Efficacy and safety of maropitant, a selective neurokinin 1 receptor antagonist, in two randomized clinical trials for prevention of vomiting due to motion sickness in dogs.

Maropitant (Cerenia), a selective neurokinin(1) receptor antagonist, was evaluated for efficacy and safety in prevention of vomiting due to motion sickness in dogs in two randomized clinical trials. One-hundred eighty-nine dogs with a history of motion sickness were enrolled at 26 veterinary clinics (across 12 US states) across the two trials; of these, 163 were fully evaluable, 19 were evaluable only for safety, and seven were not evaluable. Each trial used a two-period crossover design. Each dog was treated orally with placebo or maropitant (minimum dose of 8 mg/kg body weight using unit dosing) tablets at approximately 2 h (Trial 1) or 10 h (Trial 2) before an automobile ride of approximately 60 min, during which dogs were observed for signs of motion sickness. Following a 10-14-day washout period, each dog was administered the opposite treatment and taken for another journey (same route, driver and vehicle). Maropitant reduced the occurrence of vomiting compared to placebo by 86.1% or 76.5% when given approximately 2 or 10 h prior to travel, respectively. No significant clinical signs were observed after maropitant treatment. Maropitant was safe and effective in preventing vomiting due to motion sickness in dogs when administered at a minimum dose of 8 mg/kg body weight as oral tablets 2 or 10 h prior to travel.

Comparative efficacy of maropitant and selected drugs in preventing emesis induced by centrally or peripherally acting emetogens in dogs.

Maropitant (Cerenia; a novel, selective neurokinin(1) receptor antagonist), chlorpromazine, metoclopramide and ondansetron were compared in two randomized, placebo-controlled studies for efficacy in preventing emesis induced by emetogens acting centrally (apomorphine; Study 1) or peripherally (syrup of ipecac; Study 2) in dogs. In each study, ten male and ten female beagles were treated in a five-treatment, five-period crossover design. The five treatments were 0.9% saline (0.1 mL/kg), maropitant (1 mg/kg), metoclopramide (0.5 mg/kg), or chlorpromazine (0.5 mg/kg) all administered subcutaneously, or ondansetron (0.5 mg/kg) administered intravenously. One hour posttreatment dogs were challenged with apomorphine at 0.1 mg/kg intravenously (Study 1) or syrup of ipecac at 0.5 mL/kg orally (Study 2). Following emetogen challenge, dogs were observed for 30 min (Study 1) or 1 h (Study 2) for emesis. No clinical signs, other than those related to emesis, were observed. Efficacy of maropitant in preventing emesis induced centrally by apomorphine was not different (P > 0.05) from metoclopramide or chlorpromazine but was superior (P < 0.0001) to ondansetron. Efficacy of maropitant in preventing emesis induced by syrup of ipecac was not different (P > 0.05) from ondansetron but was superior (P

Safety and efficacy of injectable and oral maropitant, a selective neurokinin 1 receptor antagonist, in a randomized clinical trial for treatment of vomiting in dogs.

Maropitant (Cerenia), a selective neurokinin(1) receptor antagonist, was evaluated for safety and efficacy in treatment and prevention of acute vomiting due to various etiologies in dogs in a randomized clinical trial. Two-hundred seventy-eight dogs were enrolled from 29 veterinary hospitals. Two-hundred fifty-two were evaluable for efficacy, while 275 were evaluable for safety. A randomized block design was utilized (three maropitant- and one placebo-treated dog per block). Initial treatment was maropitant at 1 mg/kg body weight (0.45 mg/lb) or an equivalent volume of saline (placebo) administered subcutaneously. On the subsequent 1 to 4 days, maropitant or placebo (dependent on allocation) was administered subcutaneously or orally at approximate 24-h intervals as needed. Oral doses were administered as maropitant tablets using unit dosing to deliver a minimum dose of 2 mg/kg body weight (0.9 mg/lb) or equivalent numbers of similar placebo tablets. Dogs and housing were observed twice daily for evidence of vomiting. Emesis was significantly (P

Efficacy of injectable maropitant (Cerenia) in a randomized clinical trial for prevention and treatment of cisplatin-induced emesis in dogs presented as veterinary patients.

Chemotherapy-induced nausea and vomiting (CINV) is a common side-effect of cisplatin therapy. Maropitant (Cerenia), a novel neurokinin-1 receptor antagonist, was evaluated for prevention and treatment of cisplatin-induced emesis in tumour-bearing dogs. Dogs (n = 122) were randomly allocated to three treatment groups: T01, placebo before and after cisplatin; T02, placebo before and maropitant after cisplatin; or T03, maropitant before and placebo after cisplatin. Maropitant treatment (T02) following a cisplatin-induced-emetic event resulted in significantly fewer subsequent emetic events (P = 0.0005) than in placebo-treated dogs (T01). In placebo-treated (T01) dogs, 56.4% were withdrawn from the study because of treatment failure compared with 5.3% in group T02. When maropitant was administered prior to cisplatin treatment (T03) in a prevention regime, 94.9% did not vomit compared with only 4.9% of placebo-treated dogs, and significantly fewer emetic events (P < 0.0001) were observed in those dogs that did vomit. In summary, maropitant was safe and highly effective in reducing or completely preventing cisplatin-induced emesis.

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.

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.

Failure of a recombinant Schistosoma bovis-derived glutathione S-transferase to protect cattle against experimental Fasciola hepatica infection.

The potential of a recombinant Schistosoma bovis 28-kDa glutathione S-transferase (rSb28GST) to protect cattle against Fasciola hepatica was tested in a vaccination trial. Thirty two calves were randomly divided into four groups of eight animals. Calves of the three vaccine groups received two intramuscular injections at 3 weeks interval, of 0.250mg rSb28GST in either aluminium hydroxide (Al(OH)(3)), Quil A, or PBS emulsified in an equal volume of Freund's complete adjuvant (FCA).Animals of the control group received injections of Al(OH)(3)/PBS only. All animals were challenged orally with a total of 360 metacercariae of F. hepatica, spread over 6 weeks. All groups of vaccinated animals produced measurable IgG antibody titers to rSb28GST after vaccination. Animals immunised with FCA adjuvanted vaccine had the highest and more durable antibody titers and only sera from this group recognised an approximately 24kDa protein band from F. hepatica, that is thought to be a F. hepatica GST. Despite a good antibody response differences in cumulative faecal egg output between the groups were not statistically significant. In addition, no significant difference was found between groups in terms of total worm numbers or percentage of immature flukes recovered at necropsy. In conclusion, the recombinant S. bovis 28kDa GST was not found to adequately protect cattle against experimental F. hepatica challenge, using either aluminium hydroxide, Quil A or FCA as adjuvant.

International harmonisation of anthelmintic efficacy guidelines (Part 2).

The "International Co-operation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products (VICH)" is an international programme of co-operation between regulatory authorities and the animal health industries of the European Union, Japan and the United States of America which aims to harmonise the technical requirements for the registration of veterinary medicinal products. Australia and New Zealand participate as active observers. The objective of this second paper is to present additional guidelines established by the Working Group on anthelmintic guidelines: (1) efficacy of anthelmintics: specific recommendations for equine (VICH GL15), (2) efficacy of anthelmintics: specific recommendations for porcine (VICH GL16), (3) efficacy of anthelmintics: specific recommendations for canine (VICH GL19), (4) efficacy of anthelmintics: specific recommendations for feline (VICH GL20) and (5) efficacy of anthelmintics: specific recommendations for poultry (VICH GL21). These guidelines do not consist of rigid stipulations, but make clear recommendations on the minimal standards needed. To the veterinary profession, livestock producers and animal owners, harmonisation should mean quicker access to safer and more effective veterinary anthelmintics. In general, products should be relatively more affordable because of the reduction in registration costs and efficient use of resources by the regulatory authorities.

International harmonisation of anthelmintic efficacy guidelines.

The "International Co-operation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products (VICH)" is an international programme of co-operation between regulatory authorities and the animal health industries of the European Union, Japan, and the United States of America which aims to harmonise the technical requirements for the registration of veterinary medicinal products. Australia and New Zealand participate as active observers. The objective of the present paper is to present the guidelines established by the working group on Anthelmintic Efficacy Guidelines: (1) efficacy of anthelmintics: general requirements (VICH GL7); (2) efficacy of anthelmintics: specific recommendations for bovines (VICH GL12); (3) efficacy of anthelmintics: specific recommendations for ovines (VICH GL13); (4) efficacy of anthelmintics: specific recommendations for caprines (VICH GL14). These guidelines do not consist of rigid stipulations, but make clear recommendations on the minimal standards needed. To the veterinary profession, livestock producers and animal owners, harmonisation should mean quicker access to safer and more effective veterinary anthelmintics. In general, products should be relatively more affordable because of the reduction in registration costs and efficient use of resources by the regulatory authorities.

Changes in the morphology and the distribution of rat intestinal eosinophils during infection with the nematode Nippostrongylus brasiliensis.

Increases in the numbers of eosinophil leukocytes present in the lamina propria of intestines infected with nematodes is a well described phenomenon, yet the role of these leukocytes and their actions in this situation are not yet fully understood. Morphologic changes in these cells occur with the course of the infection, as do alterations in their location within the gut; these findings may give important clues to the function of this prominent cell. We observed changes in intestinal eosinophils in the August rat during infection with the nematode Nippostrongylus brasiliensis and found, together with the well known increases in number infiltrating the lamina propria at Day 20 (three times the levels in normal animals), a distinct change in the morphology of individual cells which included increase of the cell's overall size and changes in shape, as well as a dissemination of cytoplasmic granules in relationship to the cell's nucleus. No ultrastructural evidence of extracellular degranulation or intact eosinophil cytoplasmic granules outside the bounds of cell cytoplasmic membranes was seen. This finding is important considering the light microscopic appearance of individual eosinophil granules apparently distributed extracellularly, and lying in the connective tissue of the lamina propria, a common histopathologic observation in eosinophilic conditions. Eosinophils within the lamina propria changed their location as the infection progressed, tending to move to line up along the subepithelial zones. In addition, eosinophils were observed both at the light and electron microscopic levels to be passing through the basement membrane and into the epithelial layer. This latter phenomenon was confirmed using confocal optical slicing where eosinophils were commonly observed on the luminal side of the nuclei of the gut epithelium. These observations strongly suggest that morphologic alterations occur in eosinophils in the lamina propria and these changes may be associated with functional alterations in these cells akin to the putative phenomenon of "activation." Our findings indicate that eosinophils have the capacity to enlarge and extend their cytoplasmic processes between various components of the lamina propria and move toward the basement membrane during an active infection, as well as into, and possibly through, the intestinal epithelium. These findings emphasize the need for careful consideration of the changing morphologic status of eosinophils when investigating biologic changes associated with the activation of these cells in tissue inflammatory responses.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.