甲硝唑对鸡回忆性体液免疫应答反应的作用

本试验系统观察了甲硝唑对鸡回忆性体液免疫应答反应的作用,并与咪唑类化合物左旋咪唑进行了比较。28日龄鸡,免疫注射绵羊红细胞 牛血清白蛋白(SRBC BSA)悬液,或稀释的布氏杆菌(BA)抗原。56日龄时,以10.0、100.0mg/kg甲硝唑或10.0mg/kg 左旋咪唑饮水给药,连用3d,给药第二天同时进行第二次免疫注射。结果表明甲硝唑(10.0~100.0mg/kg)可使鸡体内对颗粒性胸腺依赖性抗原SRBC和非胸腺依赖性抗原BA抗体滴度回忆性免疫应答反应明显升高;但使鸡对可溶性胸腺依赖性抗原BSA抗体滴度回忆性免疫应答反应明显降低。与甲硝唑比较,左旋咪唑(10.0mg/kg)也存在着非常类似的作用。     

Disposition of gentamicin in the genital tract of cows

The distribution of gentamicin (G) in plasma and uterine lumen was studied following intramuscular (i.m.) and intrauterine (i.u.) treatment. A Foley catheter was inserted into one uterine horn and retained in place by inflation of the cuff. This provided a closed system for collection of uterine lumen samples and analysis of the concentration of gentamicin for 6 h following treatment. Four normal cycling and healthy cows in dioestrus were given i.m. injections of 4 mg gentamicin/kg BW and another two were given i.m. injections of 2 mg gentamicin/kg BW gentamicin. The uteri were infused with 50 ml saline containing phenolsulphonphthalein (PSP) indicator. Blood and infused solution (IS) samples were periodically collected during the 6-h period following i.m. administration. Six hours after injection, approximately 183.7 micrograms gentamicin and 39.4 micrograms gentamicin were accumulated in the uterine lumen of cows receiving 4 mg gentamicin/kg BW and 2 mg gentamicin/kg BW, respectively. The amount of gentamicin reaching the blood stream after i.m. administration of 4 mg gentamicin/kg BW was 2.89 times that reached after administration of 2 mg gentamicin/kg BW based on the area under the curve of plots of plasma concentration of gentamicin versus time. Four normal-cycling and healthy cows in dioestrus were given i.u. infusions of gentamicin (225-275 mg) diluted in 50 ml saline containing PSP indicator using a Foley catheter in a closed system. Samples from the IS and blood were collected at various intervals for 6 h after infusion. Following i.u. infusion of gentamicin, an average of 29.4% of the dose was absorbed into the bloodstream. The majority of the dose of gentamicin (70.6%) remained in the uterine lumen throughout the 6-h period.     

Effects of probenecid on blood levels and tissue distribution of ampicillin in fowls and turkeys

The effect of probenecid (a benzoic acid derivative which competitively inhibits active secretion of weak organic acids by the renal tubules) on serum ampicillin concentrations and the distribution of ampicillin in body organs was examined in fowls and turkeys. An aqueous solution of probenecid coadministered intramuscularly, at 200 mg/kg, with sodium ampicillin solution, at 25 mg/kg, resulted in peak serum antibiotic concentration of 16.5 microgram/ml. A similar dose of ampicillin administered alone produced a peak level of 4.6 microgram/ml. Subcutaneous injections of sodium ampicillin at 25 mg/kg with aqueous probenecid at 200 mg/kg resulted in a peak serum ampicillin concentration (12.8 microgram/ml) three times as high as the peak produced by the subcutaneous injection of ampicillin alone at 50 mg/kg (4.2 microgram/ml). The elimination half-life (t 1/2) of the drug (30 min) was increased to 1.5 hr by coadministration of probenecid parenterally, and serum antibiotic levels greater than or equal to 5.0 microgram/ml were maintained during 3 hours. Ampicillin seemed to be poorly absorbed from the gastrointestinal tract of fowls. A single oral bolus administration of ampicillin trihydrate aqueous suspension produced a peak of 0.6 microgram/ml, and coadministrations of aqueous probenecid suspension at 20, 50, and 100 mg/kg respectively produced peaks of 0.9, 1.25, and 1.5 microgram/ml. During 4 and 5 days, when ampicillin was added to the drinking water at rates of 200 and 50 mg/liter, serum ampicillin levels were rather low (peaks of 0.20 and 0.12 microgram/ml, respectively), and although these levels were increased by 50% with the coadministration of probenecid they were considered to be of limited clinical value for treating systemic bacterial infections. Probenecid did not change the distribution of ampicillin in the organs.     

Seasonal variation in anthelmintic response by cattle to dermally applied levamisole

Four experiments in 1978-79, and 2 in 1982 designed to define the optimum dose rate of dermally applied formulations of levamisole are described. These experiments showed that the absorption of levamisole with resultant blood levels and anthelmintic activity is strongly influenced by temperature. In warm to hot conditions percutaneous absorption is rapid and high blood levels with high anthelmintic activity against Haemonchus placei, Ostertagi sp, Trichostrongylus sp, Cooperia sp, Oesophagostomum radiatum, O. venulosum and Dictyocaulus viviparus result from dose rates of 10 mg/kg or more. In cold weather the high efficacy against H. placei, Cooperia sp, and Oesophagostomum sp is unchanged, but efficacy against Ostertagia sp, T. axei and D. viviparus decreases to the extent that a mean dose rate of 20 mg/kg (range 15 to 25 mg/kg) is necessary if the anthelmintic activity of dermally applied levamisole is to match that of either parenterally or orally administered material. These anthelmintic data are supported by the levamisole blood profile which in winter months, peaks at a figure of one quarter or less of that obtained from a similar dose rate in warm conditions. The implications of this variability in action are discussed.     

Deconvolution study of the absorption rate and disposition kinetic values of lindane in sheep.

Absorption rate and plasma and fat disposition of lindane after various lindane percutaneous treatments in shorn and unshorn sheep were investigated. To analyze data with a deconvolution method, IV administration was performed to determine the basic pharmacokinetic values of lindane in sheep. After IV administration, the steady state volume of distribution was very high (8.07 +/- 3.60 L/kg of body weight), and the mean residence time was long (28.1 +/- 11.7 hours). Deconvolution analysis indicated that lindane absorption was continuous until 33 to 41 days after spraying with a 0.025% lindane solution. Total amount of absorbed lindane in shorn (15,171 +/- 4,463 micrograms/kg) sheep was about twice that in unshorn (7,615 +/- 3,128 micrograms/kg) sheep; from deconvolution analysis, it was calculated that the time required for 50% of the available dose to be absorbed was between 115 and 179 hours. After percutaneous lindane administration, the fat concentration was compared with the available lindane dose. The apparent half-life of lindane elimination in fat was 225 +/- 47.4 hours, which is similar to the value calculated for the absorption rate constant. By comparing fat and plasma concentrations, it was calculated that for a mean plasma concentration of 5 ng/ml, the fat lindane concentration was 1.65 +/- 0.87 micrograms/g (ie, lower than the generally accepted tolerance level of 2 micrograms/g).     

The anthelmintic efficacy of five plant products against gastrointestinal trichostrongylids in artificially infected lambs

Forty-eight helminth-free lambs were divided into eight groups (A-H) of six animals. Groups A-G were infected artificially with 10,000 third stage larvae of Haemonchus contortus and 20,000 third stage larvae of Trichostrongylus colubriformis, whereas group H remained uninfected. Thirty days post-infection the lambs were treated orally with a single dosage of one of the following products: group A with 3 mg/kg body weight (BW) of an aqueous ethanol extract (70%, v/v) of the seeds of Azadirachta indica A. Juss syn. Melia azedarach L. (Meliaceae); group B with 1 g/kg BW of a raw powder of the leaves of Ananas comosus (L.) Merr. (Bromeliaceae); group C with 0.3 mg/kg BW of an aqueous ethanol extract of a 1:1 mixture (g/g) of Vernonia anthelmintica (L.) Willd. (Asteraceae) seeds and Embelia ribes Burm (Myrsinaceae) fruits; group D with 183 mg/kg BW of an aqueous ethanol extract of the whole plants of Fumaria parviflora Lam. (Fumariaceae); group E with 28 mg/kg BW of an aqueous ethanol extract of the seeds of Caesalpinia crista L. (Caesalpiniaceae); group F with 25 mg/kg BW of pyrantel tartrate and group G with 50% ethanol. Group H remained untreated. Only the ethanol extract of F. parviflora caused a strong reduction of the faecal egg counts (100%) and a 78.2 and 88.8% reduction of adult H. contortus and T. colubriformis on day 13 post-treatment. The extract was as effective as the reference compound pyrantel tartrate. Therefore, the ethanol extract itself or single constituents of F. parviflora could be a promising alternative source of anthelmintic for the treatment of gastrointestinal trichostrongylids in small ruminants.     

Efficacy of levamisole against immature and mature nematodes in goats with induced infections

Anthelmintic efficacy of levamisole against induced infections with 7- and 21-day-old Haemonchus contortus, Ostertagia circumcincta, Trichostrongylus axei, and T colubriformis was evaluated as an oral drench in goats. Group 1 (n = 8) was not treated, group 2 (n = 8) was given 3.96 mg of levamisole/kg of body weight, group 3 (n = 8) was given 7.92 mg of levamisole/kg, and group 3 (n = 7) was given 11.88 mg of levamisole/kg. Efficacy against all worms was low in goats given 3.96 mg of levamisole/kg, but was high against adult H contortus (99%) and adult T colubriformis (99.7%) in goats given 7.92 mg of levamisole/kg. Although efficacy against adults of all species was high in goats given 11.88 mg of levamisole/kg, some immature worms of all species remained in the abomasa of goats.     

Characterisation of two triple resistant field isolates of Teladorsagia from Scottish lowland sheep farms

The anthelmintic resistance status of two field isolates derived from farms (farm A and B) located near Edinburgh were examined using both controlled efficacy tests (CET) and faecal egg count reduction tests (FECRT). Efficacies against fenbendazole (FBZ), levamisole (LEV) and ivermectin (IVM) and, for one isolate, against combinations of these anthelmintics and moxidectin were determined in na?ve lambs, artificially infected with the isolates and treated with the compounds at the manufacturers recommended dose rates. (FBZ, 5mg/kg bodyweight (BW); LEV, 7.5mg/kg BW; IVM, 0.2mg/kg BW; Moxidectin (MOX) 0.2mg/kg BW). In both field isolates, the predominant species found pre-treatment and the only species found post-treatment was Teladorsagia circumcincta. Resistance to FBZ, LEV and IVM was confirmed in CET and FECRT on farm A and to the latter two compounds on farm B, which had a history of benzimidazole resistance and where TBZ resistance was also demonstrated using an egg hatch assay (EHA). For the farm A isolate CET efficacies against FBZ; IVM; LEV; FBZ + IVM; FBZ + LEV; FBZ, LEV + IVM and MOX were 59, 60, 88, 94,93, 92 and 98%, respectively. The CET efficacies for the farm B isolate were 51% and 72% for LEV and IVM, respectively.     

Efficacy, safety, and residue evaluation of levamisole gel formulation in sows

Anthelmintic efficacy, safety, and residue studies were conducted in sows and gilts with a levamisole gel containing 11.5% levamisole HCl. In 12 sows and 12 gilts, 8 mg of levamisole HCl equivalent/kg of body weight orally was 100% (resinate) and 91.1% (gel) effective against 55-day-old Ascaris suum and 100% (gel) and 96.1% (resinate) effective against Oesophagostomum dentatum. In 20 sows given levamisole gel (8 mg of levamisole HCl/kg) orally just before breeding, 4 to 6 weeks after breeding, 4 to 6 weeks before farrowing, and just before farrowing, there were no adverse effects. Transient salivation was noticed in five sows after treatment. In 4 groups of 4 sows each given levamisole gel orally to provide 8, 24, 40, or 80 mg of levamisole HCl/kg, adverse clinical signs were not observed in sows treated with 8 mg/kg. Transient salivation was noticed in one sow given 24 mg/kg, two sows given 40 mg/kg, and four sows given 80 mg/kg. Multiple emesis and chomping occurred in one sow given 80 mg/kg. Levamisole residues in edible tissues from sows given 8 mg of levamisole gel/kg orally were less than 0.1 mg/kg of muscle and fat in sows killed on posttreatment day (PTD) 3 and less than 0.1 mg/kg of kidney in sows killed on PTD 5. Liver residues averaged 0.78 mg/kg in sows killed on PTD 3 and were reduced to 0.31 mg/kg in sows killed on PTD 5. The 99% upper tolerance limit with 95% confidence on the withdrawal time to assure levamisole residues of less than 0.10 mg/kg in liver tissue was 11 days.     

High caudal epidural anaesthesia with local anaesthetics or alpha(2)-agonists in calves

The objective of this study was to examine the efficacy of a caudal epidural anaesthesia using lidocaine or xylazine in a high volume for analgesia of the flank, navel and hamstring tendon. Fourteen calves weighing 57.7 +/- 5.1 kg and 37.9 +/- 9.3 (mean +/- SEM) days old were randomly divided into two groups of seven calves each. Calves belonging to the lidocaine group were given a 2% lidocaine solution in the sacrococcygeal vertebral space epidurally at a volume of 0.4 ml/kg (8 mg/kg) body weight (BW). Animals of the xylazine group were administered an epidural anaesthesia with xylazine at a dose of 0.1 mg/kg BW, diluted with a 0.9% saline solution to a corresponding final volume of 0.4 ml/kg BW. Heart rate and respiratory rate were measured and the degree and duration of analgesia was determined by the response to a skin prick with a hypodermic needle over a period of 350 min after epidural injection. After epidural anaesthesia with lidocaine the mean heart rate increased during dorsal recumbency, whereas after xylazine both heart rate and respiratory rate decreased significantly (P < 0.05). The epidural injection of xylazine compared with lidocaine caused longer (P < 0.05) analgesia at the hamstring tendon (mean +/- SEM, 120.7 +/- 29.7 min versus 93.6 +/- 3.5 min) and at the flank (100.7 +/- 24.4 min versus 78.3 +/- 11.1 min). There were no differences in the intensity of analgesia between groups. After xylazine application analgesia at the navel was achieved for 95.0 +/- 14.1 min whereas after lidocaine injection sufficient analgesia at the navel was found in just two of seven calves for 55 and 95 min respectively. Based on above experiences, a second study was performed, in which a combination of xylazine and local anaesthetics was used and the injection volume was increased to prove the efficacy of caudal epidural anaesthesia in 15 calves (26.3 +/- 26.7 days; 57.1 +/- 19.5 kg) submitted to the clinic for regular umbilical surgery. In these cases the xylazine (0.1 mg/kg BW) was diluted with 2% lidocaine (n = 7) or 2% procaine (n = 8) to a corresponding final volume of 0.5-0.6 ml/kg BW. In all cases complete anaesthesia of the surgical area was achieved and no adverse effects were observed. Overall the high volume caudal epidural anaesthesia represents an effective, safe, cheap and easy to perform alternative for anaesthesia of the navel, flank and hamstring tendon in calves without major side effects.     

Anthelmintic resistance on goat farms in Georgia: efficacy of anthelmintics against gastrointestinal nematodes in two selected goat herds

Gastrointestinal nematode (GIN) parasitism is a major constraint to production of goats in the southeastern United States. The conventional method of control used by producers in this region is frequent use of anthelmintics during the warm season. Overuse of anthelmintics has led to an increase in the incidence of anthelmintic resistance in many parts of the world, but data on prevalence of anthelmintic resistance in GIN of goats in the southeastern United States are very limited. To address this issue, anthelmintic efficacy was determined in goat herds at the Fort Valley State University, Agricultural Research Station (FVSU-ARS) and the University of Georgia, College of Veterinary Medicine (UGA-CVM) using fecal egg count reduction (FECR) tests and DrenchRite((R)) larval development assays (LDA). At FVSU-ARS, 2-year-old Spanish goat does were randomly allocated to one of nine different treatment groups (n = 10): albendazole (ABZ; 20mg/kg body weight (BW)), fenbendazole (FBZ; 20mg/kg BW), ivermectin (IVM; 0.4 mg/kg BW), doramectin (DRM; 0.4 mg/kg BW), moxidectin (MOX; 0.4 mg/kg BW), levamisole (LEV; 12 mg/kg BW), morantel tartrate (MOR; 10mg/kg BW), a combination of IVM (0.4 mg/kg BW) and ABZ (20 mg/kg BW), and untreated controls. At UGA-CVM, goats were randomly allocated to one of five different treatment groups (n = 8): ABZ (20 mg/kg BW), IVM (0.4 mg/kg BW), MOX (0.4 mg/kg BW), LEV (12 mg/kg BW), and untreated controls. All drugs in both experiments were administered orally. Anthelmintic efficacy was calculated by comparing 14-day post-treatment FEC of treated and control animals, and percent reductions were interpreted using the World Association for the Advancement of Veterinary Parasitology guidelines for resistance. For the LDA, nematode eggs were isolated from pooled fecal samples of untreated control goats in each herd and used to perform DrenchRite((R)) assays. In the FVSU-ARS herd, MOX, LEV, the combination of IVM and ABZ, IVM, DRM, ABZ, MOR, and FBZ reduced FEC by 100, 91, 88, 78, 76, 62, 48, and 10%, respectively. In the UGA-CVM herd, MOX, LEV, ABZ and IVM, reduced FEC by 100, 94, 87, and 0%, respectively. In both herds moxidectin was the only drug tested that was fully effective. Results of the LDA were in agreement with results of the FECR tests for both herds. These data demonstrate the presence of GINs resistant to all three major anthelmintic classes in both goat herds.     

Altered metabolic hormones, impaired nitrogen retention, and hepatotoxicosis in lambs fed Kochia scoparia hay

Livestock grazing lush Kochia scoparia (L.) Schrad, sometimes experience BW loss, hyperbilirubinemia, photosensitization, and polyuria. Animals fed kochia hay may exhibit milder or negligible signs of toxicosis but fail to utilize nutrients efficiently. To characterize early aspects of kochia toxicosis and to evaluate prospective treatments, 12 wether lambs (34 +/- 3 kg) were fed prebloom kochia hay (83% OM, 15% CP, and 6.3% total oxalate) and treated as follows: 1) no treatment; 2) drenched daily with aqueous ZnSO4 to provide 30 mg of Zn/kg of BW); 3) injected i.p. twice weekly with N-acetyl-L-cysteine (CYS) in saline (21 mg/kg of BW) plus trans-stilbene oxide (TSO) in corn oil (27 mg/kg of BW); and 4) treated as 2) plus 3). Treatments were imposed factorially (2 x 2) with three lambs per treatment. Kochia intake (ad libitum) averaged .57 kg/d (1.7% of BW) for 80 d, and digestibility of DM and CP were 44 and 59%, respectively, at wk 4, but BW loss was severe (6 to 11 kg/lamb). After 14 d, serum insulin and prolactin were decreased (P less than .05) below initial values (.48 to .11 and 102 to 28 ng/ml, respectively). Serum somatotropin increased (P less than .05) from 4.5 to 6.8 ng/ml at 4 wk. Serum total bilirubin increased threefold at 3 wk (P less than .05) and declined slightly thereafter through 10 wk. Early changes in serum enzymes reflected mild hepatotoxicosis without cholestasis, whereas histopathology (at 80 d) showed diffuse hepatocyte swelling and nephrosis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Investigation of Immunmodulatory effects of levamisole and vitamin E on Immunity and some blood parameters in newborn Jersey calves

The immunmodulatory effects of dl-α tocopherol (vitamin E) and levamisole on the immune system and some blood parameters of newborn Jersey calves were investigated with the present study. Treatment groups 1, 2 and 3 were injected 13,3 ml isotonic saline solution (0,9% NaCl), 3 mg/kg levamisole HCl and 2000 IU vitamin E weekly, starting at birth until the age of two weeks. Average serum IgM levels of the control, levamisole and vitamin E calves were 111,7 ± 9,3 mg/100 ml, 251,9 ± 27,6 mg/100 ml, 202,2 ± 43,3 mg/100 ml respectively on day 22. Average serum IgG levels of the levamisole and vitamin E groups elevated, compared to the control group on days 1, 8, 15 and 22. However, there were stastistically differences in treatment and control groups for serum total cholesterol, low density lipoprotein (LDL), high density lipoprotein (HDL), triglyceride and cortisol values and whole blood counts. All differences were in the reference ranges. Levamisole and vitamin E could be used as an alternative way for their beneficial effects such as improving the humoral immune responses of calves and their safety and practical use against the neonatal period infections in the field.     

Pharmacokinetics, bioavailability, and in vitro antibacterial activity of rifampin in the horse

The pharmacokinetics and bioavailability of rifampin were determined after IV (10 mg/kg of body weight) and intragastric (20 mg/kg of body weight) administration to 6 healthy, adult horses. After IV administration, the disposition kinetics of rifampin were best described by a 2-compartment open model. A rapid distribution phase was followed by a slower elimination phase, with a half-life (t1/2[beta]) of 7.27 +/- 1.11 hours. The mean body clearance was 1.49 +/- 0.41 ml/min.kg, and the mean volume of distribution was 932 +/- 292 ml/kg, indicating that rifampin was widely distributed in the body. After intragastric administration of rifampin in aqueous suspension, a brief lag period (0.31 +/- 0.09 hour) was followed by rapid, but incomplete, absorption (t1/2[a] = 0.51 +/- 0.32 hour) and slow elimination (t1/2[d] = 11.50 +/- 1.55 hours). The mean bioavailability (fractional absorption) of the administered dose during the first 24 hours was 53.94 +/- 18.90%, and we estimated that 70.0 +/- 23.6% of the drug would eventually be absorbed. The mean peak plasma rifampin concentration was 13.25 +/- 2.70 micrograms/ml at 2.5 +/- 1.6 hours after dosing. All 6 horses had plasma rifampin concentrations greater than 2 micrograms/ml by 45 minutes after dosing; concentrations greater than 3 micrograms/ml persisted for at least 24 hours. Mean plasma rifampin concentrations at 12 and 24 hours after dosing were 6.86 +/- 1.69 micrograms/ml and 3.83 +/- 0.87 micrograms/ml, respectively. We tested 162 isolates of 16 bacterial species cultured from clinically ill horses for susceptibility to rifampin.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacokinetics of oxytetracycline hydrochloride in rabbits

Pharmacokinetics of oxytetracycline HCl (OTC) was studied in rabbits. After 10 mg of OTC/kg of body weight was administered IV, the distribution half-life was 0.06 hour, terminal half-life was 1.32 hours, volume of distribution area was 0.861 L/kg, and total body clearance was 0.434 L/kg/h. After 10 mg of OTC/kg was given IM, the absorption half-life was 2.09 hours, extent of absorption was 71.4%, and total body clearance of the absorbed fraction was 0.576 L/kg/h. Based on these kinetic data, a dosage of 15 mg of OTC/kg, every 8 hours was developed. This dose given IM for 7 consecutive days resulted in observed steady-state maximum and minimum concentrations (mean +/- SD) of 4.7 +/- 0.3 micrograms/ml and 3.2 +/- 0.6 micrograms/ml, respectively. Twice this dose (30 mg of OTC/kg, every 8 hours) given IM caused anorexia and diarrhea.     

Influence of glucocorticoid on macromolecular absorption and passive immunity in neonatal lambs

The relationship of serum cortisol to immunoglobulin absorption and gut closure in cesarean-derived neonatal lambs was evaluated in two trials. In trial 1, 21 lambs were obtained on d 136 to 138 of gestation, and in trial 2, 17 lambs were obtained on d 140 to 142 of gestation. At birth, lambs were assigned randomly to four treatments: 1) control (CO), 1 ml saline/kg BW every 4 h; 2) a drug to lower cortisol (LC), 5 mg metyrapone/kg BW every 4 h; 3) single-peak cortisol (SP), 10 IU ACTH/kg BW at 0 h; or 4) elevated cortisol (HC), 5 mg cortisol/kg BW every 4 h in trial 1 or 10 IU ACTH/kg BW every 4 h in trial 2. The treatment period was 24 and 48 h after delivery for trial 1 and 2, respectively. Lambs were fed pooled bovine colostrum every 4 h for 48 h after birth at 2 and 3.5% BW for trial 1 and 2, respectively. Compared with CO, HC increased serum cortisol, LC decreased serum cortisol and SP elevated serum cortisol concentrations through at least 8 h for both trials. In trial 1, HC and SP lambs exhibited elevated serum IgG, IgM and IgA concentrations by 20 h compared with CO. However, no difference in serum immunoglobulin concentration was observed at 36 h among CO, HC and SP. Conversely, LC had the lowest immunoglobulin concentration at 36 and 48 h, and precocious closure to immunoglobulin absorption had occurred by 20 h (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Multiple resistance in goat-derived Ostertagia and the efficacy of moxidectin and combinations of other anthelmintics

Faecal egg count reduction tests were used to identify a strain of Ostertagia circumcincta/trifurcata complex in goats which was resistant to: ivermectin (at 0.2 mg/kg and 0.4 mg/kg orally), oxfendazole (at 5 mg/kg orally), levamisole (at 12 mg/kg orally) and fenbendazole (at 5 mg/kg orally) combined with levamisole (at 9.4 mg/kg orally). The percentage reductions achieved in these faecal egg count reduction tests were respectively 27%, 83%, 82%, 79% and 82%. Moxidectin (at 0.2 mg/kg by subcutaneous injection), fenbendazole (at 10 mg/kg orally) combined with levamisole (at 18.8 mg/kg orally), ivermectin (at 0.4 mg/kg orally) combined with oxfendazole (at 10 mg/kg orally) and ivermectin (at 0.4 mg/kg orally) combined with levamisole (at 12 mg/kg orally) were effective in removing these nematodes in goats as determined by faecal egg count reduction tests. These drenches achieved reductions of 100%, 100%, 98% and 100% respectively.     

Growth hormone release after N-methyl-D,L-aspartate in sheep: dose response and effect of an opioid antagonist

The objectives of our experiments were 1) to determine the effect of N-methyl-D,L-aspartate (NMA), an agonist of the neuroexcitatory amino acids aspartate and glutamate, on growth hormone (GH) release in ovariectomized ewes, and 2) to determine the effect of naloxone, an opioid antagonist, on the GH response to NMA. Jugular blood was collected via venipuncture at 12-min intervals for 2 h before and 2 h after i.v. injection of NMA. In Exp. 1, ewes received either 0, 6, 12 or 24 mg NMA/kg BW dissolved in .9% saline solution (n = 4 per treatment). Growth hormone concentrations were similar (P greater than .1) between groups prior to injection (9.8 +/- .7 ng/ml; mean +/- SEM) and were unaffected (P greater than .1) by saline treatment. In contrast, 6, 12 or 24 mg NMA/kg BW increased mean GH concentration by 210% (P less than .04), 273% (P less than .02) and 234% (P less than .02), respectively. In Exp. 2, ewes received NMA (6 mg/kg BW) 5 min after either saline (n = 4) or naloxone (1 mg/kg BW; n = 4) pretreatment. Serum GH concentrations averaged 7.0 +/- 1.1 ng/ml before pretreatment and increased similarly (238%; P greater than .1) in both groups following NMA. In summary, NMA increased GH concentrations in ovariectomized ewes by some mechanism that does not involve opioid receptors that are antagonized by naloxone.     

Pharmacokinetics of metronidazole and its concentration in body fluids and endometrial tissues of mares.

Serum concentrations of metronidazole were determined in 6 healthy adult mares after a single IV injection of metronidazole (15 mg/kg of body weight). The mean elimination rate (K) was 0.23 h-1, and the mean elimination half-life (t1/2) was 3.1 hours. The apparent volume of distribution at steady state was 0.69 L/kg, and the clearance was 168 ml/h/kg. Each mare was then given a loading dose (15 mg/kg) of metronidazole at time 0, followed by 4 maintenance doses (7.5 mg/kg, q 6 h) by nasogastric tube. Metronidazole concentrations were measured in serial samples of serum, synovia, peritoneal fluid, and urine. Metronidazole concentrations in CSF and endometrial tissues were measured after the fourth maintenance dose. The highest mean concentration in serum was 13.9 +/- 2.18 micrograms/ml at 40 minutes after the loading dose (time 0). The highest mean synovial and peritoneal fluid concentrations were 8.9 +/- 1.31 micrograms/ml and 12.8 +/- 3.21 micrograms/ml, respectively, 2 hours after the loading dose. The lowest mean trough concentration in urine was 32 micrograms/ml. Mean concentration of metronidazole in CSF was 4.3 +/- 2.51 micrograms/ml and the mean concentration in endometrial tissues was 0.9 +/- 0.48 micrograms/g at 3 hours after the fourth maintenance dose. Two mares hospitalized for treatment of bacterial pleuropneumonia were given metronidazole (15.0 mg/kg, PO, initially then 7.5 mg/kg, PO, q 6 h), while concurrently receiving gentamicin, potassium penicillin, and flunixin meglumine IV. Metronidazole pharmacokinetics and serum concentrations in the sick mares were similar to those obtained in the healthy mares.     

Efficacy of thiabendazole, mebendazole, levamisole and ivermectin against gullet worm, Gongylonema pulchrum: in vitro and in vivo studies

In vitro and in vivo studies were conducted to evaluate the effects of thiabendazole, mebendazole, levamisole and ivermectin against Gongylonema pulchrum. For in vitro assays, third-stage larvae (L3) incubated with the drugs were administered orally to mice and the ability of larvae to invade the gastric mucosa of the animals was examined. After incubation, only those larvae treated with high concentrations of levamisole (1 and 10 microg/ml) were tightly coiled with intestines exhibiting morphological abnormalities. Good dose-response data for the drugs tested was observed at the time of worm recovery from mice, with no worms recovered at the two highest concentrations of levamisole. In vivo efficacy of the drugs against adult worms was evaluated in six groups of three rabbits, each of which was infected with 30 L3 of G. pulchrum and treated with thiabendazole at 100 mg/kg for 3 days, mebendazole at 70 mg/kg for 3 days, levamisole as a single dose of 8 mg/kg, and subcutaneously injected ivermectin as a single dose of 0.2 mg/kg or vehicles of the drugs (control) at 4 months post-infection. Necropsy 14 days after treatment revealed that levamisole, mebendazole and ivermectin reduced worm burdens by 63.2%, 22.8% and 25.8%, respectively, with no reductions in worms observed with thiabendazole. The surviving worms were principally found in the esophagus with the remainder distributed among the buccal mucosa, the tongue, and/or pharyngeal mucosa in all groups. A number of morphologically abnormal eggs were observed within the uterus and ovijector in female worms recovered from the thiabendazole-treated group. These findings suggest that levamisole exhibits in vivo efficacy against G. pulchrum infection and that the larval invasion tests using mice could be used to screen for anthelmintic susceptibility of nematodes.