Drugs online research references
J Ocul Pharmacol. 1994 Winter;10(4):633-41.
Ocular pharmacokinetics of orally administered azithromycin in rabbits.
O'Day DM, Head WS, Foulds G, Robinson RD, Williams TE, Ferraina RA.
Department of Ophthalmology and Visual Sciences, Vanderbilt University School of Medicine, Nashville, Tennessee.
Azithromycin was orally administered to Dutch-belted rabbits following extracapsular lens extraction in one eye. At various times the animals were sacrificed, and serum and ocular tissues were obtained for drug level determination by HPLC-EC. Following a single dose, peak levels of drug in ocular tissues were measured within 8 hours (cornea > 0.5 micrograms/g [15mg/kg]; > 1.5 micrograms/g [3Omg/kg]). Highest levels were obtained in iris and ciliary body ( > 15 micrograms). Measurable tissue levels persisted for at least 120 hours. Trough levels increased proportionately during drug multiple dose administration. Five days following five daily 15mg/kg doses, corneal levels exceeded 0.5 micrograms/g, and iris and ciliary levels were higher than 15 micrograms/g. Aqueous humor and serum levels were equivalent. Vitreous humor levels, though higher than aqueous humor, were consistently < 1 microgram/ml. Extracapsular cataract extraction did not significantly affect drug uptake.
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J Antimicrob Chemother. 1994 Dec;34(6):931-42.
Profiles of outer membrane proteins and lipopolysaccharide of Pseudomonas aeruginosa grown in the presence of sub-MICs of macrolide antibiotics and their relation to enhanced serum sensitivity.
Tateda K, Ishii Y, Hirakata Y, Matsumoto T, Ohno A, Yamaguchi K.
Department of Microbiology, Toho University School of Medicine, Japan.
We have previously reported that erythromycin at sub-inhibitory concentrations enhanced the serum sensitivity of some Pseudomonas aeruginosa strains. To explore the mechanism of this effect, we have now examined the influence of macrolide antibiotics on outer membrane proteins and lipopolysaccharide (LPS) of P. aeruginosa. The strains S-6 and PAO-1 of P. aeruginosa were used as susceptible and resistant strains respectively to assess enhancement of serum sensitivity by erythromycin. The strain S-6 became more serum-sensitive when grown on agar with sub-MICs of erythromycin or azithromycin, but not of josamycin, whereas no change was observed in the serum sensitivity of the strain PAO-1 after growth with any of these antibiotics. The analysis of outer membrane proteins showed that erythromycin treatment resulted in a reduction in the amount of the 38 kDa protein (OprF) and in a prominent increase of 41 kDa protein band in the strain S-6, but not in the strain PAO-1. By an immunoblotting assay, this 41 kDa protein was shown to be highly reactive to the immune serum against untreated P. aeruginosa. LPS of the strain S-6 were examined by SDS acrylamide gel electrophoresis. The treatment with erythromycin or azithromycin, but not with josamycin, reduced the amounts of LPS species with lower molecular weights although the levels of LPS species with high molecular weights were similar to those of untreated bacteria. These results suggest that the enhanced serum sensitivity of P. aeruginosa by erythromycin is associated with changes in bacterial surface components, such as outer membrane proteins and LPS.
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J Antimicrob Chemother. 1994 Dec;34(6):989-99.
The effect of a single oral dose of azithromycin on chlamydial infertility and oviduct ultrastructure in mice.
Tuffrey M, Woods C, Inman C, Ward M.
Department of Microbiology, St Marys Hospital Medical School, London, UK.
Azithromycin has been recommended for the treatment of human chlamydial genital tract infections because of the sustained, chlamydicidal levels of the antibiotic which can be achieved after a single dose. The effect of single dose azithromycin on the prevention or reversal of chlamydial-induced damage to the oviduct or to fertility was assessed in a mouse model of chlamydial salpingitis which closely mimics the human disease. C3H mice were treated with progesterone and then inoculated under the ovarian bursa with a human genital tract isolate of Chlamydia trachomatis, serovar F. Azithromycin at doses from 135-250 mg/kg was administered by oral intubation. Morphological damage to the oviduct lumen was assessed by scanning electron microscopy, while fertility was assessed by breeding experiments. Treatment of mice two or seven days after infection with 135 mg/kg azithromycin completely reversed chlamydial-induced ultrastructural changes and infertility. Treatment 12 or more days after infection, at doses as high as 250 mg/kg, failed to prevent infertility. The onset of fertility correlated with the loss of ciliated epithelia from the oviduct. However, the regeneration of ciliated epithelia following azithromycin treatment did not necessarily restore tubal patency. These results, if true for women also, indicate the need for rapid, effective antibiotic therapy for chlamydial salpingitis to prevent infertility and other sequelae of tubal damage.
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