagnostic biomarker of intrathecal inflammation has been suggested. In this review, we focused on changes in serum and cerebrospinal fluid concentration of chemokine ligand 13 in selected spirochetal neurological diseases neuroborreliosis and neurosyphilis reported in the available literature. We performed an extensive search of the literature relevant to our investigation via the MEDLINE/PubMed database. It has been proven that CXCL13 determination can provide rapid information regarding central nervous system inflammation in patients with selected spirochetosis. We described that neuroborreliosis and neurosyphilis are associated with an elevated CXCL13 concentration, mainly in the cerebrospinal fluid. Moreover, literature data suggest that CXCL13 determination is the most interesting additional marker for diagnosis and monitoring of neuroborreliosis and neurosyphilis thanks to its high sensitivity. Based on these published findings, we suggest that CXCL13 has high diagnostic utility and may be applied in laboratory diagnostics as a potential diagnostic marker in human spirochetal neurologic diseases.

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Potential Role for Interleukin-1 in the Pathophysiology of Ulcerative Colitis

Clinical Science ◽

10.1042/cs0860619 ◽

1994 ◽

Vol 86 (5) ◽

pp. 619-626 ◽

Cited By ~ 17

Author(s):

T. D. Wardle ◽

L. A. Turnberg

Keyword(s):

Ulcerative Colitis ◽

Prostaglandin E2 ◽

Inflammatory Mediators ◽

Colonic Mucosa ◽

Short Circuit ◽

Interleukin 1 ◽

Platelet Activating Factor ◽

Short Circuit Current ◽

Normal Mucosa ◽

Leukotriene C4

1. Biopsies of colonic mucosa from patients with ulcerative colitis liberated more interleukin-1β, prostaglandin E2, leukotriene C4 and platelet-activating factor into the medium in which they were cultured than biopsies from patients with irritable bowel syndrome and histologically normal mucosa. 2. Addition of interleukin-1 stimulated release of greater quantities of all these inflammatory mediators, including interleukin-1 itself, from inflamed and normal mucosa. 3. Blockade of cyclo-oxygenase with indomethacin or of lipoxygenase with ICI 207968 or of phospholipase A2 with mepacrine inhibited release of prostaglandin E2 or leukotriene C4 or both of these plus platelet-activating factor, respectively. 4. Interleukin-1 stimulated the short-circuit current across isolated rat colonic mucosa mounted in flux chambers in a dose-dependent manner (Km 2 × 10−11 mol/l). This stimulation was markedly inhibited by the removal of chloride from the bathing media. 5. Indomethacin or ICI 207968 inhibited the short-circuit current response to interleukin-1 and a combination of these antagonists produced a greater inhibition. Mepacrine caused an even greater inhibition whereas tetrodotoxin plus mepacrine inhibited the current completely. 6. These data indicate that interleukin-1, released in excess from inflamed colonic mucosa, stimulates the release of a range of inflammatory mediators as well as of more interleukin-1. It probably acts by stimulating phospholipase A2 in inflammatory cells, probably lymphocytes, and can do so in normal and inflamed mucosa. Since, in rat colonic mucosa it stimulated an electrical response in very low concentrations, it is feasible that it is involved in the chloride secretion, and hence the diarrhoea, which may occur in inflammatory reactions. Hence treatment with mepacrine seems a prospect worth pursuing.

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Lymphocytic colitis: clinical presentation and long term course

Gut ◽

10.1136/gut.43.5.629 ◽

1998 ◽

Vol 43 (5) ◽

pp. 629-633 ◽

Cited By ~ 90

Author(s):

B Mullhaupt ◽

U Güller ◽

M Anabitarte ◽

R Güller ◽

M Fried

Keyword(s):

Colonic Mucosa ◽

Clinical Presentation ◽

Collagenous Colitis ◽

Endoscopic Examination ◽

Watery Diarrhoea ◽

Lymphocytic Colitis ◽

Radiological Findings ◽

Benign Course

Background—Lymphocytic colitis is characterised by chronic watery diarrhoea with normal endoscopic or radiological findings and microscopic evidence of pronounced infiltration of the colonic mucosa with lymphocytes.Aim—To investigate the long term clinical and histological evolution of the disease in a large group of patients with well characterised lymphocytic colitis.Methods—Between 1986 and 1995 the histological diagnosis of lymphocytic colitis was obtained in 35 patients; 27 of these agreed to a follow up examination. All clinical, endoscopic, and histopathological records were reviewed at that time and the patients had a second endoscopic examination with follow up biopsies.Results—The patients initially presented with the typical findings of lymphocytic colitis. After a mean (SD) follow up of 37.8 (27.5) months, diarrhoea subsided in 25 (93%) and histological normalisation was observed in 22 (82%) of the 27 patients. Progression from lymphocytic colitis to collagenous colitis was not observed.Conclusions—Lymphocytic colitis is characterised by a benign course with resolution of diarrhoea and normalisation of histology in over 80% of patients within 38 months. Considering the benign course of the disease, the potential benefit of any drug treatment should be carefully weighed against its potential side effects.

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Diagnostic Significance of Methemoglobin Determination in Colorless Cerebrospinal Fluid

Clinical Chemistry ◽

10.1093/clinchem/38.8.1404 ◽

1992 ◽

Vol 38 (8) ◽

pp. 1404-1408 ◽

Cited By ~ 5

Author(s):

M Trbojević-Cepe ◽

Z Vogrinc ◽

V Brinar

Keyword(s):

Cerebrospinal Fluid ◽

Neurological Diseases ◽

Disease Process ◽

High Sensitivity ◽

Soret Band ◽

Spectrophotometric Analysis ◽

Diagnostic Significance ◽

Highly Sensitive ◽

Subarachnoid Hemorrhages ◽

Sensitive Spectrophotometric Method

Abstract The presence of various heme derivatives can be demonstrated spectrophotometrically in colorless cerebrospinal fluid (CSF). Because of the high sensitivity of the method, it may detect compounds that reflect a "traumatic tap" rather than a disease process. However, the presence of methemoglobin excludes the possibility of a hemorrhagic CSF being caused by traumatic lumbar puncture. Here we describe a highly sensitive spectrophotometric method involving measurement at the Soret band (400-420 nm) to detect methemoglobin (greater than or equal to 15%) in trace amounts of hemoglobin mixture (less than 0.3 mumol/L). We demonstrated methemoglobin in colorless CSF samples in 9% of 454 patients with cerebrovascular pathology and in 4% of 449 patients with other neurological diseases (n = 449). In a group of 21 patients with verified acute cerebral hematomas, methemoglobin was confirmed in 66% of colorless CSF samples after ultrafiltration. We conclude that routine spectrophotometric analysis of all CSF samples is very useful, allowing detection of xanthochromic compounds in patients with small cerebral and subdural hematomas as well as in those with minimal subarachnoid hemorrhages, hemorrhagic infarctions, or bleedings from aneurysms and neoplasms.

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Folate Insufficiency Due to MTHFR Deficiency Is Bypassed by 5-Methyltetrahydrofolate

Journal of Clinical Medicine ◽

10.3390/jcm9092836 ◽

2020 ◽

Vol 9 (9) ◽

pp. 2836

Author(s):

Maša Vidmar Golja ◽

Alenka Šmid ◽

Nataša Karas Kuželički ◽

Jurij Trontelj ◽

Ksenija Geršak ◽

...

Keyword(s):

Methylenetetrahydrofolate Reductase ◽

Fold Increase ◽

Mthfr Gene ◽

Folate Supplementation ◽

Disease States ◽

Metabolic Defects ◽

Key Enzyme ◽

Cell Processes ◽

Activity Groups ◽

Mthfr Deficiency

Adequate levels of folates are essential for homeostasis of the organism, prevention of congenital malformations, and the salvage of predisposed disease states. They depend on genetic predisposition, and therefore, a pharmacogenetic approach to individualized supplementation or therapeutic intervention is necessary for an optimal outcome. The role of folates in vital cell processes was investigated by translational pharmacogenetics employing lymphoblastoid cell lines (LCLs). Depriving cells of folates led to reversible S-phase arrest. Since 5,10-methylenetetrahydrofolate reductase (MTHFR) is the key enzyme in the biosynthesis of an active folate form, we evaluated the relevance of polymorphisms in the MTHFR gene on intracellular levels of bioactive metabolite, the 5-methyltetrahydrofolate (5-Me-THF). LCLs (n = 35) were divided into low- and normal-MTHFR activity groups based on their genotype. They were cultured in the presence of folic acid (FA) or 5-Me-THF. Based on the cells’ metabolic activity and intracellular 5-Me-THF levels, we conclude supplementation of FA is sufficient to maintain adequate folate level in the normal MTHFR activity group, while low MTHFR activity cells require 5-Me-THF to overcome the metabolic defects caused by polymorphisms in their MTHFR genes. This finding was supported by the determination of intracellular levels of 5-Me-THF in cell lysates by LC-MS/MS. FA supplementation resulted in a 2.5-fold increase in 5-Me-THF in cells with normal MTHFR activity, but there was no increase after FA supplementation in low MTHFR activity cells. However, when LCLs were exposed to 5-Me-THF, a 10-fold increase in intracellular levels of this metabolite was determined. These findings indicate that patients undergoing folate supplementation to counteract anti-folate therapies, or patients with increased folate demand, would benefit from pharmacogenetics-based therapy choices.

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Microscopic Colitis: Epidemiology, Pathophysiology, Diagnosis and Current Management—An Update 2013

ISRN Gastroenterology ◽

10.1155/2013/352718 ◽

2013 ◽

Vol 2013 ◽

pp. 1-12 ◽

Cited By ~ 18

Author(s):

Martin Alexander Storr

Keyword(s):

Colonic Mucosa ◽

Chronic Diarrhea ◽

Treatment Options ◽

Correct Diagnosis ◽

Collagenous Colitis ◽

Microscopic Colitis ◽

Normal Colonic Mucosa ◽

Clinical Value ◽

Current Management ◽

And Gender

Microscopic colitis is a common cause of chronic diarrhea. Over the last years the incidence and the prevalence of microscopic colitis are rising and this rise is largely attributed to a rising awareness, and concomitantly an increasing number of diagnoses are made. Patients with microscopic colitis report watery, nonbloody diarrhea of chronic, intermittent, or chronic recurrent course. Following an unremarkable physical examination the diagnosis of microscopic colitis is made by colonoscopy, which shows essentially a normal colonic mucosa. Biopsies taken during the colonoscopy procedure will then finally establish the correct diagnosis. Histological workup can then confirm a diagnosis of microscopic colitis and can distinguish the two distinct histological forms, namely, collagenous colitis and lymphocytic colitis. Presently both forms are diagnosed and treated in the same way; thus the description of the two forms is not of clinical value, though this may change in future. Depending on the patients age and gender 10–30% of patients investigated for chronic diarrhea will be diagnosed with microscopic colitis if biopsies are taken. Microscopic colitis is most common in older patients, especially in female patients and is frequently associated with autoimmune disorders and the consumption of several drugs. This review summarizes the present knowledge of the epidemiology, the pathophysiology, and the diagnosis of microscopic colitis and discusses the former and the present treatment options.

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DIFFERENTIAL DIAGNOSTICS OF GASTRIC CANCER AND PRECANCEROUS CHANGES OF THE GASTRIC MUCOSA USING ANALYSIS OF EXPRESSION OF SIX MICRORNAS

Russian Clinical Laboratory Diagnostics ◽

10.18821/0869-2084-2020-65-2-131-136 ◽

2020 ◽

Vol 65 (2) ◽

pp. 131-136 ◽

Cited By ~ 1

Author(s):

S. E. Titov ◽

V. V. Anishchenko ◽

T. L. Poloz ◽

Yu. A. Veryaskina ◽

A. A. Arkhipova ◽

...

Keyword(s):

Gastric Cancer ◽

Gastric Mucosa ◽

Decision Tree ◽

Diagnostic Procedures ◽

Normal Mucosa ◽

Gastric Ulcers ◽

Differential Diagnostics ◽

Diagnostic Significance ◽

Diagnostic Characteristics ◽

Specific Symptoms

The lack of specific symptoms for the early detection of gastric cancer leads to the fact that it is often diagnosed at a late stage, when the prognosis is unfavorable. The analysis of molecular markers in addition to standard diagnostic procedures is a promising approach for improving the preoperative diagnosis of both gastric cancer and precancerous changes in the mucosa. Therefore, the aim of our study was to analyze the diagnostic significance of using miRNA expression to diagnosis gastric cancer and precancerous conditions (dysplasia) in histological material. In this work, 122 samples of archival histological material in the form of paraffin blocks were used: 34 samples of gastric adenocarcinoma, 54 samples of gastric ulcers with dysplasia and 34 samples of normal gastric mucosa obtained from patients after bariatric surgery. The expression level of miRNA-145-5p, -150-5p, -20a-5p, -21-5p, -31-5p, -34a-5p, -375 was determined using real-time RT-PCR. Samples were stratified into different groups using the C-RT decision tree algorithm. All miRNAs, except miRNA-20a, were included in the decision tree, which allows stratification of samples for normal mucosa, dysplasia, and gastric cancer. Normal mucosa can be distinguished from gastric cancer only by miRNA-34a, -21, -375. Diagnostic characteristics for the detection of dysplasia: specificity - 97%, sensitivity - 87%; for the detection of gastric cancer: specificity - 91%, sensitivity - 93%. The sufficiently high values of the diagnostic characteristics for detecting dysplasia of the gastric mucosa and gastric cancer obtained in our study indicate the possibility of using expression data of a small amount of miRNAs for the effective separation of samples with tumor and precancerous changes in the stomach tissue.

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