Pharmacokinetics/Pharmacodynamics models of veterinary antimicrobial agents

Misuse and abuse of veterinary antimicrobial agents have led to an alarming increase in bacterial resistance, clinical treatment failure, and drug residues. To address these problems, consistent and appropriate dosage regimens for veterinary antimicrobial agents are needed. Pharmacokinetics/Pharmacodynamics (PK/PD) models have been widely used to establish rational dosage regimens for veterinary antimicrobial agents that can achieve effective prevention and treatment of bacterial diseases and avoid the development of bacterial resistance. This review introduces building methods for PK/PD models and describes current PK/PD research progress toward rational dosage regimens for veterinary antimicrobial agents. Finally, the challenges and prospects of PK/PD models in the design of dosage regimens for veterinary antimicrobial agents are reviewed. This review will help to increase awareness of PK/PD modeling among veterinarians and hopefully promote its development and future use.

Protective mechanisms involving enhanced mitochondrial functions and mitophagy against T-2 toxin-induced toxicities in GH3 cells.

T-2 toxin is the most toxic member of trichothecene mycotoxin. So far, the mechanism of mitochondrial toxicity and protective mechanism in mammalian cells against T-2 toxin are not fully understood. In this study, we aimed to investigate the cellular and mitochondrial toxicity of T-2 toxin, and the cellular protective mechanisms in rat pituitary GH3 cells. We showed that T-2 toxin significantly increased reactive oxygen species (ROS) and DNA damage and caused apoptosis in GH3 cells. T-2 toxin induced abnormal cell morphology, cytoplasm and nuclear shrinkage, nuclear fragmentation and formation of apoptotic bodies and autophagosomes. The mitochondrial degradative morphologies included local or total cristae collapse and small condensed mitochondria. T-2 toxin decreased the mitochondrial membrane potential. However, T-2 toxin significantly increased the superoxide dismutase (SOD) activity and expression of antioxidant genes glutathione peroxidase 1 (GPx-1), catalase (CAT), mitochondria-specific SOD-2 and mitochondrial uncoupling protein-1, -2 and -3 (UCP-1, 2 and 3). Interestingly, T-2 toxin increased adenosine triphosphate (ATP) levels and mitochondrial complex I activity, and increased the expression of most of mitochondrial electron transport chain subunits tested and critical transcription factors controlling mitochondrial biogenesis and mitochondrial DNA transcription and replication. T-2 toxin increased mitophagic activity by increasing the expression of mitophagy-specific proteins NIP-like protein X (NIX), PTEN-induced putative kinase protein 1 (PINK1) and E3 ubiquitin ligase Parkin. T-2 toxin activated the protective protein kinase A (PKA) signaling pathway, which activated the nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/PINK1/Parkin pathway to mediate mitophagy. Taken together, our results suggested that the mammalian cells could increase their resistance against T-2 toxin by increasing the antioxidant activity, mitophagy and mitochondrial function.

Research and application of colistin in animals / 中国兽医学报

Colistin is a kind of old cationic drug,which can interfere bacterial cell membrane,thus to cause bacterial death.It is mainly used for the treatment of infections caused by Gram-negative bacteria,and its antimicrobial activity against multidrug-resistant Gram-negative bacteria is also very significant.At present,colistin is widely used in veterinary medicine.This article aims to review colistin in chemical,pharmacological,and pharmacokinetic studies,and also summarizes the application and resistance of this drug,which will provide reference for the reasonable selection and use of this drug in animals.

Serotypes and antimicrobial susceptibility of Salmonella spp. isolated from farm animals in China.

Salmonella spp. can indirectly infect humans via transfer from animals and animal-derived food products, and thereby cause potentially fatal diseases. Therefore, gaining an understanding of Salmonella infection in farm animals is increasingly important. The aim of this study was to identify the distribution of serotypes in Salmonella samples isolated from chickens (n = 837), pigs (n = 930), and dairy cows (n = 418) in central China (Henan, Hubei, and Hunan provinces) in 2010-2011, and investigate the susceptibility of strains to antimicrobial agents. Salmonella isolates were identified by PCR amplification of the invA gene, serotypes were determined by using a slide agglutination test for O and H antigens, and susceptibility to 24 antimicrobials was tested using the agar dilution method. In total, 248 Salmonella strains were identified: 105, 105, and 38 from chickens, dairy cows, and pigs, respectively. Additionally, 209 strains were identified in diseased pigs from the Huazhong Agricultural University veterinary hospital. Among these 457 strains, the dominant serotypes were Typhimurium in serogroup B, IIIb in serogroup C, and Enteritidis in serogroup D. In antimicrobial susceptibility tests, 41.14% of Salmonella spp. were susceptible to all antimicrobial agents, 48.14% were resistant to at least one, and 34.72% were resistant to more than three classes. Strains were highly resistant to sulfamethoxazole-trimethoprim (39.61%), nalidixic acid (39.17%), doxycycline (28.22%), and tetracycline (27.58%). Resistance to cephalosporins and fluoroquinolones ranged from 5.25 to 7.44% and 19.04 to 24.51%, respectively. Among penicillin-resistant and cephalosporin-resistant strains, 25 isolates produced extended-spectrum ß-lactamases (ESBLs). The multidrug-resistant and ESBL-producing Salmonella strains identified in healthy animals here will present a challenge for veterinary medicine and farm animal husbandry, and could also pose a threat to public health. The level of antibiotic resistance observed in this study further highlights the need for careful and selective use of antibiotics.

Metabolic Disposition and Elimination of Cyadox in Pigs, Chickens, Carp, and Rats.

The metabolism, distribution, and elimination of cyadox (CYA) is investigated in pigs, chickens, carp, and rats to identify the marker residue and target tissue of CYA in food animals for food safety concerns. Following a single oral gavage of [(3)H]-CYA, the total radioactivity was rapidly excreted, with more than 95% of the dose excreted within 14 days in the four species. Fecal excretion of the total radioactivity was 66.2% and 51.6%, and urinary excretion of the total radioactivity was 28.35% and 44.3% in rats and pigs, respectively. Radioactivity was observed in nearly all of the tissues in the first 6 h after 7 days of consecutive oral dosing. The highest radioactivity and longest persistence were in the livers and kidneys, where the majority of the radioactivity was cleared within 7 days. A total of 15 metabolites were identified in rats, pigs, chickens, and carp, and eight new metabolites were identified for the first time in vivo. No parent drug could be detected in the tissues of rats and pigs. The major metabolites of CYA were Cy1, Cy3, and Cy6 in pigs, Cy1, Cy5, and Cy6 in chickens, Cy1, Cy2, and Cy4 in carp, and Cy1, Cy2, Cy4, and Cy5 in rats. Cy1 was suggested to be the marker residue, and the kidneys were identified as the target tissue of CYA in pigs and chickens. These results provide comprehensive information for the food safety evaluation of CYA in food animals and will improve the understanding of the pharmacology and toxicology of CYA in animals.

Veterinary drug and its impacts on human health / 中国临床药理学与治疗学

Veterinary drug is a kind of pharmaceuticals approved officially to apply in animals. It has many special features by comparison with the drug used in human. The residue of veterinary drug in edible tissues of food producing animals is a big issue concerned currently by people due to that it could arise several harmful problems on consumers. China is taking actions against any kind of residues in foods originally from animals.