The effects of a variety of oxazolidinones, with different antibacterial potencies, including linezolid, on mitochondrial protein synthesis were determined in intact mitochondria isolated from rat heart and liver and rabbit heart and bone marrow. The results demonstrate that a general feature of the oxazolidinone class of antibiotics is the inhibition of mammalian mitochondrial protein synthesis. Inhibition was similar in mitochondria from all tissues studied. Further, oxazolidinones that were very potent as antibiotics were uniformly potent in inhibiting mitochondrial protein synthesis. These results were compared to the inhibitory profiles of other antibiotics that function by inhibiting bacterial protein synthesis. Of these, chloramphenicol and tetracycline were significant inhibitors of mammalian mitochondrial protein synthesis while the macrolides, lincosamides, and aminoglycosides were not. Development of future antibiotics from the oxazolidinone class will have to evaluate potential mitochondrial toxicity.

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Aim:  To analyse the growth of Bacillus anthracis during simulations of the UK anthrax vaccine manufacturing process. Methods and Results:  Simulated vaccine production runs were performed using the toxigenic, acapsulate Sterne 34F2 strain of B. anthracis in semi‐defined medium. After rising during the logarithmic growth phase, the pH of the culture starts to fall at about 18 h from pH 8·7 to reach <7·6 at 26 h, coincident with consumption of glucose and optimal production of protective antigen (PA; 7·89 g ml−1, SD 1·0) and lethal factor (LF; 1·85 g ml−1, SD 0·29). No increased breakdown of toxin antigens was seen over the 26–32 h period. When glucose was exhausted, amino acids (principally serine) were utilized as an alternative carbon source. Sporulation was not observed during the 32 h. Conclusions:  PA and LF, the principal constituents in the UK anthrax vaccine, undergo little degradation during vaccine fermentation. The vaccine manufacturing process is robust and reproducible. Significance and Impact of the Study:  This is the first detailed analysis of the manufacturing process used for the UK acellular anthrax vaccine; insight gained into the process will support continued and safe vaccine manufacture.

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Pregnant outbred albino (CD-1) mice received (gavage, three times a day in cottonseed oil) a xylene mixture (60.2% m-xylene, 9.1% o-xylene, 13.6% p-xylene, and 17.0% ethyl benzene) on d 6-15 of gestation (d 1 being the day vaginal plugs were observed). The mice were killed on d 18, the general and reproductive health of the dams evaluated, and the fetuses examined and processed to characterize external, visceral, and skeletal malformation. At 3.6 ml/kg.d, xylene killed 12 of 38 dams and caused a significantly (p less than 0.05) smaller average weight gain during pregnancy than did the vehicle (cottonseed oil). Fetuses from dams treated with xylene at 2.4 ml/kg.d and higher doses had average fetal weights significantly lower than that of the control fetuses. However, the percent of resorptions for xylene was significantly greater than for the control only at 3.6 ml/kg-d. At 2.4, 3.0, and 3.6 ml/kg-d xylene produced a significantly (p less than 0.01) greater average percent of malformed fetuses than did the control. Cleft palate was the major malformation at all three doses. When bilateral (multiple) wavy ribs were counted as a malformation, the average percent of malformed fetuses increased from 7.8 to 10.5 at 3.0 ml/kg.d and from 9.1 to 13.4 at 3.6 ml/kg.d. It is concluded that xylene (mixed isomers) is teratogenic to the CD-1 mouse at 2.4 and 3.0 ml/kg.d, doses approaching lethal levels.

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Pregnant outbred albino mice were given formaldehyde or Sonacide (potentiated acid glutaraldehyde) by gavage on days 6--15 of gestation. The mice were killed on day 18, the general health and reproductive status of the dam evaluated, and the fetuses examined and processed in order to characterize external, visceral, and skeletal malformations. Although formaldehyde (stock solution containing 12--15% methanol as a preservative) was lethal to 22 of 34 dams treated with 185 mg/kg/day, and one of 35 dams treated with 148 mg/kg/day, these doses did not produce statistically significant (two-sided p < 0.05 versus controls) teratogenic effects in the fetuses of the surviving dams. Sonacide was also judged not to be teratogenic to the mice employed in this study, in spite of the fact that relatively high doses were employed. The highest doses of Sonacide studied (5.0 ml/kg/day, which is equivalent to 100 mg/kg/day of glutaraldehyde) killed 19 of 35 dams and caused a significant reduction in the mean weight gain of the surviving mothers. In addition, this dose produced a significant increase in the number of stunted fetuses.