Plasma disposition and faecal excretion of oxfendazole, fenbendazole and albendazole following oral administration to donkeys

Fenbendazole (FBZ), oxfendazole (fenbendazole sulphoxide, FBZSO), and albendazole (ABZ) were administered orally to donkeys at 10mg/kg bodyweight. Blood and faecal samples were collected from 1 to 120 h post-treatment. The plasma and faecal samples were analysed by high performance liquid chromatography (HPLC). The parent molecule and its sulphoxide and sulphone (FBZSO(2)) metabolites did not reach detectable concentrations in any plasma samples following FBZ administration. ABZ was also not detected in any plasma samples, but its sulphoxide and sulphone metabolites were detected, demonstrating that ABZ was completely metabolised by first-pass mechanisms in donkeys. Maximum plasma concentrations (C(max)) of FBZSO (0.49microg/mL) and FBZSO(2) (0.60microg/mL) were detected at (t(max)) 5.67 and 8.00h, respectively, following administration of FBZSO. The area under the curve (AUC) of the sulphone metabolite (10.33microg h/mL) was significantly higher than that of the parent drug FBZSO (5.17microg h/mL). C(max) of albendazole sulphoxide (ABZSO) (0.08g/mL) and albendazole sulphone (ABZSO(2)) (0.04microg/mL) were obtained at 5.71 and 8.00h, respectively, following ABZ administration. The AUC of the sulphoxide metabolite (0.84microg h/mL) of ABZ was significantly higher than that of the sulphone metabolite (0.50microg h/mL). The highest dry-faecal concentrations of parent molecules were detected at 32, 34 and 30h for FBZSO, FBZ and ABZ, respectively. The sulphide metabolite was significantly higher than the parent molecule after FBZSO administration. The parent molecule was predominant in the faecal samples following FBZ administration. After ABZ administration, the parent molecule was significantly metabolised, probably by gastrointestinal microflora, to its sulphoxide metabolite (ABZSO) that showed a similar excretion profile to the parent molecule in the faecal samples. The AUC of the parent FBZ was significantly higher than that of FBZSO and ABZ in faeces. It is concluded that the plasma concentration of FBZSO was significantly higher than that of FBZ and ABZ. Although ABZ is not licensed for use in Equidae, its metabolites presented a greater plasma kinetic profile than FBZ which is licensed for use in horses. A higher metabolic capacity, first-pass effects and lower absorption of benzimidazoles in donkeys decrease bioavailability and efficacy compared to ruminants.     

Therapeutic and prophylactic efficacy of imidocarb dipropionate on experimental Babesia ovis infection of lambs

The objective of this study was to evaluate the therapeutic and prophylactic efficacy of imidocarb dipropionate (IMDP) against babesiosis and to determine specific antibodies against Babesia ovis in experimentally infected lambs. Thirty-six 6-month-old splenectomized lambs were used. The lambs were randomly divided into six groups with six animals each, and were intravenously inoculated with 50 mL B. ovis-infected erythrocytes as follows: group I (therapy group) was treated with IMDP (1.2 mg/kg body weight) starting on the day of onset of clinical signs of babesiosis after the inoculation; group II (untreated control animals) was not treated with any therapeutic treatment after the inoculation; groups III, IV, V and VI (prophylaxis groups) were administered IMDP (2.4 mg/kg body weight) 1, 2, 3 and 4 weeks before the inoculation, respectively. The animals were housed in a tick-proof room with water and food ad libitum up to the 30th day post-inoculation (PI). The lambs were monitored from the first day PI by recording the manifestation of clinical disease, rectal temperature, and the degree of parasitaemia. All the lambs became infected with B. ovis, except five animals from group III, which were treated 1 week prior to experimental infection. Other animals showed signs of acute clinical babesiosis. The animals treated with IMDP (group I) were able to clear the parasite from the blood circulation after 48 h post-treatment. The recrudescence of B. ovis was observed in two lambs 7 days after treatment, and they were treated with the second similar dose of the drug. Six lambs (1, 1, 2 and 2 lambs in group III, IV, V and VI, respectively) from the prophylaxis groups died within 7-17 days after showing high parasitaemia and clinical symptoms of the disease. Regardless of the clinical symptoms, 83.30% and 66.66% of the lambs which were administered IMDP 1-2 and 3-4 weeks before, were determined to be protected against the virulent field strain of B. ovis.     

A comparative study on the prevalence of Theileria equi and Babesia caballi infections in horse sub-populations in Turkey

Blood and serum samples were taken from 481 horses, from a stud farm or a racecourse, and tested by microscopic examination of blood smears and cELISA for Theileria equi (T. equi) and Babesia caballi (B. caballi) infections. At the time of sampling, animals were also examined for tick infestations and clinical disease, which were not observed in any of the sampled horses. During the microscopic examination of thin blood smears, parasites were detected in the three horses from the racecourse. Overall seroprevalence of infection was detected as 18.50% (89 of 481 horses) by cELISA, with T. equi being significantly more prevalent than B. caballi. Of the 481 blood samples, 78 (16.21%) were serologically positive for T. equi and 4 (0.83%) were serologically positive for B. caballi. In addition, 7 (1.46%) samples were positive for both T. equi and B. caballi antibodies. Seropositivity rates in the racecourse horses were higher than those determined in the stud farm horses. The rates for T. equi, B. caballi and both species were 13.39, 0.52 and 0% in the horses from the stud farm and 27, 2 and 7% in the racecourse horses, respectively. These results indicate that equine piroplasmosis is more common in racehorses than studhorses and therefore it might be a serious concern in horses that participate to international races.     

Structural basis for gluten intolerance in celiac sprue

Celiac Sprue, a widely prevalent autoimmune disease of the small intestine, is induced in genetically susceptible individuals by exposure to dietary gluten. A 33-mer peptide was identified that has several characteristics suggesting it is the primary initiator of the inflammatory response to gluten in Celiac Sprue patients. In vitro and in vivo studies in rats and humans demonstrated that it is stable toward breakdown by all gastric, pancreatic, and intestinal brush-border membrane proteases. The peptide reacted with tissue transglutaminase, the major autoantigen in Celiac Sprue, with substantially greater selectivity than known natural substrates of this extracellular enzyme. It was a potent inducer of gut-derived human T cell lines from 14 of 14 Celiac Sprue patients. Homologs of this peptide were found in all food grains that are toxic to Celiac Sprue patients but are absent from all nontoxic food grains. The peptide could be detoxified in in vitro and in vivo assays by exposure to a bacterial prolyl endopeptidase, suggesting a strategy for oral peptidase supplement therapy for Celiac Sprue.     

The effect of diet type on the plasma disposition of triclabendazole in goats

The effect of two different diet types (concentrate feed+hay and grazing) on the pharmacokinetic profiles of triclabendazole following oral administration in goats was investigated. A total of 12 goats were randomly allocated into two groups which were either indoor and fed concentrate + hay ration (housed group) or were grazing on pasture (grazing group). Triclabendazole was administered orally to animals in two groups at 10 mg/kg bodyweight. Blood samples were collected from 1 h to 192 h post-treatment and analyzed by high performance liquid chromatography (HPLC). Feeding with different diets significantly effected the plasma disposition of triclabendazole sulphoxide. Maximum plasma concentration (C(max): 13.22+/-2.81 microg/ml), time to reach maximum plasma concentration (t(max): 18.4+/-2.19 h), area under the curve (AUC: 613+/-137 microg h/ml), half-life (t(1/2): 24.77+/-1.94 h) and mean resident time (MRT: 40.22+/-4.36 h) of triclabendazole sulphoxide in housed group were significantly different from those of grazing group (C(max): 10.17+/-1.51 microg/ml, t(max): 14.0+/-2.19 h, AUC: 406+/-98 microg h/ml), t(1/2): 16.16+/-1.17 h and MRT: 34.48+/-4.40 h). It is concluded that anthelmintically more active sulphoxide metabolite has higher plasma concentration when triclabendazole is administered to goats fed with concentrate feed + hay compared to grazing goats.     

Instability of ovine babesiosis in an endemic area in Turkey

This study was designed to determine the endemic status of Babesia ovis in sheep in Turkey. A total of 2000 sheep, from different age groups (i.e. 0-3, 4-6, 6-9, 10-12, and >12 months), were selected randomly from 132 sheep flocks. The presence of specific antibodies against B. ovis was diagnosed by indirect fluorescent antibody test (IFAT). A total of 843 (42.15%) serum samples were determined to be positive. The seropositivity rates in the age groups stated above were 31.90, 31.64, 47.69, 40.22, and 52.99%, respectively. The endemic status of the disease was determined by calculating the inoculation rate (h) of each group. The h value for each group was determined to be lower than 0.005, which revealed that the endemic status of B. ovis was instable. This report may indicate the necessity of vaccination.     

Antimicrobial and antioxidant activity of the essential oil and methanol extracts of Thymus pectinatus Fisch. et Mey. Var. pectinatus (Lamiaceae)

The essential oil, obtained by using a Clevenger distillation apparatus, and water-soluble (polar) and water-insoluble (nonpolar) subfractions of the methanol extract of Thymus pectinatus Fisch. et Mey. var. pectinatus were assayed for their antimicrobial and antioxidant properties. No (or slight) antimicrobial activity was observed when the subfractions were tested, whereas the essential oil showed strong antimicrobial activity against all microorganisms tested. Antioxidant activities of the polar subfraction and the essential oil were evaluated using 2,2-diphenyl-1-picrylhydrazyl, hydroxyl radical, superoxide radical scavenging, and lipid peroxidation assays. The essential oil, in particular, and the polar subfraction of the methanol extract showed antioxidant activity. The essential oil was analyzed by GC/MS, and 24 compounds, representing 99.6% of the essential oil, were identified: thymol, gamma-terpinene, p-cymene, carvacrol, and borneol were the main components. An antimicrobial activity test carried out with fractions of the essential oil showed that the activity was mainly observed in those fractions containing thymol, in particular, and carvacrol. The activity was, therefore, attributed to the presence of these compounds. Other constituents of the essential oil, such as borneol, gamma-terpinene, and p-cymene, could be also taken into account for their possible synergistic or antagonistic effects. On the other hand, thymol and carvacrol were individually found to possess weaker antioxidant activity than the crude oil itself, indicating that other constituents of the essential oil may contribute to the antioxidant activity observed. In conclusion, the results presented here show that T. pectinatus essential oil could be considered as a natural antimicrobial and antioxidant source.     

Babesia ovis infections: Detailed clinical and laboratory observations in the pre- and post-treatment periods of 97 field cases

Ovine babesiosis, caused by Babesia ovis, is of major economic importance in Turkey. The changes in the blood profile of infected animals are informative about the course of infection. The aim of the present study was to evaluate the hematological and biochemical changes in the pre- and post-treatment periods of the natural B. ovis infections. The presence of the parasites was confirmed by microscopy and polymerase chain reaction (PCR) analysis. On the basis of the clinical and laboratory findings, the infections were categorized into different groups according to the degree of anemia and the level of parasitemia. All infected sheep were treated with imidocarb dipropionate (IMDP). The blood pictures in the pre- and post-treatment periods were compared.Pancytopenia occurred in animals with severe anemia and very high parasitemia, and bicytopenia in the other groups. The platelet count (PLT), plateletcrit (PCT) and mean platelet volume (MPV) returned to the normal ranges after treatment, except those in the group with severe anemia. In the biochemical profile, B. ovis infection caused an increase in blood urea nitrogen and total bilirubin, and these parameters returned to normal levels after treatment.The indirect fluorescein antibody test (IFAT) results showed that 38.1% of the cases raised specific antibodies during the period of infection, with titers ranging from 1/160 to 1/640. All of 45 animals re-examined after treatment were seropositive, with high titers that rose up to 1/5120.     

Chemical and antioxidant properties of Laurocerasus officinalis Roem. (cherry laurel) fruit grown in the Black Sea region

Laurocerasus officinalis Roem. is a summer fruit highly characteristic of the Black Sea region. The edible parts of the fruit were tested for chemical composition and antioxidant properties. Total moisture, ash, protein, sugar, pectin, ascorbic acid, phenolic, and mineral contents of the fruit were determined. The antioxidant activity of the fruit was investigated using TLC plate and ferric thiocyanate methods. Its antioxidative character was also tested utilizing hydroxyl, DPPH, and superoxide radical scavenging activity measurements, using BHT, vitamin C, and Trolox as references. Besides being a good source of nutrients, L. officinalis was found to provide a rich source of protective antioxidant compounds. Its antioxidant and radical scavenging activities were comparable to or higher than those of the reference antioxidants. It appeared to have high mineral content. The concentrations of macroelements K, Mg, Ca, and Na were high at 2215 +/- 10.5, 179 +/- 11, 153 +/- 0.8, and 55 +/- 0.3 mg/kg, respectively, and the concentrations of trace elements Mn, Fe, Zn, and Cu were 24.2 +/- 1.3, 8.3 +/- 0.8, 1.9 +/- 0.2, and 0.8 +/- 0.1 mg/kg, respectively. In addition, the fruit showed very low contents of Pb, Ni, Co, and Cr, below the detection limits, which is considered to be a good food quality. As it is a rich source of protein, sugar, ascorbic acid, minerals, and antioxidants, L. officinalis is well worth further studies regarding its components possessing important health benefits and inclusion in the daily diet.