Comparative Disposition Kinetics of Albendazole in Sheep Following Oral and Intraruminal Administration

The pharmacokinetics of albendazole was studied in sheep following single oral and intraruminal administration at nematocidal dose rates. The disposition curves of its metabolites indicated increased uptake of the drug in sheep following intraruminal as compared to oral dosing (p<0.05). The increased bioavailability of benzimidazole anthelmintics given by the intraruminal route could be exploited for optimizing the use of anthelmintic for sustained parasite control in small ruminants.     

"Coulomb Staircase" at Room Temperature in a Self-Assembled Molecular Nanostructure

Double-ended aryl dithiols [alpha,alpha'-xylyldithiol (XYL) and 4,4'-biphenyldithiol] formed self-assembled monolayers (SAMs) on gold(111) substrates and were used to tether nanometer-sized gold clusters deposited from a cluster beam. An ultrahigh-vacuum scanning tunneling microscope was used to image these nanostructures and to measure their current-voltage characteristics as a function of the separation between the probe tip and the metal cluster. At room temperature, when the tip was positioned over a cluster bonded to the XYL SAM, the current-voltage data showed "Coulomb staircase" behavior. These data are in good agreement with semiclassical predictions for correlated single-electron tunneling and permit estimation of the electrical resistance of a single XYL molecule (approximately18 ± 12 megohms).     

Probing the Local Effects of Magnetic Impurities on Superconductivity

The local effects of isolated magnetic adatoms on the electronic properties of the surface of a superconductor were studied with a low-temperature scanning tunneling microscope. Tunneling spectra obtained near magnetic adsorbates reveal the presence of excitations within the superconductor's energy gap that can be detected over a few atomic diameters around the impurity at the surface. These excitations are locally asymmetric with respect to tunneling of electrons and holes. A model calculation based on the Bogoliubov-de Gennes equations can be used to understand the details of the local tunneling spectra.     

Oestrogen,Progesterone and Oxytocin Receptors and COX‐2 Expression in Endometrial Biopsy Samples from the Induction of Ovulation to Luteolysis in Llamas (Lama glama)

Endometrial expression of oestrogen (ERα), progesterone (PR) and oxytocin receptor (OR) and cyclooxygenase‐2 (COX‐2) was evaluated from the induction of ovulation to luteolysis in llamas. Ovarian activity was daily assessed by ultrasonography in five females. Ovulation was induced immediately after the detection of an ovulatory follicle by a GnRH injection (Day 0). Endometrial samples were obtained by transcervical biopsies from the left and right horns on day 0 and days 4, 8, 10 and 12 post‐GnRH. Blood samples were collected daily for progesterone and estradiol‐17β determinations by RIA. An immunohistochemical technique was used to study receptors population and COX‐2 expression which were then evaluated by two independent observers. The expression of ERα and PR was highest on day 0 in the luminal epithelium and stroma in association with high plasma estradiol‐17β concentrations. Thereafter, a decrease in ERα population was registered on day 4 and a new increase of its expression was observed between days 8 and 12 in those cell types. Conversely, PR population was gradually down‐regulated until its lowest expression was reached on day 10 post‐GnRH in the luminal epithelium. Content of OR was similar throughout the study in all cell types. The expression of COX‐2 was highest from day 8 to 12 post‐GnRH in the luminal epithelium, in relation to the time of maximal PGF_2α release. Both steroid receptors populations and COX‐2 expression were similar between horns. Meanwhile, OR expression was higher in the right than in the left uterine horn. In summary, this study showed that the loss of endometrium sensitivity to progesterone by days 8–10 post‐induction of ovulation and the concomitant increase of COX‐2 expression could play a key role in the mechanism of luteolysis and somehow be related to the short corpus luteum lifespan of llamas.     

Influence of Diet Type and Pretreatment Fasting on the Disposition Kinetics of Albendazole in Sheep

The influence of the quality and quantity of diets on the disposition kinetics of albendazole were studied in sheep in two different experiments. The plasma concentration profiles of albendazole sulphoxide and albendazole sulphone were measured following intraruminal administration of albendazole at 5.0 mg/kg body weight in weaner sheep offered three different diets: 100% green Sorghum spp., 100% dry mature Cenchrus ciliaris hay and a 50:50 mix of these two diets. The peak plasma concentrations and the availability of the albendazole metabolites, as measured by the area under the concentration–time curve, were significantly higher (p<0.01) in the animals offered exclusively dry fodder compared to other diets. Changing the diet from dry to green fodder resulted in a significantly lower systemic availability of the drug metabolites. It is suggested that a decreased transit time of the digesta in the bowel on the green diet, with its high water content, limited the systemic availability of the drug by reducing the time available for gastrointestinal absorption.An experiment on the influence of different levels of pretreatment fasting on the pharmacokinetics of albendazole revealed significantly higher (p<0.05) plasma concentrations of the anthelmintically active sulphoxide metabolite from 12 h onwards following administration of the drug in animals subjected to 24 h of pretreatment fasting compared to other groups with pretreatment fasting of 8, 12 or 18 h. The area under the concentration–time curve and the minimum residence time of the drug metabolites were significantly greater (p<0.05) in animals that had been fasted for 24 h. It is suggested that fasting induces a decrease in the flow of digesta through the gastrointestinal tract of ruminants and prolongs the duration of dissolution of the drug, resulting in enhancement of the absorption of albendazole and of the systemic availability of its metabolites.     

Hormonal changes and follicular activity after treatment with intravaginal progesterone‐releasing devices in llamas

Plasma progesterone (P₄) concentrations and follicular activity after administration of different P₄ doses were evaluated in 33 adult female llamas treated with intravaginal devices. In Study 1, a group of llamas (n = 10) was treated with an intravaginal device (IVD) containing 160 (n = 5) or 780 mg of P₄ (n = 5). Based on the results from the first study, in Study 2, females with follicles at different stages of development were treated with the IVD containing 780 mg of P₄ (n = 21) or remain untreated (control; n = 12) to evaluate the effect of P₄ on follicular activity. In Study 1, the IVD containing 160 mg of P₄ induced follicular turnover in 60% of females while the remaining 40% of llamas developed persistent follicles. Thus, this device controlled follicular activity in llamas, although it promotes the persistence of follicles present at start of treatment. Conversely, in both studies, the IVD containing 780 mg of P₄ suppressed follicular development and hasten the emergence of a new follicular wave in all females regardless of the follicular phase at insertion. Additionally, in Study 2, this device effectively concentrated the appearance of follicles with ovulatory diameter at a definite time after treatment in comparison with control animals. In conclusion, treatment with an IVD containing 780 mg of P₄ would be considered for the control of follicular activity in llamas as it ensures the presence of a young follicle with ovulatory diameter by day 6 after the end of treatment in all females.