Colitis model

OA were aborted in 2003 due to the development of mild to moderate liver fibrosis in dogs treated for 9 months with high doses of pralnacasan. This was in spite of recent evidence demonstrating the effectiveness of pralnacasan treatment in the acute dextran sulfate sodium (DSS)-induced colitis model, which resembles Crohn s disease (CD) characteristics, and in transient ischemia induced brain damage. 

HV145 Kanauchi O., A. Andoh, T. Iwanaga, et al. Germinated barley foodstuffs attenuate colonic mucosal damage and mucosal nuclear factor kappa B activity in a spontaneous colitis model. J Gastroenterol Hepatol 1999 14(12) 1173-1179. 

Meenan J, Hommes DW, Mevissen M, Dijkhuizen S, Soule H, Moyle M, BuUer HR, Ten Kate FW, Tytgat GN, van Deventer SJ (1996) Attenuation of the inflammatory response in an animal colitis model by neutrophil inhibitory factor, a novel p 2-integrin antagonist. Scand J... 

Monosubstituted Mn(ii)-based complexes, which catalyze the dismutation of superoxide as shown by stopped-flow kinetic analysis, were tested for antiinflammatory activity in the mouse acetic acid-induced colitis model. As can be seen from Table 3, all of the SOD mimics are anti-inflammatory. Histological analysis of the colonic tissue confirmed these results. Of particular importance is the observation that Mn(ii) complexes that have no SOD activity, specifically the Mn(ii) dichloro complexes of 1,4,7,10,13-pentaazacyclohexadecane and 1,4,7,11,14-pentaazacycloheptadecane, do not protect against the colonic inflammation induced by acetic acid when the compounds are administered in-tracolonically at a dose of 30mgkg These results are consistent with a role for superoxide as a mediator of neutrophil-dependent inflammation. Consistent with this hypothesis is the observation that SC-52608 inhibits neutrophil-dependent inflammation induced by the intradermal administration of leukotriene 64, a neutrophil chemoattractant. ... 

Figure 4.4 Histological sections ofthe colon showing the effects of oral nanocrystalline silver (NP) on a rat colitis model, where colitis was produced using a single intracolonic injection of dinitrobenzenesulfonic acid (DNBS). Treatment groups consisted of oral administration of nanosilver particles (40, 4 or 0.4 mg kg ) or sulfasalazine suspension. Placebo and untreated groups served as controls. Colonic sections were stained with hematoxylin and eosin and examined microscopically, (a) Treated with NP ...

Colon inflammation 1. AEA levels are elevated in the colon of DNBS-treated mice and in the colon submucosa of TNBS-treated rats, two animal models of inflammatory bowel diseases, and in the biopsies of patients with ulcerative colitis, to control inflammation 1. Inhibitors of degradation (both FAAH and cellular re-uptake)... 

Animal models In rat acetic acid colitis the severity of inflammation can be decreased by methoxypolyethyleneglycohSOD, catalase, allopurinol and SAZ (Keshavarzian et al., 1990 Haydek et al.,... 

There is now little doubt that ROMs are produced in excess in patients with aaive IBD. That, at least in experimental colitis, they are rather more than irrelevant epiphenomena is indicated by the anti-inflammatory effect of specific antioxidants. Proof that this is also the case in human disease awaits the outcome of further controlled trials of specific agents interfering with ROM production. Whilst induction of NO production has been shown to occur in association with inflammation and tissue damage in both humans and in animal models, the significance of this is as yet unclear. 

There is some support for a role for free radicals in the pathogenesis of ischaemic colitis from animal studies. Murthy and Qi (1992) used a spin trap to demonstrate increased production of free radicals up to 60 min after reperfusion, whereas Douglas etal. (1989) demonstrated increases in malondialdehyde and conjugated dienes (presumptive measures of lipid peroxidation) in a rat model of ischaemic colitis. There is no data relating to human ischaemic colitis. 

Boughton-Smith, N.K., Evans, S.M. and Whittle, B.J.R. (1992a). Elevated nitric oxide synthase activity in inflamed colon from a rat model of colitis. Gut 33, S12. 

Keshavarzian, A., Doria, M.I., Sedghi, S., Kanofeky, J.R., Hecht, D., Holmes, E.W., Ibrahim, C., List, T., Urban, G., Gaginella, T. and Fields, J.Z. (1992a). Mitomycin C-induced colitis in rats a new animal model of acute colonic inflammation implicating reactive oxygen metabolites. J. Lab. Clin. Med. 120, 778-791. 

Yamada, T., Sartor, R.B., Marshall, S. and Grisham, M.B. (1992). A chronic model of distal colitis induced by bacterial cell wall polymers activation of leukocyte nitric oxide synthesis. Gastroenterology 102, A715. 

Albee, W.E., Jacobs, J., Phillips, M., Fisher, L., Panetta, J.A. and Gidda, J.S. (1992). The healing and protective effects of LY213829 in a model of formalin-immune mediated rabbit colitis. Gastroenterology 102, A589. 

Boirivant, M., Fuss, I.J., Chu, A. and Strober, W. (1998) Oxazolone colitis a murine model of T helper cell type 2 colitis treatable with antibodies to interleukin 4. Journal of Experimental Medicine 188, 1929-1939. 

Investigations performed in rats with experimental acute pancreatitis [196] or ulcerative colitis [197] have shown that both rectal and oral administration of rifaximin decreased colonic bacterial translocation towards mesenteric lymph nodes. In the model of ANP [196] not only was the intra-abdominal spread of enteric bacteria (fig. 8) significantly reduced but also the pancreatic damage was lessened by rifaximin treatment. 

Fiorucci S, Distrutti E, Mencarelli A, Barban-ti M, Palazzini E, Morelli A Inhibition of intestinal bacterial translocation with rifaximin modulates lamina propria monocytic cells reactivity and protects against inflammation in a rodent model of colitis. Digestion 2002 66 246-256. 

Recent experimental data, coming particularly from animal models of IBD, are consistent with the hypothesis that gut flora and bacterial products are implicated in the initiation and/or perpetuation of chronic intestinal inflammation. Purified bacterial products can initiate and perpetuate experimental colitis [1,2]. 

Based on the experimental observation of a beneficial effect of intracolonic amoxicillin-clavulanic acid in a rat model of colitis, Casellas et al. [33] used an enteric-coated amoxicillin-clavulanic acid (1 g amoxicillin plus 250 mg clavulanic acid, t.i.d.) in active UC. They also evaluated the release of inflammatory mediators (IL-8, TXB2, PGE2) in rectal dialysates. After short-term treatment, this formulation decreased intraluminal release of IL-8 and other inflammatory mediators and led to an improvement of patients with active UC. 

A group from La Jolla Pharmaceuticals has released data on their novel hydrazines in recent scientific [20,59,60] and patent literature [61,62], A series of arylallyl hydrazines (e.g., 8 and 9) were shown to be potent, irreversible inhibitors of rat and human SSAO/VAP-1 [59]. LJP-1207 (8, IC50 = 2nM, human) was evaluated in a series of in vivo inflammation models. Significant efficacy was observed in a mouse ulcerative colitis, mouse LPS-induced septic shock, and the rat carrageenan foot models [20], in a mouse model that resembles human multiple sclerosis [63], and in a transient forebrain ischemia model in estrogen-treated ovariectomized female rats [60]. 

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