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Biomedical subjects

L M Gregory

Publications and source records attributed to L M Gregory.

11 recordsLinked to original sources
PubMed2001

Systemic activity of the avermectins against the cat flea (Siphonaptera: Pulicidae).

Ivermectin has potent systemic activity against numerous species of nematodes and arthropods, but there are some important species in these two groups, such as the cat flea, Ctenocephalides felis (Bouché), that appear to be refractory to it. In an effort to determine if the lack of systemic activity against C. felis is specific to ivermectin, or if it is a class-wide phenomenon, 20 avermectin derivatives were tested in an artificial membrane flea feeding system at concentrations of 20, 10, and 1 microg/ml. Results showed that ivermectin had LC90 and LC50 values against fleas of 19.1 and 9.9 microg/ml, respectively. Only four of the other 19 compounds evaluated possessed both LC90 and LC50 values more potent than ivermectin and even then the advantage was modest. Among those four compounds was a two-fold increase in potency relative to ivermectin when the LC90 values were considered (range, 9.2-10.3 microg/ml) and a two- to eight-fold increase when the LC50 values were examined (range, 1.23-5.26 microg/ml). Neither the possession nor the number of oleandrosyl sugars on the macrocyclic backbone were relevant for additional flea activity because among these four compounds were two disaccharides, a monosaccharide and an aglycone. Also, bond disposition between C-22 and 23 did not contribute to increase in activity because these molecules comprise members with either single or double bonds. One of these avermectin analogs was scaled-up and tested subcutaneously in a dog at >100 times the commercial ivermectin dosage and zero efficacy was observed against the flea. We conclude that even the best in vitro avermectin does not have the in vivo potential to become a commercial oral or subcutaneous flea treatment for companion animals.

Animals↗
PubMed2001

Systemic efficacy of nodulisporic acid against fleas on dogs.

Nodulisporic acid A (NSA) is a novel natural product from a new structural class that was shown previously to have insecticidal activity against blowfly larvae. To determine if there was useful systemic efficacy against fleas (Ctenocephalides felis). NSA was evaluated in an artificial membrane flea feeding device and in dogs. In the artificial membrane flea feeding device, adult C. felis were allowed to feed on bovine blood containing various concentrations of NSA through a Parafilm membrane. NSA killed the fleas with a 50% lethal concentration of 0.68 microg/ml and was approximately 10-fold more potent than the systemic insecticide ivermectin. In the initial probe dog test, a single beagle was challenged with 100 C. felis before oral dosing with 15 mg/kg of NSA. Flea counts conducted at 72 hr postdosing showed an 88% reduction relative to control. Re-challenge of the same dog at 5 days postdosing showed 50% reduction of fleas at day 7, demonstrating some residual flea activity. In a confirmatory study, 8 dogs were challenged with 100 fleas just before oral dosing with 15 mg/kg of NSA (4 dogs) or vehicle (4 dogs). There was 99% reduction of fleas at 48 hr postdosing in the NSA-treated dogs relative to control. Additional challenges with 100 fleas were performed on these 8 dogs at 48-hr intervals to determine the duration of efficacy, and there was 97, 51, and 0% reduction of fleas relative to control on days 4, 6, and 8, respectively. No adverse effects were observed in the dogs in these studies. These data show that NSA has potent oral activity in the dog for the control of fleas, while lacking overt mammalian toxicity.

Administration, Oral↗
PubMed2001

Systemic efficacy of nodulisporamides against fleas on dogs.

Nodulisporic acid A (NSA) has been shown previously to be safe in dogs and to deliver >90% flea control for 4 days following a single oral administration. Three newly prepared nodulisporamide derivatives were subsequently identified from an artificial membrane flea feeding system as exhibiting potency substantially greater than NSA. To determine if they have superior in vivo activity, these 3 nodulisporamides, as well as NSA, were evaluated in dogs at 15 mg/kg/os. Parasite challenges were made by placing 100 live Ctenocephalides felis fleas onto the dorsum of dogs every 48 hr and examining efficacy at each of those intervals over a 22-day period. Results showed that NSA produced >90% efficacy at day 2 and 81% efficacy at day 4, and its residual flea killing fell to approximately 50% by day 6 posttreatment. All dogs treated with the 3 new experimental nodulisporamides were 100% protected from flea challenges to day 8 posttreatment, and 2 of the compounds continued to produce >90% residual activity to 2 wk posttreatment. Pharmacokinetic analysis showed that plasma profiles and half-lives of NSA and these 3 new compounds correlated closely with flea efficacy. These results demonstrate that specific substitutions to the pharmacophore of NSA can substantially increase the duration of activity against fleas.

Administration, Oral↗
PubMed2000

Development of an assay for the screening of compounds against larvae of the cat flea (Siphonaptera: Pulicidae).

Larvae of the cat flea, Ctenocephalides felis (Bouché), are the target of numerous growth regulators. This study explores the development of an assay that tests the susceptibility of cat flea larvae to a wide range of compounds. Different rearing media and containment units were tested that would facilitate optimization. Larvae of various ages were compared, and 7-d-old larvae were found to be optimal because they were the most uniform in size and age and exhibited a need to feed. The assay could be used to distinguish insecticides from growth inhibitors. The insecticides chlorpyrifos and carbaryl caused 100% larval mortality in 24 h at 10 ppm, and cythioate and fipronil killed the larvae at concentrations of > or = 100 ppm within 24 h. The insect growth regulators methoprene and pyriproxifen caused molt delay at concentrations of 100 ppm and bioallethrin delayed molt at 1,000 ppm. This assay can be used to identify compounds that are specific to cat flea larvae that may be useful in the control of cat flea infestations.

Animals↗
PubMed1997

The 9-arginine residue of alpha-conotoxin GI is responsible for its selective high affinity for the alphagamma agonist site on the electric organ acetylcholine receptor.

The two agonist-binding domains of the electric organ nicotinic acetylcholine receptor are located at the alphagamma and alphadelta subunit interfaces. alpha-Conotoxins GI and MI are competitive antagonists of this receptor and, like d-tubocurarine, bind to the alphagamma site with much higher affinity than to the alphadelta site. In the present study, alpha-conotoxin SIA also displayed strong affinity for the alphagamma site but no measurable affinity for the alphadelta site, thus showing even greater site-selectivity. In contrast, alpha-conotoxin SI does not distinguish between the two agonist sites, although its sequence differs from that of GI at only three positions: GI, ECCNPACGRHYSC; SI, ICCNPACGPKYSC. Analogues of SI and GI modified at these three positions were studied to identify the determinants of GI's alphagamma selectivity. Substituting arginine for proline at position 9 produced peptides which displayed "GI-like" selectivity for the alphagamma site. Conversely, substituting proline for arginine at position 9 resulted in "SI-like" nonselective inhibitors. An SI analogue having alanine in place of proline 9 did not distinguish between the two agonist sites and displayed about the same affinity as SI, indicating the importance of the arginyl cation. Interchanging the residues at position 1 or at position 10 influenced the affinity for the receptor but did not measurably change peptide selectivity. Therefore, of the three sequence differences in SI and GI, the variation at position 9, proline and arginine, respectively, is sufficient to account for GI's selective high-affinity binding to the alphagamma site on the electric organ acetylcholine receptor.

Amino Acid Sequence↗
PubMed1996

Eprinomectin: a novel avermectin for use as a topical endectocide for cattle.

Eprinomectin (MK-397 or 4"-epi-acetylamino-4"-deoxy-avermectin B1) is a novel avermectin selected for development as a topical endectocide for all cattle, including lactating dairy cows. Herein, we show its anthelmintic, insecticidal and miticidal activity. To determine its anthelmintic capabilities, eprinomectin was tested topically on Jersey calves at 0.08, 0.2, or 0.5 mg kg-1 in a probe formulation against experimental infections of adult Haemonchus placei, ostertagia ostertagi, Trichostrongylus axei, T. colubriformis, Cooperia oncophora, C. punctata, Nematodirus helvetianus, Oesophagostomum radiatum and Dictyocaulus viviparus. Eprinomectin removed > or = 99% and > or = 98% of the adult stage of every species at the 0.5 and 0.2 mg kg-1 dosage levels, respectively. The lowest dosage (0.08 mg kg-1) produced maximal or near maximal efficacy against most of the adult endoparasites with the exception of T. colubriformis (87%) and C. oncophora (88%). In a separate test, eprinomectin was evaluated topically against the immature stages of species at the same dosages. Results showed > or = 99% and > or = 98% removal of the immature stages of each species at the 0.5 and 0.2 mg kg-1 dosage levels, respectively. The 0.08 mg kg-1 dosage maintained > or = 97% efficacy against 6 species with reduced activity against H. placei (42%) and N. helvetianus (66%). For ectoparasites, eprinomectin was tested topically at 0.16, 0.24, 0.32 or 0.5 mg kg-1 on mixed breed cattle naturally infested with the sucking louse, Linognathus vituli. Complete elimination of lice at all dosages was observed by day 14. Topical delivery of eprinomectin at 0.16, 0.24, 0.32 or 0.5 mg kg-1 to Holstein calves experimentally challenged with horn fly, Haematobia irritans, produced 100% efficacy to challenge by week 2 post-treatment in all dosages groups and 94% and 99% efficacy to challenge at the 0.32 and 0.5 mg kg-1 dosage groups, respectively, at week 4. Topical delivery of eprinomectin at 0.16, 0.24 or 0.5 mg kg-1 to Deutsches Fleckvieh cattle infested with mange mites, Chorioptes bovis, produced > or = 95% control at all dosages levels by day 14 post-treatment and was maintained at or near this efficacious level for the 6-week duration of the trial. No adverse reaction was observed in any animal in any of these tests. In summary, these experimental data indicate that eprinomectin is an excellent broad-spectrum endectocide for cattle and is suitable for topical delivery.

Administration, Topical↗
PubMed1996

Reproductive strategies of the cat flea (Siphonaptera:Pulicidae): parthenogenesis and autogeny?

The objective of this study was to determine if there is evidence of parthenogenesis or autogenous reproduction in the cat flea, Ctenocephalides felis (Bouché). To examine parthenogenesis, 400 newly eclosed virgin female fleas were collected from a laboratory colony and 100 were placed into each of 4 feeding cages and fed bovine blood through a Parafilm membrane. Three of the feeding cages were monitored for egg production for 7 d and each group of 100 virgin female fleas produced an average 1,119 eggs per cage, but none was viable. Fifty male fleas were added to those 3 feeding cages on day 7, and within 24 h the female fleas began ovipositing fertile eggs and nearly quadrupled their egg output. The other cage in which no males were introduced served as a control and did not produce a single viable egg in the 14-d experimental period. A similar experiment examined the continuance of virgin females to lay nonviable eggs and it was found that they continued to lay nonviable eggs for at least 58 d. Egg production was also studied in unfed fleas and it was found that unfed fleas did not produce eggs. These results suggest that neither parthenogenetic reproduction nor autogeny are exhibited by the cat flea.

Animals↗
PubMed1995

A further comparison of the thumb-counting and comb-counting techniques used to determine Ctenocephalides felis infestation levels on dogs.

A comparison was made to determine whether thumb-counting or comb-counting was more accurate for determining flea infestation levels on dogs when performed for equal periods of time. To accomplish this, ten beagle dogs were each infested with 100 adult fleas, Ctenocephalides felis. After the fleas were allowed to disperse for 1 h the dogs were examined using the thumb-counting method. The time required to cover each dog and the number of fleas counted were recorded. Thumb-counting times ranged from 3.0 to 4.8 min. Each of the dogs was then examined by the comb-counting method for the same amount of time it had been thumb-counted. The thumb-counting method detected a geometric mean of five (range, 0-13) fleas per dog, while comb-counting recovered a mean of 73.5 (range, 57-87) fleas per dog. These results were significantly different (P < 0.01), indicating that the differences in accuracy previously recorded for the two methods are independent of time. The standard deviations for both methods were also statistically significantly different, suggesting that comb-counting is also more precise than the thumb-counting method.

Animals↗
PubMed1995

Effect of combing time on cat flea (Ctenocephalides felis) recovery from dogs.

Combing the haircoat to count fleas has been used to determine the efficacy of insecticides against fleas on dogs, but no standardization of method has been reported. In this study, the effect of combing time on flea recovery from dogs was examined. Six beagle dogs were infested with 100 unfed, adult Ctenocephalides felis (Bouché) on each of three consecutive days. A crossover design, balanced for carryover effects, was used to evaluate flea removal rates from each dog by comb-counting for three different time intervals; i.e. 5, 10 and 15 min. Each dog was combed once at each time interval on a different day, over three consecutive days. The results showed that the majority of fleas were recovered in the first 5 min of combing and there were no significant differences (P > or = 0.19) in the total number of fleas recovered between the 5, 10 or 15 min protocols. Moreover, the standard deviation and coefficient of variation increased with an increase in the amount of time spent combing, resulting in a decrease in precision for the longer protocols. Therefore, the comb time of 5 min provided a precise and accurate representation of the number of fleas present on an animal and could be useful as a standard measure of flea infestation levels in efficacy trials.

Animal Husbandry↗
PubMed1994

Comparison of thumb-counting and comb-counting methods to determine Ctenocephalides felis infestation levels on dogs.

Comb-counting and thumb-counting were compared in a cross-over study to determine which was more accurate for quantifying flea infestation levels on dogs. Twenty beagle dogs were used in the study and infested with either 50 or 100 adult fleas (Ctenocephalides felis). Two groups of five dogs each were infested with either 50 or 100 fleas per dog, and then comb-counted with a fine-toothed flea comb for 8 min periods. An additional two groups of five dogs each were also given 50 or 100 fleas, and then thumb-counted. The counting time for this technique is both lower and more variable because the fleas are only observed and not captured; thus, the speed at which the dog is covered must be increased in order to prevent counting the same fleas more than once. The mean time of thumb-counting per dog was 3.2 min. Fleas removed during comb-counting were placed back on the dog they were taken from after the count was concluded. At the cross-over point, the ten dogs that had been comb-counted were then thumb-counted and the ten dogs that had been thumb-counted were comb-counted. The results showed that comb-counting recovered significantly (P < or = 0.05) more fleas than did thumb-counting. On dogs given 50 and 100 fleas, comb-counting gave mean percentage recoveries of 67.6% and 75.4%, respectively, whereas thumb-counting found means of 8.8% and 7.7%, respectively. The order in which the counting methods were employed produced no significant effect (P > 0.05) on the number of fleas counted.

Animals↗