Effects of p,p''-DDT on the Rat Brain Concentrations of Biogenic Amine and Amino Acid Neurotransmitters and Their Association with p,p''-DDT-Induced Tremor and Hyperthermia

Male, Fischer strain 344 adult rats were given various doses (25-100 mg/kg) of p,p'-DDT by oral gavage, and levels of biogenic amines, their metabolites, and amino acid neurotransmitters, tremor activity, and rectal temperature were measured at several intervals (2, 5, 12, and 24 h) after dosing. Dose-related increases in rectal temperature and in tremor activity were observed at 50-100 mg/kg 12 h after dosing. Tremorigenic doses of DDT increased the 5-hydroxyindoleacetic acid (5-HIAA) level in hypothalamus, brainstem, and striatum, whereas doses of 75 and 100 mg/kg increased the 3-methoxy-4-hydroxyphenylglycol (MHPG) level in hypothalamus and brainstem and the 3,4-dihydroxyphenylacetic acid level in striatum. Six amino acids were assayed in the brainstem, hypothalamus, and striatum; aspartate and glutamate levels were increased only in brainstem at 25-100 mg/kg. No consistent changes in concentrations of taurine, glutamine, glycine, or gamma-aminobutyric acid were observed in any of the regions assayed. Time-related increases in rectal temperature were seen 2-12 h after dosing, and the presence of tremor was observed 5-12 h after dosing; for both the time of peak effect was at 12 h. The DDT-induced hyperthermia and tremor were associated with dose- and time-related increases in levels of 5-HIAA, MHPG, aspartate, and glutamate. It is suggested that an increase in the turnover rate of 5-hydroxytryptamine (5-HT) may be responsible for the DDT-induced hyperthermia, whereas increases in the metabolism of 5-HT and norepinephrine may be involved in the tremor.     

The Effect of Different Levels of Selenium in Mineral Mixtures and Salt Licks on Selenium Status in Sheep

This paper describes 3 experiments comparing the effect of 10, 25 and 40 mg Se/kg, as sodium selenite, in mineral mixtures and salt licks fed to sheep. The supplement was given during the indoor season from October to May to 7 different flocks, each consisting of 50 to 100 sheep, in areas with selenium deficiency problems. The average selenium level in the basic diets did not exceed 0.05 mg/kg. Selenium status was monitored in the blood of ewes and lambs, and in milk. Blood selenium in lambs correlated well with blood selenium in their dams (r = 0.85). Selenium levels in milk on day 1 (colostrum) correlated well with selenium levels in dams (r = 0.92) and in offspring (r = 0.87). Statistically significant differences were found between the different flocks. In areas with extreme selenium deficiency, 10 mg Se/kg in mineral mixtures and salt licks proved insufficient. A content of 25 mg Se/kg, providing a daily intake of about 0.4 mg selenium, resulted in selenium levels in ewes’ blood, ewes’ milk and in the offspring that should prevent selenium deficiency disease without causing any toxic effects.     

Carbonic anhydrase activity in the blood of adult sheep, fetal sheep and lambs

The activity of carbonic anhydrase (E.C.4.2.1.1) (CA) has been measured in the blood of adult and fetal sheep and lambs. The mean activity in adult sheep was 0.89 enzyme units (EU) per 100 micrograms of Hb. The activity in fetal sheep aged 90 days was just below 20% of this and in fetuses near full term was just under 40% of the mean adult level. The regression line gave an increase of CA activity (per 100 micrograms Hb) of 0.004 EU/day. The appearance of CA in fetal blood normally occurred before any detectable production of adult Hb. One aberrant fetus showed early development of the adult pattern in the red cells, having adult type Hb and adult levels of CA during the period of 116-128 days of fetal age. In the period after birth the CA level in the blood rose rapidly, reaching the adult level 30 days after birth. During this period activity per 100 micrograms HB increased by 0.014 EU/day, significantly faster than during fetal life.     

Immunomodulatory activity of boswellic acids of Boswellia serrata Roxb

Extract of gum resin of B. serrata containing 60% acetyl 11-keto beta boswellic acid (AKBA) along with other constituents such as 11-keto beta-boswellic acid (KBA), acetyl beta-boswellic acid and beta-boswellic acid has been evaluated for antianaphylactic and mast cell stabilizing activity using passive paw anaphylaxis and compound 48/80 induced degranulation of mast cell methods. The extract inhibited the passive paw anaphylaxis reaction in rats in dose-dependant manner (20, 40 and 80 mg/kg, po). However, the standard dexamethasone (0.27 mg/kg, po) revealed maximum inhibition of edema as compared to the extract. A significant inhibition in the compound 48/80 induced degranulation of mast cells in dose-dependant manner (20, 40 and 80 mg/kg, po) was observed thus showing mast cell stabilizing activity. The standard disodium cromoglycate (50 mg/kg, ip) was found to demonstrate maximum per cent protection against degranulation as compared to the extract containing 60% AKBA. The results suggest promising antianaphylactic and mast cell stabilizing activity of the extract.     

Antiviral Activity of a bis-Benzimidazole Against Experimental Rhinovirus Infections in Chimpanzees

The marked antiviral activity of (S,S-1,2-bis(5-methoxy-2-benzimidazolyl)-1,2-ethanediol (Abbott 36683) against rhinoviruses in tissue culture warranted investigation of its antiviral activity in vivo. Antiviral levels in mouse sera were attained with an oral dose as small as 10 mg/kg and detectable antiviral levels of drug were also found in lung, liver, kidney, intestinal contents, and urine of mice given a single 300 mg/kg oral dose. Antiviral serum levels were also obtained when monkeys were given a single oral dose of Abbott 36683. Six chimpanzees were infected with 100 median tissue culture infective dose units (TCID(50)) of rhinovirus 30. Three of the animals were treated with Abbott 36683, 100 mg/kg daily for 4 consecutive days. Virus shedding occurred in the infected controls but could not be demonstrated in the treated animals from postinfection days 1 to 8. Two of the treated animals did, however, shed virus on day 9. The compound was retested in chimpanzees at dosage levels of 15 and 50 mg/kg daily for 4 days. Each animal was challenged with 100 TCID(50) of rhinovirus 49. Partial protection was obtained. In a third trial, a single 100 mg/kg dose of the compound was administered to chimpanzees infected with rhinovirus 44. Virus was isolated from all throat smears taken from treated animals, indicating that at the lowest drug level no protection occurred.     

The influence of supplemental vitamins A and E on ovine humoral immune response

These experiments determined if supplemental vitamins A and/or E would enhance ovine antibody responses. All-rac-alpha-tocopheryl acetate was fed to lambs approximately 6 months old (30 to 40 kg) at levels of 33 (controls), 121, 276, 396, and 476 mg/kg of feed (which are total vitamin E levels). Primary and secondary immunizations with 10 mg keyhole limpet hemocyanin (KLH) were given. A nonlinear dose response of serum antibody titers was observed and the 476 mg vitamin E/kg treatment significantly enhanced (P less than 0.05) the peak primary response over controls. Retinyl acetate fed at five levels ranging from 7000 (the control level) to 97,400 IU/kg feed failed to influence antibody production to 10 mg KLH of lambs about 6 months old (29 to 41 kg). There was no detectable response to an ovalbumin antigen (100 mg). Neonatal lambs were injected with retinyl palmitate or the carrier of the injected vitamin. These lambs failed to raise antibody titers to either of the antigens administered (10 mg KLH, 100 mg ovalbumin). This was apparently due to a neonatal period of immune paralysis to certain antigens. A preliminary study showed that no KLH-specific antibodies are detectable in lambs immunized earlier than 7 weeks of age. Lambs in this age range were utilized in the last trial in which four treatments were applied: 3000 mg oral vitamin E, 400,000 IU injected vitamin A, 4 ml of the injectable vitamin A carrier, or no treatment. Half of the animals in each of these groups were immunized with 15 mg KLH and 1 ml Brucella ovis bacterin and the other half served as nonimmunized controls. No significant differences in titers to KLH were observed. Lambs receiving 3000 mg vitamin E or the carrier produced secondary peak anti-B. ovis titers higher (P less than 0.05) than those of the untreated controls.     

Long-term feeding of concentrate fumigated with carbon tetrachloride to sheep

Growing male lambs and female sheep were fed for several months on concentrate fumigated with carbon tetrachloride. Residues of 100 ppm CC1₄ drastically reduced concentrate consumption. At the level of 35 ppm growth was proportional to the diminished intake. The concentrate containing 20 ppm did not affect growth, sexual development or reproductive activity of sheep of either sex. The acceptable daily intake of CC1₄ is about 0.7 mg/kg body weight. It is concluded that cereals fumigated with CC1₄ for insect control may be used, after thorough airing, for sheep feed.     

Multiple resistance to anthelmintics by Haemonchus contortus and Trichostrongylus colubriformis in sheep in Brazil

The objective of this study was to determine the level of resistance of Haemonchus contortus and Trichostrongylus colubriformis in sheep to levamisole, albendazole, ivermectin, moxidectin, closantel and trichlorfon. The parasites were isolated from sheep naturally infected by gastrointestinal nematodes and were then kept in monospecifically-infected lambs for production of infective larvae (L3) of both species. Forty-two lambs, at three months of age, were simultaneously artificially infected with 4000 L3 of H. contortus and 4000 L3 of T. colubriformis. The animals were allocated into seven groups with six animals each that received one of the following treatments: Group 1--control, no treatment; Group 2--moxidectin (0.2mg/kg body weight (BW)); Group 3--closantel (10mg/kg BW); Group 4--trichlorfon (100mg/kg BW); Group 5--levamisole phosphate (4.7 mg/kg BW); Group 6--albendazole (5.0mg/kg BW); and Group 7--ivermectin (0.2mg/kg BW). Nematode fecal egg counts (FEC) were carried out on the day of treatment and again at 3, 7, 10 and 14 days post-treatment. On the same occasions, composite fecal cultures were prepared for each group for production of L3, which were identified into genus. The animals were sacrificed for worm counts at 14 days after treatment. The efficacy of each treatment was calculated from the arithmetic mean of the FEC or worm burden of the treated group, compared with the values of the control group. Only trichlorfon and moxidectin treatments resulted in a significant reduction of H. contortus recorded at necropsy (73% and 45% respectively). Moxidectin reduced T. colubriformis worm burdens by 82% and albendazole by 19%. All other anthelmintics resulted in no significant reduction in the numbers of worms found at necropsy. In conclusion, the isolates of H. contortus and T. colubriformis showed multiple resistance to all groups of anthelmintics tested. This is the first report, based on the controlled efficacy test, to show resistance of T. colubriformis to macrocyclic lactones in Brazil.     

Residues of lindane in adipose tissue of lambs and sheep from islands Krk and Cres

Concentrations of lindane from adipose tissue i.e. omentum of sheep from homesteads of island Krk that were treated with lindane, were compared with the concentrations of lindane measured in adipose tissue of non treated sheep from husbandry cooperative on island Cres. Evaluation of food safety for this samples were estimated by comparing obtained results and maximum tolerance concentration (MTC) for lindane (2.0 and 0.2 mg/kg). In treated lambs from Krk measured concentrations of lindane were in range from 0.0038 to 1.8644 mg/kg, and in treated sheep from 0.0094 to 1.646 mg/kg. In control group of lambs and sheep concentration of lindane was < or = 0.0051 mg/kg. Estimation of food safety based on the results from this research are discussable, regarding the fact that MTC prescribed before year 2007 was 2.0 mg/kg. When the new law Regulations of MTC for residues of pesticides in food and animal feed (NN 119/07) came into the force prescribed MTC was 0.02 mg/kg. If food safety of sheep meat from Krk would be estimated based on latter, then 73.4% of samples of lamb meat and 80% of sheep meat could be proclaimed unsafe for human consumption. It is encouraging that after completion of using lindane in year 2005, levels of lindane in adipose tissue of lamb from Krk in year 2006 were under the concentration set by new legislate (< 0.02 mg/kg).     

Net mineral requirements for the growth and maintenance of Somali lambs

Minerals are limiting factors in animal production, and the knowledge of mineral requirements for livestock is crucial to the success of a commercial enterprise. Hair sheep may have different mineral requirements than those presents by the international committees. A study was carried to evaluate the net calcium (Ca), phosphorus (P), magnesium (Mg), sodium (Na), potassium (K), zinc (Zn), iron (Fe), manganese (Mn) and copper (Cu) requirements for the growth and maintenance of Brazilian Somali lambs. A total of 48 hair lambs (13.5±1.8 kg) aged 60±15 days were allocated to individual pens. Eight animals were slaughtered at the beginning of the experiment to serve as a reference group to estimate initial empty BW (EBW) and initial body composition. The remaining lambs (n=40) were assigned to a completely randomized design with eight replications in five levels of metabolizable energy (ME; 4.93, 8.65, 9.41, 10.12 and 11.24 MJ/kg DM). When the lambs of a given treatment reached an average BW of 28 kg, they were slaughtered. Initial body composition was used to calculate the retention of minerals. Mineral body composition was fit using a logarithmic equation in the form of a nonlinear model. The maintenance requirements were estimated from regressions of mineral retention in the empty body on mineral intake. The body mineral concentration decreased in lambs with a BW ranging from 15 to 30 kg. The net mineral requirements (100 g/day of average daily gain (ADG)) decreased from 0.52 to 0.51 g for Ca, 0.28 to 0.23 g for P, 0.02 to 0.02 g for Mg, 0.09 to 0.08 g for Na, 0.11 to 0.09 g for K, 1.30 to 1.08 mg for Zn, 3.77 to 3.22 mg for Fe, 0.08 to 0.06 mg for Mn and 0.09 to 0.08 mg for Cu when BW increased from 15 to 30 kg. The daily net requirements for maintenance per kilogram of BW were 30.13 mg of Ca, 27.58 mg of P, 1.26 mg of Mg, 4.12 mg of Na, 8.11 mg of K, 0.133 mg of Zn, 0.271 mg of Fe, 0.002 mg of Mn and 0.014 mg of Cu. The results of this study indicate that the net mineral requirements for weight gain and maintenance in Brazilian Somali lambs are different than the values that are commonly recommended by the main evaluation systems for feed and nutritional requirements for sheep. These results for the nutritional requirements of minerals may help to optimize mineral supply for hair sheep.     

Additional studies of sheep haemopexin: genetic control, frequencies and postnatal development

This study presents evidence that sheep haemopexin phenotypes are genetically controlled by three alleles, HpxA, HpxB1 and HpxB2, of a single autosomal locus. Frequencies of two alleles, HpxA and HpxB (HpxB encompasses two isoalleles, HpxB1 and HpxB2), were studied in eight sheep breeds in Czechoslovakia. The frequency of the HpxA allele was highest (ranging from 0.81 in Merino to 1.0 in East Friesian sheep). Qualitative and quantitative changes in haemopexin during postnatal development were studied by starch gel electrophoresis and rocket immunoelectrophoresis respectively. In electrophoresis, 1- or 2-day-old lambs had two very weak zones corresponding in mobility to two slower zones of adult animals. Later, the third more anodic zone appeared and gradually increased in intensity. In 1-month-old lambs the patterns were practically identical with those of adult animals. Using rocket immunoelectrophoresis, the level of haemopexin shortly after birth was practically zero. It rose sharply till the sixth day of life; then the level continued to rise slowly till about 1 month of age. The mean haemopexin level in adult sheep was 64.5 +/- 18.26 (SD) mg/100ml serum, ranging from 30.5 to 116.5 mg/100ml.     

A comparative study of hepatic DNA repair, DNA replication and hepatotoxicity in the CD-1 mouse following multiple administrations of dimethylnitrosamine

The objective of this study was to quantify hepatic DNA repair and DNA replication following multiple administrations of dimethylnitrosamine (DMN) and to determine if these events were correlated with hepatotoxicity. Male CD-1 mice, 50-100 days old, were dosed daily, p.o., with DMN in water at dose levels of 2, 4, 7 and 10 mg/kg for 2 weeks. After 2, 7 and 14 days of dosing, hepatocytes were isolated by an in situ perfusion procedure, incubated in the presence of [3H] thymidine, and fixed. Unscheduled as well as scheduled DNA synthesis were assessed by quantitative autoradiography. Unscheduled DNA synthesis (UDS) represents DNA repair while scheduled DNA synthesis (S phase) represents DNA replication. In addition, the animals' serum was examined for enzymes which indicate hepatic toxicity. After 1, 7 and 14 days of dosing, animals were orbital-bled and the serum was analyzed for serum glutamic pyruvic transaminase (SGPT), serum glutamic oxalacetic transaminase (SGOT), alkaline phosphatase (AP) and gamma-glutamyl transpeptidase (GGT). No morbidity or mortality was observed at dose levels of 2 and 4 mg/kg, but all animals receiving 7 and 10 mg/kg died after 4-6 days of dosing. GGT or AP were not elevated at any dose level or at any time point examined. At 4 mg/kg only a slight increase (less than or equal to 2 X) in the concentration of SGOT and SGPT was observed but a sharp increase (greater than 20 X) in replicative DNA synthesis was seen. The 2 mg/kg dose level of DMN did not increase replicative DNA synthesis and SGOT and SGPT were not elevated above control values at any time point following dosing at 2 mg/kg. A weakly positive DNA repair response was observed for dose levels of 4, 7 and 10 mg/kg DMN after two consecutive days of dosing. No DNA repair was observed after either 7 or 14 days of dosing at the 2 and 4 mg/kg/day levels. These results indicate that hepatic toxicity is associated with the induction of replicative DNA synthesis (S phase) but not with the induction of DNA repair. The results also confirm and extend a previous study (Doolittle et al., 1987b) indicating that a significant elevation in hepatic DNA replication is induced by hepatocarcinogens after multiple administrations of dose levels which do not alter hepatic DNA replication after a single administration. This finding indicates that the utility of the in vivo-in vitro hepatocyte assay may be enhanced by using a multi-dose protocol.     

Effect of physiological (in lamb) or drug-induced (in adult) immaturity of ram spermatozoa on seminal plasma alpha-glucosidase activity

We have been able to collect ejaculates from four pre-pubertal Finnish Landrace and Suffolk lambs. Respective seminal plasma alpha-glucosidase specific activity was low (less than 0.3 mU/mg) whatever the season of observation. At puberty, it reached a level higher than 1 mU/mg as observed in adult rams. Administration of alpha-chlorohydrin to 14 adult rams (25 mg/kg/day during 25 days) led to the appearance of immature sperm. Seminal plasma alpha-glucosidase activity dropped from 1.5 to 0.5 mU/mg in both breeds, while fructose was raised from 2 to 6 mg/ml. L-carnitine and blood plasma testosterone remained unchanged during treatment. Semen characteristics appeared normal one month after the end of treatment when fructose concentration decreased simultaneously and enzymatic activity increased during two months to normal levels. The present findings suggest that seminal plasma alpha-glucosidase may be considered as a useful epididymal marker in ram.     

Reproductive performance of the Y'ankasa sheep of Nigeria

The reproductive performance of the Y'ankasa sheep of Nigeria was studied to determine any seasonal effects on their breeding pattern. The study also aimed at documenting the reproductive performance levels of these animals as a basis for evaluating the results of any breeding improvement program in Nigeria using indigenous or exotic breeds of sheep. The study shows that this breed of sheep is a year-round breeder although some months favor lambing more than others. The age at first lambing and the lambing interval for these animals are 15.5 months and 9.7 months respectively. For 1975, the conception and lambing rates were 87.8% and 139% respectively. The rates for 1976 were 91% and 148%. Seventy-seven percent of the lambing were singles and the rest twins. The sex ratio, number of females per 100 lambs, was 49%. Lamb mortality rate up to 3 months of age was 12.0%. The lambs in our study grew very slowly, gaining only 15 kg in a 9-month period. By 10 months of age these lambs wieghed only 20 kg.     

Antioxidant activity and low toxicity of (E)-1-(1-(methylthio)-1-(selenopheny) hept-1-en-2-yl) pyrrolidin-2-one

The aim of the present study was to evaluate the potential pharmacological and toxicological properties of (E)-1-(1-(methylthio)-1-(selenopheny) hept-1-en-2-yl) pyrrolidin-2-one (compound 1), an organoselenium compound. In vitro experiments showed that compound 1 presented a reduction in the lipid peroxidation induced by Fe2? in thiobarbituric acid-reactive species (TBARS) production, and in the generation of reactive species caused by Fe2?/malonate in DCFH-DA oxidation. The high dose (500 mg/kg) induced an increase on ALT but not on AST activity. Hepatic, but not cerebral, δ-ALA-D activity from mice treated with 500 mg/kg presented a significant inhibition. Brain catalase activity was significantly inhibited by 100 mg/kg whereas hepatic catalase activity showed a significant increase at all doses. Hepatic lipid peroxidation was diminished only at lowest dose (100 mg/kg) whereas for brain tissue, all doses induced a significant reduction in TBARS levels. Brain and liver ascorbic acid contents were increased only at highest dose of compound 1. Urea and creatinine levels were not significantly altered by treatments. This is a promising compound with antioxidant activity and low toxicity, suggesting the potential beneficial activity of compound 1 against oxidative damage in many parameters studied in rats and mice.     

Effect of diamfenetide on experimental infections of Fasciola hepatica in lambs: anthelmintic and clinical investigations.

The activity of diamfenetide (N,N'-[oxybis(2,1-ethan diyloxy-4,1-phenylene)] bis acetamide) was studied in lambs experimentally inoculated with Fasciola hepatica. The drug was given orally at a dose level of 100 mg/kg either 1,3,5,7, or 9 weeks postinoculation. It was 100% effective 1, 3, and 5 weeks postinoculation, 73% effective 7 weeks postinoculation, and 57% effective 9 weeks postinoculation. Serum gamma-glutamyl transpeptidase activity remained normal in all lambs for 5 weeks after infection; it then began to increase in infected, untreated lambs at 6 weeks, and had increased 5- to 6-fold 9 weeks postinoculation in infected lambs. This enzyme activity was the most sensitive hematologic parameter used in this test to detect hepatobiliary damage by the parasite. The drug was well tolerated at the dose level used.     

Glutathione peroxidase activities in sheep and rat muscle and some effects of selenium deficiency.

The activity and distribution of the selenium-containing enzyme, glutathione peroxidase, has been determined in muscle fractions in normal adult rats and sheep. Skeletal and cardiac muscle have been examined, and in both types of muscle the major proportion of the enzyme appeared in the cytosol fraction. Enzyme activity was higher in cardiac muscle than in skeletal muscle in both species, and based on total protein present in fractions, it appears that rat muscle contains more enzyme activity than sheep muscle. In tissues from lambs born to selenium-deprived ewes the levels of enzyme were significantly depressed. Two sampling periods were selected, the first when the lambs were 2-3 weeks of age and the second at slaughter when they were 10 weeks old. Muscle, plasma and erythrocyte levels of the enzyme indicated that the most sensitive measure of selenium deficiency is likely to be that of the erythrocyte enzyme level.     

Antikinetoplastid activity of 3-aryl-5-thiocyanatomethyl-1,2,4-oxadiazoles

A series of 5-thiocyanatomethyl- and 5-alkyl-3-aryl-1,2,4-oxadiazoles were synthesized and evaluated for their activity against kinetoplastid parasites. Formation of the oxadiazole ring was accomplished through the reaction of benzamidoximes with acyl chlorides, while the thiocyanate group was inserted by reacting the appropriate 5-halomethyl oxadiazole with ammonium thiocyanate. The thiocyanate-containing compounds possessed low micromolar activity against Leishmania donovani and Trypanosoma brucei, while the 5-alkyl oxadiazoles were less active against these parasites. 3-(4-Chlorophenyl)-5-(thiocyanatomethyl)-1,2,4-oxadiazole (compound 4b) displayed modest selectivity for L. donovani axenic amastigote-like parasites over J774 macrophages, PC3 prostate cancer cells, and Vero cells (6.4-fold, 3.8-fold, and 9.1-fold, respectively), while 3-(3,4-dichlorophenyl)-5-(thiocyanatomethyl)-1,2,4-oxadiazole (compound 4 h) showed 30-fold selectivity against Vero cells but was not selective against PC3 cells. In a murine model of visceral leishmaniasis, compound 4b decreased liver parasitemia caused by L. donovani by 48% when given in five daily i.v. doses at 5mg/kg and by 61% when administered orally for 5 days at 50 mg/kg. These results indicate that aromatic thiocyanates hold promise for the treatment of leishmanial infections if the selectivity of these compounds can be improved.     

Dose-dependent activity of albendazole against benzimidazole-resistant nematodes in sheep: relationship between pharmacokinetics and efficacy

The relationship between the pharmacokinetic behaviour and the anthelmintic efficacy of albendazole (ABZ) against benzimidazole (BZD)-resistant nematodes was studied in sheep. A micronized ABZ suspension was orally administered at two different dose levels to sheep naturally infected with BZD-resistant gastrointestinal (GI) nematodes. The experimental animals were allocated into the following groups (n = 8): (a) untreated control; (b) orally treated with ABZ at 3.8 mg/kg b.w.; and (c) orally treated with ABZ at 7.5 mg/kg b.w. Plasma samples were obtained serially over 72 h post-treatment from both treated groups and analysed by HPLC to measure the concentrations of ABZ and its sulphoxide (ABZSO) and sulphone (ABZSO(2)) metabolites. Faecal egg counts were performed prior to treatment and at the necropsy day. All experimental animals were sacrificed 10 days after treatment to perform GI worm counts. While ABZ parent drug was not recovered in the bloodstream, ABZSO and ABZSO(2) were the molecules found in plasma. ABZSO was the metabolite measured at the highest concentrations in the bloodstream for up to 36 (treatment at 3.8 mg/kg) or 60 h (treatment at 7.5 mg/kg) post-administration. There was a proportional relationship between the administered ABZ dose and the measured plasma concentrations of both ABZ metabolites. Over a 100% increment on the plasma AUC values for the anthelmintically active ABZSO metabolite was observed at the 7.5 mg/kg compared to the 3.8 mg/kg treatment. The low efficacy patterns (< 24%) observed against the GI nematodes investigated indicate a high level of resistance to ABZ given at 3.8 mg/kg an efficacious therapeutic dose rate recommended in some countries. However, the higher and prolonged plasma drug concentration measured after the 7.5 mg/kg treatment resulted in an improved efficacy pattern (estimated by both faecal egg and adult worm counts) against most of the GI nematodes studied compared to that obtained at the lower dose rate. A direct relationship between drug pharmacokinetic behaviour and anthelmintic efficacy against BZD-resistant nematodes in sheep was shown in the current work, although individual variation precluded the observation of statistically significant differences in worm counts.