Screening of polysaccharides from the differently processed products of Angelica sinensis with the best liver protection effect on chicken and the intervention mechanism study based on tandem mass tag proteomics and multiple reaction monitoring approach.

The incidence of colibacillosis in poultry is on the rise, significantly affecting the chicken industry. Ceftiofur sodium (CS) is frequently employed to treat this disease, resulting in lipopolysaccharide (LPS) buildup. Processing plays a vital role in traditional Chinese veterinary medicine. The potential intervention in liver injury by polysaccharides from the differently processed products of Angelica sinensis (PDPPAS) induced by combined CS and LPS remains unclear. This study aims to investigate the protective effect of PDPPAS on chicken liver injury caused by CS combined with LPS buildup and further identify the polysaccharides with the highest hepatoprotective activity in chickens. Furthermore, the study elucidates polysaccharides' intervention mechanism using tandem mass tag (TMT) proteomics and multiple reaction monitoring (MRM) methods. A total of 190 1-day-old layer chickens were randomly assigned into 12 groups, of which 14 chickens were in the control group and 16 in other groups, for a 10-day trial. The screening results showed that charred A. sinensis polysaccharide (CASP) had the most effective and the best hepatoprotective effect at 48 h. TMT proteomics and MRM validation results demonstrated that the intervention mechanism of the CASP high-dose (CASPH) intervention group was closely related to the protein expressions of FCER2, TBXAS1, CD34, AGXT, GCAT, COX7A2L, and CYP2AC1. Conclusively, the intervention mechanism of CASPH had multitarget, multicenter regulatory features.

Pharmacokinetics of ceftiofur sodium in Peekapoo dogs following a single intravenous and subcutaneous injection.

The present study aimed to determine the pharmacokinetic profiles of ceftiofur (as measured by ceftiofur and its active metabolites concentrations) in a small-size dog breed, Peekapoo, following a single intravenous or subcutaneous injection of ceftiofur sodium. The study population comprised of five clinically healthy Peekapoo dogs with an average body weight (BW) of 3.4 kg. Each dog received either intravenous or subcutaneous injection, both at 5 mg/kg BW (calculated as pure ceftiofur). Plasma samples were collected at different time points after the administration. Ceftiofur and its active metabolites were extracted from plasma samples, derivatized, and further quantified by high-performance liquid chromatography. The concentrations versus time data were subjected to noncompartmental analysis to obtain the pharmacokinetic parameters. The terminal half-life (t1/2 λz ) was calculated as 7.40 ± 0.79 and 7.91 ± 1.53 hr following intravenous and subcutaneous injections, respectively. After intravenous treatment, the total body clearance (Cl) and volume of distribution at steady-state (VSS ) were determined as 39.91 ± 4.04 ml hr-1  kg-1 and 345.71 ± 28.66 ml/kg, respectively. After subcutaneous injection, the peak concentration (Cmax ; 10.50 ± 0.22 µg/ml) was observed at 3.2 ± 1.1 hr, and the absorption half-life (t1/2 ka ) and absolute bioavailability (F) were calculated as 0.74 ± 0.23 hr and 91.70%±7.34%, respectively. The pharmacokinetic profiles of ceftiofur and its related metabolites demonstrated their quick and excellent absorption after subcutaneous administration, in addition to poor distribution and slow elimination in Peekapoo dogs. Based on the time of concentration above minimum inhibitory concentration (T > MIC) values calculated here, an intravenous or subcutaneous dose at 5 mg/kg of ceftiofur sodium once every 12 hr is predicted to be effective for treating canine bacteria with a MIC value of ≤4.0 µg/ml.

PK/PD modeling of Ceftiofur Sodium against Haemophilus parasuis infection in pigs.

BACKGROUND: Ceftiofur Sodium is widely used in China. Our aim was to determine Ceftiofur Sodium activity and optimize dosing regimens against the pathogen Haemophilus parasuis using an in vitro and ex vivo pharmacokinetics/pharmacodynamics modeling approach. By adopting these strategies, we wanted to extend the effective life of Ceftiofur Sodium in reduce drug-resistance in pigs. RESULTS: We established an H. parasuis infection model in pigs, and assessed the pharmacokinetics of Ceftiofur Sodium in both healthy and infected animals. After Ceftiofur Sodium (10 mg/kg, i.m.) administration to healthy and H. parasuis-infected pigs, plasma based desfuroylceftiofur (a metabolite of Ceftiofur Sodium) was measured by High Performance Liquid Chromatography. The pharmacokinetics of Ceftiofur Sodium (desfuroylceftiofur) was consistent with a two-compartment open model, with first-order absorption. We observed no significant differences (P > 0.05) in pharmacokinetic parameters between healthy and infected pigs. Pharmacodynamics data showed that Ceftiofur Sodium was highly inhibitory against H. parasuis, with MIC, MBC, and MPC values of 0.003125, 0.0125 and 0.032 µg/mL, respectively. Desfuroylceftiofur in plasma also had strong bactericidal activity. Almost all H. parasuis cultured in plasma medium of Ceftiofur Sodium-inoculated healthy pigs, at each time point, were killed within 24 h. A weaker antibacterial activity was measured in infected-pig plasma medium at 18, 24, 36, and 48 h, after Ceftiofur Sodium inoculation. Pharmacokinetic parameters were combined with ex vivo pharmacodynamic parameters, and the bacteriostatic effect (36.006 h), bactericidal effect (71.637 h) and clearance (90.619 h) within 24 h, were determined using the Hill equation. Dose-calculation equations revealed the optimal dose of Ceftiofur Sodium to be 0.599-1.507 mg/kg. CONCLUSIONS: There were no significant differences in Ceftiofur Sodium pharmacokinetic parameters between healthy and infected pigs, although pharmacokinetics/pharmacodynamics fitting curves showed obviously differences. The optimal dose of Ceftiofur Sodium was lower than recommended (3 mg/kg), which may provide improved treatments for Glässers disease, with lower drug-resistance possibility.

Pharmacokinetics of ceftiofur sodium in cats following a single intravenous and subcutaneous injection.

Ceftiofur, a third-generation cephalosporin antibiotic, is being extensively used by pet doctors in China. In the current study, the detection method was developed for ceftiofur and its metabolites, desfuroylceftiofur (DCE) and desfuroylceftiofur conjugates (DCEC), in feline plasma. Then, the pharmacokinetics studies were performed following one single intravenous and subcutaneous injection of ceftiofur sodium in cats both at 5 mg/kg body weight (BW) (calculated as pure ceftiofur). Ceftiofur, DCE, and DCEC were extracted from plasma samples, then derivatized and further quantified by high-performance liquid chromatography. The concentrations versus time data were subjected to noncompartmental analysis to obtain the pharmacokinetics parameters. The terminal half-life (t1/2λz ) was calculated as 11.29 ± 1.09 and 10.69 ± 1.31 hr following intravenous and subcutaneous injections, respectively. After intravenous treatment, the total body clearance (Cl) and volume of distribution at steady-state (VSS ) were determined as 14.14 ± 1.09 ml hr-1  kg-1 and 241.71 ± 22.40 ml/kg, respectively. After subcutaneous injection, the peak concentration (Cmax ; 14.99 ± 2.29 µg/ml) was observed at 4.17 ± 0.41 hr, and the absorption half-life (t1/2ka ) and absolute bioavailability (F) were calculated as 2.83 ± 0.46 hr and 82.95%±9.59%, respectively. The pharmacokinetic profiles of ceftiofur sodium and its related metabolites demonstrated their relatively slow, however, good absorption after subcutaneous administration, poor distribution, and slow elimination in cats. Based on the time of drug concentration above the minimum inhibitory concentration (MIC) (T>MIC) calculated in the current study, an intravenous or subcutaneous dose at 5 mg/kg BW of ceftiofur sodium once daily is predicted to be effective for treating feline bacteria with a MIC value of ≤4.0 µg/ml.

Carbonized polymer dots-based molecular imprinting: An adsorbent with enhanced selectivity for highly efficient recognition and removal of ceftiofur sodium from complex samples.

Highly selective removal of residual cephalosporin antibiotics from complex systems is crucial for human health and ecological environment protection. Herein, a newly molecularly imprinted polymer adsorbent (CPDs-NH2@MIP) with enhanced selectivity for ceftiofur sodium (CTFS) was developed by using the special carbonized polymer dots (CPDs-NH2) as functional monomer. The CPDs-NH2 has a nano-spherical structure and functionalized groups (CC, -NH2) via the incomplete carbonization polymerization of citric acid, acrylamide and ethylenediamine, which can accurately interact with CTFS by overcoming steric hindrance, resulting in more precisely imprinted sites and reducing non-imprinted regions in MIP. The presented CPDs-NH2@MIP exhibited excellent adsorption capacity for CTFS (68.62 mg g-1), achieving equilibrium within 10 min, and highly selectivity in mixed solution containing five coexisting substances, with an imprinted factor (5.61). Compared with commercial adsorbents and MIPs prepared with traditional chain functional monomers, the CPDs-NH2@MIP showed significant advantage in selective recognition and separation of target. Analysis of microstructure and mechanism proved that usage of the spherical functional monomer generated precise imprinting sites and dense structure in CPDs-NH2@MIP, which effectively enhanced the selectivity in complex system combined with hydrogen bonding interaction. The idea of designing and using spherical functional monomer will promote the practicality of molecularly imprinted polymer adsorbents.

Silver nanoparticles modified ZnO nanocatalysts for effective degradation of ceftiofur sodium under UV-vis light illumination.

Light-induced photocatalytic degradation of ceftiofur sodium (CFS) has been assessed in the presence of plasmonic zinc oxide nanostructures (ZnONSTs), like, ZnO nanoparticles, ZnO nanorods (ZnONRs) and ZnO nanoflowers (ZnONFs). Silver nanoparticles (Ag NPs) loaded ZnO nanostructures (Ag-ZnONSTs) are obtained through seed-assisted chemical reaction followed by chemical reduction of silver. The surface modification of ZnO nanostructures by Ag NPs effectually altered their optical properties. Further, the surface plasmonic effect of Ag NPs facilitates visible light absorption by ZnONSTs and improved the photogenerated electron and hole separation, which makes the ZnONSTs a more active photocatalyst than TiO2 (P25) nanoparticles. Especially, Ag-ZnONRs showed higher CFS oxidation rate constant (k' = 4.6 × 10-4 s-1) when compared to Ag-ZnONFs (k' = 2.8 × 10-4 s-1) and Ag-ZnONPs (k' = 2.5 × 10-4 s-1), owing to their high aspect ratio (60:1). The unidirectional transport of photogenerated charge carriers on the Ag-ZnONRs may be accountable for the observed high photocatalytic oxidation of CFS. The photocatalytic oxidation of CFS mainly proceeds through •OH radicals generated on the Ag-ZnONRs surface under light illumination. In addition, heterogeneous activation of peroxymonosulfate by Ag-ZnONRs accelerates the rate of photocatalytic mineralization of CFS. The quantification of oxidative radicals supports the proposed CFS oxidation mechanism. Stability studies of plasmonic Ag-ZnONSTs strongly suggests that it could be useful to clean large volume of pharmaceutical wastewater under direct solar light irradiation.

A highly sensitive and selective method for the determination of ceftiofur sodium in milk and animal-origin food based on molecularly imprinted solid-phase extraction coupled with HPLC-UV.

The effective analysis of cephalosporin antibiotics in food animals has attracted considerable attention. Herein, a high-performance liquid chromatograph equipped with a UV method based on molecularly imprinted-solid phase extraction (MISPE-HPLC-UV) was developed for preconcentration, cleanup and determination of ceftiofur sodium (CTFS) in food samples. In this method, an eco-friendly molecularly imprinted polymer (MIP) was synthesized and employed as an adsorbent, which exhibited excellent selectivity towards CTFS in water, and adsorption equilibrium could be reached within 1 h. Under the optimized conditions, good linearity was obtained for CTFS in the range of 0.005-1.0 mg L-1 with a lower LOD of 0.0015 mg L-1, and the average recoveries were higher than 91.9% (RSD less than 8.5%) at three spiked levels in milk, chicken, pork and beef samples. After 20 cycles, the recovery of the MISPE cartridge for CTFS was still higher than 95%, which proved that the MISPE-HPLC-UV method was highly sensitive and selective for the analysis of CTFS in food samples.

Pharmacokinetic Modeling of Ceftiofur Sodium Using Non-linear Mixed-Effects in Healthy Beagle Dogs.

Ceftiofur (CEF) sodium is a third-generation broad-spectrum cephalosporin commonly used in an extra-label manner in dogs for the treatment of respiratory and urinary system infections. To contribute to the literature supporting CEF use in companion animals, we have developed a compartmental, non-linear mixed-effects (NLME) model of CEF pharmacokinetics in dogs (PK). We then used the mathematical model to predict (via Monte Carlo simulation) the duration of time for which plasma concentrations of CEF and its pharmacologically active metabolites remained above minimum inhibitory concentrations (respiratory tract Escherichia coli spp.). Twelve healthy beagle dogs were administered either 2.2 mg/kg ceftiofur-sodium (CEF-Na) intravenously (I.V) or 2.2 mg/kg CEF-Na subcutaneously (S.C). Plasma samples were collected over a period of 72 h post-administration. To produce a measurement of total CEF, both CEF and CEF metabolites were derivatized into desfuroylceftiofur acetamide (DCA) before analysis by UPLC-MS/MS. No adverse effects were reported after I.V or S.C dosing. The NLME PK models were parameterized using the stochastic approximation expectation maximization algorithm as implemented in Monolix 2018R2. A two-compartment mamillary model with first-order elimination and first-order S.C absorption best described the available kinetic data. Final parameter estimates indicate that CEF has a low systemic clearance (0.25 L/h/kg) associated with a low global extraction ratio E = 0.02) and a moderate volume of distribution (2.97 L/kg) in dogs. The absolute bioavailability after S.C administration was high (93.7%). Gender was determined to be a significant covariate in explaining the variability of S.C absorption. Our simulations predicted that a dose of 2.2 mg/kg CEF-Na S.C would produce median plasma concentrations of CEF of at least 0.5 µg/mL (MIC50) for ~30 h.

Highly efficient removal of ceftiofur sodium using a superior hydroxyl group functionalized ionic liquid-modified polymer.

The occurrence of cephalosporin antibiotics in water resources has caused increasing concerns about their potential effects on ecosystem and human health. However, reports on the efficient removal of these antibiotics are limited. In this work, a superior hydroxyl-functionalized ionic liquid based polymer (PS-[Hemim][Cl]) was prepared for highly efficient removal of ceftiofur sodium (CFS) antibiotic from aqueous solutions, and the effect of various factors on the adsorption was investigated. It was found that the PS-[Hemim][Cl] exhibited a super-high adsorption capacity of 1260.5 mg/g for CFS within 60 min and kept high removal efficiency in a wide range of antibiotic concentrations from 5 ppb level to 1000 mg/L. Even the concentration of common inorganic ions was 1000 times higher than that of CFS, the adsorption efficiency remained above 93%. At the same time, the PS-[Hemim][Cl] showed excellent adsorption performance for the antibiotics with similar structure to CFS. Compared with commercially available adsorbents, the adsorption capacity of PS-[Hemim][Cl] for CFS was 4-468 times higher under the same experimental conditions. The application of PS-[Hemim][Cl] to real wastewater containing different concentrations of CFS was investigated and promising results were reported. Additionally, preliminary mechanism studies suggested that electrostatic attraction, hydrogen bond and ion exchange synergistically contributed to the highly efficient adsorption of CFS.

Sonochemical synthesis of porous NiTiO3 nanorods for photocatalytic degradation of ceftiofur sodium.

Porous NiTiO3 nanorods were synthesized through the sonochemical route followed by calcination at various temperature conditions. Surface morphology of the samples was tuned by varying the heat treatment temperature from 100 to 600°C. The synthesized NiTiO3 nanorods were characterized by transmission electron microscopy, X-ray photoelectron spectroscopy, X-ray diffraction, diffused reflectance spectroscopy, photoluminescence spectroscopy and Brunauer-Emmett-Teller (BET) analyses. The characterization studies revealed that the NiTiO3 nanomaterial was tuned to porous and perfectly rod shaped structure during the heat treatment at 600°C. The porous NiTiO3 nanorods showed visible optical response and thus can be utilized in the photocatalytic degradation of ceftiofur sodium (CFS) under direct sunlight. The photoluminescence intensity of the porous NiTiO3 nanorods formed while heating at 600°C was lower than that of the as-synthesized NiTiO3 sample owing to the photogenerated electrons delocalization along the one dimensional nanorods and this delocalization resulted in the reduction of the electron-hole recombination rate. The photocatalytic degradation of ceftiofur sodium (CFS) was carried out using NiTiO3 nanorods under the direct sunlight irradiation and their intermediate products were analysed through HPLC to deduce the possible degradation mechanism. The porous NiTiO3 nanorods exhibited an excellent photocatalytic activity towards the CFS degradation and further, the photocatalytic activity was increased by the addition of peroxomonosulfate owing to the simultaneous generation of both OH and SO4-.

Pulmonary pharmacokinetics of desfuroylceftiofur acetamide after nebulisation or intramuscular administration of ceftiofur sodium to weanling foals.

REASONS FOR PERFORMING STUDY: Administration of ceftiofur sodium via nebulisation has been recommended for the treatment of bronchopneumonia in horses, despite the lack of pharmacokinetic and safety data. OBJECTIVES: To compare concentrations of desfuroylceftiofur acetamide (DCA) in plasma and pulmonary epithelial lining fluid (PELF) of foals after nebulisation or i.m. administration of ceftiofur sodium and to determine if nebulisation of ceftiofur sodium induces airway inflammation. STUDY DESIGN: Randomised experimental study. METHODS: Six weanling foals received ceftiofur sodium (2.2 mg/kg bwt daily for 5 doses) by the i.m. route and 6 foals received the same dose by nebulisation. Concentrations of DCA in plasma and PELF were measured after Doses 1 and 5, and differential cell counts were performed on bronchoalveolar lavage samples obtained after Dose 5. RESULTS: Foals receiving ceftiofur sodium via nebulisation had significantly lower peak concentrations (0.15 ± 0.12 vs. 6.15 ± 0.75 mg/l) and area under the curve (1.26 ± 0.96 vs. 37.63 ± 4.01 mg●h/l) in plasma compared with those receiving the drug by the i.m. route. In contrast, foals receiving ceftiofur sodium via nebulisation had significantly higher peak concentrations (4.52 ± 2.91 vs. 0.73 ± 0.73 mg/l) and area under the curve (24.14 ± 14.09 vs. 5.91 ± 3.28 mg●h/l) in PELF compared with those receiving the drug by the i.m. route. Cell concentration and differential cell count in bronchoalveolar lavage fluid of foals nebulised with ceftiofur sodium were not significantly different from those of foals nebulised with saline. CONCLUSIONS: Administration of ceftiofur sodium via nebulisation is well tolerated and DCA concentrations in PELF remain above the minimum inhibitory concentration of the drug required to inhibit the growth of 90% of Streptococcus zooepidemicus for approximately 24 h after administration. Nebulised ceftiofur sodium warrants further investigation for the treatment of bacterial infections of the lower respiratory tract in horses.

High surface area Ag-TiO2 nanotubes for solar/visible-light photocatalytic degradation of ceftiofur sodium.

Titanium dioxide nanotubes (TiO2 NTs) with very high surface area (469 m(2)/g) have been synthesized through a simple hydrothermal method and their surface has been modified using silver nanoparticles (Ag NPs). The Ag NPs deposited TiO2 NTs (Ag-TiO2 NTs) show an extended optical response from UV to visible region coupled with a surface plasmon resonance band and thus can be utilized as a plasmonic photocatalyst. The photoluminescence intensity of TiO2 NTs is lower than that of TiO2 nanoparticles due to the delocalization of photogenerated electrons along the one dimensional nanotubes which reduces the rate of charge recombination. The Langmuir adsorption constant of Ag-TiO2 NTs (for ceftiofur sodium adsorption) is twice that of P25 TiO2. The Ag-TiO2 NTs exhibit excellent photocatalytic activity toward the degradation of ceftiofur sodium (CFS) due to high surface area and mesoporosity of TiO2 NTs. The addition of peroxomonosulfate in the photocatalytic system greatly amplifies the CFS degradation owing to the simultaneous generation of both OH and SO4(-). The catalyst retains its photocatalytic activity at least up to four consecutive cycles.