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.     

Exploration of developmental approaches to companion animal antimicrobials: providing for the unmet therapeutic needs of dogs and cats

AAVPT Workshop White Paper Committee. Exploration of developmental approaches to companion animal antimicrobials: providing for the unmet therapeutic needs of dogs and cats. J. vet. Pharmacol. Therap. 33 , 196–201. The American Academy of Veterinary Pharmacology and Therapeutics (AAVPT) and the United States Pharmacopeia (USP) co‐sponsored a workshop to explore approaches for developing companion animal antimicrobials. This workshop was developed in response to the shortage of antimicrobials labeled for dogs and cats, as there is a shortage of approved antimicrobials for the range of infectious diseases commonly treated in small animal practice. The objective of the workshop was to identify alternative approaches to data development to support new indications consistent with the unmet therapeutic needs of dogs and cats. The indications for currently approved antimicrobials do not reflect the broader range of infectious diseases that are commonly diagnosed and treated by the veterinarian. Therefore, the labels for these approved antimicrobials provide limited information to the veterinarian for appropriate therapeutic decision‐making beyond the few indications listed. Industry, veterinary practice, and regulatory challenges to the development of new antimicrobial indications were discussed. The workshop resulted in short‐ and long‐term recommendations. Short‐term recommendations focus on the use of additional data considerations for product labeling. Long‐term recommendations center on legislative or regulatory legal initiatives. The workshop recommendations will need collaboration from industry, academia, and regulatory authorities and a legal shift in the drug approval and availability processes.     

Sorption/desorption behaviour of sulfonylurea herbicides as affected by the addition of fresh and composted olive cake to soil

The olive industry generates residues which can be applied as amendments to soils in their original form (olive cake) or after composting or vermicomposting processes. The addition, fresh or incubated, of these amendments to soil and of their different organic fractions was studied in relation to the sorption/desorption of three sulfonylurea herbicides, bensulfuron‐methyl, chlorsulfuron and prosulfuron. Herbicide sorption was low or very low, slightly promoted by the addition of the agricultural by‐products, especially olive cake, and mainly affected by pH of the soil solution, with the organic carbon content having no significant effect on herbicide retention. Desorption was only reduced when fresh olive cake was added. The incubation of soil and amendments for 3 months did not modify herbicide sorption, but made desorption reversible except for olive cake. The transformation of the organic matter of the amendments due to humification and maturity processes are likely to be responsible for this behaviour. Different organic fractions were removed to assess the influence of each fraction on sulfonylurea sorption. Only the removal of all studied organic fractions increased herbicide sorption, revealing the role of humin and mineral fractions in this process. Therefore, the use of organic amendments is not useful for reducing the risk of movement of ionisable molecules in soil.     

Pharmacokinetics of lidocaine and its active metabolites in dogs

The pharmacokinetics of lidocaine in dogs were investigated following the intravenous and intramuscular administration of single doses of lidocaine hydrochloride. The mean elimination rate constant and the mean specific clearance determined for the intravenous portion of the study were 0.786 h^-1 and 2.40 1/kg/h, respectively. Following intramuscular administration the mean absorption rate constant was 7.74 h^-1. Absorption was nearly complete as the percentage of an intramuscular dose absorbed averaged 91.9%. Concentrations of two N-deethylated metabolites, determined following the administration of lidocaine suggest that monoethylglycinexylidide is eliminated rapidly while glycinexylidide is more slowly eliminated. The relative contribution of these metabolites to the therapeutic and toxic effects of lidocaine and the potential for glycinexylidide accumulation during lidocaine administration remain to be investigated.     

TOXIN-PRODUCING ASPERGILLUS ISOLATED FROM DOMESTIC PEANUTS

Nine species of fungi isolated from stored domestic peanuts were grown in the laboratory on sterilized peanuts and were incorporated into diets fed to ducklings. Symptoms of acute toxicity resulted only after consumption of one of the diets and this one contained material incubated with the fungus, Aspergillus flavus Link ex Fries.     

Ribonucleic acid: effect on conditioned behavior in rats

Acquisition of a behavioral response motivated by shock was enhanced in rats chronically treated with yeast ribonucleic acid, and resistance to extinction was greater in rats so treated than in controls. This extends the role of ribonucleic acid to include a behavioral effect in laboratory mammals treated with a purified preparation from yeast.