Comparative effects of tetrandrine and berbamine on subcutaneous air pouch inflammation induced by interleukin-1, tumour necrosis factor and platelet-activating factor

The effects of the bisbenzylisoquinoline alkaloids tetrandrine and berbamine on the action of IL-1, TNF and PAF were investigated in the rat subcutaneous air pouch model of inflammation. Both compounds were equipotent in the suppression of leukocyte infiltration into air pouches induced by IL-1 and TNF, with ED₅₀ values in the range 20–30 mg/kg/3 days. Both were also equiptent in suppression of PMN infiltration induced by PAF with ED₅₀ values in the same range as that for IL-1 and TNF. However, tetrandrine was more potent than berbamine as a suppressant of PAF-induced MNC infiltration, but much less potent than berbamine in carageenen-induced PMN infiltration. These results suggest that these bisbenzylisoquinolines may have value in the therapy of chronic inflammatory diseases where IL-1, TNF and PAF have a role in pathogenesis.     

Effect of twenty-three chemotherapeutic agents on the adherence and growth of Giardia lamblia in vitro

The sensitivity of Giardia lamblia to 23 chemotherapeutic agents was evaluated in vitro with a Growth Inhibition Assay and a recently developed Adherence Inhibition Assay. Of the four established anti-giardia drugs, tinidazole, metronidazole, and furazolidone were found to have strong inhibitory effects on both growth and adherence, while mepacrine had a strong effect on growth only. Three drugs (mefloquine, doxycycline and rifampin) not previously used in giardiasis were found to have significant activity in vitro and may deserve consideration for clinical evaluation of efficacy. Also, the concurrent use of these two in vitro methods provided significant insights into the modes of action of some of these drugs on G. lamblia.     

Identification of cathepsin C mutations in ethnically diverse papillon-Lefèvre syndrome patients

INTRODUCTION—Papillon-Lefèvre syndrome (PLS) is an autosomal recessive disorder characterised by palmoplantar keratoderma and severe, early onset periodontitis, which results from deficiency of cathepsin C activity secondary to mutations in the cathepsin C gene. To date, 13 different cathepsin C mutations have been reported in PLS patients, all of which are homozygous for a given mutation, reflecting consanguinity.
AIM—To evaluate the generality of cathepsin C mutations in PLS, we studied an ethnically diverse group of 20 unrelated families.
METHODS—Mutations were identified by direct automated sequencing of genomic DNA amplified for exonic regions and associated splice site junctions of the cathepsin C gene. Long range PCR was performed to determine the genomic structure of the cathepsin C gene.
RESULTS—The cathepsin C gene spans over 46 kb, with six introns ranging in size from 1.6 to 22.4 kb. Eleven novel mutations and four previously reported mutations were identified in affected subjects from 14 families. Missense mutations were most common (9/15), followed by nonsense mutations (3/15), insertions (2/15), and deletions (1/15). Among these 14 probands, two were compound heterozygotes. Affected subjects with transgressions of the dermal lesions onto the knees or elbows or both had mutations in both the pro- and mature regions of the enzyme, although most were in the mature region.
CONCLUSION—Mutations in the mature region of cathepsin C were more likely to be associated with the transgressions of the dermatological lesions, although the results were not statistically significant. A comprehensive list of all cathepsin C mutations described to date, representing 25 mutations from 32 families with PLS and related conditions, is also presented.


Keywords: cathepsin C; genetics; severe early onset periodontitis; hyperkeratosis