Laminins are a large family of heterotrimeric basement membrane molecules that mediate crucial cell functions such as adhesion, proliferation, migration, and differentiation. Up to now, three distinct laminins have been identified in the normal human small intestinal epithelium. Laminin-1 (alpha1beta1gamma1) and laminin-5 (alpha3beta3gamma2) are mainly expressed at the base of villus cells, whereas laminin-2 (alpha2beta1gamma1) is restricted to the bottom of the crypts. The expression of these molecules has not yet been studied in Crohn's disease (CD), but it could be altered, in light of the important changes occurring in the architecture of the crypt-villus axis under the active state of the disease. To test this hypothesis, the expression of laminin alpha1, alpha2, and alpha3 subunits was analyzed in control, inflamed, and corresponding uninflamed CD small intestinal specimens by indirect immunofluorescence and reverse transcriptase-polymerase chain reaction. Surprisingly, alpha1 and alpha3 remained strongly expressed by all villus cells, whereas alpha2, normally expressed in the bottom of the crypts in control and uninflamed CD specimens, was lacking in inflamed CD specimens. However, this loss of alpha2 expression was associated with a significant up-regulation of both alpha1 and alpha3 expression in the crypts of inflamed CD specimens. A significant up-regulation of the alpha1 subunit was also observed in the crypts of uninflamed CD specimens. At the transcript levels, alpha1 was found significantly higher in inflamed than uninflamed CD specimens. Taken together, these observations identify important alterations in laminin expression in the small intestine with CD and suggest that compositional changes in the epithelial basement membrane may play a role in this disease.

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The activities of various compounds isolated from plants traditionally used against leishmaniasis in populations from the tablelands of the Guyanas have been examined. The leishmanicidal activity of plant extracts was evaluated by in uitro testing on promastigote and amastigote stages of Leishmania amazonensis and by in uiuo tests on L. amazonensis in mice. The leaves of Jacaranda copaia (Aublet) D. Don yielded two compounds: ursolic acid and jaracanone. Ursolic acid showed an interesting activity in uitro with an ED-against amastigotes of 0.02mM and no toxicity to macrophages at twice this dose. Jacaranone displayed a marked activity against promastigotes in uitro with an ED-of 0.02 mM. Both compounds have weak in uiuo antileishmanial activity. Similar synthetic compounds such as quinol and quinone acetates were prepared and showed increased activity in experimental cutaneous leishmaniasis in mice.