Cyclic Adenosine 3′, 5′ Monophosphate: A Possible Indicator of Premalignant Changes in the Large Bowel

Cyclic adenosine 3′, 5′ monophosphate (cyclic-AMP) has been estimated in mucosal biopsy samples removed from the descending colon and rectum at endoscopy to investigate the possibility of using this substance for monitoring pre-malignant changes in the large bowel. Four groups of patients have been studied: those with normal large bowel and rectal mucosa; those with non-malignant inflammatory bowel disease; those with an adenomatous polyp in the descending colon or sigmoid colon; and those with a rectal adenocarcinoma. No difference was found in the cyclic-AMP content of ‘normal’ rectal mucosa, ‘normal’ colonic mucosa, ‘diseased’ colonic mucosa, carcinomas, and uninvolved mucosa adjacent to the polyps. Less cyclic-AMP was found in the polyps than in adjacent uninvolved mucosa. Conversely, more cyclic-AMP was found in the carcinomas than in adjacent uninvolved mucosa. It is concluded that although cyclic-AMP may be a very useful parameter for delineating the extent of the disease in individual patients, it is not a suitable biochemical marker for the screening of neoplastic changes in the large bowel in the population as a whole.

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Expression of interleukin 1β and interleukin 1β converting enzyme by intestinal macrophages in health and inflammatory bowel disease

Gut ◽

10.1136/gut.42.2.214 ◽

1998 ◽

Vol 42 (2) ◽

pp. 214-219 ◽

Cited By ~ 121

Author(s):

M E McAlindon ◽

C J Hawkey ◽

Y R Mahida

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Colonic Mucosa ◽

Peripheral Blood Monocyte ◽

Interleukin 1Β ◽

Enzyme Linked Immunosorbent Assay ◽

Normal Colonic Mucosa ◽

Converting Enzyme ◽

Inflammatory Bowel ◽

Targeted Inhibition

Background—In the lipopolysaccharide (LPS) stimulated peripheral blood monocyte, the precursor form of interleukin 1β (IL-1β, 31 kD) is processed by IL-1β converting enzyme (ICE) to the mature, bioactive form (17 kD). IL-1β is a proinflammatory cytokine which is likely to have a role in the pathogenesis of inflammatory bowel disease (IBD).Aims—To investigate the expression and processing of IL-1β and ICE by tissue macrophages from normal and IBD colonic mucosa.Methods—Mucosal biopsy specimens and lamina propria cells from normal and IBD colons were studied by reverse transcription polymerase chain reaction (RT-PCR), western blot analysis, and ELISA (enzyme linked immunosorbent assay).Results—Normal colonic macrophages synthesised only the precursor form of IL-1β whereas in IBD the mature form was also produced. Similarly, cells from normal colonic mucosa synthesised ICE as the precursor (p45) only, whereas macrophages from IBD colons produced active (p20) ICE. Ac-Tyr-Val-Ala-Asp-CHO, a specific peptide aldehyde inhibitor of ICE, significantly reduced the amount of mature IL-1β released by isolated IBD macrophages (from a median of 1.2 (range 0.78–4.42) ng/ml to 0.43 (0.21–1.6) ng/ml; p<0.01).Conclusions—Exposure of normal colonic macrophages to LPS only induces the production of the precursor form of IL-1β, because the cells fail to activate ICE. In contrast, IBD colonic macrophages are able to activate ICE and hence release mature IL-1β in a manner similar to circulating monocytes. This is consistent with IBD macrophages being recently recruited from the circulating monocyte population. Targeted inhibition of ICE may represent a novel form of therapy in IBD.

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Inflammation and Cancer IV. Colorectal cancer in inflammatory bowel disease: the role of inflammation

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00079.2004 ◽

2004 ◽

Vol 287 (1) ◽

pp. G7-G17 ◽

Cited By ~ 750

Author(s):

Steven H. Itzkowitz ◽

Xianyang Yio

Keyword(s):

Colorectal Cancer ◽

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Colonic Mucosa ◽

Normal Colonic Mucosa ◽

Sporadic Colorectal Cancer ◽

Increased Risk ◽

Inflammatory Bowel ◽

Repair Genes

Patients with ulcerative colitis and Crohn's disease are at increased risk for developing colorectal cancer. To date, no known genetic basis has been identified to explain colorectal cancer predisposition in these inflammatory bowel diseases. Instead, it is assumed that chronic inflammation is what causes cancer. This is supported by the fact that colon cancer risk increases with longer duration of colitis, greater anatomic extent of colitis, the concomitant presence of other inflammatory manifestations such as primary sclerosing cholangitis, and the fact that certain drugs used to treat inflammation, such as 5-aminosalicylates and steroids, may prevent the development of colorectal cancer. The major carcinogenic pathways that lead to sporadic colorectal cancer, namely chromosomal instability, microsatellite instability, and hypermethylation, also occur in colitis-associated colorectal cancers. Unlike normal colonic mucosa, however, inflamed colonic mucosa demonstrates abnormalities in these molecular pathways even before any histological evidence of dysplasia or cancer. Whereas the reasons for this are unknown, oxidative stress likely plays a role. Reactive oxygen and nitrogen species produced by inflammatory cells can interact with key genes involved in carcinogenic pathways such as p53, DNA mismatch repair genes, and even DNA base excision-repair genes. Other factors such as NF-κB and cyclooxygenases may also contribute. Administering agents that cause colitis in healthy rodents or genetically engineered cancer-prone mice accelerates the development of colorectal cancer. Mice genetically prone to inflammatory bowel disease also develop colorectal cancer especially in the presence of bacterial colonization. These observations offer compelling support for the role of inflammation in colon carcinogenesis.

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Relevance of Segmental Colitis with Diverticulosis (SCAD) to Other Forms of Inflammatory Bowel Disease

Canadian Journal of Gastroenterology ◽

10.1155/2009/540420 ◽

2009 ◽

Vol 23 (6) ◽

pp. 439-440 ◽

Cited By ~ 7

Author(s):

Hugh J Freeman

Keyword(s):

Older Adults ◽

Inflammatory Bowel Disease ◽

Inflammatory Process ◽

Colonic Mucosa ◽

Clinical Course ◽

Normal Colonic Mucosa ◽

Endoscopic Evaluation ◽

Inflammatory Bowel ◽

Definition Of ◽

Segmental Colitis

A well localized inflammatory process involving only the sigmoid colonic segment associated with diverticulosis (SCAD), has become increasingly recognized as a distinct clinical and pathological disorder, usually described in older adults, often with rectal bleeding. Although some resolve spontaneously, most patients appear to respond to treatment only with 5-aminosalicylate. Endoscopic evaluation reveals a nonspecific inflammatory process localized in the sigmoid colon that usually completely resolves with histologically normal colonic mucosa. Recurrent symptoms with evidence of recurrent segmental colitis may occur, but most have an entirely benign clinical course. Further definition of the underlying molecular signalling that occurs in this apparently distinctive disorder may be critically important to understand the elements of a colonic inflammatory process that can completely and spontaneously resolve.

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Image Retrieval Method for Multiscale Objects from Optical Colonoscopy Images

International Journal of Biomedical Imaging ◽

10.1155/2017/7089213 ◽

2017 ◽

Vol 2017 ◽

pp. 1-13 ◽

Cited By ~ 2

Author(s):

Hirokazu Nosato ◽

Hidenori Sakanashi ◽

Eiichi Takahashi ◽

Masahiro Murakawa ◽

Hiroshi Aoki ◽

...

Keyword(s):

Colonic Mucosa ◽

New Technology ◽

Medical Doctor ◽

Retrieval Method ◽

Optical Colonoscopy ◽

Early Stages ◽

Bowel Diseases ◽

Colon And Rectum ◽

Inflammatory Bowel ◽

High Level

Optical colonoscopy is the most common approach to diagnosing bowel diseases through direct colon and rectum inspections. Periodic optical colonoscopy examinations are particularly important for detecting cancers at early stages while still treatable. However, diagnostic accuracy is highly dependent on both the experience and knowledge of the medical doctor. Moreover, it is extremely difficult, even for specialist doctors, to detect the early stages of cancer when obscured by inflammations of the colonic mucosa due to intractable inflammatory bowel diseases, such as ulcerative colitis. Thus, to assist the UC diagnosis, it is necessary to develop a new technology that can retrieve similar cases of diagnostic target image from cases in the past that stored the diagnosed images with various symptoms of colonic mucosa. In order to assist diagnoses with optical colonoscopy, this paper proposes a retrieval method for colonoscopy images that can cope with multiscale objects. The proposed method can retrieve similar colonoscopy images despite varying visible sizes of the target objects. Through three experiments conducted with real clinical colonoscopy images, we demonstrate that the method is able to retrieve objects of any visible size and any location at a high level of accuracy.

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Transporter function and cyclic AMP turnover in normal colonic mucosa from patients with and without colorectal neoplasia

BMC Gastroenterology ◽

10.1186/1471-230x-12-78 ◽

2012 ◽

Vol 12 (1) ◽

Cited By ~ 26

Author(s):

Karen Kleberg ◽

Gerda Majgaard Jensen ◽

Dan Ploug Christensen ◽

Morten Lundh ◽

Lars Groth Grunnet ◽

...

Keyword(s):

Cyclic Amp ◽

Colonic Mucosa ◽

Colorectal Neoplasia ◽

Normal Colonic Mucosa

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Macrophage heterogeneity in normal colonic mucosa and in inflammatory bowel disease.

Gut ◽

10.1136/gut.29.11.1531 ◽

1988 ◽

Vol 29 (11) ◽

pp. 1531-1538 ◽

Cited By ~ 77

Author(s):

M C Allison ◽

S Cornwall ◽

L W Poulter ◽

A P Dhillon ◽

R E Pounder

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Colonic Mucosa ◽

Normal Colonic Mucosa ◽

Inflammatory Bowel

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Tissue origin of peptide-responsive eicosanoid production in rabbit intestine

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1989.257.6.g879 ◽

1989 ◽

Vol 257 (6) ◽

pp. G879-G886

Author(s):

L. E. Leduc ◽

R. D. Zipser

Keyword(s):

Small Intestine ◽

Colonic Mucosa ◽

Enteric Bacteria ◽

Normal Colonic Mucosa ◽

Muscularis Mucosa ◽

Rabbit Intestine ◽

Eicosanoid Release ◽

Inflammatory Bowel ◽

Pg E2 ◽

Tissue Origin

Different layers of rabbit large and small intestine display different peptide sensitivity and different profiles of eicosanoid release. Isolated perfused mesenteric pedicle alone, with muscularis/submucosa or with muscularis and mucosa from normal small bowel, normal colon, or inflamed colon were stimulated with bradykinin (BK) or n-formyl-methionyl-leucyl-phenylalanine (fMLP). Released prostaglandin (PG)E2, thromboxane (Tx)B2, and leukotriene (LT)B4 were assayed using extensively validated radioimmunoassays. In rabbit colon, PGE2 arises primarily from the mesentery, while in small intestine the muscularis/mucosa releases 70-80% of the total PGE2. BK releases no significant thromboxane from healthy colon, although both muscularis/submucosa and mucosa respond in inflamed colon. In contrast, fMLP stimulates thromboxane from muscularis/submucosa and mucosa of even healthy colon, while release is greatly potentiated in inflammation. Lipoxygenase in the colon is regulated differently than cyclooxygenase; it is not stimulated by BK in either healthy or inflamed colon. fMLP releases equal amounts of LTB4 from healthy and inflamed colon, but release was primarily from healthy colonic mucosa, whereas it was distributed throughout mesenteric pedicle, muscularis, and mucosa in inflamed colon. The ability of normal colonic mucosa to release proinflammatory LTB4 in response to a chemotactic factor (fMLP) produced by enteric bacteria suggests a possible role for these compounds as a stimulus for inflammation in some patients with inflammatory bowel disease.

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Fecal Calprotectin, CRP and Leucocytes in IBD Patients: Comparison of Biomarkers With Biopsy Results

Journal of the Canadian Association of Gastroenterology ◽

10.1093/jcag/gwaa009 ◽

2020 ◽

Author(s):

Barry D Kyle ◽

Terence A Agbor ◽

Shajib Sharif ◽

Usha Chauhan ◽

John Marshall ◽

...

Keyword(s):

Ulcerative Colitis ◽

Fecal Calprotectin ◽

Dependent Manner ◽

Ascending Colon ◽

C Reactive Protein ◽

Concentration Dependent Manner ◽

Reactive Protein ◽

Inflammatory Bowel ◽

Descending Colon ◽

Active Inflammation

Abstract Background This study aimed to compare fecal calprotectin (FC) levels with other commonly used parameters as part of patient care during evaluation for inflammatory bowel disease (IBD). Methods We recruited adult IBD patients with ulcerative colitis (UC) and Crohn’s disease (CD) and compared the results of the patient’s biopsy results (i.e., inflamed versus noninflamed) for six sites (i.e., ileum, ascending colon, transverse colon, descending colon, sigmoid colon, rectum) with concentrations of C-reactive protein (CRP), total leucocytes and fecal calprotectin (FC). Results We found that FC was significantly elevated in a concentration-dependent manner that correlated with the number of active inflammation sites reported in biopsy. Although CRP and leucocyte measurements trended upwards in line with inflammation reported from biopsy, the results were highly variable and highlighted poor reliability of these biomarkers for indicating IBD inflammation. Conclusions These results strongly suggest that FC correlates best with biopsy reports and is a superior marker than CRP and leucocytes.

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