“…Other treatments for such patients have not had beneficial effects over the long term and may not be well tolerated. [30][31][32][33] Our shortterm study suggests that anti-TNF-a therapy with cA2 may represent a new treatment option for patients with moderate-to-severe Crohn's disease. Further studies will be necessary to determine the longterm efficacy of a single infusion of cA2 as well as the efficacy and safety of repeated treatments.…”
“…Other treatments for such patients have not had beneficial effects over the long term and may not be well tolerated. [30][31][32][33] Our shortterm study suggests that anti-TNF-a therapy with cA2 may represent a new treatment option for patients with moderate-to-severe Crohn's disease. Further studies will be necessary to determine the longterm efficacy of a single infusion of cA2 as well as the efficacy and safety of repeated treatments.…”
“…Blood for GLP-2 RIA was collected in a final volume of 10% Trasylol, EDTA, Diprotin A (5,000 KIU/ml:32 mM:0.1 nM), and plasma was stored at Ϫ80°C before analysis by RIA (6). Semiquantitative RT-PCR was carried out with aliquots analyzed from a range (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) of cycle numbers to ensure linearity for mouse TGF-␣ mRNA as previously described (8,9,34). The PCR conditions were 94°C for 1 min and 68°C for 2 min for 30 cycles.…”
Section: Methodsmentioning
confidence: 99%
“…Although these latter agents are generally effective they do not specifically target the intestine and their side effects may be considerable, precluding longterm use in patients with chronic IBD. Newer targeted approaches to immunosuppressive and anti-inflammatory therapy, including use of monoclonal antibodies against lymphocyte antigens (24,48) or tumor necrosis factor (TNF) (46,50), interleukin-4 (IL-4) delivery via adenoviral gene transfer (29), and antisense oligonucleotides for suppression of intercellular adhesion molecule activity (ICAM), are currently under evaluation.…”
The pathology of Crohn’s disease and ulcerative colitis is characterized by chronic inflammation and destruction of the gastrointestinal epithelium. Although suppression of inflammatory mediators remains the principle component of current disease therapeutics, strategies for enhancing repair and regeneration of the compromised intestinal epithelium have not been widely explored. The demonstration that a peptide hormone secreted by the intestinal epithelium, glucagon-like peptide-2 (GLP-2), is a potent endogenous stimulator of intestinal epithelial proliferation in the small bowel prompted studies of the therapeutic efficacy of GLP-2 in CD1 and BALB/c mice with dextran sulfate (DS)-induced colitis. We report here that a human GLP-2 analog (h[Gly2]GLP-2) significantly reverses weight loss, reduces interleukin-1 expression, and increases colon length, crypt depth, and both mucosal area and integrity in the colon of mice with acute DS colitis. The effects of h[Gly2]GLP-2 in the colon are mediated in part via enhanced stimulation of mucosal epithelial cell proliferation. These observations suggest that exploitation of the normal mechanisms used to regulate intestinal proliferation may be a useful adjunct for healing mucosal epithelium in the presence of active intestinal inflammation.
“…Among these, CD4+ T lymphocytes have an important role in the pathogenesis of human IBD; this association is supported by the clinical effects of monoclonal anti CD4+ antibodies in patients with Crohn's disease [6]. Inflammatory bowel disease patients with concomitant leukemia when treated with bone marrow transplantation can remain in long-term remissions, suggesting that the host immune dysregulation has an important role in the perpetuation of this disease [7].…”
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