Pharmacokinetics of monepantel and its sulfone metabolite, monepantel sulfone, after intravenous and oral administration in sheep

The pharmacokinetic properties of the developmental Amino-Acetonitrile Derivative (AAD), monepantel and its sulfone metabolite, monepantel sulfone were investigated in sheep following intravenous (i.v.) and oral administrations. The sulfone metabolite was rapidly formed and predominated over monepantel 4 h after dosing, irrespective of the route of administration. The steady-state volume of distribution, total body clearance and mean residence time of monepantel were 7.4 L/kg, 1.49 L/(kg·h) and 4.9 h, respectively and 31.2 L/kg, 0.28 L/(kg·h) and 111 h, respectively for monepantel sulfone. The overall bioavailability of monepantel was 31%, but it was demonstrated that approximately the same amount of monepantel sulfone was produced whether monepantel was given intravenously or orally ( AUC _(0–∞) oral/ AUC _(0–∞) i.v. of 94% for monepantel sulfone), making oral administration a very efficient route of administration for monepantel in terms of the amount of sulfone metabolite generated. Because monepantel sulfone is the main chemical entity present in sheep blood after monepantel administration and because it is also an active metabolite, its pharmacokinetic properties are of primary importance for the interpretation of future residue and efficacy studies. Overall, these pharmacokinetic data aid in the evaluation of monepantel as an oral anthelmintic in sheep.     

Different isolates from Leishmania braziliensis complex induce distinct histopathological features in a murine model of infection

The aim of this study was to evaluate the histopathological features in tissues of mice infected by human isolates (I, II, and III) or the reference M2903 strain of Leishmania braziliensis complex. BALB/c and C57Bl/6 mice were infected in the hind footpad with 10⁶ stationary-phase promastigotes of L. braziliensis complex. The evolution of lesions was observed for 10 weeks and the animals were then euthanized and liver, spleen and popliteal lymph nodes were collected. Tissues were stained with hematoxylin and eosin and analyzed by immunohistochemistry assay. Increased thickness of infected footpads was observed in all animals, lesions were nodular and non-ulcerated. Mice infected with isolate I presented inflammatory infiltrates consisting predominantly of mononuclear cells in all tissues examined, and also a great number of megakaryocytes, compared with other isolates. Infection with isolate II led to an infected footpad enlargement not seen in other isolates. In addition, mononuclear infiltrates in the liver and hemosiderin in spleen were noted. Conversely, mice infected with either isolate III or M2903 strain only showed an increased number of megakaryocytes in spleen. All tissues examined had detectable amastigote forms of Leishmania by immunohistochemistry in all groups. Taking together, our results showed an unforeseen behavior of different isolates of L. braziliensis complex that led to diverse pathological findings.     

Intersprout competition in the potato II. Competition for nutrients during pre-emergence growth after planting

Summary The influence of temperature, number of sprouts per tuber and concentration of supplementary inorganic nutrients on sprout growth and intersprout competition for tuber substrates during emergence was investigated in the potato varietyArran Pilot. The rate of sprout growth was found to be a positive function of initial tuber fresh weight. Dry weight data at emergence indicated that individual sprouts on multi-sprout tubers exhibited mutual interference for substrates from the tuber. The intensity of this interference increased with temperature in the range 7 25 C, but interference was reduced, and in some cases eliminated, by supplying inorganic nutrients in the rooting medium. It was concluded that a component of the inorganic nutrient solution used could replace the tuber factor the supply of which limited sprout growth. The effects of temperature and inorganic nutrient concentration on the partitioning of dry matter within the plant are deseribed and diseussed.

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Zusammenfassung Die Einflüsse von Temperatur, ursprünglichem Knollengewicht, der Anzahl Keime pro Knolle und der Konzentration zus?tzlicher anorganischer N?hrstoffe auf das Keimwachstum sowie die Konkurrenz zwischen den Keimen um das Knollensubstrat w?hrend des Auflaufens wurden an der KartoffelsorteArran Pilot untersucht. Ween Knollen in ein n?hrstofffreies Medium gepflanzt wurden (Versuch 1), glich die Auflaufrate der Keime einer positiv linearen Funktion der Temperatur über einen Bereich von 7 C bis 25 C, aber sie war nicht signifikant beeinflusst durch die Zahl der Keime pro Knolle (Tabelle 1 und 2). Die einzelnen Keime von Knollen mit vielen Keimen konkurrierten um das Substrat der Mutterknolle, und die St?rke dieser Interferenz nahm mit steigender Temperatur w?hrend des Auflaufens zu (Abb. 1 und 2). In den Versuchen 2 und 3 wurde die Auflaufzeit durch die Beigabe einer anorganischen Volln?hrl?sung zum Wurzeln?hrboden verkürzt, aber sie wurde nicht signifikant beeinflusst durch die Zahl der Keime pro Knolle (Tabelle 4). Eine Erh?hung der N?hrstoffkonzentration in der anorganischen L?sung hatte eine Erh?hung des durchschnittlichen Trockengewichtes der Keime und des durchschnittlichen Trockengewichtes der Keime pro Knolle beim Auflaufen zur Folge (Abb. 4 und 5). In Versuch 2 setzte die Gabe von anorganischen N?hrstoffen die Intensit?t der Konkurrenz zwischen den Keimen um das Substrat aus der Knolle betr?chtlich herab, was darauf hindeutet, dass ein Bestandteil der verwendeten N?hrl?sung den “Knollenfaktor”, der das Keimwachstum begrenzt, ersetzen k?nnte. Im Versuch 3 dagegen wurde die Interferenz um die Substrate aus der Knolle durch die Konzentration der verwendeten N?hrstoffe nicht beeinflusst. Diese Abweichung zwischen den zwei Versuchen dürfte mit dem unterschiedlichen Grad der Interferenz zwischen den Wurzelsystemen der einzelnen Keime für die Zufuhr der verwendeten N?hrstoffe in Zusammenhang stehen (Tabelle 5). Die Temperatur nach dem Auspflanzen übte einen betr?chtlichen Einfluss auf die Verteilung der Trockensubstanz innerhalb des Stengel-systems aus. Anzahl, L?nge und Trockengewicht der Stolonen pro Keim (Abb. 3) und das Verh?ltnis des Stolonentrockengewichtes zum gesamten Trockengewicht der Stengel (Tabelle 3) waren in umgekehrter Bezichung von der Temperatur abh?ngig, in den Versuchen 1 und 3 stand das Verh?ltnis des Stolonentrockengewichtes zum gesamten Stengelgewicht in umgekehrter Bezichung zur Anzahl Keime pro Knolle: in Versuch 3 war diese Beziehung aber nicht signifikant beeinflusst durch die Konzentration der mineralischen N?hrstoffe. Diese Ergebnisse wiesen darauf hin, dass neben der Temperatur ein spezifischer Faktor in der Mutterknolle auf das Stolonenwachstum einwirkte und dass dieser Faktor nicht durch eine den Knollen zur Verfügung stehende mineralischen N?hrstoffl?sung ersetzt werden kann. In den Versuchen 2 und 3 erweiterte sich das Stengel/Wurzel-Verh?ltnis mit der Erh?hung der Konzentration der verwendeten anorganisehen N?hrstoffe, aber es war nicht signifikant beeinflusst durch die Zahl der Keime pro Knolle.

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Résumé L’auteur a recherché, sur la variété de Pomme de terreArran Pilot, l’influence de la température, du poids initial du tubercule, du nombre de germes par tubercule et de la concentration en éléments nutritifs inorganiques supplémentaires sur la croissance du germe et la compétition entre les germes pour les réserves du tubercule pendant la levée. Quand les tubercules sont plantés dans un milieu dépourvu d’éléments nutritifs (expérience 1), la vitesse d’émergence d’un germe est une fonction linéaire positive de la température dans les limites de 7 C à 25 C mais n’est pas significativement influencéc par le nombre de germes par tubercule (tableau 1 et 2). Les germes des tubercules à plusieurs germes rivalisent individuellement pour les réserves du tubercule-mère et il se révèle que l’intensité de cette interférence s’accro?t avec l’augmentation de la température pendant l’émergence (Fig. 1 et 2). Dans les expériences 2 et 3, le temps d’émergence est réduit par l’application au milieu d’enracinement d’une solution nutritive complète inorganique, mais n’est pas significativement influencé par le nombre de germes par tubercule (Tableau 4). Une augmentation de la concentration en éléments nutritifs inorganiques entra?ne, lors de l’émergence, une augmentation du poids sec moyen d’un germe et une augmentation du poids sec moyen de tous les germes du tubercule (Fig. 4 et 5). Dans l’expérience 2 l’application d’éléments nutritifs inorganiques réduit l’intensité de la compétition entre germes pour les réserves du tubercule, ce qui signifie qu’un composant de la solution nutritive utilisée remplace le facteur du tubercule qui limite la croissance du germe. Cependant, dans l’experience 3, la compétition pour les réserves du tubercule n’est pas influencée par la concentration des éléments nutritifs appliqués. La différence dans les deux expériences peut provenir des différences dans le degré d’interaction entre les systèmes radiculaires des germes individuels pour les approvisionnements en éléments nutritifs appliqués (Tableau 5). La température après plantation exerce une influence considérable sur la répartition de la matière sèche dans le système radiculaire. Le nombre, la longucur et le poids sec de stolons par germe (Fig. 3) et le rapport du poids sec des stolons au poids total sec des germes (Tableau 3) sont des fonctions inverses de la température. Dans les expériences 1 et 3 le rapport poids sec des stolons au poids total des germes est inversément relié au nombre de germes par tubercule, mais dans l’expérience 3 ce rapport n’est pas significativement influencé par la concentration externe des éléments minéraux. Ces résultats indiquent qu’en plus des effets de la température, un facteur spécifique provenant du tubercule-mère influe sur la croissance du stolon, et que ce facteur ne peut être remplacé par un apport externe d’éléments nutritifs minéraux. Dans les expériences 2 et 3 le rapport bourgeon/ racine augmente avec l’accroissement de la concentration en éléments nutritifs inorganiques appliqués mais n’est pas significativement influencé par le nombre de germes par tubercule.

     

SYSTEMATIC TESTING OF QUALITY IN GRASS VARIETIES

The degree of precision obtained In the quality testing of grass varieties under two systems of management was examined (1) in a single cut, (2) under a system of proportionate bulking of produce from individual cuts during a season, and (3) after pooling two seasons' data from two centres.
Crude protein, crude fibre, soluble carbohydrate, and in vitro digestible dry matter were determined. The components of variance were analysed and in the data from single cuts varietal differences in digestibility of 2.10 were significant (P=0.05). Using data from two seasons at two centres, a high degree of precision was obtained for all attributes in a grazing management system and varietal differences in digestibility of 1.25% were significant.
Variation due to location and season was greater in hay cuts taken 10 days after ear emergence. In both systems varieties differed more in soluble carbohydrate content than in the other chemical components.     

Toxic shock syndrome in a horse with Staphylococcus aureus pneumonia

A 3-year-old Thoroughbred gelding was examined because of clinical signs of pneumonia and shock. Mucous membrane petechiation and ventral edema were observed and considered to be a result of vasculitis. Epidermal necrosis developed on the distal portions of the limbs. The horse had a persistent high fever that was unresponsive to nonsteroidal anti-inflammatory treatment, and Staphylococcus aureus was isolated from a nasal swab specimen and 2 transtracheal wash fluid samples. Antimicrobial, anti-inflammatory, and supportive treatment resulted in clinical improvement. However, resolution of the pulmonary infection required long-term (42 days) antimicrobial administration. Staphylococcus aureus strains isolated from this horse were positive for the toxic shock syndrome toxin-1 gene and were shown to produce toxic shock syndrome toxin-1, the causative factor in toxic shock syndrome in humans. The horse's clinical signs were attributed to toxic shock syndrome secondary to pulmonary S. aureus infection.     

Estimation of linkage disequilibrium in a sample of the United Kingdom dairy cattle population using unphased genotypes

The association between genetic marker alleles was estimated for two regions of the bovine genome from a random sample of 50 young dairy bulls born in the United Kingdom between 1988 and 1995. Microsatellite marker genotypes were obtained for six markers on chromosome 2 and seven markers on chromosome 6, spanning 38 and 20 cM, respectively. Two different methods, which do not require family information, were used to estimate population haplotype frequencies. Haplotype frequencies were estimated for pairs of loci using the expectation-maximization algorithm and for all linked loci using a Bayesian approach via a Markov chain-Monte Carlo algorithm. Significant (P = 0.0007) linkage disequilibrium was detected between pairs of loci in syntenic groups (that is, loci in the same linkage group), extending to about 10 cM. No significant linkage disequilibrium was detected between markers in nonsyntenic regions. Given the observed level of linkage disequilibrium, mapping methods based on population-wide association might provide a better resolution than traditional quantitative trait loci mapping methods in the U.K. dairy cattle population and may reduce the required sample sizes of the experiments.     

Strategies to reduce feedlot cattle heat stress: effects on tympanic temperature

Three experiments were conducted to evaluate the effect of different management strategies on body temperature of feedlot steers finished in the summer months. In Exp. 1, 24 crossbred steers were chosen to assess the effect of altered feed intake and feeding time on tympanic temperature (TT) response. Managed feeding (MF) treatments were applied for 22 d only and provided 1) ad libitum access to feed at 0800 (ADLIB), 2) feed at 1600 with amount adjusted so that no feed was available at 0800 (BKMGT), 3) feed at 1600 at 85% of predicted ad libitum levels (LIMFD). During heat stress conditions on d 20 to 22 of MF, LIMFD and BKMGT had lower (P < 0.05) TT than ADLIB from 2100 through 2400. A carryover effect of limit-feeding was evident during a severe heat episode (d 36 to 38) with LIMFD steers having lower (P < 0.05) TT than ADLIB. In Exp. 2, TT were obtained from 24 crossbred steers assigned to three treatments, consisting of no water application (CON), water applied to feedlot mound surfaces from 1000 to 1200 (AM) or 1400 to 1600 (PM). From 2200 to 0900 and 1200 to 1400, steers assigned to morning sprinkling treatment had lower (P < 0.05) TT than steers assigned to afternoon sprinkling treatment. In Exp. 3, 24 steers were utilized in a 2 x 2 factorial arrangement of treatments with factors of feeding time [0800 (AMF) and 1400 (PMF)] and sprinkling (WET and DRY). Tympanic temperatures were monitored under hot environmental conditions on d 30 to 32 and 61 to 62. A feeding time x sprinkling interaction (P < 0.001) was evident on d 30 to 32, although AMF/DRY steers had the highest (P < 0.05) TT. On d 61 to 62, TT of PMF steers was higher (P < 0.05) than AMF between 1500 to 1800. Use of sprinklers can effectively reduce TT of feedlot cattle, whereas shifting to an afternoon vs morning feeding time was most beneficial when bunks were empty several hours prior to feeding.     

Ritual slaughter: animal friendly slaughter and protection of animals in Islam

A report is given on history and procedures of ritual slaughter from the point of view of a Moslem representative. The term sacrifice and the religious meaning of the offering feast are explained on the basis of the Abrahamian tradition. The social aspect of ritual slaughter is that two thirds of the slaughtered animal are given to the poor or served as meal to guests and relatives. One third is saved for the own family only. The Islamic religion acknowledges the responsibility of man for animals as creatures of god whose life and well-being have to be protected, nobody is allowed to subject animals to pain, suffering and damage without a sound reason. The ritual slaughter aims at complete debleeding. Blood is symbol life and soul and the breath of life. It must leave the body completely before consumption because it is not allowed to eat animals alive. Electric stunning is allowed if the animal is unconscious and not dead. The consumption of dead animals is forbidden by religion. It is recommended to introduce more veterinarian expert knowledge in the discussion.