Effect of lacrimal punctal occlusion on tear production and tear fluorescein dilution in normal dogs.

OBJECTIVE: To evaluate effects of lacrimal punctal plugs positioned in either the upper, lower, or combination of upper and lower lacrimal canaliculi on plug retention and tolerance; tear production, as measured by the Schirmer tear test; and the dilution of fluorescein within the tear film in normal dogs. MATERIAL AND METHODS: Lacrimal punctal plugs were positioned in the lower, upper, or combination of lower and upper plugs in six laboratory-quality Beagles under topical anesthesia. Retention of plugs was evaluated daily from 8 to 23 days by visual inspection and slit-lamp biomicroscopy. Schirmer tear tests (STT 1 without topical anesthesia) were performed at 48-h intervals. Dilution of fluorescein was determined at 5- and 45-min post-fluorescein instillations once weekly. RESULTS: Lacrimal punctal plugs of 0.4 and 0.6 mm in diameter were retained for 14 (lower plugs: 100%) and 23 days (75%), and for the upper plugs at 8 days less often (75%), and were infrequently locally nonirritating. Combination of lower and upper plugs seemed to adversely affect retention of either plug. When loss of the plugs occurred, a next larger size plug was necessary suggesting some stretching of the lacrimal canaliculi occurred. Pre- and postplug placement STT results indicated no change with lower and combination lacrimal punctal plugs, but decreased levels following upper lacrimal punctal plugs. Tear fluorescein levels at 5 and 45 min in control eye (no punctum plugs) were 3.39% and 0.14%, respectively. With lower, upper, and the combination of lower and upper lacrimal puncta plugs, tear fluorescein levels at 45 min were higher than the controls (lower: 0.76%; upper: 0.45%, and combination 0.56%). CONCLUSION: Lacrimal punctal silicone plugs are retained for 8-23 days in the lower, upper, and combined lower and upper canaliculi at high rates. Effects on STT levels appear limited. Fluorescein within the tear film persists longer with all different positioned lacrimal punctum plugs than in the control eyes.

Topoisomerase II inhibitors induce cleavage of nuclear and 35-kb plastid DNAs in the malarial parasite Plasmodium falciparum.

The topoisomerase II-specific inhibitors VP-16 and ciprofloxacin were used to investigate the presence of topoisomerase II activities associated with nuclear and 35-kb plastid DNAs of the malarial parasite Plasmodium falciparum. The eukaryotic topoisomerase II inhibitor VP-16 induced cleavage of both nuclear and 35-kb parasite DNAs. In contrast, ciprofloxacin, a fluoroquinolone drug known to act on the bacterial type II topoisomerase DNA gyrase, only induced cleavage of the Plasmodial 35-kb DNA. Drug-induced cleavage resulted in the protection of the 5'- but not 3'- ends of the cleaved nuclear and 35-kb DNAs from exonuclease digestion, suggesting that the 5'-ends of the broken DNA were protein-linked, a property reminiscent of DNA cleavage mediated by topoisomerase II enzymes. Furthermore, DNA cleavage induced by both VP-16 and ciprofloxacin was heat-reversible. This is the first evidence that P. falciparum contains two distinct topoisomerase II activities that are molecular targets for chemotherapeutic agents.