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Biomedical subjects

W L Shoop

Publications and source records attributed to W L Shoop.

At least 37 records · Page 2Linked to original sources

Structure and activity of avermectins and milbemycins in animal health.

The avermectins and, to a lesser extent, the milbemycins, have revolutionized antiparasitic and antipest control over the last decade. Both avermectins and milbemycins have macrocyclic lactone structures that are superimposable, they are produced by the same genus of soil dwelling organisms, they have the same mode of action, they exert this action against the same nematode/acarine/insect spectrum of targets, and they show the same mechanism-based toxicity in mammals. Reports suggesting that milbemycins have a different mode of action from avermectins with implications that there will be no mutual resistance to the groups have been shown to be false. Contributing to the belief that there were differences in mode of action between the two groups are the vague definitions of resistance presently in use which rely on the ability of the parasite to survive treatment at the manufacturer's recommended use level. More appropriately, drug resistance should be defined as 'a change in gene frequency of a population, produced by drug selection, which renders the minimal, effective dosage previously used to kill a defined portion (e.g. 95%) of the population no longer equally effective'. This type of definition would allow us to detect changes in susceptibility of a population earlier and is essential when comparing different chemicals to determine if there is mutual resistance to them. It is concluded that much effort has been expended by pharmaceutical, government, and academic scientists searching for broad-spectrum second generation avermectin and milbemycin products, but none has exceeded the original avermectin in any fundamental way. The newer avermectin and milbemycin compounds that have appeared claim niches in the market place based on emphasis of certain narrow parts of the overall spectrum. Consequently, there are no second generation avermectins and milbemycins at present and all newer compounds from this mode of action class are viewed as siblings of the first generation.

Animals↗

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↗

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↗

Neodiplostomum seoulensis n. comb. (Trematoda: Neodiplostomidae).

Fibricola seoulensis Seo, Rim, and Lee, 1964 was described from rats in Seoul, Korea and was later found to be a natural parasite in the intestine of humans. At the time this species was described, the classification of this and other strigeiform flukes was based largely on the phylogeny of the host; those adult worms parasitic in birds were placed in Neodiplostomum and those parasitic in mammals were placed in Fibricola. A recent analysis of this group produced a classification that was based on the phylogeny of the worms themselves and suggested that certain metacercarial and adult characters were more important in determining the phylogenetic position of these worms than was the host. In light of the new classification, we examined newly collected metacercariae and re-examined fixed adults of F. seoulensis and found their characters to be more compatible with the genus Neodiplostomum. The characters included a neodiplostomulum metacercaria with 4 transverse commissures and an adult stage with symmetrical anterior testis and vitellaria in both the fore- and hindbody. Therefore, it is recommended that F. seoulensis be recombined as Neodiplostomum seoulensis.

Animals↗

Ivermectin binding sites in sensitive and resistant Haemonchus contortus.

Membranes from both ivermectin-sensitive and -resistant Haemonchus contortus L3 larvae were examined for the presence of high affinity [3H]ivermectin binding sites. Both tissue preparations displayed high affinity drug binding sites (Kd = 0.13 nM). Receptor density (Bmax = 0.4 pmol/mg) was the same in both the sensitive and resistant nematodes suggesting that target site modification was not involved in the development of drug resistance in this particular strain of H. contortus. The H. contortus ivermectin binding site appeared to be similar to the well characterized Caenorhabditis elegans ivermectin binding site with respect to affinity for ivermectin and receptor density.

Animals↗

Mutual resistance to avermectins and milbemycins: oral activity of ivermectin and moxidectin against ivermectin-resistant and susceptible nematodes.

To determine whether there is mutual resistance to avermectin and milbemycin anthelmintics, ivermectin and moxidectin sheep drenches were tested against ivermectin-resistant and susceptible isolates of Ostertagia circumcincta and Trichostrongylus colubriformis in sheep. None of the isolates had been exposed to moxidectin previously. The dosage of ivermectin required to remove 95 per cent of the ivermectin-resistant O circumcincta and T colubriformis were 23 times and six times larger, respectively, than the dosages required to remove the same percentage of susceptible isolates. The dosages of moxidectin required to remove 95 per cent of the ivermectin-resistant O circumcincta and T colubriformis were 31 times and nine times larger, respectively, than the dosages required to remove the same percentage of susceptible isolates. It is concluded that the worms resistant to ivermectin were also resistant to moxidectin.

Administration, Oral↗

Ivermectin resistance.

In this review of ivermectin resistance, Wesley Shoop discusses the definition of resistance, catalogs all known cases of ivermectin resistance, argues that overmectins and milbemycins belong in the same action family, discusses the possibility of resistance in the filariae, and suggests that detection of ivermectin resistance is the area where future research is most needed.

Journal Article↗

Anthelmintic activity of paraherquamide in calves.

Paraherquamide, an oxindole alkaloid metabolite of Penicillium paraherquei and Penicillium charlesii, was tested against the adult stages of nine common gastrointestinal and lung nematodes of calves at single, oral dosages of 0.5, 1.0, 2.0 or 4.0 mg kg-1. At dosages 1.0-4.0 mg kg-1 there was 95% or more removal of Haemonchus placei, Ostertagia ostertagi, Trichostrongylus axei, Trichostrongylus colubriformis, Cooperia oncophora, Nematodirus helvetianus, Oesophagostomum radiatum, and Dictyocaulus viviparus. Cooperia punctata, the dosage-limiting species, was virtually unaffected by any dosage except the highest, which produced an efficacy of 89%. The 0.5 mg kg-1 dosage was 95% or more efficacious against H. placei, O. ostertagi, C. oncophora, and D. viviparus, but weaknesses were evident against the other five species. No adverse reaction was observe in any calf.

Animals↗

Acute toxicity of paraherquamide and its potential as an anthelmintic.

Paraherquamide, an oxindole alkaloid metabolite of Penicillium paraherquei and P charlesii, is a new anthelmintic with potential broad-spectrum use. In initial trials, it had an excellent safety profile in cattle and sheep at doses efficacious against a dozen or more helminths, but recently it produced unexpected and severe toxicosis in dogs at doses far below those that were safe in the ruminants. To provide data on which to build rational safety tests in the future, we tested the acute toxicity of paraherquamide administered PO to male CD-1 mice and compared its profile with the most potent anthelmintic known, ivermectin. The estimated doses lethal to 50% of a group of mice were 14.9 and 29.5 mg/kg of body weight for paraherquamide and ivermectin, respectively. The no-effect doses were 5.6 and 18.0 mg/kg for paraherquamide and ivermectin, respectively. Signs of intoxication in paraherquamide-treated mice, if they developed, emanated within 30 minutes of administration, irrespective of dose, and consisted of either mild depression with complete recovery or a 5- to 10-minute period of breathing difficulty followed by respiratory failure and death by 1 hour after treatment. Gross necropsy findings in paraherquamide-treated mice that died in the high-dose group were normal. Ivermectin-related toxicity was slower and more predictable, taking place over a 3-day period, with dose-dependent signs of intoxication consisting of tremors, ataxia, recumbency, coma, and death. Necropsy of ivermectin-treated mice that died in the high-dose group revealed dehydration, a condition most likely resulting from the coma-induced state.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Vertical transmission of helminths: Hypobiosis and amphiparatenesis.

Vertical transmission has evolved in at least five lines of helminths and involves prenatal or, more commonly, transmammary pathways to the offspring. In this article, vertical transmission, hypobiosis and paratenesis are combined in a strategy for transmission called amphiparatenesis. Although many believe that vertical transmission of parasites is rare, Wesley Shoop suggests that it is not only significant in the evolution of certain helminths but it may have been one of the pivotal adaptations in the evolution of the eukaryotes and is essential in their continued existence.

Journal Article↗

Anthelmintic activity of paraherquamide in dogs.

Paraherquamide, an oxindole alkaloid metabolite of Penicillium paraherquei and Penicillium charlesii, was tested against the common gastrointestinal nematodes of dogs at a single oral dosage of 0.5, 1.0, or 2.0 mg kg-1. Efficacy was poor (less than 85%) against Ancylostoma caninum, Uncinaria stenocephala, Toxascaris leonina, Trichuris vulpis, and Strongyloides stercoralis at the low- and mid-dosage levels. At the high dosage level, good efficacy (91%) was observed only against S. stercoralis. Adverse reactions were observed in all dogs at every dosage level and included depression, ataxia, and protrusion of the nictitating membrane.

Animals↗

Susceptibility of insecticide-susceptible and wild house flies (Diptera: Muscidae) to abamectin on whitewashed and unpainted wood.

Unpainted plywood panels treated with 0.1% abamectin (avermectin B1) provided greater than 90% control of house flies, Musca domestica L., susceptible to insecticides for 4 wk and greater than 70% control for 7 wk compared with 46-92% control observed with permethrin at the same time and rate of application. Efficacy of abamectin on whitewashed panels was similar to that observed on unpainted panels, whereas permethrin was ineffective on whitewashed panels at all rates tested (range, 0.001-0.1%) at all intervals after treatment. Bioassays of newly colonized house flies resistant to permethrin indicated that wild populations may be cross-resistant to abamectin.

Animals↗

Anthelmintic activity of the macrocyclic lactone F28249-alpha in sheep.

The macrolytic lactone F28249-alpha was titrated in experimentally infected sheep and found to be highly effective against most of the common gastrointestinal nematodes as a single oral dose, given at a rate of 0.025, 0.05, or 0.1 mg/kg. Specifically, maximal activity was evident at even the lowest dosage against adult Haemonchus contortus, Ostertagia circumcinta, Trichostrongylus axei, and T colubriformis and L4 O circumcinta. Activity against Oesophagostomum columbianum was also high at all dosages, with a calculated ED95 of 0.029 mg/kg. Cooperia curticei was eliminated at 0.1 mg/kg, but control was erratic at the lower dosages. The greatest weakness of this compound was its activity against C oncophora. The activity against this parasite was weak (less than or equal to 85%) at all dosages, and the dosage-response curve was flat, suggesting dosages substantially higher than those given would be necessary for high-order control of this species.

Administration, Oral↗

Transmammary transmission of mesocercariae of Alaria marcianae (Trematoda) in experimentally infected primates.

A lactating primate, Callithrix jacchus, was infected experimentally with 600 mesocercariae of Alaria marcianae 10 days after parturition to determine if she would transmit the mesocercariae to her offspring. Her twin infants were examined 4 wk postinoculation and 16 mesocercariae were found in their tissues. The female was mated again and gave birth to a litter of triplets. She was not given additional mesocercariae. One infant died within hours of birth without suckling and was found negative for any stage of A. marcianae. The other 2 were allowed to nurse for 5 wk, examined and found to be infected with a total of 115 mesocercariae in various tissues, 1 metacercaria in the lungs, and 1 immature and 2 fully formed ovigerous adults in the small intestines. The female was examined at the same time and 246 mesocercariae were recovered. No other stage was found. Histological examination of her mammary glands revealed numerous mesocercariae in the milk-laden alveoli.

Animals↗