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Test D-methionine (D-met) as an otoprotectant from kanamycin-induced ototoxicity and determine the lowest maximally protective D-met dose.Auditory brainstem responses (ABR) were measured at 4, 8, 14, and 20 kHz at baseline and two, four, and six weeks after kanamycin and D-met administration initiation. ABR threshold shifts assessed auditory function. Following six-week ABR testing, animals were decapitated and cochleae collected for outer hair cell (OHC) quantification.Eight groups of 10 male pigmented guinea pigs were administered a subcutaneous kanamycin (250 mg/kg/dose) injection once per day and an intraperitoneal D-met injection (0 (saline), 120, 180, 240, 300, 360, 420, or 480 mg/kg/day) twice per day for 23 days.Significant ABR threshold shift reductions and increased OHC counts (p ≤ 0.01) were measured at multiple D-met-dosed groups starting at two-week ABR assessments. A 300 mg/kg/day optimal otoprotective D-met dose provided 34-41 dB ABR threshold shift reductions and OHC protection. Lesser, but significant, D-met otoprotection was measured at lower and higher D-met doses.D-met significantly reduced ABR threshold shifts and increased OHC percentages compared to kanamycin-treated controls. Results may be clinically significant particularly for multidrug-resistant tuberculosis patients who frequently suffer from kanamycin-induced hearing loss in developing countries.

This study tested multiple dosing epochs of pre-loaded D-methionine (D-met) for otoprotection from noise-induced hearing loss (NIHL).Auditory brainstem response (ABR) thresholds were measured at baseline, 1 day, and 21 days following a 6-hour 105 dB sound pressure level (SPL) octave band noise (OBN) exposure. Outer hair cell (OHC) counts were measured after day 21 sacrifice.Three groups of five Chinchillas laniger each were given a 2-day regimen comprising five doses of D-met (200 mg/kg/dose) intraperitoneally (IP) starting 2, 2.5, or 3 days prior to noise exposure. A control group (n = 5) received five doses of equivalent volume saline IP starting 2.5 days prior to noise exposure.ABR threshold shifts from baseline to day-21 post-noise exposure were reduced in all D-met groups versus controls, reaching significance (p0.05) in the 3-day group. D-met groups showed reduced OHC loss relative to controls at day-21 post-noise exposure, reaching significance (p0.05) at all frequency regions in the 3-day group and at the 2, 4, and 8 kHz frequency regions in the 2.5-day group.D-met administration in advance of noise-exposure, without further administration, significantly protects from noise-induced ABR threshold shift and OHC loss.

Background Tobramycin is a critical cystic fibrosis treatment however it causes ototoxicity. This study tested d-methionine protection from tobramycin-induced ototoxicity and potential antimicrobial interference. Methods Auditory brainstem responses (ABRs) and outer hair cell (OHC) quantifications measured protection in guinea pigs treated with tobramycin and a range of d-methionine doses. In vitro antimicrobial interference studies tested inhibition and post antibiotic effect assays. In vivo antimicrobial interference studies tested normal and neutropenic Escherichia coli murine survival and intraperitoneal lavage bacterial counts. Results d-Methionine conferred significant ABR threshold shift reductions. OHC protection was less robust but significant at 20kHz in the 420mg/kg/day group. In vitro studies did not detect d-methionine-induced antimicrobial interference. In vivo studies did not detect d-methionine-induced interference in normal or neutropenic mice. Conclusions d-Methionine protects from tobramycin-induced ototoxicity without antimicrobial interference. The study results suggest d-met as a potential otoprotectant from clinical tobramycin use in cystic fibrosis patients.

In order to obtain fertilized ova from White Leghorn chickens in the early cleavage stages, a nonsurgical procedure using prostaglandins (PG) was developed to induce premature oviposition of uncalcified eggs. The experimental design consisted of two 5 x 5 factorial arrangements of treatments using combinations of 0, .5, 1, 2, and 3 micrograms of PGF2 alpha and PGE1 or PGF2 alpha and PGE2. Frequency of PG-induced oviposition was highest (100%) with 1 microgram of PGF2 alpha and 3 micrograms of PGE1 or PGE2. Induced oviposition frequency decreased at the higher (2 and 3 micrograms of each PG) dosages. In general, induction time decreased as PG levels were increased; the minimum induction time was observed with injection of 3 micrograms of PGF2 alpha with 2 or 3 micrograms of PGE1 (1.8 min). There was a significant interaction for frequency of induced oviposition between PGF2 alpha and PGE1 (P less than .05), but not between PGF2 alpha and PGE2. There was also a significant interaction between PGF2 alpha and PGE2 (P less than .01) for induction time, which was not observed with PGF2 alpha and PGE1. Oviposition could not be induced earlier than 5 to 5.5 h after the previous oviposition. Prostaglandin-induced oviposition provides an alternative to euthanasia, surgery, or manual expulsion for collection of precalcified eggs in the early cleavage stages.