1,721,310 research outputs found
Efficacy of chlortetracycline for controlling goat coccidiosis in Burundi.
Eighteen cross-bred goats of Burundi naturally infected to varying degrees with multiple coccidia species of the genus Eimeria were orally administered 25 mg/kg body weight/day chlortetracycline. Effectiveness percentages more elevated than 99.0% were reached within the 9th day of treatment. No adverse reactions have ever been reported. Results demonstrate that the antibiotic is effective for the control of coccidiosis of goats naturally infected in Burundi
Pharmacogenetics of cytochrome P450 in veterinary species: an update.
Recent advances in genetics have spurred growth in research linking genetics and pharmacology. Pharmacogenetics focuses
on genetic causes of individual variations in drug response, while pharmacogenomics is the genome-wide analysis of
genetic determinants of drug efficacy and toxicity. Historically, human pharmacogenomics began as early as the 1950s, with
observed differences in drug response and toxicity in racial/ethnic groups. The majority of phase I drug-metabolizing enzymes,
and mostly cytochromes P450 (CYPs), are known to be polymorphic; therefore, studying CYP genetic polymorphisms is of
great importance to understand the variability in responses to xenobiotics.
By comparison, veterinary pharmacogenetics is relatively still underdeveloped. Above and beyond a gap between veterinary
and life sciences researchers and the minor amount of funds available for fundamental and applied research, other genetic
(species, breed, sex) and dynamic non-genetic factors (age, induction/inhibition phenomena, health-related conditions,
diet), have historically been attributed major importance. To the best of our knowledge, only four reviews describing CYP
genetic polymorphisms in species of veterinary interest have been published so far, and most of data concern canine CYPs.
In this species, the prevalence of a known CYP1A2 stop codon seems to vary considerably between and within dog breeds.
Similarly, breed has been proved as a key genetic factor affecting CYP expression and function in food-producing species, e.g.
cattle, chicken, horse and pigs.
Actually, the genome sequencing and analysis projects and the advances in high-throughput genotyping and DNA
sequencing have dramatically changed the approach to CYP pharmacogenetics and pharmacogenomics. This has been
recently proved also in cattle (CYP3A) and pigs (CYP2E1). Furthermore, this genome-wide approach has also uncovered novel genes and genetic variants (i.e., nuclear receptors, contributing
to CYP regulation) as well as new biological pathways influencing not only drug metabolism/response (i.e.,
productivity traits).
In conclusion, CYP genetic polymorphisms have been associated with differences in drug metabolism and/or response and
productivity traits in veterinary species. Further studies are needed to characterize the expression, the transcriptional activity
and post-translational effects of these and other related genetic polymorphisms
Efficacy of ivermectin in reducing gastrointestinal nematode fecal egg counts in goats in Burundi.
Cross-bred goats in Burundi infested with gastrointestinal nematodes were submitted to fecal investigations and injected subcutaneously with ivermectin. In Experiment 1, goats were treated with 200 mu g kg(-1) bw ivermectin. In Experiment 2, animals were administered twice that dose. In Experiment 3, goats suspected to be resistant to other anthelmintics were treated with 200 mu g kg(-1) bw ivermectin. In Experiment 4, two doses of the same strength were injected with an interval of 7 days. Results demonstrate that 200 mu g kg(-1) bw ivermectin is effective for the control of gastrointestinal nematodes of goats in Burundi; this dosage is also effective against nematodes suspected to be resistant to other anthelmintics. The administration of 400 mu g kg(-1) bw did not induce greater or more prolonged effectiveness percentages. The supposed decrease of ivermectin's residual activity on Day 28 might be avoided by administering two doses with an interval of 7 days. No adverse effects were observed in treated animal
Triphenyltin acetate (TPTA)-induced cytotoxicity to mouse thymocytes.
To perform a better investigation of the toxic activity of triphenyltin acetate (TPTA) already described in vivo, primary cultures of murine thymocytes were incubated for 2 to 32 h with graded amounts (0.5-8 microM) of the triorganotin compound. The cytotoxic activity has been evaluated with the Trypan blue dye exclusion test, the 3-(4,5-dimethyl-thiazol-2-yl)-2,5 diphenyl-tetrazolium bromide (MTT) assay for cell survival and the cellular release of lactate dehydrogenase. Following 2 h of incubation with TPTA, a dose-dependent reduction (P < 0.05) of cellular viability occurred and marked increases (P < 0.05) of the MTT cytotoxic index and of lactate dehydrogenase leakage were also observed. These findings indicate that TPTA is as cytotoxic to mice thymocytes, as other triphenyltin derivatives are to other species
Postnatal development of hepatic, hydrolytic and conjugative drug-metabolizing enzymes in female horses
Little is known about the effects of aging on the hepatic drug metabolizing capacity of horses despite the relatively long lifespan characterizing this species. A wide array of cytochrome P450 (CYP)-dependent monooxygenases, carboxylesterases and transferases were assayed in liver microsomes from 50 female horses in an age range between less than 1 year to over 12 years. Rather unexpectedly, both the CYP content and the activity of NADPH cytochrome c reductase rose as a function of age. Accordingly, a general increasing trend was recorded in the rate of the in vitro metabolism of the substrates reported to be related to CYP2B-, CYP2E- or CYP3A, although, as detected by Western immunoblotting, only the levels of proteins recognized by anti-rat CYP3A- and CYP2B antibodies appeared to increase consistently. Also the carboxylesterases and uridindiphosphoglucuronyl-transferase (UGT) activity toward 1-naphthol displayed a similar trend, glutathione S-transferase accepting 3,4-dichloronitrobenzene as a substrate being the only enzyme activity showing an age-related decline. A positive correlation was also found between liver cadmium content and CYP amount as well as the activities of most monooxygenases (except for those related to CYP1A), carboxylesterases, and UGT. While confirming that a number of enzyme activities are less expressed in foals, our results contradict the general view that the drug metabolizing capacity drops in elder individuals. Although several other factors can influence the kinetics of foreign compounds in aged animals, data from this study may provide insight in understanding possible age-related differences in drug efficacy and the response to toxic substances in horse
CD4+, CD8+ lymphocyte depletion and cytotoxicity induced by the organotin TPTA in the mouse.
Apoptosis and CD4+, CD8+ lymphocyte depletion following triphenyltin acetate (TPTA) exposure in mice thymic primary culture.
Absolute quantification and modulation of cytochrome P450 3A isoforms in cattle liver
In humans and laboratory animals, knowledge about cytochrome P450 (CYP) regulation and function is detailed and very extensive. However, CYPs have still been incompletely characterized in veterinary species so far. In this study, mRNA levels of three CYP3A enzymes (CYP3A28, CYPA38 and CYPA48) were measured in cattle liver by using quantitative real-time RT-PCR (qPCR) assays and an absolute quantification approach. In particular, the possible presence of breed-differences in CYP3A expression was investigated in five different meat cattle breeds (Charolais, CH; Piedmontese, PM; Blonde d’Aquitaine, BA; Marchigiana, MA; Valdostana, VALD) and the potential transcriptional effect of the
prototypical inducer phenobarbital (PB) upon the CYP3A isoforms was evaluated.
Cytochrome P450 3A38 showed the highest amounts of gene copy numbers, followed by CYP3A48 and CYP3A28. Significant breed-differences in CYP3A gene abundances were found, and PB significantly up-regulated all the CYP3As isoforms. The data provide new information about CYP3A expression in cattle, particularly the heterogeneity in the pattern of expression of distinct hepatic CYP3As (CYP3A38>3A48>>3A28), the significant effect of breed, and their common up-regulation following the exposure to PB, although with different orders of magnitude
Subacute toxicity of triphenyltin acetate (TPTA) in the rabbit: clinical observations and hematologic, hematochemical and enzymatic changes
Twenty-eight immature male rabbits were divided into four experimental groups and administered a standard diet containing respectively 0, 15, 75 and 150 ppm of triphenyltin acetate (TPTA) for 70 days. The highest dose group showed a decrease in erythrocyte count, haemoglobin content and packed cell volume. As early as on day 35, leucopenia and lymphopenia were recorded in all treated groups, thereby confirming the well-known immunosuppressive activity of organo-tin compounds. Both total serum protein and albumin levels apparently altered by TPTA treatment. Conversely, there was a dose-dependent increase for both alpha 2-globulin fraction and blood urea nitrogen serum levels, suggesting a possible renal involvement
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