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A number of substituted imidazo[1,2-a]pyridines and related analogues were selected for biochemical characterization in vitro against both the purified gastric proton pump enzyme, H+/K(+)-ATPase, and the intact gastric gland. The inhibitory activity in these two in vitro models was then examined for correlation with the gastric antisecretory potency determined for these compounds in vivo by using the histamine-stimulated Heidenhain pouch dog. Analysis of the biological data suggested that the inhibitory activity of the analogues determined in two in vitro models is predictive of their in vivo gastric antisecretory activity following intravenous, but not oral, administration. Furthermore, the good correlation observed between the in vitro and in vivo models suggests that these compounds are gastric proton pump inhibitors in vivo. A molecular modeling study of these compounds using the active analogue approach has defined the molecular volume which is shared by the active analogues, as well as the molecular volume which is common to the inactive analogues. Graphical representation of the difference between these molecular volumes can be interpreted in terms of a hypothetical description of the pharmacophore by means of which 3-(cyanomethyl)-2-methyl-8-(phenylmethoxy)imidazo[1,2-a]pyridine, Sch 28080 (1) and its analogues interact with the gastric proton pump enzyme, H+/K(+)-ATPase.

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This series of cases demonstrated a statistically significant reduction of pocket depths and gain of attachment and bone after 8 and 16 months with no difference between the 2 preparations.

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The data suggest that the cartilage changes after meniscectomy in this animal model are caused by the surgical trauma, subsequent limb misuse, and altered load distribution, and initially associated by a decrease not an increase in bone mineral density of the proximal tibia. Moreover, the cartilage changes progressed without a simultaneous increase of the bone mineral density at corresponding sites.

The purpose of this study was to compare weightbearing radiographs with histologic cartilage evaluation in a rabbit meniscectomy model of the early stage of osteoarthrosis. Fifteen rabbits had a medial meniscectomy performed in one knee and a sham operation in the other knee. Five rabbits each were sacrificed at 13, 25, and 40 weeks after surgery. Radiographic joint space width and histologic cartilage changes of the medial knee compartment were quantified. Five non-operated knees and five knees in which the meniscus had been removed immediately before the evaluations served as control specimens. Overall, the joint space of the peripheral part of the medial knee compartment was narrower in knees operated on for meniscus removal than in sham-operated knees (P < 0.003). In the knees with the meniscus removed, more cartilage changes were seen at the joint surface area of contact on radiographs than in the sham-operated knees (P < 0.0015). Indeed, the area of contact had cartilage changes similar to those in the whole medial compartment. However, there was no correlation between the degree of histologic cartilage change and the corresponding joint space measurements. Joint space width as measured on weightbearing radiographs is reduced after meniscectomy in the rabbit, but it does not reflect the degree of cartilage damage of the loaded joint surfaces in early stages of osteoarthrosis.