Flubendazole metabolism and biotransformation enzymes activities in healthy sheep and sheep with haemonchosis

Bártíková, H., Křížová, V., Lamka, J., Kubíček, V., Skálová, L., Szotáková, B. Flubendazole metabolism and biotransformation enzymes activities in healthy sheep and sheep with haemonchosis. J. vet. Pharmacol. Therap . 33 , 56–62.
The aim of this project was to study the influence of haemonchosis, a common parasitic infection of small ruminants caused by Haemonchus contortus , on the activity of biotransformation enzymes and on in vitro flubendazole (FLU) biotransformation in liver and small intestine of lambs ( Ovis aries ). Twelve lambs were divided into three groups: non-infected animals, animals orally infected with larvae of H. contortus ISE strain for 7 weeks and for 11 weeks. At the end of the experiment, hepatic and intestinal subcellular fractions were prepared and used for assays of biotransformation enzymes activities and FLU metabolism testing. The activities of hepatic cytochromes P450, flavine monooxygenases and carbonyl-reducing enzymes were decreased in infected animals. UDP-glucuronosyl transferase activity was significantly lower (by 35%) in 11 weeks infected animals than that in control animals. When in vitro metabolism of FLU was compared in control and infected animals, significantly lower velocity of FLU reduction was found in infected animals. Slower FLU reduction may be beneficial for the haemonchosis treatment using FLU, because FLU will remain longer in the organism and could cause longer contact of parasites with FLU.     

Gross pathology and histopathology of haemonchosis in sheep and goats in Iraq

The response of Awassi sheep and a local breed of goats to H. contortus, the prevalent ovine and caprine strongyloid species in Iraq, was studied. A dose of 500 H. contortus (sheep origin) larvae kg-1 body wt. induced clinical and pathological changes of haemonchosis. Although the percentage recovery of worms was higher in sheep, the pathological (gross and microscopic) changes were more marked in infected goats. The extensive abomasal changes noted in goats were, in general, accompanied by a higher density or larvae in the gastric wall; the pathology did not necessarily depend upon parasite count alone and a definite relationship could not be established. The tissue changes in the goats are possibly of immunological origin, although a genetic resistance may operate, primarily at the level of worm establishment.     

A possible relationship between haemonchosis and haemoglobin polymorphism in Merino sheep in Kenya.

It is known that sheep show polymorphism for haemoglobin in that three phenotypes (HbA, HbB AND HbAB) are normally found. Since it has been suggested, on the basis of haematological values, that HbA type sheep are more able to survive in Haemonchus contortus endemic environments, a preliminary study was conducted on the performance of set-stocked Merino ewes and lambs in relation to their haemoglobin phenotypes. The results provided some evidence that, in Merino sheep at least, those with HbA type show 'self-cure' more frequently and effectively than those with HbB and HbAB types. Examination of the PCV values and total body weights of Merino eres showed a similar trend, ie, the HbA types had the highest haematological parameters and the heaviest body weights, while the HbB types were consistently lowest. It would appear that the practical significance of these results justifies investigation on a larger scale.     

Influence of exogenous gonadotropin-releasing hormone on ovarian function in beef cows after short- and long-term nutritionally induced anovulation

The effect of pulsatile infusion of gonadotropin-releasing hormone (GnRH) on follicular function was evaluated in nutritionally induced anovulatory beef cows. After 4 (short; n = 12) or 18 wk (long; n = 12) of anovulation, cows were randomly assigned within anovulatory group to either 2 microg of GnRH treatment or saline (control; i.v.) every hour for 5 d. Ovarian structures were monitored by daily ultrasonography. Growth rate of the largest follicle (P < 0.01) and maximal size of the largest follicle during treatment were greater (P < 0.01) for GnRH vs control cows. At exsanguination after 5 d of GnRH treatment, the size of the second-largest follicle was greater (P < 0.05) in short (i.e., 4 wk) anovulatory cows than in long (i.e., 18 wk) anovulatory cows and the largest follicle tended (P < 0.10) to be larger in long vs short anovulatory cows. Short anovulatory GnRH-treated cows had more small follicles than short anovulatory control cows or long anovulatory GnRH-treated or control cows (anovulation x GnRH; P < 0.10). Follicular fluid (FFL) concentrations of estradiol (P < 0.01) and androstenedione (P < 0.05) were greater in GnRH vs control cows. Concentrations of insulin-like growth factor-I were greater (P < 0.10) in large vs small follicles in cows that were anovulatory for 4 wk, but not in cows that were anovulatory for 18 wk. The amount of insulin-like growth factor-binding protein (IGFBP)-3 in FFL was greater (P < 0.05) in 4- vs 18-wk anovulatory cows. Amounts of IGFBP-2, -4, and -5 were greater (P < 0.001) in FFL of small (< 5 mm) vs large (> or = 5 mm) follicles regardless of treatment. We conclude that pulsatile treatment with GnRH for 5 d stimulates similar growth of the largest follicles in short- and long-term anovulatory beef cows, and that the duration of anovulation is not a major factor that limits follicular growth w hen anovulatory cowsare treated with GnRH. The primary intrafollicular factors associated with increased follicular size were increased concentrations of estradiol, progesterone, and insulin-like growth factor-I,and decreased concentrations of IGFBP-2, -4, and -5. Increased duration of anovulation was associated with decreased concentrations of IGF-I and IGFBP-3 in FFL.     

Influence of dietary protein on the pathophysiology of haemonchosis in lambs given continuous infections

Mixed-sex groups of three-month-old Finn Dorset and Dorset Horn lambs were given complete diets containing either high or low protein. A trickle infection with Haemonchus contortus of 200 larvae, given three times a week, began one month later for a 17 week period. Erythrokinetic, metabolic, digestibility and balance studies were conducted with the male lambs during weeks 12 to 14 of the infection. Clinical signs of haemonchosis became evident only in the low protein diet group. The infection was characterised by severe macrocytic anaemia, hypoproteinaemia, hypoalbuminaemia, reduced survival, high egg counts and a significantly greater worm burden. In the high protein diet group many lambs developed resistance to further infection in contrast to the low protein group in which no resistance developed. Live-weight gain was not affected by infection in the high protein diet group but decreased in the lambs given the low protein diet compared with uninfected controls. However, infection did not appear adversely to affect the digestive efficiency, nitrogen retention or iron absorption in either dietary group although loss of appetite occurred in the low protein group. Examination of a sample joint from the carcases showed infection was associated with a marked reduction in muscle mass in lambs given the low protein diet relative to the control animals.     

Influence of supplementation with dietary soyabean meal on resistance to haemonchosis in Hampshire down lambs

The influence of dietary protein supplementation on resistance to haemonchosis was examined in Hampshire down lambs fed either a basal diet or a diet supplemented with soyabean. At seven months of age the lambs were challenged with an initial loading dose of Haemonchus contortus, followed by a trickle infection three times a week. Blood and faecal samples were collected three times a week and bodyweights were recorded weekly. After 10 weeks the lambs were slaughtered and their worm burdens and carcase composition determined. Although their mean worm burdens were similar, the lambs given the basal diet had higher faecal egg counts, lower packed red cell volumes and lower concentrations of total plasma protein and plasma albumin than the lambs given the supplemented diet. The dietary supplementation also improved the carcase composition of the lambs.     

Clinical and biochemical alterations in calves with nutritionally induced polioencephalomalacia

Polioencephalomalacia (PEM) was induced in calves by feeding a semipurified, low-roughage diet of variable copper and molybdenum composition. Two formulations resulting in Cu-insufficient and Cu-sufficient forms of the diet were fed (n = 10 and 4 calves, respectively); both diets induced PEM. Clinical signs of disease developed as early as 15 days after transition to the experimental diets and included impaired vision, decreased response to external stimuli, and abnormal gait. Grossly evident cerebrocortical lesions consisted of laminar areas of cavitation and/or autofluorescence seen under UV illumination. Hepatic Cu concentration was decreased in calves fed the Cu-insufficient diet, but not below normal range. During the course of feeding either diet, rumen pH decreased, rumen volatile fatty acid concentrations increased, rumen and blood lactic acid concentrations increased, and rumen and plasma thiamine concentrations increased. The thiamine pyrophosphate effect on erythrocyte transketolase activity was unaltered in calves of either diet group. This nutritionally induced form of PEM does not appear to be related to Cu deficiency or reduction in plasma or rumen thiamine concentration.     

Serodiagnosis of haemonchosis with a somatic antigen (Hc26) in several breeds of sheep.

Sera from 53 sheep belonging to Castellano, Churro, Manchego, and Merino breeds were analyzed to test the diagnostic value of a 26-kD antigen from adult Haemonchus contortus at prepatency and early and late patency of experimental haemonchosis. Animals that received zero, 1, or 2 infections with the parasite were tested. In addition, sera from 20 experimentally infected and 10 noninfected Texel sheep were used to test the antigen. Sera from 37 infected animals at prepatency as well as at patency in primary and secondary infection were found positive with the 26-kD antigen. However, sera from 10 animals with the lowest worm burdens (second infection) did not recognize the antigen during early patency (day 28 postinfection). IgG1 was the only isotype implicated in antigen recognition because IgG2, IgA, and IgM, in the same sera, showed no reactivity with the peptide. Antigen specificity was confirmed because hyperimmune sera against infective larvae and adult stages of the most common gastrointestinal nematodes found in natural infections in sheep (Trichostrongylus colubriformis and Teladorsagia circumcincta) did not recognize this peptide. The antigen was recognized only by anti-adult H. contortus hyperimmune sera and appeared to be absent in the L3 parasite stage. In addition, the partial N-terminal amino acid sequence of the diagnostic peptide is reported.     

The pathogenicity of haemonchosis in sheep and goats in Iraq: 1. Clinical, parasitological and haematological findings

The response of Awassi sheep and the local breed of Iraqi goats to primary infection with a prevalent trichostrongylid nematode, Haemonchus contortus, was compared by examining their worm burden and the pathogenic effects of the parasite on these hosts following experimental infection. The results showed that the goats had lower worm burdens and had suffered less severe clinical and haematological disturbances than the Awassi sheep. The worm counts in sheep were higher than in goats but the count of the mucosal phase of the larvae was higher in goats. These differences are possibly immunologic in origin though a genetic resistance may operate, primarily at the level of worm establishment. The pathophysiological changes are correlated with parasitological and clinical observations in the two host species.     

The FAMACHA system for managing haemonchosis in sheep and goats by clinically identifying individual animals for treatment

Escalating anthelmintic resistance has made it essential to develop alternative ways of worm management for reducing selection for worm resistance, and one of the most promising approaches is to treat only those animals unable to cope with worm challenge, thus favouring unselected worms originating from untreated animals. Only clinical evaluation of anaemia (FAMACHA system) and the body condition score are regarded as being of practical value or having potential, respectively, for repeatedly examining flocks or herds and identifying individuals for treatment. Only the FAMACHA system has been tested well enough for use under practical farming conditions. However, further investigation is needed on its effect on animal production, and methods to reduce labour. Trials over several seasons showed that most sheep under severe Haemonchus contortus challenge required no, or only one treatment over a full summer season. A small minority (usually < 5%) needed more than two treatments. Most sheep could cope without regular treatment. With sufficient training, clinical evaluation of anaemia was found reliable for practical use. The overwhelming majority of trainees (some poorly literate) were able to implement the FAMACHA system successfully. The dynamics of haemonchosis in a flock can easily be monitored. Farmers, farm workers and veterinarians all rated the system very highly (> 80%) and treatment costs dropped by approximately 58%. The heritability of FAMACHA values obtained by clinical evaluation was high at 0.55 +/- 0.17% in a Merino stud with +/- 550 young rams and ewes which were the progeny of 21 sires. The FAMACHA system may not be as applicable to goats as to sheep, but further work is necessary. The main benefits of the system are the reduction in treatments, its use for discriminating between animals of varying ability to cope with infection (thus allowing genetic selection), and its lowering of selection pressure on H. contortus for anthelmintic resistance.     

Partitioning of energy in pregnant beef cows during nutritionally induced body weight fluctuation

The purpose of this study was to determine if the efficiency of energy retention in pregnant cows was dependent on the time during the pregnancy that feed was offered. Our hypothesis was that restricting feed intake during the second trimester of gestation and providing the saved feed during the third trimester was less energetically efficient than providing the feed during the second trimester. Twenty cows (4 breed composite: 1/4 Hereford, 1/4 Angus, 1/4 Red Poll, and 1/4 Pinzgauer) that had produced 1 calf before the study were fed a diet that consisted of (DM basis) 67.3% chopped corn silage, 27.0% alfalfa hay, 5.5% corn, and 0.2% NaCl. When the cows were 87 +/- 0.6 d pregnant, the first nutrient balance measurement was conducted. Six subsequent nutrient balance measurements were taken on d 122 +/- 0.6, 143 +/- 0.6, 171 +/- 0.6, 206 +/- 0.6, 241 +/- 0.6, and 262 +/- 0.6 of gestation. Each nutrient balance measurement consisted of a 96-h total collection of feces and urine and a 24-h indirect calorimetry measurement. Ten cows were fed for moderate BW gain during the entire pregnancy, and 10 cows were feed-restricted in the second trimester and realimented during the third trimester (low-high, L-H). The BW of the cows at parturition (559 +/- 14 kg) did not differ between treatments (P = 0.20). There was a general trend for the proportion of ME intake retained to decrease in moderate cows as pregnancy progressed. The proportion of ME intake retained in L-H cows decreased during the first 49 d of feed restriction, but the proportion of ME retained after 77 d of restriction was greater than that retained at 49 d of restriction. During realimentation, there were no time effects for efficiency of ME conversion to retained energy, but efficiency was greater for L-H cows than moderate cows (P < 0.001). The ability of the cow to adapt its energy metabolism during periods of moderate feed restriction and realimentation allows development of management strategies that alter the time interval of the production cycle during which supplemental feed is offered. Total savings in feed offered during the production year are minimal, but management strategies can be developed that shift which feed resources are being used.     

High sulfide concentrations in rumen fluid associated with nutritionally induced polioencephalomalacia in calves

Nine 115- to 180-kg, hay-adapted, Holstein steers were fed an experimental diet with added sodium sulfate that induces polioencephalomalacia (PEM). Five calves developed the disease. Thiamine concentrations in blood, CSF, brain, and liver were not indicative of thiamine deficiency. The odor of hydrogen sulfide in eructated rumen gas was associated with the onset of PEM. Sulfide concentrations in rumen fluid were measured 1 or 2 times a week by 2 techniques. Sulfide concentrations progressively increased in all 9 calves after the feeding of the PEM-inducing diet commenced. The highest concentrations coincided with the onset of clinical signs of PEM and were significantly higher in the calves that developed PEM than in those that did not. This suggests that PEM can result from sulfide toxicosis following excess production of sulfide in the rumen.     

波杂山羊捻转血矛线虫病的诊疗报告

羊捻转血矛线虫病又名捻转胃虫病 ,是寄生于羊真胃内的一种寄生虫病。临床上以消瘦、贫血、腹泻、生长发育停滞等为特征 ,尤其是幼羊 ,发病后常引起死亡。给养羊业带来严重的经济损失。 2 0 0 2年 7月份本院兽医院诊断了 1例山羊捻转血矛线虫病例 ,现报道如下1　发病情况大丰市西团镇某农户饲养了 3 5只波杂山羊 ,系用纯种波尔山羊冻精与本地白山羊杂交所生杂交一代 ,现已有 2月龄。1个月前发现羊群精神不振 ,食欲减退 ,吃奶减少 ,大便拉稀 ,呈渐进性消瘦 ,体温正常 ,用庆大 小诺霉素治疗后未见好转 ,至 7月 2 5日已陆续死亡 2 4只。 7月 2…     

Influence of selenium on antibody production in sheep

Three experiments were carried out, using sheep fed a marginally low selenium diet, to study the effect of selenium supplementation on the antibody response to tetanus toxoid and on the serum IgG concentration. Six groups of three six-month-old lambs were fed a basal diet containing 0.13 mg Se kg-1 supplemented with either 0.1, 0.5 or 1.0 mg Se kg-1, as sodium selenite or as selenomethionine. These animals generally showed enhanced antibody response to tetanus toxoid, parainfluenza-3 virus and Corynebacterium pseudotuberculosis, and their total serum IgG concentrations were higher than in unsupplemented control animals although few responses were statistically significant. In two field studies significantly higher titres to tetanus toxoid were detected in ewes injected with 100 mg selenium as barium selenate, although no influence on serum IgG concentrations was detected. Lambs from selenium supplemented ewes had significantly higher titres to tetanus toxoid than lambs from ewes in the control group. Dietary vitamin E supplementation had a similar effect on the antibody response to tetanus toxoid in ewes, though no additive effect was seen when vitamin E was given together with selenium.