PubMed · 9118636
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B Santucci, C Cannistraci, E Camera, A Cristaudo, M Picardo. 1996. Thimerosal positivities.. https://doi.org/10.1111/j.1600-0536.1996.tb02422.x
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The solubilities in isopropyl myristate (S(IPM)) and pH 4.0 buffer (S(AQ)) and the partition coefficients between IPM and pH 4.0 buffer (K(IPM:AQ)) have been measured for a series of 1,3-bisalkylcarbonyl-5-fluorouracil prodrugs (1,3-AC-5-FU). The 1,3-AC-5-FU prodrugs were each over 500 times more soluble in IPM, but all members of the series, whose solubilities could be estimated, were much less soluble in pH 4.0 buffer than 5-FU. The abilities of the 1,3-AC-5-FU prodrugs to deliver total 5-FU species through hairless mouse skin from IPM suspensions (J(i)) were also measured. The 1,3-diacetyl derivative 2, which exhibited the highest S(AQ) in the series, gave the highest J(i) value. Although the series of 1,3-AC-5-FU prodrugs was generally effective at increasing J(i) (three to ten times), the best 1,3-AC-5-FU prodrug was not as effective as the best 1- or 3-alkylcarbonyl-5-FU prodrug (1- or 3-AC-5-FU) at increasing J(i) and their ability to increase the concentration of total 5-FU species in the skin was generally less than that of the 1-AC-5-FU prodrugs, but greater than that of the 3-AC-5-FU prodrugs. Thus, the 1-AC-5-FU prodrugs remain the best prodrugs with which to enhance the topical delivery of 5-FU.
A study was undertaken to compare the efficacy of recombinant interferon (rIFN)-alphaA to plasmid DNA encoding IFN-alpha1 against ocular herpes simplex virus type 1 (HSV-1) infection. The topical application of rIFN-alphaA (100-300 units/eye) onto the cornea of mice subsequently infected 24 h later with HSV-1 antagonized viral-induced mortality. The enhancement in cumulative survival in the rIFN-alphaA-treated mice correlated with a reduction of viral titers recovered in the eye and trigeminal ganglion (TG) at 3 and 6 days post-infection. The protective effect was site-specific such that when rIFN-alphaA was administered orally or intranasally, no efficacy against HSV-1 was observed. However, the protective effect was time-dependent. Specifically, when the rIFN-alphaA (100-1000 units/eye) was administered at 24 h post-infection, no protective effect was observed against HSV-1 compared to the vehicle-treated group. In contrast, plasmid DNA (100 microg/eye) containing the IFN-alpha1 transgene showed significant protection when topically applied 24 h post-infection. Although the transgene was found to traffic distal from the site of application (eye), including the trigeminal ganglion and the spleen where CD11b(+) and CD11c(+) cells express the transgene, the migration of the transgene did not correlate with efficacy. Collectively, the results suggest that naked DNA encoding type I IFN applied post-infection provides a greater degree of protection against ocular HSV-1 infection in comparison with recombinant protein effectively antagonizing viral replication and spread.
The effect of permethrin impregnated plastic strips (Die No Mite Strips) was evaluated on Dermanyssus gallinae populations in aviary systems for layers in Sweden. Two application strategies of the strips were tested: (A) attached in the housing system, allowing the birds to rub against the strips and thereby get the acaricide released onto their plumage, and (B) attached out of reach of the hens, at two different sites (perches and egg-belt lids) of the inner surfaces of the system, where the mites sheltered during the day. On two farms with 2030 (A) and 3384 (B) hens, and existing mite populations, strips were mounted for 20 and 10 weeks, respectively, and mite numbers were monitored by traps. With application A an overall mite reduction of 53% was observed, while with B the mean mite numbers decreased by 39% at the perches and 92% at the egg-belt lid. The strips were originally designed for caged hens afflicted by ectoparasites that stay on the host for most of their life cycle. However, since D. gallinae spends most of its time off the host, it was not possible to control the parasite with application A. Resistance tests performed on mites from both treated and control compartments where application A was used showed no indication of resistance to permethrin, while 95% of the mites survived a 48 h exposure to the compound where application B was performed. Thus, permethrin resistant mites appeared to be the main reason for the failure to control D. gallinae with application B.