microscopic-observation-of-lymphocyte-dynamics-in-rat-peyer-s-patches

Microscopic Observation of Lymphocyte Dynamics in Rat Peyer's Patches

Na&#239;ve lymphocytes recirculate from the blood to the lymphoid tissues under physiological condition and it is commonly recognized as an important ...

National Defense Medical College

Jikei University School of Medicine

Uric acid is excreted from blood into the intestinal lumen, yet the roles of uric acid in intestinal diseases remain to be elucidated. The study aimed to determine whether uric acid could reduce end points associated with nonsteroidal anti-inflammatory drug (NSAID)-induced enteropathy.

Uric acid ameliorates indomethacin-induced enteropathy in mice through its antioxidant activity.

We isolated two novel probiotics strains (s193 and s292) from Funazushi, which is a traditional Japanese fermented food, and evaluated its effects on DSS-induced colitis to determine the possible underlying mechanisms.

Novel probiotics isolated from a Japanese traditional fermented food, Funazushi, attenuates DSS-induced colitis by increasing the induction of high integrin αv/β8-expressing dendritic cells.

We herein describe a 69-year-old man suffering from chronic diarrhea caused by lansoprazole (LPZ)-induced collagenous colitis (CC) accompanied with protein-losing enteropathy (PLE), diagnosed by increased fecal alpha-1 antitrypsin clearance and the findings of leakage from the descending colon to the sigmoid colon on scintigraphy. MR enterocolonography (MREC) was also performed for differentiating digestive diseases, and inflamed findings were observed around the same portion as those on scintigraphy, suggesting that this region was responsible for protein loss in this case. The MREC findings improved after the cessation of LPZ, and hypoalbuminemia also improved simultaneously. This case suggests that MREC may be a new and useful diagnostic tool for CC with PLE.

Evaluation by MR Enterocolonography of Lansoprazole-induced Collagenous Colitis Accompanied with Protein-losing Enteropathy.

Human intestinal spirochetosis (HIS) is a colorectal infection caused by the Brachyspira species of intestinal spirochetes, whose pathogenicity in humans remains unclear owing to the lack of or mild symptoms. We monitored the 5-year clinical course of a woman diagnosed with HIS in whom ulcerative colitis (UC) had been suspected. Following a positive fecal occult blood test, she underwent a colonoscopic examination at a local clinic where she was diagnosed with "right-sided" UC concomitant with incidentally detected HIS, and was referred to our hospital. Colonoscopic, histopathological, and cytological examination revealed localized erosive colitis in the ascending and the right transverse colon concomitant with HIS resembling skip lesions of UC. Initially, we chose the wait-and-watch approach; however, she gradually developed bloody diarrhea. Metronidazole improved her abdominal symptoms, as well as her colonoscopic and histopathological findings, suggesting that HIS was responsible for her colorectal inflammation. This case reveals (1) a possible pro-inflammatory role of HIS, (2) difficulties in diagnosing HIS in chronic proctocolitis, and (3) a possible inclusion of some HIS cases in "UC". HIS could mimic UC and might be included in differential diagnoses for UC. Antibiotic administration is necessary following the detection of HIS, particularly in patients demonstrating an atypical presentation of UC.

Human intestinal spirochetosis mimicking ulcerative colitis.

Liver fibrosis is a life-threatening disorder for which no approved therapy is available. Recently, we reported that mouse hepatic stellate cell (HSC) activation increased free cholesterol (FC) accumulation, partly by enhancing signaling through sterol regulatory element-binding protein 2 (SREBP2) and microRNA-33a (miR-33a), which resulted in HSC sensitization to transforming growth factor-β (TGFβ)-induced activation in a "vicious cycle" of liver fibrosis.

Vitamin A-coupled liposome system targeting free cholesterol accumulation in hepatic stellate cells offers a beneficial therapeutic strategy for liver fibrosis.

Sphingosine-1-phosphate (S1P) receptor 1, a therapeutic target of the S1P agonist FTY720, plays a crucial role in lymphocyte migration and is expressed in several cells including naïve T lymphocytes and endothelial cells. 2-Acetyl-4-tetrahydroxybutyl imidazole (THI), an inhibitor of S1P lyase, exhibits immunomodulatory activity through increasing the S1P concentration in the secondary lymphoid organs, but its effects on colitis remain unclear. This study aimed to clarify how THI affects colitis and migration of naïve T lymphocytes in Peyer's patches (PPs).

Amelioration of colitis through blocking lymphocytes entry to Peyer's patches by sphingosine-1-phosphate lyase inhibitor.

The enhanced recruitment of leukocytes to the inflamed colon is a key feature of ulcerative colitis (UC). The gut-specific adhesion molecules involved in leukocyte recruitment have emerged as recent therapeutic targets. Nicotine absorbed from smoking has been reported to work protectively in UC patients. Our hypothesis is that nicotine may suppress the aberrant leukocyte recruitment and colonic inflammation via the suppression of the overexpressed gut-specific adhesion molecules in the inflamed colon. To test this hypothesis, the severity of colitis and the degree of leukocyte recruitment induced by gut-specific adhesion molecules were assessed in dextran sulfate sodium (DSS) colitis mice (C57BL/6J mice treated with 3% DSS) with or without nicotine treatment. We also studied the in vitro changes in the expression of adhesion molecules by using a vascular endothelial cell line. DSS-induced colitis was accompanied by increases in disease activity index (DAI), histological score, recruitment of leukocytes, and the expression of adhesion molecules, mucosal vascular addressin cell adhesion molecule-1 (MAdCAM-1) and VCAM-1. Nicotine treatment significantly attenuated MAdCAM-1 expression, leukocyte recruitment, DAI, and histological score. The expression of β7-integrin, the ligand for MAdCAM-1, on leukocytes was not affected by nicotine treatment. In vitro study, the TNF-α-enhanced mRNA expression of MAdCAM-1 was reduced by the coadministration of nicotine in a dose-dependent manner, possibly via nicotinic receptor activation. These results supported our hypothesis that nicotine treatment ameliorated colitis through the suppression of MAdCAM-1 expression on the microvessels in the inflamed colon. Further investigation is warranted on the role of nicotine in the treatment of UC.

Nicotine treatment ameliorates DSS-induced colitis by suppressing MAdCAM-1 expression and leukocyte recruitment.

We herein report a 44-year-old man suffering from systemic edema due to protein-losing enteropathy (PLE) with superior mesenteric vein (SMV) obstruction and development of collateral veins, which subsequently proved to be a chronic result of thrombosis and a complication of Crohn's disease (CD). PLE was supposedly induced by both intestinal erosion and thrombosis-related lymphangiectasia, which was histologically proven in his surgically-resected ileal stenosis. Elemental diet and anti-TNFα agent improved his hypoalbuminemia after surgery. The rarity of the simultaneous coexistence of SMV obstruction and PLE and the precedence of these complications over typical abdominal symptoms of CD made the clinical course complex.

Atypical Clinical Presentation of Crohn's Disease with Superior Mesenteric Vein Obstruction and Protein-losing Enteropathy.

Although studies using conventional animal models have shown that specific stressors cause irritable bowel syndrome (IBS), it is unclear whether depression itself causes IBS. Our aim was to establish a rat model to determine if depression itself promotes the onset of IBS and to elucidate the role of gut microbiota in brain-gut axis pathogenesis during coincident depression and IBS.

Depression Promotes the Onset of Irritable Bowel Syndrome through Unique Dysbiosis in Rats.

We herein present the case of an immunocompetent 63-year-old man who had previously undergone resection of Crohn's disease (CD)-related small intestinal obstruction more than 30 years ago. He had not been receiving any medication for many years, but had recently started to suffer from ileus. A stenosed site of ileo-cecal anastomosis was identified and therefore was surgically resected, which was diagnosed as CD with small intestinal extramedullary plasmacytoma (EMP). The subsequent progression of CD was successfully controlled by anti-TNFα agents without any recurrence of EMP for over 3 years, implying the clinical benefit and safety of the biological therapy. This was the first known case of a patient who received anti-TNFα agents after a resection of small intestinal EMP accompanied with CD.

Article	Year
Uric acid ameliorates indomethacin-induced enteropathy in mice through its antioxidant activity. Journal of gastroenterology and hepatology\| PubMed ID: 28295549	2017
Novel probiotics isolated from a Japanese traditional fermented food, Funazushi, attenuates DSS-induced colitis by increasing the induction of high integrin αv/β8-expressing dendritic cells. Journal of gastroenterology\| PubMed ID: 28631049	2018
Evaluation by MR Enterocolonography of Lansoprazole-induced Collagenous Colitis Accompanied with Protein-losing Enteropathy. Internal medicine (Tokyo, Japan)\| PubMed ID: 29033425	2018
Human intestinal spirochetosis mimicking ulcerative colitis. Clinical journal of gastroenterology\| PubMed ID: 29204849	2018
Vitamin A-coupled liposome system targeting free cholesterol accumulation in hepatic stellate cells offers a beneficial therapeutic strategy for liver fibrosis. Hepatology research : the official journal of the Japan Society of Hepatology\| PubMed ID: 29243365	2018
Amelioration of colitis through blocking lymphocytes entry to Peyer's patches by sphingosine-1-phosphate lyase inhibitor. Journal of gastroenterology and hepatology\| PubMed ID: 29336057	2018
Nicotine treatment ameliorates DSS-induced colitis by suppressing MAdCAM-1 expression and leukocyte recruitment. Journal of leukocyte biology\| PubMed ID: 29901817	2018
Atypical Clinical Presentation of Crohn's Disease with Superior Mesenteric Vein Obstruction and Protein-losing Enteropathy. Internal medicine (Tokyo, Japan)\| PubMed ID: 30210116	2019
Depression Promotes the Onset of Irritable Bowel Syndrome through Unique Dysbiosis in Rats. Gut and liver\| PubMed ID: 30602220	2019
Crohn's Disease Accompanied with Small Intestinal Extramedullary Plasmacytoma. Internal medicine (Tokyo, Japan)\| PubMed ID: 30918171	2019

Kazuhiko Shirakabe

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