Disposition of 3H-selamectin and 3H-ivermectin in the brain of the cat flea Ctenocephalides felis felis using micro-image analysis

In addition to intrinsic potency and metabolic stability, the disposition of an antiparasitic drug within the target parasite plays a major role in determining drug activity. A novel technique that allows the disposition of radiolabelled drugs to be visualised within the body of the cat flea (Ctenocephalides felis felis) is described. The concentrations of two macrocyclic lactones, (3)H-selamectin and (3)H-ivermectin, within the supra- and sub-oesophageal ganglia of the flea brain following in vitro feeding of fleas on different doses of drug solubilised in calf blood have been measured. Drug disposition was visualised in cryostat sections of fleas using a micro-image analysis (MIA). A relationship between the concentration of radioactivity in the ganglia and the dose of drug in the blood meal was obtained. The concentration of selamectin in the ganglia was significantly higher than ivermectin at all doses investigated. The enhanced concentration of selamectin, at a site rich in glutamate-gated chloride channels may, in part, explain the higher potency of selamectin against fleas compared to ivermectin.     

Dose–Response Studies for Pituitary and Testicular Function in Male Dogs Treated with the GnRH Superagonist, Deslorelin

We tested the effect of dose of GnRH superagonist on pituitary and testicular function in a study with four groups of four male dogs. The Controls received blank implants and the other three groups received implants containing 3, 6 or 12 mg deslorelin (d ‐Trp⁶‐Pro⁹‐des‐Gly¹⁰‐GnRH ethylamide). In all deslorelin‐treated groups, there was initially an acute increase in plasma concentrations of LH and testosterone, followed by declines such that both hormones became undetectable after approximately 12 days. There was a dose–response in some of these early aspects of the hormone profiles. With respect to long‐term effects of treatment, the 12‐mg dose had significantly greater effects than the smaller doses for the duration of minimum testicular volume [366 ± 77, mean ± SEM (3 mg), 472 ± 74 (6 mg), and 634 ± 59 (12 mg) days], absence of ejaculate [416 ± 88 (3 mg), 476 ± 83 (6 mg), and 644 ± 67 (12 mg) days], undetectable plasma concentrations of LH and testosterone [367 ± 64 (3 mg), 419 ± 72 (6 mg), and 607 ± 69 (12 mg) days], the delay until complete recovery of LH and testosterone secretion [394 ± 65 (3 mg), 484 ± 72 (6 mg) and 668 ± 47 (12 mg) days], and the delay until testes had regrown to normal volume [408 ± 77 (3 mg), 514 ± 74 (6 mg), 676 ± 59 (12 mg) days]. The time taken to restore full ejaculates was also longest for the 12‐mg dose: 716 ± 67 (12 mg) days vs 440 ± 66 (3 mg) and 538 ± 83 (6 mg) days after implantation. There was no correlation between delay to recovery of normal ejaculate quality and body mass. We conclude that the dose–response relationship with deslorelin implants is not expressed with respect to the degree of suppression of reproduction, but on the maximum duration of suppression and thus to delay until recovery.     

Impacts on Streams from the Use of Sulfur-Based Compounds for Dechlorinating Industrial Effluents

We evaluate environmental impacts associated with sulfur-baseddechlorinating agents (sodium bisulfite and sodium thiosulfate)commonly used in industrial wastewater treatment by presentingdata from two examples for Department of Energy facilities inTennessee and Kentucky. One case involved a fish kill (> 24,000 fish) caused directly by sodium bisulfite; the second describes a near-miss situation resulting from over-dosing with sodium thiosulfate. Toxicity tests showed that overfeed situations withsodium thiosulfate or sodium bisulfite can depress pH and dissolved oxygen, causing mortality of fish. Bacteria also can metabolize some sulfur-based dechlorinating agents, thereby increasing the potential for reductions in pH and concentrationsof dissolved oxygen. Although removing toxic levels of chlorine is important when releasing chlorine-containing wastewaters to aquatic systems, waste-treatment plant operators should also beaware of significant impacts that can occur if sulfur-based dechlorinating agents are used to excess.     

Novel chemotaxonomic markers of the Alternaria infectoria species-group

Two new structurally related metabolites, novae-zelandin A (1) and novae-zelandin B (2), as well as the novel metabolite 4Z-infectopyrone (3) were purified from extracts of filamentous fungi belonging to the Alternaria infectoria species-group. The structures were elucidated by a combination of 1D and 2D NMR spectroscopic data and MS data. 1-3 are important chemotaxonomic markers of the A. infectoria species-group and exhibit structures similar to those of known biologically active compounds, suggesting that they could be potential phytotoxins.