Evaluation of a Bacillus stearothermophilus tube test as a screening tool for anticoccidial residues in poultry.
(25/100)
A Bacillus stearothermophilus var. calidolactis C953 tube test was evaluated for its ability in detecting the residue of selected anticoccidial drugs in poultry, specially sulfamethazine, furazolidone, and amprolium. Various concentrations of each drug were injected into chicken liver and kidney tissues and these tissues were tested to determine the drug detection limits for each drug. The detection limit was defined as the drug concentration at which 95 % of the test results were interpreted as positive. The limits of detection in liver tissue were 0.35 microgram/ml for furazolidone, 0.70 microgram/ml for sulfamethazine and 7.80 microgram/ml for amprolium. In kidney tissues, they were 0.30 microgram/ml for furazolidone, 0.54 microgram/ml for sulfamethazine, and 7.6 microgram/ml for amprolium. It was concluded that this tube test could be used to screen for the residue of these three drugs in poultry. (+info)
Antiproliferative activities of two novel quinuclidine inhibitors against Toxoplasma gondii tachyzoites in vitro.
(26/100)
OBJECTIVES: To study the antiproliferative effects of ER119884 and E5700, two quinuclidine-based inhibitors of squalene synthase (SQS), against Toxoplasma gondii tachyzoites in epithelial cells. METHODS: The antiproliferative effects of the quinuclidine derivatives, alone or in combination with epiminolanosterol or antifolates, were analysed, resulting in the construction of isobolograms. The ultrastructure of treated tachyzoites was analysed by transmission electron microscopy. RESULTS: The quinuclidine derivatives demonstrated selective anti-T. gondii activity, arresting parasite growth with IC50 values of 0.66 and 0.23 microM for ER119884 and E5700, respectively, after 24 h of interaction and 0.44 and 0.19 microM after 48 h of interaction. Both compounds induced remarkable alterations in the parasite ultrastructure, such as mitochondrial swelling and the presence of autophagosome-like structures, after 24 h of treatment. Combination of these quinuclidine derivatives with the antifolates sulfadiazine and pyrimethamine produced a synergic effect. When epiminolanosterol was combined with E5700, the effect observed was synergic, whereas the combination with ER119884 produced no interaction. CONCLUSIONS: E5700 and ER119884 demonstrated selective activity against T. gondii tachyzoites and are a possible alternative to be used in association with the current therapy. The ultrastructural alterations observed suggest a possible interference with lipid metabolism. (+info)
Impact of spiramycin treatment and gestational age on maturation of Toxoplasma gondii immunoglobulin G avidity in pregnant women.
(27/100)
The objective of the present study was to investigate the maturation of immunoglobulin G (IgG) avidity after Toxoplasma gondii seroconversion during pregnancy and the factors that affect IgG avidity over time. The study used 309 serum samples from 117 women and a multiple linear mixed regression analysis to show the patterns of variation of IgG avidity throughout gestation. The IgG avidity ratios and the patterns of their evolution with time were quite diverse among the women and were statistically heterogeneous (P = 0.011); however, the trend was toward a statistically significant increase (P < 0.0001). On average, a 1.0167-fold increase was observed for each additional gestational week after the putative date of infection. At 12 weeks after putative infection (the expected IgG avidity maturation time), the mean avidity ratio was 16.6% (95% confidence interval, 15.4 to 17.9%). At all times, the avidity ratio remained significantly heterogeneous among the women (P < 0.05); for 95% of them, that ratio ranged from 7.8 to 35.3% at 12 weeks after putative infection. Maternal age at the putative time of infection did not influence the maturation of IgG avidity. However, on average, a 1.009-fold decrease (P = 0.03) in that avidity was observed for each additional week of gestational age before infection and a 1.03-fold increase (P = 0.0003) was observed for each additional week of delay to the onset of spiramycin treatment. The rate of increase in the avidity ratio was lower if infection occurred late in pregnancy and higher if the delay to treatment was long. This information cannot allow accurate determination of the delay since the time of infection. The present results provide support for interpretation of the assay and caution against overinterpretation. (+info)
Assessment of feed additives and contaminants: an essential component of food safety.
(28/100)
Feed additives make the bulk of chemicals used in animal production, thus representing a major issue for safety of foods of animal origin. This paper summarizes the approaches adopted by the European Food Safety Authority to perform risk analysis of feed additives as regards the whole food production chain, including target species, consumers, occupational exposure and the environment. Feed safety must consider also environmental contaminants; in particular feeds can be a major vehicle for human dietary intake of persistent pollutants such as polychlorinated biphenyls. Critical issues include toxicological characterization, pathways of feed contamination as well as transfer to animal products. The possible effects of feed additives and contaminants on the overall safety and nutritional quality of human diet are discussed. (+info)
Treatment of canine pediatric Neospora caninum myositis following immunohistochemical identification of tachyzoites in muscle biopsies.
(29/100)
A 7-week-old Irish wolfhound was evaluated for an abnormal hind limb gait. Quadriceps muscle atrophy was pronounced and patellar reflexes were absent bilaterally. Neospora caninum myositis was diagnosed by histopathologic and serologic examination and immunohistochemical staining of muscle. Substantial clinical improvement was noted after 18 weeks of treatment with clindamycin. (+info)
Roles of P-glycoprotein, Bcrp, and Mrp2 in biliary excretion of spiramycin in mice.
(30/100)
The multidrug resistance proteins P-glycoprotein (P-gp), breast cancer resistance protein (Bcrp), and multidrug resistance-associated protein 2 (Mrp2) are the three major canalicular transport proteins responsible for the biliary excretion of most drugs and metabolites. Previous in vitro studies demonstrated that P-gp transported macrolide antibiotics, including spiramycin, which is eliminated primarily by biliary excretion. Bcrp was proposed to be the primary pathway for spiramycin secretion into breast milk. In the present study, the contributions of P-gp, Bcrp, and Mrp2 to the biliary excretion of spiramycin were examined in single-pass perfused livers of male C57BL/6 wild-type, Bcrp-knockout, and Mrp2-knockout mice in the presence or absence of GF120918 (GW918), a P-gp and Bcrp inhibitor. Spiramycin was infused to achieve steady-state conditions, followed by a washout period, and parameters governing spiramycin hepatobiliary disposition were recovered by using pharmacokinetic modeling. In the absence of GW918, the rate constant governing spiramycin biliary excretion was decreased in Mrp2(-) knockout mice (0.0013 +/- 0.0009 min(-1)) relative to wild-type mice (0.0124 +/- 0.0096 min(-1)). These data are consistent with the approximately 8-fold decrease in the recovery of spiramycin in the bile of Mrp2-knockout mice and suggest that Mrp2 is the major canalicular transport protein responsible for spiramycin biliary excretion. Interestingly, biliary recovery of spiramycin in Bcrp-knockout mice was increased in both the absence and presence of GW918 compared to wild-type mice. GW918 significantly decreased the rate constant for spiramycin biliary excretion and the rate constant for basolateral efflux of spiramycin. In conclusion, the biliary excretion of spiramycin in mice is mediated primarily by Mrp2 with a modest P-gp component. (+info)
Structural biology of membrane-acting peptides: conformational plasticity of anticoccidial peptide PW2 probed by solution NMR.
(31/100)
The bottleneck for the complete understanding of the structure-function relationship of flexible membrane-acting peptides is its dynamics. At the same time, not only the structure but also the dynamics are the key points for their mechanism of action. Our model is PW2, a TRP-rich, cationic peptide selected from phage display libraries that shows anticoccidial activity against Eimeria acervulina. In this manuscript we used a combination of several NMR techniques to tackle these difficulties. The structural features of the membrane-acting peptide PW2 was studied in several membrane mimetic environments: we compared the structural features of PW2 in SDS and DPC micelles, that were reported earlier, with the structure properties in different lipid vesicles and the peptide free in water. We were able to unify the structural information obtained in each of these systems. The structural constraints of the peptide free in water were fundamental for the understanding of plasticity necessary for the membrane interaction. Our data suggested that the WWR sequence is the region responsible for anchoring the peptide to the interfaces, and that this same region displays some degree of conformational order in solution. For PW2, we found that affinity is related to the aromatic region, by anchoring the peptide to the membrane, and specificity is related to the N- and C-termini, which are able to accommodate in the membrane due to its plasticity. (+info)
Functional analysis of the interplay between translation termination, selenocysteine codon context, and selenocysteine insertion sequence-binding protein 2.
(32/100)
A selenocysteine insertion sequence (SECIS) element in the 3'-untranslated region and an in-frame UGA codon are the requisite cis-acting elements for the incorporation of selenocysteine into selenoproteins. Equally important are the trans-acting factors SBP2, Sec-tRNA[Ser]Sec, and eEFSec. Multiple in-frame UGAs and two SECIS elements make the mRNA encoding selenoprotein P (Sel P) unique. To study the role of codon context in determining the efficiency of UGA readthrough at each of the 10 rat Sel P Sec codons, we individually cloned 27-nucleotide-long fragments representing each UGA codon context into a luciferase reporter construct harboring both Sel P SECIS elements. Significant differences, spanning an 8-fold range of UGA readthrough efficiency, were observed, but these differences were dramatically reduced in the presence of excess SBP2. Mutational analysis of the "fourth base" of contexts 1 and 5 revealed that only the latter followed the established rules for hierarchy of translation termination. In addition, mutations in either or both of the Sel P SECIS elements resulted in differential effects on UGA readthrough. Interestingly, even when both SECIS elements harbored a mutation of the core region required for Sec incorporation, context 5 retained a significantly higher level of readthrough than context 1. We also show that SBP2-dependent Sec incorporation is able to repress G418-induced UGA readthrough as well as eRF1-induced stimulation of termination. We conclude that a large codon context forms a cis-element that works together with Sec incorporation factors to determine readthrough efficiency. (+info)