Ridogrel enemas in distal ulcerative colitis

Jj, Auwerda; Zijlstra, Frank; Cj, Tak; Hf, van den Ingh; Jh, Wilson; Rj, Ouwendijk

doi:10.1097/00042737-200104000-00016

Cited by 16 publications

(6 citation statements)

References 13 publications

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“…Mucosal thromboxane levels were reduced in all patients, but the level of the anti‐inflammatory mediators IL‐6 and TNF were unchanged. Five patients responded clinically to the treatment, but this was not always associated with a decrease in the endoscopic or histological scores of inflammation 83 . This preliminary study may suggest some efficacy to this therapy, but as yet no further studies have been undertaken.…”

Section: Current Topical Therapiesmentioning

confidence: 79%

Topical agents for idiopathic distal colitis and proctitis

Lawrance

2010

J of Gastro and Hepatol

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Rectally administered topical agents have demonstrated efficacy in the maintenance of distal colitis (DC) and proctitis and as they are rarely associated with significant blood drug levels, side effects are infrequent. The topical 5-aminosalicylic acid (5-ASA) suppositories and enemas target different regions of the distal colon and are effective for proctitis and DC, respectively. They demonstrate clinical results that are better than oral 5-ASAs and are preferred to topical steroids with better clinical, endoscopic and histological outcomes, without the risk of adrenal suppression. Disease resistant to topical agents, however, can be extremely difficult to manage. The addition of oral 5ASAs, steroids, immunosuppressants and the anti-tumor necrosis factor-α agents may be effective, but can result in significant side effects and not all patients will respond to the therapies. It is for these patients that new and novel therapies are required. Novel topical agents have been proposed for the management of resistant DC. These agents included butyrate, cyclosporine, and nicotine enemas, as well as tacrolimus suppositories, and tacrolimus, ecabet sodium, arsenic, lidocaine, bismuth, rebamipide and thromboxane enemas. While some of these agents appear to demonstrate impressive outcomes, the majority have only been examined in small open-labeled studies. There is thus a desperate need for more randomized double-blinded placebo controlled studies to investigate the clinical utility of these topical therapies. This review summarizes the efficacy of the established topical therapies, and explores the available data on the new and novel topical agents for the management of DC and proctitis.

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Section: Current Topical Therapiesmentioning

confidence: 79%

Topical agents for idiopathic distal colitis and proctitis

Lawrance

2010

J of Gastro and Hepatol

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“…6-Keto-PGF 1 α is thought to possess anti-inflammatory, immunosuppressive, and immunomodulatory actions. TXB 2 enhances leucocyte recruitment and causes focal mucosal ischemia and injury through platelet activation and aggregation [49]. …”

Section: Discussionmentioning

confidence: 99%

Lung and Intestine: A Specific Link in an Ulcerative Colitis Rat Model

Liu

Wang

Yang

et al. 2013

Gastroenterology Research and Practice

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Background. To investigate the link and mechanisms between intestine and lung in the ulcerative colitis (UC) rat model. Materials and Methods. We used the UC rat model by immunological sensitization combined with local 2, 4, 6-trinitrobenzene sulfonic acid (TNBS) in 50% ethanol enema, observed dynamically animal general state and body weight, examined the histological and functional changes in the colon, lung, liver, and kidney tissues, and detected microvascular endothelium response towards inflammation characterized with the expression of iNOS, TXB2, P-selectin, ICAM-1, and vascular endothelial growth factor A (VEGF-A) in the colon and lung tissue. Results. Pulmonary function results suggested ventilator disorder, and pathological findings showed interstitial pneumonia. There were no significant changes in the liver and kidney function and histopathology. The colon and lung tissue iNOS, TXB2, P-selectin, ICAM-1, and VEGF-A expression of the model rats was significantly higher than the normal rats at both time points. Conclusions. Our study is the first to demonstrate the close association between the large intestine and lung in the immune-TNBS-ethanol-induced UC rat model. Different organs and tissues with the same embryonic origin may share the same pathological specificities in a disease. The present study provided a new way of thinking for pathological changes in clinical complex diseases manifested with multiorgan damage.

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“…A series of trials targeting excess thromboxane in ulcerative colitis were completed, using a selective thromboxane antagonist, ridogrel (Janssen Research Foundation, Beerse, Belgium). Ridogrel was administered to ulcerative colitis patients both as an oral agent as well as an enema in placebo‐controlled trials, 104, 105 but failed to demonstrate efficacy and meet specified trial end points. Given that microvascular dysfunction appears to play a critical role in the process of chronic intestinal inflammation, the potential for agents targeting mechanisms of microvascular dysfunction may undergo further evaluation as adjuvant strategies, potentially targeting endothelin, thromboxane, or excess superoxide anion generation.…”

Section: Microvascular Dysfunction In Ibdmentioning

confidence: 99%

The Intestinal Microvasculature as a Therapeutic Target in Inflammatory Bowel Disease

Hatoum

Heidemann

Binion

2006

Annals of the New York Academy of Sciences

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Chronic inflammation is a complex biologic process which involves immune as well as non-immune cells including the microvasculature and its endothelial lining. Growing evidence suggests that the microvasculature plays an integral role in the pathophysiology of inflammatory bowel disease (IBD; Crohn's disease and ulcerative colitis). The microvasculature contributes to chronic inflammation through altered leukocyte recruitment, impaired perfusion, and angiogenesis leading to tissue remodeling. These diverse areas of IBD microvascular biology represent therapeutic targets that are currently undergoing investigation.

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Ridogrel enemas in distal ulcerative colitis

Abstract: This pilot study shows that Ridogrel enemas selectively reduce mucosal TxB2 concentration.

Cited by 16 publications

References 13 publications

Topical agents for idiopathic distal colitis and proctitis

Topical agents for idiopathic distal colitis and proctitis

Lung and Intestine: A Specific Link in an Ulcerative Colitis Rat Model

The Intestinal Microvasculature as a Therapeutic Target in Inflammatory Bowel Disease

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