In the recent past years, important efforts towards the prudent use of antimicrobials have been made in order to optimize antibacterial use, and maximize therapeutic effect while minimizing the development of resistance. Knowledge on the occurrence of resistance in bacteria could help in improving the clinical success of therapeutic decisions. Since the discovery of amoxicillin, this drug has been extensively used throughout the world in veterinary medicine, alone and also in combination with clavulanic acid. This paper provides information regarding the current situation of resistance to amoxicillin (and amoxicillin-clavulanic acid) in animals in Europe. Most data comes from food-animal species, mainly from several national monitoring programmes of antimicrobial resistance, and information on companion animals is also available.
From a human safety perspective, the administration of ivermectin to food producing animal species entails potential risks related to the presence of drug residues in edible tissues, milk, and other derived products. The European Medicines Agency has established the maximum residue limits for ivermectin in the European Union, with values of 100 μg·kg(-1) in fat and liver and 30 μg·kg(-1) in kidney for all mammalian food producing species, in order to ensure that the amount of ivermectin that can be found in animal foodstuff is below dangerous levels for the consumers. According to these values, withdrawal periods after subcutaneous injection were recently established in the European Union (2009), in 49 days for products containing ivermectin as a single active substance or in combination with closantel, and in 66 days when combined with clorsulon. The marker residue for ivermectin was found to be H(2)B(1a), which is the major component of the parent compound. The tissue distribution of residues and the overall ratios of marker to total residues were generally similar in most species, and the highest concentrations of ivermectin residues were found in fat and liver with high levels also detected in injection site muscles. Ivermectin is not licensed for use in animals from which milk is produced for human consumption, however its extra-label use should be considered regarding human safety, due to its long persistence in milk and milk-derived products.
The antiparasitic activity of ivermectin depends on the presence of an active drug concentration at the site of parasites location for an adapted length of time. Ivermectin interactions with another concurrently administered drug can occur. Concomitant administration of some drugs can increase the bioavailability of simultaneously administered ivermectin. This can, in some cases, become a useful pharmacological strategy to improve its antiparasitic efficacy and to delay the development of resistance in livestock or, in other cases, lead to adverse drug reactions and toxicities. On the other hand, other interactions can result in lower levels of this drug, determining that moderate resistant residual populations of the parasites may persist to contaminate pastures. The characterisation of ivermectin interactions can be used to predict and optimise the value of the parasiticide effects. This article reviews the pharmacological interactions of ivermectin in several domestic animal species.
To investigate the possible influence of the single nucleotide polymorphism (SNP) of the estrogen receptor-β gene, rs1256049 (Rsa) in exon 5, on the frequency of rheumatoid arthritis (RA), 263 RA patients and 174 control subjects with osteoarthritis (OA) were recruited. Rsa polymorphism was detected using a PCR-RFLP, Polymerase Chain Reaction-Restriction Fragment Length Polymorphism method. The occurrence of both mutant allele (G) and genotype (GG) were significantly higher in RA than in OA patients (allele P = 0.008, OR: 1.501, 95%CI: 1.12-2.02). In RA patients, GG genotype frequency was higher in severe RA patients than mild RA patients. Moreover, there was significant difference between severe RA patients and OA patients (P = 0.009), also the allele distribution was significant different between severe RA, mild RA, and OA patients (P = 0.025, 95%CI = 0.61-0.93). With respect to gender, GG genotype was statistically more frequent in female RA patients than that of OA, while such an association was not observed in men. Above all, the presence of the GG genotype could be a risk factor for RA and such trend might be different in gender, although additional larger scale study is needed.
The influence of the polymorphism of the estrogen receptor-beta gene, cytosine-adenine (CA) dinucleotide repeat in intron 6, in the occurrence of rheumatoid arthritis (RA) was investigated. Forty-seven RA patients and 36 control subjects with osteoarthritis (OA) were recruited. CA repeat polymorphism was examined using denaturing high-performance liquid chromatography (WAVE DNA Fragment Analysis System). The mean number of CA repeats was significantly higher in RA than in OA patients. Two groups were established:
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