Faecal excretion profile of moxidectin and ivermectin after oral administration in horses

A study was undertaken to evaluate and compare faecal excretion of moxidectin and ivermectin in horses after oral administration of commercially available preparations. Ten clinically healthy adult horses, weighing 390-446 kg body weight (b.w.), were allocated to two experimental groups. Group I was treated with an oral gel formulation of moxidectin at the manufacturer's recommended therapeutic dose of 0.4 mg/kg b.w. Group II was treated with an oral paste formulation of ivermectin at the recommended dose of 0.2 mg/kg b.w. Faecal samples were collected at different times between 1 and 75 days post-treatment. After faecal drug extraction and derivatization, samples were analysed by High Performance Liquid Chromatography using fluorescence detection and computerized kinetic analysis.For both drugs the maximum concentration level was reached at 2.5 days post administration. The ivermectin treatment groups' faecal concentrations remained above the detectable level for 40 days (0.6 +/- 0.3 ng/g), whereas the moxidectin treatment group remained above the detectable level for 75 days (4.3 +/- 2.8 ng/g). Ivermectin presented a faster elimination rate than moxidectin, reaching 90% of the total drug excreted in faeces at four days post-treatment, whereas moxidectin reached similar levels at eight days post-treatment. No significant differences were observed for the values of maximum faecal concentration (C(max)) and time of C(max)(T(max)) between both groups of horses, demonstrating similar patterns of drug transference from plasma to the gastrointestinal tract. The values of the area under the faecal concentration time curve were slightly higher in the moxidectin treatment group (7104 +/- 2277 ng.day/g) but were not significantly different from those obtained in the ivermectin treatment group (5642 +/- 1122 ng.day/g). The results demonstrate that although a 100% higher dose level of moxidectin was used, attaining higher plasma concentration levels and more prolonged excretion and gut secretion than ivermectin, the concentration in faeces only represented 44.3+/- 18.0% of the total parental drug administered compared to 74.3 +/- 20.2% for ivermectin. This suggests a higher level of metabolization for moxidectin in the horse.     

Hepatic cirrhosis in a five-month-old dog

The clinicopathological features of an unusual case of a five-month-old male Spanish mastiff, which was presented with clinical signs indicative of severe hepatic failure, are reported. Fluid replacement therapy, colloid plasma expanders, antibiotics and diuretic drugs were unsuccessful in improving the animal's general condition, and euthanasia was elected by the owner. On necropsy, ascites and severe cirrhosis, with extensive periacinar necrosis, was found. Cirrhosis is a rare lesion in young dogs. The most common causes are circulatory disturbances, hereditary metabolic disorders or poisoning, such as aflatoxicosis and anticonvulsant therapy. The possible involvement of canine adenovirus in this case is discussed.     

Non-bioequivalence of various trademarks of enrofloxacin and Baytril in cows

Including Baytril, in various parts of the world many commercial preparations of enrofloxacin for parenteral administration are being employed for the treatment of bacterial diseases in cows. To optimize clinical responses and to minimize development of bacterial resistance to this agent, the copied pharmaceutical preparations must comply with some key pharmacokinetic features when bioequivalence studies are performed. To assess whether or not there was bioequivalence among nine commercial preparations of enrofloxacin and the original one, a controlled pharmacokinetic study was carried out. These was done utilizing the microbiological agar-diffusion test as quantitative/qualitative analytical method. A non-compartmental model defined kinetic variables. Results for Baytril revealed that maximal serum concentration (Csmax) was only matched by one preparation while area under the curve (AUC) of the serum concentration/activity of enrofloxacin and metabolites in time was not matched by any preparation. Time to Csmax (Tmax), elimination half-life, and shape of the time-serum concentrations of enrofloxacin profiles obtained for the nine generic preparations differ significantly somehow from the corresponding data obtained for the reference enrofloxacin. The need for studies to demonstrate bioequivalence becomes mandatory if similar preparations of enrofloxacin become commercially available. Enrofloxacin should be used selectively and cautiously to limit development of bacterial resistance. Non-bioequivalence of relevant pharmacokinetic values, such as Csmax and bioavailability (AUC) would facilitate development of bacterial resistance and limit the useful life span of this antibacterial agent.     

Alteration of body composition in rats: effect of organic chromium and L-carnitine

A growth trial was carried out to test the effect of organic, trivalent chromium and L-carnitine on the body composition of growing rats. At the same time, an evaluation of different measurement methods (weight of epididymal fat pad, adipocyte morphometry, total body electrical conductivity) was performed. Outbred Wistar rats of 30 days of age were fed diets of different (0, 10 and 20%) protein level. The diets were supplemented with 4 mg/kg Cr as chromium nicotinate, and 100 mg/kg L-carnitine. The experimental feeding lasted 15 days, after a 5-day-long adjustment period. It was found that Cr addition increased feed intake. Both treatments caused changes in body composition, increasing fat and protein deposition. Organic chromium had no effect at either protein level, while L-carnitine improved the protein retention only at an optimum (20%) protein supply. No statistically significant correlation was found between total body electrical conductivity (TOBEC) and body composition, which could be attributed to the great individual differences. A close correlation was found among total body fat percentage, weight of epididymal fat pad and the adipocyte surface. The data suggest that there is an interaction between dietary protein supply and the effect of repartitioning agents.     

Clinical and magnetic resonance imaging findings in 92 cats with clinical signs of spinal cord disease

Medical records of 92 cats presented with clinical signs of spinal cord disease, which had undergone magnetic resonance imaging (MRI), were reviewed. The cats were grouped into seven categories based upon the diagnosis suggested by results of MRI, cerebrospinal fluid analysis and other diagnostic procedures: neoplastic (n=25), inflammatory or infectious (n=13), traumatic (n=8), vascular (n=6), degenerative (n=5), anomalous (n=3) and those with an unremarkable MRI (n=32). There were two independent predictors of abnormal MRI findings: severity of clinical signs and presence of spinal pain. Abnormal MRI findings and speed of onset of disease were significantly associated with survival. For the 32 cats with unremarkable MRI findings, only nine died due to spinal disease and, therefore, the median survival time (MST) was not reached (lower 95% confidence interval (CI)=970 days). For the 60 cats with abnormal MRI findings, 37 died due to their disease and the MST was 138 days (95% CI: 7-807).     

The pharmacokinetics and metabolism of ivermectin in domestic animal species

The pharmacokinetic properties of drugs are closely related to their pharmacological efficacy. The kinetics of ivermectin are characterised, in general terms, by a slow absorption process, a broad distribution in the organism, low metabolism, and slow excretion. The kinetics vary according to the route of administration, formulation, animal species, body condition, age, and physiological status, all of which contribute to differences in drug efficacy. Characterisation of ivermectin kinetics can be used to predict and optimise the value of the parasiticide effects and to design programmes for parasite control. This article reviews the pharmacokinetics of ivermectin in several domestic animal species.     

Genetic immunization with the immunodominant antigen P48 of Mycoplasma agalactiae stimulates a mixed adaptive immune response in BALBc mice

A DNA vaccine against contagious agalactia was developed for the first time, encoding the P48 of Mycoplasma agalactiae. Specific immune responses elicited in BALB/c mice were evaluated. Both total IgG and IgG1 were detected in mice vaccinated with pVAX1/P48. Proliferation of mononuclear cells of the spleen, levels of gamma interferon, interleukin-12, and interleukin-2 mRNAs were enhanced in immunized animals. Results indicate that pVAX1/P48 vaccination induced both T_h1 and T_h2 immune responses. Nucleic acid immunization could be a new strategy against M. agalactiae infections and may be potentially used to develop vaccines for other Mycoplasma diseases.     

Milk production,intake, digestion,blood parameters,and ingestive behavior of cows supplemented with by-products from the biodiesel industry

This study aimed to evaluate the intake, digestion, blood parameters, and feeding behavior of crossbred dairy cows (Holstein?×?Gir) managed on Panicum maximum Jacq. cv. Tanzania-1 and provided supplementation with groundnut cake, sunflower cake, or palm kernel cake (to replace soybean meal). Sixteen cows were randomly assigned in a Latin square design with four treatments and four experimental periods. The consumption of nutrients from the pasture did not vary between experimental treatments. Cows receiving the palm kernel cake supplement had a reduced crude protein, non-fibrous carbohydrate, and total digestible nutrient intake and an increase in the average consumption of ether extract. There was also a reduction in the digestibility of dry matter. The inclusion of supplements in the diet did not influence the average time spent eating, ruminating, or resting. The mean values of respiratory and heart rates showed thermal comfort during the trial period. There was a reduction in blood urea nitrogen with palm kernel cake supplementation, and the values of total protein, albumin, and glucose were also significantly different with this supplement. It is recommended that cakes of groundnut cake and sunflower cake seed be used for a total replacement of soybean meal supplements for lactating cows, but the use of palm kernel cake is not recommended.

     

Lack of a type-2 glycosyltransferase in the fish pathogen Flavobacterium psychrophilum determines pleiotropic changes and loss of virulence

Flavobacterium psychrophilum is an important fish pathogen, responsible for Cold Water Disease, with a significant economic impact on salmonid farms worldwide. In spite of this, little is known about the bacterial physiology and pathogenesis mechanisms, maybe because it is difficult to manipulate, being considered a fastidious microorganism. Mutants obtained using a Tn4351 transposon were screened in order to identify those with alteration in colony morphology, colony spreading and extracellular proteolytic activity, amongst other phenotypes. A F. psychrophilum mutant lacking gliding motility showed interruption of the FP1638 locus that encodes a putative type-2 glycosyltransferase (from here on referred to as fpgA gene, Flavobacterium psychrophilum glycosyltransferase). Additionally, the mutant also showed a decrease in the extracellular proteolytic activity as a consequence of down regulation in the fpgA mutant background of the fpp2-fpp1 operon promoter, responsible for the major extracellular proteolytic activity of the bacterium. The protein glycosylation profile of the parental strain showed the presence of a 22 kDa glycosylated protein which is lost in the mutant. Complementation with the fpgA gene led to the recovery of the wild-type phenotype. LD₅₀ experiments in the rainbow trout infection model show that the mutant was highly attenuated. The pleiotropic phenotype of the mutant demonstrated the importance of this glycosyltranferase in the physiology and virulence of the bacterium. Moreover, the fpgA mutant strain could be considered a good candidate for the design of an attenuated vaccine.