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  • 1
    Electronic Resource
    Electronic Resource
    Anti-colitic efficacy of SC-41930 in colitic cotton-top tamarins (1993)
    Springer
    Inflammation research 39 (1993), S. C36 
    Details
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To evaluate anti-colitic efficacy, eight cotton-top tamarins (CTTs) with histologically confirmed persistent active colitis were given the anti-inflammatory agent SC-41930 (10 mg/kg BW by gavage BID) for eight weeks. Colonic endoscopy and biopsy observations, CBCs and clinical chemistries, and stool consistency were evaluated pre-, mid-, and posttreatment. Colitic activity was graded histologically from A1 (mild) to A5 (severe); results varied among the seven animals that completed the study: five improved, one worsened, and one was unchanged. Serum enzyme levels were significantly reduced with treatment. Stool condition remained puddly throughout treatment and body weights did not vary from pretreatment levels. However, SC-41930 produced histological evidence (reduced numbers of polymorphonuclear cells) of anti-colitic efficacy over an eight-week treatment period in CTTs with persistent active colitis. These results support the use of the CTT colitis model to evaluate efficacy of therapeutic agents and provide useful predictive information to aid in the medical management of human IBD.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01972713
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Anti-inflammatory activity of the leukotriene B4 receptor antagonist, SC-41930, in colitic cotton-top tamarins (1994)
    Springer
    Inflammation research 41 (1994), S. C254 
    Details
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Cotton-top tamarins (CTTs) with histologically confirmed persistent and active colitis were given the leukotriene B4 (LTB4) receptor antagonist, SC-41930, (10 mg/kg BW, by gavage b.i.d.) for eight weeks. Anti-inflammatory activity was evaluated by colonic biopsy, stool consistency and the level of the lipid mediators LTB4 and prostaglandin E2 (PGE2) in rectal dialysates. Stool consistency did not improve with treatment but did not worsen. Blood chemistry (ALT, AST, LDH) and hematological parameters neither showed any untoward effects of SC-41930 treatment nor was there any effect on body weight. In rectal dialysate LTB4 levels were significantly reduced from pretreatment level of 4.87±1.46 ng/ml to 1.07±0.67 and 2.45±0.13 ng/ml at 4 and 8 weeks, respectively, and higher prostaglandin E2 (PGE2) over time. Histologically, 5/7 improved, 1/7 remained the same and 1/7 worsened. Oral SC-41930 treatment was safe and associated with an anti-colitic effect. The reduced LTB4 levels (affecting granulocyte degranulation and recruitment into tissues) and increased PGE2 (perhaps exerting a mucosal protective effect) may, in part explain the observed efficacy of this compound in active tamarin colitis. Use of the CTT model could provide insight into the inflammatory mediator contribution to idiopathic colitis and serve as a useful bridge between preclinical pharmacology and the assessment of these compounds in the medical management of human inflammatory bowel disease.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01987659
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    Inflammatory mediator changes in cotton-top tamarins (CTT) after SC-41930 anti-colitic therapy (1993)
    Springer
    Inflammation research 39 (1993), S. C8 
    Details
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Use of the CTT model provides insight into the inflammatory mediator contribution in the pathogenesis of idiopathic colitis. To evaluate anti-colitic efficacy, the leukotriene B4 receptor antagonist and anti-inflammatory agent, SC-41930, was administered (10 mg/kg BW by gavage BID) for 8 weeks to CTTs with histologically confirmed persistent and defined active colitis. The inflammatory mediators LTB4, PGE2, TXB2, and PAF were assayed in colonic dialysate that was collected after 11/2 h from four CTTs pre-, mid-, and post-treatment, frozen at −70°C, and analyzed by RIA after HPLC purification. LTB4 levels were lower at mid- and post-treatment and had little inter-animal variation post-treatment. PGE2 and PAF levels were elevated during SC-41930 treatment, but there was a trend towards lower thromboxane B2 levels. Reduced LTB4 (PMN degranulation and chemotaxis) and increased PGE2 (mucosal-protective effect) may, in part, explain the observed efficacy of SC-41930 in active tamarin colitis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01972704
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    Paper (German National Licenses)
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  • 4
    Electronic Resource
    Electronic Resource
    Inflammatory mediators in cotton-top tamarins (CTT) with acute and chronic colitis (1991)
    Springer
    Inflammation research 34 (1991), S. 178-180 
    Details
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Spontaneous colitis in CTT's presents cytological characteristics similar to chronic ulcerative colitis in humans, e.g. inflammatory cell infiltrate and crypt abscesses. To better characterize CTT colitis as a potential model for human inflammatory bowel disease (IBD), inflammatory mediators identified in colonic tissue of human IBD patients and/or experimental colitis models were assayed. Inflammatory mediator changes in plasma and colon from tamarins with acute (n=10) and chronic (n=10) colitis (by mucosal biopsy) were assayed by RIAs. Similar inflammatory mediators were found in the CTT's with acute colitis. In the plasma, PAF and PGE2 levels were lower in acute colitis CTT's, no LTB4 was detected, and histamine levels were not different from chronic colitic animals. In the colon, myeloperoxidase and interleukin-1β were significantly higher in acute colitis, PGE2 and LTB4 were higher but not significantly, and PAF was not different from chronic CTT's. These data suggest that a combination of events are occurring in the pathogenesis of tamarin colitis that involves some of the same mediators that are found in the human disease and in other experimental models. The importance of these findings to human IBD remains for further investigation; however, the spontaneous primate model offers an exciting approximation of the disease development and merits further investigation for understanding the pathogenesis of human IBD as well as to aid in development of targeted therapeutics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01993271
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    Paper (German National Licenses)
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