Water consumption and wastage behaviour in pigs: implications for antimicrobial administration and stewardship.

Daily water use and wastage patterns of pigs have major effects on the efficacy of in-water antimicrobial dosing events when conducted for metaphylaxis or to treat clinical disease. However, daily water use and wastage patterns of pigs are not routinely quantified on farms and are not well understood. We conducted a prospective, observational 27-day study of the daily water use and wastage patterns of a pen group of 15 finisher pigs reared in a farm building. We found that the group of pigs wasted a median of 36.5% of the water used per day. We developed models of the patterns of water used and wasted by pigs over each 24-h period using a Bayesian statistical method with the brm() function in the brms package. Both patterns were uni-modal, peaking at 1400-1700, and closely aligned. Wastage was slightly greater during hours of higher water use. We have shown that it is feasible to quantify the water use and wastage patterns of pigs in farm buildings using a system that records and aggregates data, and analyses them using hierarchical generalised additive models. This system could support more efficacious in-water antimicrobial dosing on farms, and better antimicrobial stewardship, by helping to reduce the quantities of antimicrobials used and disseminated into the environment.

Review: Water medication of growing pigs: sources of between-animal variability in systemic exposure to antimicrobials.

On many Australian commercial pig farms, groups of growing pigs are mass-medicated through their drinking water with selected antimicrobials for short periods to manage herd health. However, delivery of medication in drinking water cannot be assumed to deliver an equal dose to all animals in a group. There is substantial between-animal variability in systemic exposure to an antimicrobial (i.e. the antimicrobial concentration in plasma), resulting in under-dosing or over-dosing of many pigs. Three sources of this between-animal variability during a water medication dosing event are differences in: (1) concentration of the active constituent of the antimicrobial product in water available to pigs at drinking appliances in each pen over time, (2) medicated water consumption patterns of pigs in each pen over time, and (3) pharmacokinetics (i.e. oral bioavailability, volume of distribution and clearance between pigs and within pigs over time). It is essential that factors operating on each farm that influence the range of systemic exposures of pigs to an antimicrobial are factored into antimicrobial administration regimens to reduce under-dosing and over-dosing.

Comparison of magnetic resonance urography to dimercaptosuccinic acid scan for the identification of renal parenchyma defects in children with vesicoureteral reflux.

OBJECTIVE: The objective of this study was to compare the accuracy of dimercaptosuccinic acid (DMSA) renal scan to magnetic resonance urography (MRU) in the identification of renal parenchyma defects (RPD). MATERIALS AND METHODS: Twenty-five children with history of acute pyelonephritis and vesicoureteral reflux underwent DMSA scan and MRU to determine the presence of RPD. DMSA scans and MRUs were each evaluated by two radiologists and agreement achieved by consensus. Discordant DMSA-MRU findings were re-evaluated in a side-by-side comparison and an ultimate consensus reached. RESULTS: The ultimate consensus diagnosis was 18 kidneys with RPDs in 15 patients, of which five were classified as mild RPDs, six as moderate RPDs, and seven as severe RPDs. Although DMSA scan and MRU were similar in their ability to diagnose RPDs, MRU was considered to represent the true diagnosis in 11 of the 12 discordant cases in consensus review by four pediatric radiologists. MRU showed a much higher inter-observer agreement with a weighted kappa of 0.96 for both kidneys compared to 0.71 for the right kidney and 0.86 for the left kidney by DMSA scan. CONCLUSIONS: Our results suggest that MRU is superior to DMSA scan in the identification of renal parenchyma defects.

Epoxide ring opening and related reactivities of cyclopenta polycyclic aromatic hydrocarbons: quantum mechanical studies.

A series of 13 cyclopenta polycyclic aromatic hydrocarbons have been studied using quantum mechanical methods. The three-dimensional molecular structure of each carbocation that might result from the opening of a protonated epoxide ring formed between the carbon atoms completing the cyclopenta ring was computed with AM1. AM1 and ab initio calculations, using a split valence basis set, were then used to predict the direction of ring opening and obtain information about the reactivity of the carbocation. These calculations have shown that for all carbocations studied the cationic charge is well distributed throughout the molecule. The largest CH group charges are approximately 0.3 electron. If the protonated epoxide ring can open so that the nominal charge is on a CH group that is attached to the central ring of an anthracenic core, that carbocation will be greatly favored. For carbocations of this type, the unoccupied alpha' position (the CH group opposite the position of attachment to the anthracenic core) has as much or more of the cation charge as the nominally charged CH position. The group charges, and other properties related to electrostatic reactivity, clearly favor addition of nucleophiles at the unoccupied alpha' position over addition at the nominally charged position. However, when the addition of small nucleophiles at both of these positions is modeled for two such examples, the results favor addition at the nominally charged position in one case and are equivocal in the other case. The group charges and other reactivities considered characterize the electrostatic part of the interaction.(ABSTRACT TRUNCATED AT 250 WORDS)

Prediction of the reactivities of cyclopenta-polynuclear aromatic hydrocarbons by quantum mechanical methods.

1. The direction of epoxide ring opening may be predicted using the techniques of theoretical chemistry by comparing the computed total energy of the two possible carbocations formed. 2. To predict the direction of epoxide ring opening and the potential binding of aceanthrylene 1,2-epoxide to biopolymers, quantum mechanical calculations were performed on the two potential hydroxy carbocations. 3. The 2-hydroxy carbocation (II) was favoured over the 1-hydroxy carbocation by 11.8 kcal/mol. Molecule II had more positive charge at the meso carbon group than at the nominally charged 1 position. Both the lowest unoccupied molecular orbital and the molecular electrostatic potential confirm this result, and indicate the possibility of unusual adducts to biopolymers. 4. Similar calculations on the equivalent epoxides of acenaphthylene and acephenanthrylene do not show the same results. 5. Modelling the addition products of II with small nucleophiles indicates that these unusual addition products do not form, and that the interaction is controlled by electronic effects and not electrostatic effects. 6. The calculations on acephenanthrylene demonstrate the importance of including the hydroxyl group when making predictions relative to epoxide ring opening. 7. Molecular descriptors are surrogates for the interaction of that molecule with an often unknown biological target. In cases where molecular descriptors are used without information about the target, small quantitative differences may not be appropriate discriminators.

Quantum mechanical studies of the structure and reactivities of the diol epoxides of benzo[c]phenanthrene.

Benzo[c]phenanthrene has a crowded bay region that has been called a fjord region. As a result of the interaction between the atoms across the fjord region, it is a nonplanar molecule with a significant barrier between two helical structures. The crowding in the fjord region also affects the three-dimensional structure of the fjord region diol epoxide. Quantum mechanical studies have been performed to determine the structure and reactivities of the fjord region diol epoxides. Eight local minimum energy three-dimensional structures have been found for the trans diol of 1,2,3,4-tetrahydro-3,4-dihydroxybenzo[c]phenanthrene 1,2-epoxide. They can be characterized by three dichotomies: one between syn and anti, one between quasidiaxial and quasidiequatorial, and the third that depends on nonplanarity of the parent polycyclic aromatic hydrocarbon due to interactions in the crowded bay region, that we have named "in" and "out" based on the position of the epoxide oxygen relative to the distal ring. The structures with the epoxide oxygen on the same side of the saturated ring as the distal ring (in-) are more stable than the structures where the epoxide is on the opposite side (out-). The calculated lowest energy syn and anti structures for the diol epoxide of benzo[c]-phenanthrene are both in-quasidiequatorial, in agreement with experiment. Analysis of the results indicates that the electrostatic interaction across the fjord region could be responsible for the increased stability of the syn-in-quasidiequatorial structure compared to the syn-in-quasidiaxial structure and the stability of the in- structures in general when compared to the out- structures.(ABSTRACT TRUNCATED AT 250 WORDS)