In vitro metabolism of EPN and EPNO in susceptible and resistant strains of house flies

EPN is twice as toxic as EPNO to house flies from both the Diazinon-resistant strain and the susceptible strain. EPN and EPNO are also eight times more toxic to the susceptible than the resistant strain. This is due to the ability of the resistant strain to metabolize these compounds to a greater extent. Metabolism by the glutathione S-transferases present in the 100,000g supernatant is more extensive than that by the NADPH-dependent microsomal mixed-function oxidases. The glutathione S-transferases are the major route of metabolism for EPN and appear to be the principal mechanism conferring resistance. EPN was metabolized by the microsomal fraction via oxidative desulfuration to the oxygen analog, EPNO, and by oxidative dearylation to p-nitrophenol. EPNO was metabolized by the same system to p-nitrophenol and desethyl EPNO as well as to an unknown metabolite. The soluble fraction metabolized EPN to p-nitrophenol, S-(p-nitrophenyl)glutathione, O-ethyl phenylphosphonothioic acid, and S-(O-ethyl phenylphosphonothionyl)glutathione. The identification of the latter conjugate demonstrates a new type of metabolite of organophosphorus compounds. EPNO was metabolized by the soluble fraction to p-nitrophenol and S-(p-nitrophenyl)glutathione.     

Spectral interactions of insecticide synergists with microsomal cytochrome P-450 from insecticide-resistant and susceptible house flies

The spectral interactions of 45 insecticide synergists and related compounds with oxidized and reduced cytochrome P-450 from microsomes of insecticide-resistant and -susceptible house flies were investigated. The type III interaction typical of piperonyl butoxide was the most common spectral interaction for the compounds studied. In addition to this, several other varients of the type III interaction were noted. In general these responses with house fly microsomes were similar to those reported for mammals, although some minor species and strain differences were observed. The cytochrome P-450 from susceptible house flies, although reported previously not to exhibit type I difference spectra with many xenobiotics, was found to elicit this spectral response with several methylenedioxyphenyl compounds.     

Biochemical genetics of oxidative resistance to diazinon in the house fly

The genetics and biochemistry of oxidative resistance to diazinon were investigated in a diazinon-resistant strain of the house fly, Musca domestica L. The resistant strain was crossed with a multimarker susceptible strain and substrains containing portions of the resistant strain genome were prepared. Resistance, microsomal oxidase, and cytochrome P-450 spectral characteristics were then compared in the different strains. The major gene for resistance to diazinon is semidominant and is located on chromosome II, 13 crossing over units from the recessive mutant stubby wing. Additional resistance genes occur on chromosome II and on other chromosomes as well. Resistance to diazinon was introduced into a susceptible mutant-marked strain via genetic crossing over. Increases in parathion oxidase, total and P-450-specific N- and O-demethylase activity, and resistant strain type I binding spectrum were introduced along with resistance, indicating genes controlling these parameters and resistance are either identical or closely linked. No increase in activity of cytochrome P-450 itself was introduced into the mutant strain. Additional genes controlling the amount of cytochrome P-450 and several spectral changes characteristic of the resistant strains are apparently controlled by genes located at different loci on chromosome II. Resistance factors on other chromosomes are also present, but were not characterized.     

Comparison of tracheal aspirates before and after high-speed treadmill exercise in racehorses

OBJECTIVE: To determine whether percentages of neutrophils in tracheal aspirate (TA) samples collected from racehorses are increased after exercise and whether interpretation of results from TA samples taken before and after exercise agree. DESIGN: Case series of 40 young Thoroughbred and Standardbred racehorses in race training presented for evaluation of poor performance. PROCEDURE: TA samples were collected endoscopically from racehorses presented for poor performance 24 h before and 1 to 2 h after high speed treadmill exercise testing. Aliquots of the retrieved fluid were cytocentrifuged and smears were stained with Diff-Quik. Mean neutrophil counts were expressed as percentages of the total number of inflammatory cells counted and subsequently were categorised as either above or below an accepted cut-off of 20%. Comparisons between percentages of neutrophils before and after exercise were made. RESULTS: Percentage of neutrophils from TA samples obtained from racehorses after exercise was significantly higher than neutrophil percentages from TA samples collected from the same horse before exercise. In horses with TA specimens that were categorised as having < or = 20% neutrophils before treadmill exercise, the percentage of neutrophils in their TA specimens after exercise was, on average, significantly higher and was greater than the cut-off value of 20%. CONCLUSION: Recent strenuous exercise may change the proportion of neutrophils in lower airways of racehorses and practitioners should be aware of this when collecting and interpreting the results from TA samples. The most practical time for collection of a TA sample to obtain the most diagnostically useful information might be after a suitable washout period of at least 1 to 2 h post-exercise.     

Metal Mine Tailings and Sludge CO-Deposition in a Tailings Pond

In the Lower Cell of the Heath Steele mine tailings arealocated 50 km north of the city of Miramichi, New Brunswick,Canada, tailings and lime treatment sludge were co-depositedand the effluent occasionally exceeded regulatory dischargelimits for total suspended solids (TSS), especially on verywindy days. A combined field and laboratory investigationwas undertaken during 1998-1999 to identify the cause of thehigh TSS. The methodology included field measurement of windvelocity and sampling of bed tailings, sludge,suspended sediment, and the water cover. The samples werethen subjected to various laboratory examinations using x-raydiffraction, scanning electron microscopy interfacedwith energy dispersion x-ray spectroscopy, critical shearstress measurements, and water chemistry analysis. Thesuspended sediment was found to be composed primarily ofcalcite and metal hydroxides derived from the bed sludge inthe cell. Only a very small amount of tailings (less than5%) was detected in the suspended sediment. The sludge,which covered the tailings in the shallow western section ofthe Lower Cell at depths less than 1 m, was a loose, low-densitymaterial with a low critical shear stress (approximately 0.058 Pa). In shallow water cover (less than 1 m), calculated bed shearstress mobilized by wind-induced waves and return currents exceeded the critical shear on a number of occasions, resultingin resuspension of the sludge and hence high TSS. Although occasional elevated zinc concentrations appeared to follow a similar pattern to high TSS, there was no evidence that thesuspended sludge sediments would release metals into the watercover, due to the high pH of the Lower Cell water cover. Since the tailings did not resuspend significantly, it was clear thatat water cover depth less than 1 m, sludge was eroded instead oftailings, and thus provided a barrier against tailings resuspension. As part of the final closure scheme for the HeathSteele tailings area, sludge and tailings were dredged and relocated from areas where the water cover was < 1 m to deeperwater cover areas to ensure that the effluent met required totalsuspended solids discharge criteria.     

Coughing in thoroughbred racehorses: risk factors and tracheal endoscopic and cytological findings

A matched case-control study was made of 100 thoroughbred horses which were coughing and 148 control horses which were free of clinical signs of respiratory tract disease. The variables identified by multivariable conditional logistic regression as being significantly associated with coughing included age (the risk decreased with age), the stage of training (horses in early training were at greatest risk), the time since the last race (horses that had never raced were at greatest risk) and the time since they were last transported (horses transported more than 14 days previously were more likely to cough than those transported within the last week). The coughing horses were significantly more likely to have high scores for upper and lower tracheal mucus and pharyngeal lymphoid hyperplasia. In addition, the tracheal aspirates of the coughing horses had increased odds of neutrophilia and were more likely to have intracellular bacteria than the control horses. However, a considerable proportion of the control horses had cytological and/or endoscopic evidence of airway inflammation.