Multiple mouse model

Figure 5 The C y-normalized cross-species exposure-response continuum for 7 across multiple pharmacology models [42]. A listed value (Cx) is the C iU (nM) affecting a response in assay X. RAM(r), rat radial arm maze DSR(nhp), nonhuman primate delayed spatial response task e-phys(r), rat electrophysiology model NOR(r), rat novel object recognition cGMP(m,r), mouse/rat cerebellar cGMP trem(nhp), nonhuman primate tremor rot(m), mouse rotarod.

Similarly, under certain disease conditions, altered NA innervation and/or AR signaling capacity impairs sympathetic communication with cells of the immune system, influencing disease progression. Altered catecholamine communication with the immune system is evident in autoimmune diseases such as arthritis and multiple sclerosis [5-7] and in infectious diseases, such as leprosy and a mouse model of acquired immunodeficiency syndrome [15, 43, 44], The impact of altered NA innervation of... 

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]. 

Selective COX-2 inhibitors have also been shown to prevent early and late forms of colorectal neoplasia in rat models. Reddy et al. showed that administration of celecoxib inhibited aberrant colonic crypt foci (ACF) induction and multiplicity by about 40-49% in an azoxymethane-induced ACF rat model (81). Later the same investigators also showed that dietary administration of celecoxib can inhibit both the incidence and multiplicity of colon tumors by about 93 % and 97 %, respectively in the same rat model (82). Other researchers reported similar results with the Min mouse model (52). There is little data on human clinical trials with selective COX-2 inhibitors for colorectal tumor prevention. Recently Steinbach et al. conducted a double-blind, placebo-controlled study with 77 patients with FAP, and reported that treatment with celecoxib, a selective COX-2 inhibitor, for 6 mo led to a significant reduction (28%) in the number of colorectal polyps in these patients (50). Collectively, COX-2 nonspecific or specific NSAIDs appear to have chemopreventive activity against colorectal cancer development. Selective... 

The intramuscular injection of naked pDNA has also been evaluated for therapy of EAE, a mouse model of multiple sclerosis. The disease is induced in mice by s.c. injection of myelin basic protein (MBP) or proteolipid protein (PLP). In a recent study, mice were injected i.m. with pDNA encoding either IL-4/IgG or TGF / 48 hours prior to each MBP injection (on days zero and seven) (Piccirillo and Prud -homme, 1999). The disease severity was 70% lower in the IL-4/IgG or TGF / -treated mice and the mean clinical scores were significantly reduced in both groups. In addition, the IL-4 and TGF -treated mice had significantly reduced CNS inflammation, reduced T cell proliferative responses to MBP and low levels of the Th 1 cytokines IL-12 and IFN7. Thus, the pDNA therapy appeared to shift the mice to a Th2 response, which was therapeutic and reduced the severity of the disease. 

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