Pharmacokinetic assessment of the monepantel plus oxfendazole combined administration in dairy cows

Monepantel (MNP) is a novel anthelmintic compound launched into the veterinary pharmaceutical market. MNP is not licenced for use in dairy animals due to the prolonged elimination of its metabolite monepantel sulphone (MNPSO₂) into milk. The goal of this study was to evaluate the presence of potential in vivo drug‐drug interactions affecting the pattern of milk excretion after the coadministration of the anthelmintics MNP and oxfendazole (OFZ) to lactating dairy cows. The concentrations of both parent drugs and their metabolites were measured in plasma and milk samples by HPLC. MNPSO₂ was the main metabolite recovered from plasma and milk after oral administration of MNP. A high distribution of MNPSO₂ into milk was observed. The milk‐to‐plasma ratio (M/P ratio) for this metabolite was equal to 6.75. Conversely, the M/P ratio of OFZ was 1.26. Plasma concentration profiles of MNP and MNPSO₂ were not modified in the presence of OFZ. The pattern of MNPSO₂ excretion into milk was also unchanged in animals receiving MNP plus OFZ. The percentage of the total administered dose recovered from milk was 0.09 ± 0.04% (MNP) and 2.79 ± 1.54% (MNPSO₂) after the administration of MNP alone and 0.06 ± 0.04% (MNP) and 2.34 ± 1.38% (MNPSO₂) after the combined treatment. The presence of MNP did not alter the plasma and milk disposition kinetics of OFZ. The concentrations of the metabolite fenbendazole sulphone tended to be slightly higher in the coadministered group. Although from a pharmacodynamic point of view the coadministration of MNP and OFZ may be a useful tool, the presence of OFZ did not modify the in vivo pharmacokinetic behaviour of MNP and therefore did not result in reduced milk concentrations of MNPSO₂.     

Pharmacokinetics of cefquinome in healthy and Pasteurella multocida‐infected rabbits

The pharmacokinetics of cefquinome were studied in healthy and Pasteurella multocida‐infected rabbits after a single intramuscular (IM) injection at 2 mg/kg of its sulfate salt. Twelve female New Zealand white rabbits (2.0–2.5 kg) were used; six of them served as controls, and the other six had been infected with P. multocida; the experiments were conducted 1–2 days after nasal inoculation of P. multocida when rabbits showed the signs of respiratory infection. Plasma concentrations of cefquinome were determined using high‐performance liquid chromatography. The values of elimination half‐life, area under the curve, area under the first moment curve, and mean residence time were significantly lower in infected rabbits (0.48 hr, 4.54 hr*μg/ml, 3.63 hr* hr*μg/ml and 0.8 hr, respectively) than healthy rabbits (0.72 hr, 9.11 hr*μg/ml, 9.85 hr* hr*μg/ml and 1.1 hr, respectively), whereas total body clearance was significantly higher in infected than healthy rabbits. Therefore, P. multocida infection caused significant changes in some of the pharmacokinetic parameters of cefquinome in rabbits. These pharmacokinetic changes may affect dose regimen when used in P. multocida‐infected rabbits.     

CD117‐ and vimentin‐positive telocytes in the bovine teat sphincter

Mastitis is a common economically relevant problem in dairy farming. As the major entry for pathogens is the papillary duct, one of the first defence mechanisms is the teat sphincter. This sphincter shows a rhythmic contractility of yet unknown origin. Searching for possible modulatory pacemaker cells, teat sphincters of eight cows were stained immunohistochemically with antibodies against CD117 and vimentin and evaluated microscopically for the presence of telocytes. CD117‐ and vimentin‐positive telocytes with telopodes were found in close contact with smooth muscle cells. Our findings present a first evidence of telocytes in the teat of bovines.     

Fine structure of the canal neuromasts of the lateral line system in the adult zebrafish

The mechanosensory lateral line system of fish is responsible for several functions such as balance, hearing, and orientation in water flow and is formed by neuromast receptor organs distributed on head, trunk and tail. Superficial and canal neuromasts can be distinguished for localization and morphological differences. Several information is present regarding the superficial neuromasts of zebrafish and other teleosts especially during larval and juvenile stages, while not as numerous data are so far available about the ultrastructural characteristics of the canal neuromasts in adult zebrafish. Therefore, the aim of this study was to investigate by transmission electron microscopy the ultrastructural aspects of cells present in the canal neuromasts. Besides the typical cellular aspects of the neuromast, different cellular types of hair cells were observed that could be identified as developing hair cells during the physiological turnover. The knowledge of the observed cellular types of the canal neuromasts and their origin could give a contribution to studies carried out on adult zebrafish used as model in neurological and non‐neurological damages, such as deafness and vestibular disorders.     

Safety of standardized Macleaya cordata extract in an eighty‐four‐day dietary study in dairy cows

The objective of this study was to evaluate the safety of a standardized Macleaya cordata Extract Product (MCEP) containing the quaternary benzophenanthridine alkaloids, sanguinarine and chelerythrine, when fed to dairy cows. Thirty‐six dairy cows were randomized into three groups with twelve cows/treatment in two replica pens for each treatment group: control (C) without MCEP added to feed, treatment 1 (SANG‐1000) with MCEP added to feed at 1,000 mg/animal/day (1.5 mg/kg bw/day) and treatment 2 (SANG‐10000) with MCEP added to feed at 10,000 mg/animal/day (15.5 mg MCEP/kg bw/day). After two weeks of acclimation, animals were observed for an 84‐day experimental period, with body weight, feed intake and milk production measured daily. Milk composition was analysed every two weeks. Haematological analyses were performed on Day 0 and Day 84, and clinical chemistry analyses were performed on Day 84 of the study. There was no statistically significant difference (p > .10) among the three groups on body condition score, milk production or milk composition over the study period. There were no significant differences in body weight gain or feed consumption among the three groups. Animals in the SANG‐10000 group had significantly higher mean corpuscular volume (MCV) than the C group (p < .1) and lower mean corpuscular haemoglobin concentration (MCHC) than the SANG‐1000 group (p < .1). Concentrations of sanguinarine and chelerythrine in milk samples collected on Day 84 were below the detection limit (LOD) as measured by high‐performance liquid chromatography‐mass spectrometry (HPLC‐MS/MS). In conclusion, this study presents compelling data supporting the hypothesis that the test product MCEP, when included in the TMR at up to 10,000 mg/animal/day (15.5 mg MCEP/kg bw/day), is well tolerated by dairy cows.     

Effect of resistant starch on the intestinal health of old dogs: fermentation products and histological features of the intestinal mucosa

The effects of resistant starch (RS) intake on nutrient digestibility, microbial fermentation products, faecal IgA, faecal pH, and histological features of the intestinal mucosa of old dogs were evaluated. The same formulation was extruded in two different conditions: one to obtain elevated starch cooking degree with low RS content (0.21%) and the other lower starch cooking with high RS content (1.46%). Eight geriatric Beagles (11.5 ± 0.38 years old) were fed each diet for 61 days in a crossover design. Food intake, nutrient digestibility, fermentation products, faecal pH, and faecal IgA were examined via variance analysis. Histological results of intestinal biopsies were assessed via Wilcoxon test for paired data. The morphometric characteristics of large intestine crypts were evaluated via paired t tests (p < .05). Protein, fat, and energy digestibilities were higher for the low‐RS diet (p < .05). Dogs receiving the high‐RS diet had lower faecal pH and higher values for propionate, butyrate, total volatile fatty acids, and lactate (p < .05). No differences between diets were found in the histological parameters of the gut mucosa, and only a tendency for deeper crypts in the descending colon was observed for dogs fed the high‐RS diet (p = .083). The intake of a corn‐based kibble diet manufactured with coarse ground raw material and low starch gelatinization to obtain 1.4% of RS affected microbial fermentation products and faecal pH and tended to increase crypt depth in the descending colon of old dogs.     

Effect on Rendement Napole genotype on metabolic markers in Ossabaw pigs fed different levels of fat

We investigated effects of Rendement Napole (RN ) genotype on metabolic markers in Ossabaw pigs fed diets with different levels of dietary fat. Thirty‐two pigs, belonging to either the wild‐type (WT , rn⁺/rn⁺) or carrier (CAR , RN ^?/rn⁺) genotypes (n  = 16/genotype), were divided into two dietary groups, (high fat [HF ] or low fat [LF ]) diets, for 12 weeks (n  = 8 pigs/genotype/diet) after which pigs were killed for gene expression analysis by RT ‐PCR . Feeding HF diet caused increased daily gain (ADG , p  <  .05) and final body weight (BW ) (p  <  .05) in comparison with the LF diet (p  <  .05). Feed efficiency (gain:feed) was higher (p  <  .05) in pigs on the HF and was higher (p  <  .05) in CAR pigs compared to WT . There was genotype × diet interaction (p  =  .05) on final BW such that CAR animals on LF diet had the same final BW as animals of both genotypes on HF diet. Carrier pigs on LF diet had higher (p  <  .05) average daily gain and gain:feed than WT pigs. There was a trend (p  <  .08) for a higher feed consumption in pigs on the LF diet. Backfat thickness was higher (p  <  .01) in pigs on the HF diet. Serum triglyceride was higher (0.62 vs. 0.33 mg/dl, p  <  .01) in pigs on HF diet. Serum insulin was higher (p  <  .05) in CAR versus WT pigs (0.40 vs. 0.015 μg/ml). Pigs on the HF diet had a higher (p  <  .05) serum insulin compared to those on the LF diet (0.032 vs. 0.023 μg/ml). Carnitine palmitoyl transferase 1‐alpha was higher (p  <  .05) in the longissimus dorsi and semitendinosus muscles of pigs on HF diet. Acyl‐CoA oxidase I was elevated (p  <  .05) in the liver of pigs on HF diet. Fatty acid synthase was lower in the longissimus dorsi muscle, liver and mesenteric fat (p  <  .05) of carrier pigs. The RN gene regulates specific metabolic markers in the Ossabaw pigs.