Estimating dissolved phosphorus losses from legacy sources in pastures: The limits of soil tests and small-scale rainfall simulators.

A legacy of using P fertilizers on grazed pastures has been enhanced soil fertility and an associated increased risk of P loss in runoff. Rainfall simulation has been extensively used to develop relationships between soil test P (STP) and dissolved P (DP) in runoff as part of modeling efforts scrutinizing the impact of legacy P. This review examines the applicability of rainfall simulation to draw inferences related to legacy P. Using available literature, we propose a mixing layer model with chemical transfer to describe DP mobilization from pasture soils where readily available P in the mixing layer is rapidly exhausted and contact time controls DP concentrations responsible for subsequent DP mobilization. That conceptual model was shown to be consistent with field monitoring data and then used to assess the likely effect of rainfall simulation protocols on DP mobilization, highlighting the influence of soil preparation, scale and measurement duration, and, most important, hydrology that can facilitate the physical transport of P into and out of surface flow. We conclude that rainfall simulation experimental protocols can have severe limitations for developing relationships between DP in runoff and STP that are subsequently used to estimate legacy P contributions to downstream water resources.

Efficacy of doramectin against naturally acquired nematode infection in Iberian swine.

Studies were carried out to determine the therapeutic efficacy of doramectin, administered intramuscularly at a dose of 300 microg/kg live weight, against naturally acquired helminths of extensively farmed Iberian pigs. The first study (slaughter study) evaluated, through necropsy of the study animals, the product's efficacy against gastrointestinal and pulmonary nematodes (Ascaris suum, Oesophagostomum dentatum and Metastrongylus sp.) whilst the second, faecal egg count reduction study, (FECR study) evaluated the drug's efficacy only against gastrointestinal helminths (A. suum, Trichuris suis and Oesophagostomum sp.). The first study used 20 animals divided into two equal groups of 10 on the basis of body weight and faecal egg count. One group constituted saline treated controls and the other was doramectin treated. On Day 14 post treatment half of the animals in each group were necropsied and the number of parasites present counted. On Day 15 the remaining half of each group underwent the same procedure. The second study was carried out with 40 animals divided equally into two groups of 20. This study determined the effect of doramectin treatment on faecal egg counts as an indicator of parasite burden. The first study demonstrated an efficacy of 100% against adult Metastrongylus sp. and A. suum, whilst the efficacy against O.dentatum was 96.3%. The second study indicated that at Day 21 post treatment there was a 100% reduction in egg counts in faeces in comparison to untreated controls.

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.

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.

Activity of doramectin against nematode and arthropod parasites of swine.

The efficacy of doramectin, a novel avermectin, was assessed against both naturally-acquired and experimentally-induced infections of gastrointestinal roundworms, lungworms, kidneyworms, lice and mites in studies conducted across North America and Europe. Twenty-two studies evaluated efficacy against fourth larval and adult stages of the following nematode species: Hyostrongylus rubidus, Ascaris suum, Strongyloides ransomi, Oesophagostomum dentatum, Oesophagostomum quadrispinulatum, Trichuris suis, Metastrongylus spp. and Stephanurus dentatus. Efficacy was evaluated against the louse Haematopinus suis in six studies and against the mite Sarcoptes scabiei in four studies. A common study design was employed for each study type. In all studies, animals were allotted at random to a doramectin-treated or a saline-treated group. The doramectin-treated group received the drug at 300 micrograms kg-1 by intramuscular injection while the saline-treated group received saline by the same route. In the nematode studies, worm burdens were determined for each animal at slaughter 14-16 days after treatment. Efficacy against each nematode species/stage was assessed on the basis of percentage reduction in geometric mean worm burden in doramectin-treated animals compared with saline-treated controls. In louse and mite studies, counts were made immediately before treatment and then at weekly intervals for four weeks. Efficacy was based on a comparison of the level of infestation on the day of treatment with that on the last day of test. Data from individual studies were combined to derive a single estimate of efficacy against each of the parasite species represented in the study program. Efficacy of doramectin was 98% or greater against all nematode species except T. suis for which the efficacy was 87% and 79% against adult and fourth larval stage, respectively. Efficacy was 100% against both Haematopinus suis and Sarcoptes scabiei.

Effect of formulation on the pharmacokinetics and efficacy of doramectin.

The pharmacokinetics of doramectin, a novel avermectin, were evaluated following parenteral administration in a range of oil-based formulations in an attempt to optimise the formulation. Therapeutic and persistent efficacies against Cooperia oncophora were also evaluated. This approach led to the identification of formulations based upon sesame oil and ethyl oleate which gave more prolonged doramectin plasma concentrations with no loss in therapeutic efficacy and improved persistent efficacy following subcutaneous administration to cattle at a dosage of 200 micrograms kg-1. The importance of using both pharmacokinetic and efficacy end points to distinguish between formulations is discussed. All formulations were well tolerated as evidenced by the absence of any reaction to injection either in the form of behavioural responses, injection site swelling or postmortem lesions. Sesame oil with ethyl oleate was the best parenteral vehicle tested for doramectin, allowing the expression of a high level of therapeutic and persistent efficacy and offering the benefit of excellent injection site toleration.

Persistent efficacy of doramectin against experimental nematode infections in calves.

Three studies were conducted involving cattle exposed to experimental nematode infections. These studies were designed to investigate the prophylactic activity of a single subcutaneous treatment of doramectin at 200 micrograms kg-1 body weight against infections of Ostertagia ostertagi, Cooperia oncophora and Dictyocaulus viviparus. For each study, parasite-naive calves were randomly allocated to either a treated or a matched control group. One group received doramectin and the other received doramectin and the other received either no treatment or an injection of saline at 1 ml per 50 kg body weight by the subcutaneous route. Thereafter, all calves received a daily oral challenge of infective larvae of the particular parasite species on test in each study. Challenge of each pair of treatment/control groups continued for periods of 14, 21 or 28 days. An interval of 14-21 days was then allowed to permit the parasites which had established to mature, after which all animals were slaughtered and their worm burdens determined using standard techniques. Geometric mean worm burdens were calculated from the log worm counts and used to estimate percentage efficacy. Accumulated burdens of C. oncophora in doramectin-treated cattle resulting from a daily challenge infection for 14 or 21 days were reduced by 99.2% and 90.7% respectively, in comparison with those of non-treated control animals. For D. viviparus, burdens were reduced by 100% and 99.9% after a 21 or 28 day challenge, respectively. The corresponding figures for O. ostertagi were 99.9% after a 21 day challenge and 93.7% after a 28 day challenge.

Activity of doramectin against nematode endoparasites of cattle.

A series of 28 controlled anthelmintic studies, involving 634 cattle, was conducted throughout North America and Europe to evaluate the efficacy of doramectin against a broad range of gastrointestinal parasitic nematode species and lungworms in naturally and experimentally infected animals. Within each study, one or two groups were treated with doramectin at 200 micrograms kg-1 and another group received no drug treatment. Worm burdens were estimated by standardised techniques, and efficacy assessed on reduction of worm burdens in doramectin-treated animals. Doramectin was at least 99.6% effective (P < 0.0002) in eliminating the immature and adult stages of the following 14 species of nematodes: Ostertagia ostertagi (including inhibited), Ostertagia lyrata, Haemonchus placei, Trichostrongylus axei, Trichostrongylus colubriformis, Cooperia oncophora (including inhibited), Cooperia pectinata, Cooperia punctata, Cooperia spatulata, Cooperia surnabada, Bunostomum phlebotomum, Strongyloides papillosus, Oesophagostomum radiatum and Dictyocaulus viviparus. Efficacy against adult Trichostrongylus longispicularis, Nematodirus spathiger and Trichuris spp. was 93.1%, 96.5% and 94.6%, respectively. Efficacies against adult and fourth-stage larvae of Nematodirus helvetianus, the dose-limiting species, were 73.3% and 75.5%, respectively.

Doramectin--a potent novel endectocide.

Doramectin, 25-cyclohexyl-5-O-demethyl-25-de(l-methylpropyl)avermectin A1a, was selected as the best of a series of novel avermectins prepared by mutational biosynthesis. The primary evaluation of its in vivo antiparasitic activity was carried out using a rat Trichostrongylus colubriformis model and a rabbit Psoroptes cuniculi model. In each case the new avermectin performed favourably relative to dihydroavermectin B1a (DHAVM), the major component of ivermectin. Doramectin was extensively evaluated in cattle using an experimental micelle formulation, proving highly effective in cattle infected with Ostertagia ostertagi, Cooperia oncophora and Dictyocaulus viviparus when administered subcutaneously at 200 micrograms kg-1. The plasma pharmacokinetic characteristics of doramectin in cattle following intravenous administration revealed a plasma half-life of approximately 89 h. In the micelle formulation, doramectin administered subcutaneously at 400 micrograms kg-1 provided persistent activity against infection of cattle with C. oncophora and O. ostertagi for at least 8 and 12 days respectively.

Efficacy of doramectin in the prevention of gastrointestinal nematode infections in grazing cattle.

Two studies were performed to investigate the efficacy of doramectin in the prevention of infection with Ostertagia ostertagi and Cooperia oncophora in grazing calves. In each study, 24 parasite-naive calves were randomly allotted to two equal groups and treated with either doramectin at 200 micrograms kg-1 or saline prior to mid-season turnout (Day 0) onto contaminated pasture. Faecal egg counts were carried out twice weekly from 15 to 64 days after turnout and the cumulative faecal egg count was calculated for each group of calves. In the doramectin-treated animals, eggs first appeared in the faeces 19 days and 22 days later than in controls for Studies 1 and 2, respectively. Mean cumulative faecal egg counts over the 64 days were reduced in the doramectin-treated groups by 71% and 87% for Studies 1 and 2, respectively (P < 0.01). The potential utility of injectable doramectin in the seasonal control of gastrointestinal nematode infestations in relation to these findings is discussed.

Spectrum of activity of doramectin against cattle mites and lice.

A series of 16 studies was conducted involving 288 cattle with naturally acquired or experimentally induced mite or louse infestations to evaluate the efficacy of doramectin. Four studies were conducted against the mite species Psoroptes bovis and two against the mite species Sarcoptes scabiei. Ten studies involved cattle with one or more of the following louse species: Damalinia bovis, Haematopinus eurysternus, Linognathus vituli and Solenopotes capillatus. In each study, a group of at least nine but not more than 25 cattle were randomly allocated to a control or a treated group. One group was treated with doramectin at 200 micrograms kg-1 and the other group received no medication. Mites or lice were quantified by species immediately before treatment and at weekly intervals for 4 weeks thereafter. Doramectin was 100% efficacious against infestations of P. bovis, Sarcoptes scabiei, H. eurysternus, L. vituli and Solenopotes capillatus. The drug reduced infestations of D. bovis by a mean of 82%.

Efficacy of doramectin against warble fly larvae (Hypoderma bovis).

The efficacy of doramectin in the treatment of cattle harbouring naturally acquired infestations of first, second and third instar larvae of Hypoderma bovis was determined in two studies carried out in the Burgundy region of France. In the first study, cattle on six farms with a history of H. bovis infestations were treated during October 1989 with either doramectin at a dose of 200 micrograms kg-1 liveweight (186 animals) or with an equivalent volume of saline (157 animals). During the following March and April, all animals were examined for the presence of warbles. In the second study, cattle on four farms with warbles present in their backs were treated during March 1990, with either doramectin or saline (as before). The viability of larvae within each warble on all the animals was then assessed every 2 days for 14 days. In Study 1, no warbles were present in any of the doramectin-treated cattle at any time, whereas warbles were found in 135 saline-treated animals. In Study 2, all larvae in warbles on the backs of the doramectin-treated cattle were dead by Day 14 after treatment, whereas viable larvae were still present in warbles in the backs of all saline-treated cattle. No adverse reaction to doramectin treatment was observed in any animal at any time. It was concluded that doramectin is both safe and 100% efficacious in the treatment of first, second and third instar H. bovis infections of cattle.

Doramectin, a new avermectin highly efficacious against gastrointestinal nematodes and lungworms of cattle and pigs: two studies carried out under field conditions in Germany.

Two field studies were carried out to confirm the efficacy of doramectin in cattle and pigs in Europe. A total of 40 cattle harbouring naturally acquired infections of gastrointestinal nematodes, including Ostertagia spp., Oesophagostomum spp., Cooperia spp., Haemonchus spp., Nematodirus spp. and Trichuris spp., were allocated to a treated or a control group (20 animals/group), and 100 harbouring naturally acquired infections of gastrointestinal nematodes and lungworms, including Oesophagostomum spp., Metastrongylus spp., Ascaris suum and Trichuris suis, were allocated to either a treated (60 pigs) or a control (40 pigs) group. Animals in the treated groups received an injection of doramectin at 200 micrograms/kg (1 ml/50 kg) for cattle or 300 micrograms/kg (1 ml/33 kg) for swine. Animals in the control groups received saline at 1 ml/50 kg for cattle or 1 ml/33 kg for swine. The cattle were injected by the subcutaneous route in the lateral mid-line of the neck and the pigs were injected intramuscularly in the neck. Faecal egg counts were determined for all animals on days--7, 0, 7, 14 and 21 of the studies, where day 0 was the day of treatment. The mean daily weight gain of doramectin-treated animals was significantly higher than that of the control animals over the 21 days of the studies (P < 0.0007 for cattle and P = 0.0001 for swine). At 21 days after treatment, the mean faecal egg counts of the doramectin-treated animals were significantly lower than those of the control animals and were reduced by 100% as compared with pretreatment levels. No adverse reaction to treatment was observed in any animal during either study.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of the morantel sustained release trilaminate in the control of parasitic gastroenteritis in first season grazing cattle.

A novel intraruminal bolus developed for the sustained delivery of the anthelmintic morantel tartrate was evaluated in the seasonal control of parasitic gastroenteritis in first season grazing calves. The morantel sustained release trilaminate is a trilaminate sheet consisting of a central lamina of a morantel tartrate/ethylene vinyl acetate matrix coated on both sides with a thin impermeable layer of ethylene vinyl acetate. A symmetrical pattern of circular perforations punched through the device controls the release of morantel. Administration of the trilaminate to calves significantly reduced their faecal egg output compared with untreated controls and thus reduced pasture larval contamination. Clinical parasitic gastroenteritis was prevented in the treated calves and there were significant reductions in their worm burdens compared with the untreated control calves both during and at the end of the grazing season. The control of parasitic gastroenteritis resulted in a significantly greater (P less than 0.0001) weight gain, of 45 kg, by the treated calves.

The efficacy of sulbactam-ampicillin in the therapy of respiratory disease associated with ampicillin resistant Pasteurella species in housed calves.

Sulbactam-ampicillin is a combination of sulbactam, a beta-lactamase inhibitor, and ampicillin, a broad spectrum beta-lactam antibiotic. The efficacy of sulbactam-ampicillin was evaluated in the treatment of calf respiratory disease associated with ampicillin-sensitive and ampicillin-resistant strains of Pasteurella haemolytica and Pasteurella multocida. Treatment with sulbactam-ampicillin was compared with treatment with ampicillin alone in 123 Friesian calves, between three and five weeks old, exhibiting clinical signs of respiratory disease. Seven of the 59 calves treated with ampicillin died whereas only one death occurred in the 64 calves treated with sulbactam-ampicillin. In the calves which survived, treatment with sulbactam-ampicillin resulted in a significantly better clinical response, as measured by the reduction in severity of clinical signs. The results of bacteriological examinations indicated that there was a marked increase in the proportion of ampicillin-resistant isolates of P haemolytica subsequent to treatment with ampicillin, whereas the proportion of ampicillin-resistant isolates of P. haemolytica recovered from calves treated with sulbactam-ampicillin had declined. The superior efficacy of sulbactam-ampicillin observed in this study is explained by the inhibitory effect of sulbactam on beta-lactamases produced by resistant bacteria, thus rendering them susceptible to the ampicillin.

Possible role of histamine in the genesis of pulmonary arterial disease in cats infected with Toxocara cati.

Kittens between 12 and 20 weeks of age were orally dosed with 6000 infective ova of Toxocara cati. Animals were sacrificed at intervals between one and eight weeks after infection to study the development of pulmonary arterial lesions. After two weeks, marked leucocyte infiltration and mild thickening of the media of some of the smaller arteries was apparent histologically . Cellular inflammatory activity progressively increased up to four weeks after infection when intimal proliferation was evident in many of the arteries. After six weeks, the arterial walls were grossly thickened with pronounced intimal proliferation which after eight weeks had resulted in complete occlusion of some vessels. The progressive arterial occlusion was associated with a three- to four-fold increase in the parenchymal mast cell population and a corresponding increase in lung histamine content. The possible role of histamine in the genesis of the arteriopathy is discussed.

The transfer of calcium during perfusion of the placenta and intact and thyroparathyroidectomized sheep.

Placental perfusions were carried out in six ewes during the last two weeks of gestation. Perfusions were carried out using autologous fetal blood and the flow rates adjusted to give a perfusion pressure of 50--70 mmHg. Perfusion plasma calcium concentrations rose steadily throughout the perfusions achieving a mean increase of 1.65 mmol/1 above initial concentration within 100 minutes. A further three ewes in the last two weeks of gestation were thyroparathyroidectomized and normal plasma calcium concentration maintained by an intravenous infusion of calcium borogluconate. After three days, placental perfusions were carried out as before. The mean perfusion plasma calcium concentration achieved by those three ewes in a period of 100 minutes showed an increase of 1.25 mmol/1. It is concluded that the presence of the fetus is not necessary for the continued active transfer of calcium across the placenta from mother to fetus. The reduced rate of accumulation of calcium in the perfusate in TXPTX ewes is attributed to a decline in 1,25-DHCC concentrations in both maternal and fetal circulations. The implications of these results in relation to fetal calcium homeostasis and the placental transfer of calcium are discussed.

Calcium homeostasis in the fetal pig.

Acute studies have been carried out with pregnant sows and their fetuses during the last 2 weeks of gestation. In blood samples obtained simultaneously it was shown that the concentrations of ionized calcium, calcitonin and parathyroid hormone (PTH) in fetal plasma were all greater than the corresponding values in maternal plasma. In contrast, the fetal concentrations of 24,25-dihydroxy vitamin D3 were lower than maternal and those of 1,25-dihydroxy vitamin D3 were not significantly different. In one experiment the circulatory level of fetal PTH was shown to be higher than in the sow by both an immunoradiometric assay and a very sensitive cytochemical assay. The latter showed the fetal: maternal ratio to be approximately three. This inappropriately high level of fetal PTH was unaffected by short term hypocalcaemic and hypercalcaemic changes in the fetal circulation. Although part of this fetal PTH may have been secreted in response to the action of beta-catecholamines released as a result of the experimental conditions, the transplacental gradient of PTH was also demonstrated in the chronically catheterized fetus. A short term period of either hypercalcaemia or hypocalcaemia induced in the mother was without consistent effect upon plasma calcium concentration in the fetus. However, an increase in ionized calcium concentration in the fetal plasma was found to follow the cessation of a period of maternal hypocalcaemia. It can be seen that the porcine fetus possesses the important elements of a calcium homeostatic mechanism, namely parathyroid hormone, calcitonin and the biologically active metabolites of vitamin D. Although the degree of independence from the mother is somewhat less than in the sheep, it is concluded that the porcine fetus is largely autonomous with respect to calcium homeostasis.