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G A Conder

Publications and source records attributed to G A Conder.

At least 19 recordsLinked to original sources
PubMed2006

World association for the advancement of veterinary parasitology (WAAVP): second edition of guidelines for evaluating the efficacy of anthelmintics in swine.

Guidelines are provided for evaluating the efficacy of anthelmintics in swine which, in conjunction with other sets of guidance such as those of the International Cooperation on Harmonization of Technical Requirements for Registration of Veterinary Medicinal Products (VICH GL7 and VICH GL16), should encourage the adoption of uniform registration requirements globally. Testing of efficacy should be carried out according to the principles of "Good Clinical Practice" (VICH GL9, 2000). Data obtained according to these guidelines should be internationally acceptable for the registration of anthelmintics for swine. Further, the use of the guidelines should expedite development, government review, and approval of anthelmintics for swine, as well as contribute towards reducing costs and the number of experimental animals used for drug testing.

Animals↗
PubMed2004

Interrelationships among physicochemical properties, absorption and anthelmintic activities of 2-desoxoparaherquamide and selected analogs.

The interrelationships between physicochemical properties, absorption and potency of 2-desoxoparaherquamide and five analogs, representing a new anthelmintic class, were evaluated in in vitro and in vivo assays. At pH 7.5, rates of drug absorption by the gastrointestinal nematode Haemonchus contortus and jird small intestine, parameterized by the permeability coefficient, P(e), ranged from 1.2-2.4 x 10(-4) cm/min (nematode) to 2.5-5.5 x 10(-3) cm/min (jird). In the jird intestine, absorption was pH-dependent, with P(e) at pH 7.5 being twice that at pH 4.5, reflecting the negative influence of protonation on transport of these weakly basic molecules. Each compound rapidly paralyzed H. contortus during in vitro exposure to therapeutically relevant concentrations (1-10 microm). The kinetics of drug action on motility in vivo mirrored their in vitro effects; motility concentrations were reduced in nematodes collected from jird stomach 3 h following oral drug dosing, by which time > or =50% clearance of the parasites had occurred. The nematode/medium partition coefficient K ranged from 10.1 to 16.1, consistent with the lipophilic nature of the compounds. The time required to reduce motility in vitro by 50% (t50*) and P(e) were used to determine C(n)*, the concentration of drug in the nematode at t50*, as an indicator of intrinsic potency. In the jird, the apparent potencies of the compounds were insensitive to route of administration (i.e. oral = i.v. = i.p. = i.m.) for H. contortus and two other gastrointestinal nematodes, Ostertagia ostertagi and Trichostrongylus colubriformis; topical administration, however, required three to 10-fold higher doses for equivalent efficacy.

Absorption↗
PubMed1999

Persistent efficacy of doramectin injectable against artificially induced infections with Cooperia punctata and Dictyocaulus viviparus in cattle.

Three studies were conducted to evaluate the persistent efficacy of doramectin injectable solution against experimental challenges with infective larvae of Cooperia punctata and Dictyocaulus viviparus. In each study, four groups of ten randomly-assigned calves, negative for trichostrongyle-type eggs on fecal examination, were treated subcutaneously in the midline of the neck with saline (1 ml/50 kg) on Day 0 or doramectin (200 microg/kg = 1 ml/50 kg) on Day 0, 7, or 14. Two additional calves from the same pool of animals were randomly assigned as larval-viability monitors and received no treatment. On Days 14-28, approximately 1000 and 50 infective larvae of Cooperia spp. and D. viviparus, respectively, were administered daily by gavage to each animal in Groups T1-T4. On Day 28, the two larval-viability monitor calves were inoculated in a similar manner with a single dose of approximately 30000 and 2000 larvae of Cooperia spp. and D. viviparus, respectively. Equal numbers of calves from each treatment group were killed on Days 42-45, as well as the two viability monitor animals to enumerate worm numbers. A 2% or 5% aliquot of small intestinal contents and washings were examined for worm quantification and identification, while 100% of the lung recoveries were quantified and identified. For each study and across the three studies, geometric mean worm recoveries for each treatment group were calculated from the natural log transformed data (worm count + 1) and were used to estimate percentage reduction. In the three studies, doramectin injectable solution was 97.5% efficacious against lungworms for up to 28 days and was 99.8% efficacious in reducing infection resulting from challenge with infective larvae of C. punctata for at least 28 days post-treatment.

Animals↗
PubMed1999

Persistent efficacy of doramectin pour-on against artificially induced infections of nematodes in cattle.

Two studies were conducted to determine the persistent efficacy of doramectin pour-on against an artificial, trickle challenge of mixed nematodes in calves. In each study, 42, 4-8 months old calves were randomly assigned into four groups of 10 animals each (T1-T4), plus two larval-viability monitor animals. All animals were treated with fenbendazole (10 mg kg(-1)) 14 days prior to the start of the study to clear any existing infection. Doramectin pour-on at 500 microg kg(-1) was used on each animal in Groups T2, T3, and T4 with intervals of 1 week (Day 0, 7, and 14, respectively). Calves in Group T1 were treated with saline solution on Day 0 and at the same volumetric rate (1 ml 10 kg(-1)) as the doramectin treated animals. All treatments were applied in a single passage along the midline of the back, from the withers to the tailhead. Subsequently, trickle inoculations with infective larvae were administered to all calves for 22 consecutive days (Days 14-35). Doramectin pour-on provided > or = 91.9% efficacy against challenge with Dictyocaulus viviparus, Haemonchus spp., and Ostertagia ostertagi for up to 35 days post-treatment and against challenge with Cooperia oncophora, Cooperia punctata, and Oesophagostomum radiatum for up to 28 days post-treatment.

Abomasum↗
PubMed1999

Efficacy of a pour-on formulation of doramectin against lice, mites, and grubs of cattle.

OBJECTIVE: To determine effectiveness of a pour-on formulation of doramectin against Damalinia bovis, Haematopinus eurysternus, Linognathus vituli, Solenopotes capillatus, Chorioptes bovis, Sarcoptes scabiei, Hypoderma bovis, and Hypoderma lineatum. ANIMALS: Cattle of various ages with naturally acquired or artificial infestations with 1 or more species of lice, mites, or grubs. PROCEDURE: In 10 louse and 6 mite studies, cattle were treated with doramectin (500 microg/kg, topically) on day 0, and parasite counts were performed approximately weekly from days 0 to 35. In 6 grub studies, cattle expected to harbor Hypoderma spp were treated before emergence of warbles. After warbles began to emerge, they were counted every 2 weeks, and grubs were collected and identified by species. RESULTS: Burdens of D bovis, H eurystemus, L vituli, and S capillatus on doramectin-treated cattle were 0 by 28 days after treatment. Burdens of C bovis and S scabiei decreased to 0 in naturally infested cattle and approximately 0 in artificially infested cattle by day 14 to 15. In grub studies, 107 of 136 control cattle had warbles, whereas 2 of 136 doramectin-treated cattle had 1 warble each, which represented a cure rate of 98.5%. CONCLUSION AND CLINICAL RELEVANCE: One topical application of doramectin was highly efficacious against common species of lice, mites, and grubs known to affect performance, health, and appearance of cattle.

Administration, Topical↗
PubMed1999

Efficacy of topically administered doramectin against eyeworms, lungworms, and gastrointestinal nematodes of cattle.

OBJECTIVE: To evaluate efficacy of topically administered doramectin against eyeworms, lungworms, and gastrointestinal nematodes of cattle. ANIMALS: 400 cattle (20 cattle in each of 20 trials). PROCEDURE: Trials were conducted in North America; natural and experimentally induced infections were used. In each trial, cattle were allocated randomly to control (placebo [saline [0.9% NaCl] solution at 1 ml/10 kg of body weight] or untreated; n = 10) or doramectin-treated (500 microg/kg of body weight; 10) groups. Treatments were applied in a single passage along the midline of the back, from the withers to the tailhead. Cattle were euthanatized > or =14 days after treatment, and worm burdens were determined by use of standard techniques. RESULTS: Efficacy of doramectin was > or =95.3% against adults of Thelazia gulosa, T skrjabini, Dictyocaulus viviparus, Haemonchus contortus, H placei, Ostertagia lyrata, O ostertagi, Trichostrongylus axei, Bunostomum phlebotomum, Capillaria spp, Cooperia oncophora, C pectinata, C punctata, C spatulata, C surnabada, Nematodirus spathiger, Strongyloides papillosus, T colubriformis, Oesophagostomum radiatum, and Trichuris spp. Efficacy was 95.1% against fourth-stage larvae of D viviparus, H placei, O lyrata, O ostertagi, T axei, C oncophora, C punctata, C spatulata, C surnabada, N helvetianus, T colubriformis, O radiatum, and Trichuris spp. In addition, efficacy against inhibited fourth-stage larvae of O ostertagi and Ostertagia spp was > or =98.1%. CONCLUSIONS AND CLINICAL RELEVANCE: A single topical application of doramectin pour-on was efficacious against a broad range of nematode species in cattle.

Administration, Topical↗
PubMed1998

Anthelmintic beta-hydroxyketoamides (BKAs).

We have prepared several anthelmintic coumarins based on the beta-hydroxyketoamide (BKA) template and have shown that this template remains valid over a wide range of changes to the coumarin moiety allowing for the inclusion of carbocyclic, bicyclic, and heterocyclic rings.

Animals↗
PubMed1998

Field efficacy of doramectin pour-on against naturally-acquired, gastrointestinal nematodes of cattle in North America.

Seven studies were conducted under field conditions in North America to evaluate the therapeutic efficacy of doramectin in a pour-on formulation at a dosage of 500 microg/kg (1 ml/10 kg) for cattle harboring naturally-acquired infections of gastrointestinal nematodes, including species of Haemonchus, Ostertagia, Trichostrongylus, Bunostomum, Cooperia, and Oesophagostomum. In each study, 40 to 100 cattle were randomly allocated to a saline- or doramectin-treated group in a tiered manner based on Day -7 bodyweight. On Day 0, the cattle received either saline or doramectin topically, according to their treatment group. Weather and safety observations were made following treatment. No adverse reaction to treatment was observed at any time during these studies. Fecal egg count (FEC) determinations were carried out on each animal on Days -7, 0, 7, 14, and 21. Reductions in FEC for the doramectin-treated animals compared to saline-treated cattle were > or = 96.0% by Day -7 and > or = 99.0% on Days 14 and 21 for each study. Across all studies regardless of weather conditions, the reduction by Day 21 for the doramectin-treated animals compared to saline controls was 99.7% (p < or = 0.0001) and compared to pretreatment levels in doramectin-treated cattle was 99.9% (p < or = 0.0001). Doramectin pour-on should provide a useful new treatment for controlling nematode parasites of cattle.

Animals↗
PubMed1998

Comparative in vitro effects of closantel and selected beta-ketoamide anthelmintics on a gastrointestinal nematode and vertebrate liver cells.

PNU-87407 and PNU-88509, beta-ketoamide anthelmintics that are structurally related to each other and to the salicylanilide anthelmintic closantel, exhibit different anthelmintic spectra and apparent toxicity in mammals. The basis for this differential pharmacology was examined in experiments that measured motility and adenosine triphosphate (ATP) levels in larval and adult stages of the gastrointestinal nematode, Haemonchus contortus, and in a vertebrate liver cell line and mitochondria. PNU-87407 and PNU-88509 both exhibited functional cross-resistance with closantel in larval migration assays using closantel-resistant and -sensitive isolates of H. contortus. Each compound reduced motility and ATP levels in cultured adult H. contortus in a concentration- and time-dependent manner; however, motility was reduced more rapidly by PNU-88509, and ATP levels were reduced by lower concentrations of closantel than the beta-ketoamides. Tension recordings from segments of adult H. contortus showed that PNU-88509 induces spastic paralysis, while PNU-87407 and closantel induce flaccid paralysis of the somatic musculature. Marked differences in the actions of these compounds were also observed in the mammalian preparations. In Chang liver cells, ATP levels were reduced after 3 h exposures to > or = 0.25 microM PNU-87407, > or = 1 microM closantel or > or = 10 microM PNU-88509. Reductions in ATP caused by PNU-88509 were completely reversible, while the effects of closantel and PNU-87407 were irreversible. PNU-87407, closantel and PNU-88509 uncoupled oxidative phosphorylation in isolated rat liver mitochondria, inhibiting the respiratory control index (with glutamate or succinate as substrate) by 50% at concentrations of 0.14, 0.9 and 7.6 microM, respectively.

Adenosine Triphosphate↗
PubMed1997

Persistent efficacy of doramectin against experimental challenge with Ostertagia ostertagi in cattle.

Two studies were conducted in North America to evaluate the persistent efficacy of doramectin injectable solution against experimental challenge with infective larvae of Ostertagia ostertagi. In both studies, four groups of 10 randomly-assigned calves, negative for trichostrongyle-type eggs on fecal examination, were treated subcutaneously in the midline of the neck with saline (1 ml 50 kg-1) on Day 0 or doramectin (200 micrograms kg-1 = 1 ml 50 kg-1) on Day 0, 7, or 14. Two additional calves from the same pool of animals were randomly assigned as larval-viability monitors and received no treatment. Beginning on Day 14 and continuing through Day 28, the 40 treated calves each were given approximately 1000 infective larvae of O. ostertagi by gavage daily; the two larval-viability monitors were inoculated in a similar manner with approximately 30,000 larvae as a single dose on Day 28. Animals were slaughtered on Day 42 in one study and on Days 42, 43, or 46 in the second. The abomasum from each calf was harvested and processed for worm recovery. A 2% aliquot of abomasal contents plus wash was examined for worm quantification and identification. Geometric mean O. ostertagi burdens were calculated from the log (O. ostertagi count + 1) and were used to estimate percentage reduction. In both studies, doramectin injectable solution was > or = 99.6% efficacious in reducing infection resulting from challenge with infective larvae of O. ostertagi for at least 21 days posttreatment; by 28 days posttreatment, efficacy was 87.3% in one study and 99.7% in the other.

Animals↗
PubMed1996

Phenotypic analysis of airway eosinophils and lymphocytes in a Th-2-driven murine model of pulmonary inflammation.

In order to investigate whether the pulmonary response to helminth antigens mimics that seen in allergic inflammation of the airways, we have examined the phenotypic characteristics of lymphocytes and eosinophils recruited to the airways following Nippostrongylus brasiliensis (N.b.) infection. Specifically, the cellular response was divided into an early and a late phase. During the early response there was a small but significant increase in neutrophil numbers recovered by bronchoalveolar lavage (BAL). Phenotypic analysis of BAL leukocytes revealed an early rise in the percentage of BAL lymphocytes expressing the naive T cell markers CD45RB and L-selectin, and the activation marker IL-2R. In addition, during the early response, there was an increased percentage of lymphocytes expressing the gamma delta TCR, but not the alpha beta TCR. In contrast, the late response was marked by a much larger accumulation, in the lungs and BAL, of memory CD4+ T lymphocytes and an influx of small, hypodense eosinophils which produced LTB4 and LTC4 on stimulation with calcium ionophore. At this time there was a substantial increase in the number of T lymphocytes and eosinophils expressing ICAM-1 and the integrins VLA-4 and LFA-1, implicating these adhesion molecules in inflammatory cell recruitment to the airways. We conclude that the pattern and phenotypic characteristics of the cellular recruitment seen following N.b. infection resemble those seen in early- and late-phase allergic inflammation of the airways in asthma, and therefore N.b. may be used to model these aspects of the disease.

Animals↗
PubMed1996

Viability of infective larvae of Haemonchus contortus, Ostertagia ostertagi, and Trichostrongylus colubriformis following exsheathment by various techniques.

Various techniques were examined to determine optimum conditions for exsheathing infective larvae of 3 important ruminant parasites (Haemonchus contortus, Ostertagia ostertagi, and Trichostrongylus colubriformis). In repeated experiments, aliquots of 10(5)-10(6) infective larvae, 1-2 mo old, of each parasite were incubated in each of 4 exsheathing media (distilled water, Earle's balanced salt solution + carbon dioxide, nematode washing buffer + carbon dioxide, or sodium hypochlorite) for 1 or 18 hr. In each case, the percentage of larvae exsheathed and infectivity for jirds was determined. Results of these studies indicate that no single exsheathing technique of those studied is optimum for every parasite. In addition, caution must be used in drawing conclusions from in vitro studies using exsheathed larvae because techniques that routinely provide high percentages of exsheathment also appear to reduce viability.

Animals↗
PubMed1996

Infectivity of Hymenolepis diminuta for the jird, Meriones unguiculatus, and utility of this model for anthelmintic studies.

The jird (Meriones unguiculatus) has been shown to be a useful model host for the cestodes Taenia crassiceps and Echinococcus multilocularis. This report outlines a novel model in which hydrocortisone-treated jirds (0.02% in the feed) are infected with another cestode, Hymenolepis diminuta. Jirds were inoculated with 5 freshly harvested cysticercoids of H. diminuta prior to (day 0, -1, or -5) or after (day 1 or 5) switching to medicated feed; in some cases, jirds were never medicated. On days 7, 14, 21, or 28 postinoculation (PI), jirds were killed by CO2 inhalation and their small intestines were examined for tapeworms. Hymenolepis diminuta established, grew, and developed to the gravid adult state in jirds. They persisted longer in medicated (21 days) than in nonmedicated (7 days) animals, and generally higher levels of infection were obtained when jirds were inoculated immediately prior to switching to medicated feed. Treatment of infected jirds on day 4 or days 4, 5, and 6 PI with selected anthelmintics followed by necropsy on day 7 PI discriminated drugs with known activity against tapeworms from those with little or no activity. This rodent in vivo model should provide a useful adjunct for anthelmintic studies.

Animals↗
PubMed1995

Anthelmintic profile of the cyclodepsipeptide PF1022A in in vitro and in vivo models.

A novel cyclodepsipeptide of fungal origin, PF1022A, recently was reported to have anthelmintic activity. To supplement published reports and determine potential utility of PF1022A as a ruminant anthelmintic, the compound was examined in in vitro and in vivo models. Assays used measured motility of Haemonchus contortus (intrinsic drug potency), ATP levels (parasite death), and activity against H. contortus, Ostertagia ostertagi, and Trichostrongylus colubriformis in the jird (spectrum, potency, and efficacy by various routes). The potency of PF1022A in reducing motility is greater than commercial anthelmintics. Examination of ATP levels in PF1022A-paralyzed H. contortus indicates that worms are not killed, suggesting the compound acts as a neurotoxin in nematodes. In the jird, PF1022A has activity orally against each of the parasites studied and at doses comparable to all commercial anthelmintics, except the macrocyclic lactones which are more potent. Unfortunately, for some nematode species, parenteral delivery is ineffective at realistic doses.

Adenosine Triphosphate↗
PubMed1994

Enhanced larval cyst growth of Echinococcus multilocularis in praziquantel-treated jirds (Meriones unguiculatus).

Jirds (Meriones unguiculatus) inoculated intraperitoneally with cystic material of Echinococcus multilocularis were given daily oral treatments of praziquantel at 300 mg/kg of body weight (bw) or dimethyl sulfoxide vehicle for five-day treatment regimens starting at 29 days postinoculation (PI) up to 69 days PI. At 39 or 49 days PI, the growth of the larval cystic mass (LCM) in jirds following a single or two five-day treatment regimens was significantly enhanced (P < 0.05) by 129.0% (2.3-fold) or 102.9% (2.0-fold), respectively. At 59 or 69 days PI following three or four five-day treatments with praziquantel, LCM growth was enhanced by 47.8% (1.5-fold) and 44.1% (1.4-fold), respectively, but was no longer significantly different than that in control jirds. A single five-day treatment on 29-33 days PI (with necropsy at 69 days PI) significantly enhanced the growth of the LCM by 87.6% (1.9-fold). Parasites from praziquantel treatment regimens examined ultrastructurally showed consistent damage to the germinal membrane evidenced by vacuolization and rupture of syncytial cytoplasm, rupture and coalescence of the electron-lucent vesicles just below the microvilli of the tegumental surface, and swelling and rounding of mitochondria. At 39 days PI, increased blebbing of the germinal membrane into the lumen of the LCM in praziquantel-treated animals was observed by scanning electron microscopy. The treatment-induced blebs were identified as nucleated germinal cells by transmission electron microscopy and appeared to be responsible for metastasis and enhanced growth of the LCM. Although praziquantel damaged the ultrastructural integrity of the LCM, treatment failed to inhibit larval cyst growth or protoscolex development.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Protective immunity to Haemonchus contortus induced by immunoaffinity isolated antigens that share a phylogenetically conserved carbohydrate gut surface epitope.

Whole gut homogenates of the blood-sucking nematode Haemonchus contortus induce protective immunity in goats, and some of these gut Ag are conserved among related parasitic nematode species. To identify gut Ag that induce protective immunity and have phylogenetically conserved epitopes, mAb were made to gut-surface Ag of H. contortus. Forty-nine mAb reacted with microvilli of the parasite gut. Two of these mAb (42/10.6.1 and 42/53.3.5) were analyzed here. Both of the mAb bound to the microvillar surface of freshly isolated gut, and each mAb recognized carbohydrate epitopes, based on sensitivity to periodate oxidation. The 42/10.6.1 epitope occurred on at least 18 proteins in Western blots and in several H. contortus tissues. Proteins recognized by this mAb localized to membrane and excretory/secretory fractions of the worm. This epitope was also identified on the gut and other tissues and multiple proteins of related adult and larval nematodes, including larval Ancylostoma caninum and a mixed population of the free-living nematode Caenorhabditis elegans. In contrast, the 42/53.3.5 mAb bound to the gut surface and recognized proteins of 100 and 46 kDa from adult H. contortus gut. Four proteins of 100, 52, 46, and 30 kDa were isolated from the 42/53.3.5 immunoaffinity columns, and except for the 30-kDa protein, each was recognized by both the 42/10.6.1 and 42/53.3.5 mAb. Epitopes recognized by each mAb were distinct from one another and phosphorylcholine. When used to immunize goats, Ag isolated by both mAb induced protection that significantly (p < 0.05) reduced total worm counts after challenge infections compared with the control groups.

Animals↗
PubMed1993

Demonstration of co-resistance of Haemonchus contortus to ivermectin and moxidectin.

Studies were conducted to determine whether organisms which are resistant to ivermectin are also resistant to moxidectin. The mechanisms of action of moxidectin and ivermectin were compared by measuring the changes in membrane conductance they induced in leg muscle fibres of the common shore crab (Pachygrapsus crassipes) by using standard micro-electrode techniques. Meriones unguiculatus (jirds) were infected with ivermectin-resistant or -susceptible strains of Haemonchus contortus, treated with moxidectin or ivermectin at a dose which routinely clears more than 98 per cent of the susceptible strain, and examined for parasite clearance. The results showed that moxidectin induced a rapid loss of membrane resistance in the muscle preparation, and that the effect was almost 50 per cent reversible with the chloride channel-blocker picrotoxinin; this pattern of activity is qualitatively similar to that of ivermectin. In the jird model, moxidectin achieved a clearance of only < or = 47.2 per cent against ivermectin-resistant H contortus at a dose which invariably clears > or = 98 per cent of an ivermectin-susceptible strain. These results indicate that moxidectin and ivermectin share a common mechanism of action, and that organisms that are resistant to ivermectin are also likely to be resistant to moxidectin.

Animals↗