Free fatty acohols have been established as lipid components of E. coli K-12. Using combined gas liquid chromatography-mass spectrometry, the major alcohols in aerobically grown cells were identified as 1-tetradecanol (18%), 1hexadecanol (28%), 1-octadecanol (14%), and 2 -p e n t a d e c a n o l (27%). Small amounts of 1-hexadecenol (3%), 2-tridecanol (8%), and 2-tetradecanol (1.5%) were also detected. Analysis of anaerobically grown cells has shown a selective decrease of the secondary alcohols. 2-Pentadecanol was present as only 7% of the total alcohol fraction, and only traces of 2-tridecanol and 2-tetradecanol were found. The major alcohols in anaerobic cells were 1-tetradecanol, 1-pentadecanol, 1-hexadecenol and 1-hexadecanol. The above observations strongly suggest two pathways for the synthesis of fatty alcohols in E. coli..One pathway synthesizes the primary alcohols and does not require molecular oxygen, and a separate pathway synthesizes the secondary alcohols and has a requirement for molecular oxygen.
This study was initiated to determine whether a comparative pharmacokinetic (PK) approach could be used to expand the pool of approved anthelmintics for minor ruminant species. Accordingly, the PK profiles of six anthelmintics (levamisole, albendazole, fenbendazole, moxidectin, doramectin, and ivermectin) in sheep, goats, and cattle were determined. The PK values determined for each anthelmintic included Tmax, Tlast, Cmax, AUC, AUC/dose, and Cmax/dose. The results of this study demonstrate that a comparative PK approach does not show commonality in the way these six anthelmintics are individually processed by these three ruminants. While some drugs demonstrated identical PK profiles between sheep and goats, none of these drugs demonstrated PK profiles in sheep and goats comparable to the PK profiles found in cattle. The results from this study suggest drug approval across these three ruminants is not a viable concept. However, the resulting PK profiles for each combination of drug and ruminant species represents a new dataset that can be used to support the US FDA Center for Veterinary Medicine's Minor Use/Minor Species indexing process for drug approvals in minor species such as sheep and goats.
Eighteen Holstein dairy cows ranging in body weight from 500-700 kg and with an average milk yield of 37 ± 6 kg/day were used to investigate the depletion of florfenicol (FFL) in milk and plasma of dairy cows. Three groups of six were administered FFL: Group A, intramammary (IMM) infusion of ~2.5 mg FFL/kg BW at three consecutive milking intervals (total amount of ~7.5 mg/kg BW); Group B, one IMM infusion (20 mg/kg BW) into one quarter and Group C, one subcutaneous (SC) treatment (40 mg/kg BW). IMM infusions were into the right front quarter. Cows were milked daily at 06:00 and 18:00 h. The highest concentrations (C ) and time to C (T ) were: 1.6 ± 2.2 μg·FFL/mL milk at 22 h (Group A), 5.5 ± 3.6 μg·FFL/mL milk at 12 h (Group B), and 1.7 ± 0.4 μg·FFL/mL milk at 12 h (Group C). The half-lives (t ) were ~19, 5.5, and 60 h, for Groups A, B, and C, respectively. FFL was below the limit of detection (LOD) by 60 h in three Group B cows, but above the LOD at 72, 84, and 120 h in three cows. FFL was above the LOD in milk from Group C's cows for 432-588 h. Plasma values followed the same trends as milk. The results demonstrate that IMM-infused FFL is bioavailable and below the LOD within 72-120 h. The concentration of FFL was detectable in both plasma and milk over the course of 2-3 weeks after SC administration. The absence of residue depletion data presents problems in determining safe levels of FFL residues in milk and edible tissues. The data presented here must not be construed as approval for extra-label use in food animals.
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