Crystal structure and electrical properties of textured Ba2Bi4Ti5O18 ceramics

Highly textured Ba2Bi4Ti5O18 ceramic was prepared by spark plasma sintering (SPS). X-ray diffraction of the ceramics revealed the coexistence of a major ferroelectric phase (Space group, SG: B2cb) and a minor paraelectric phase (SG: I4/mmm) at room temperature. A diffused phase transition was observed at around 240 °C. The evolution of the switching current peaks in the electric current vs. electric field (I-E) loops with increasing temperature was interpreted by the structural changes and temperature dependent polarisation reversal processes. The slim polarisation vs. electric field (P-E) loops, the extra switching current peaks in the I-E loops and the non-zero piezoelectric d33 coefficient indicate that Ba2Bi4Ti5O18 is a relaxor ferroelectric material. The recoverable energy density (0.41 ± 0.01 J/cm3) of Ba2Bi4Ti5O18 ceramics in the perpendicular direction to the SPS pressing direction is close to that of Pb(Mg1/3Nb2/3)O3-based ceramics. The obtained results suggest Ba2Bi4Ti5O18 ceramics might be promising for energy storage applications

Comparative Pharmacokinetics and Preliminary Pharmacodynamics Evaluation of Piscidin 1 Against PRV and PEDV in Rats

Antimicrobial peptide (Piscidin-1) is an effective natural polypeptide, which has great influence and potential on porcine epidemic diarrhea virus (PEDV) and pseudorabies virus (PRV). As an alternative antibiotic substitute, Piscidin-1 was subjected for pharmacokinetics study with three administration routes (i.v, i.m, and p.o) after a single dose of 2 mg/kg in rats and preliminary pharmacodynamics including antiviral activity in cell against PEDV and PRV. Based on 50 percent tissue culture infective dose (TCID50), there were about 2 and 10% virus survived ratios for Piscidin-1 against PRV and PEDV, respectively. The plaque test showed 1 and 2 μg/ml Piscidin-1 could eliminate 95% PRV and 85% PEDV, respectively. The main pharmacokinetics parameters of Cmax, AUC0−∞, Ke, t1/2, Tmax, MRT, and Clb in plasma were not applicable value, 25.9 μg*h/ml, 0.041 h−1, 16.97 h, not available value, 22.77 h, 0.067 L/h*kg after i.v administration, 2.37 μg/ml, 18.95 μg*h/ml, 0.029 h−1, 23.50 h, 0.33 h, 30.12 h, 0.095 L/h*kg after i.m administration and 0.73 μg/ml, 9.63 μg*h/ml, 0.036 h−1, 19.46 h, 0.50 h, 26.76 h, 0.171 L/h*kg after p.o administration. The bioavailability values after i.m and p.o administrations were calculated as 73.17 and 37.18%, respectively. The i.m administration was selected for pharmacokinetics study in ileum content against PEDV. The main pharmacokinetic parameters of Cmax, AUC0−∞, Ke, t1/2, Tmax, MRT, and Clb in ileum content were 1.67 μg/ml, 78.40 μg*h/ml, 0.034 h−1, 20.16 h, 8.12 h, 36.45 h, 0.026 L/h*kg. The Cmax values in plasma (2.37 μg/ml) and ileum content (1.67 μg/ml) were higher than the effective inhibitory concentration determined in the plaque test, and this indicates that Piscidin-1 might have effective inhibition effect against PRV and PEDV after administration of 2 mg/kg i.m. The results of this study represent the first investigations toward the pharmacokinetic characteristics of piscidin-1 in plasma upon three different administration routes, among which i.m. resulted in the highest bioavailability (73.17%). Furthermore, the pharmacokinetics study of ileum content indicated Piscidin-1 might have good effect against PEDV and could be regarded as an alternative antibiotic in clinical veterinary in the future study

Optimal Regimens and Cutoff Evaluation of Tildipirosin Against Pasteurella multocida

Pasteurella multocida (PM) can invade the upper respiratory tract of the body and cause death and high morbidity. Tildipirosin, a new 16-membered-ring macrolide antimicrobial, has been recommended for the treatment of respiratory diseases. The objective of this research was to improve the dose regimes of tildipirosin to PM for reducing the macrolides resistance development with the pharmacokinetic/pharmacodynamic (PK/PD) modeling approach and to establish an alternate cutoff for tildipirosin against PM. A single dose (4 mg/kg body weight) of tildipirosin was administered via intramuscular (i.m.) and intravenous (i.v.) injection to the pigs. The minimum inhibitory concentration (MIC) values of clinical isolates (112) were measured in the range of 0.0625–32 μg/ml, and the MIC50 and MIC90 values were 0.5 and 2 μg/ml, respectively. The MIC of the selected PM04 was 2 and 0.5 μg/ml in the tryptic soy broth (TSB) and serum, respectively. The main pharmacokinetic (PK) parameters including the area under the curve at 24 h (AUC24 h), AUC, terminal half-life (T1/2), the time to peak concentration (Tmax), peak concentration (Cmax), relative total systemic clearance (CLb), and the last mean residence time (MRTlast) were calculated to be 7.10, 7.94 μg∗h/ml, 24.02, NA h, NA μg/ml, 0.46 L/h∗kg, 8.06 h and 3.94, 6.79 μg∗h/ml, 44.04, 0.25 h, 0.98 μg/ml, 0.43 L/h∗kg, 22.85 h after i.v. and i.m. induction, respectively. Moreover, the bioavailability of i.m. route was 85.5%, and the unbinding of tildipirosin to serum protein was 78%. The parameters AUC24 h/MIC in serum for bacteriostatic, bactericidal, and elimination activities were calculated as 18.91, 29.13, and 34.03 h based on the inhibitory sigmoid Emax modeling. According to the Monte Carlo simulation, the optimum doses for bacteriostatic, bactericidal, and elimination activities were 6.10, 9.41, and 10.96 mg/kg for 50% target and 7.86, 12.17, and 14.57 mg/kg for 90% target, respectively. The epidemiological cutoff value (ECV) was calculated to be 4 μg/ml which could cover 95% wild-type clinical isolates distribution. The PK-PD cutoff (COPD) was analyzed to be 0.25 μg/ml in vitro for tildipirosin against PM based on the Monte Carlo simulation. Compared with these two cutoff values, the finial susceptible breakpoint was defined as 4 μg/ml. The data presented now provides the optimal regimens (12.17 mg/kg) and susceptible breakpoint (4 μg/ml) for clinical use, but these predicted data should be validated in the clinical practice

PK-PD Analysis of Marbofloxacin against Streptococcus suis in Pigs

Marbofloxacin is a fluoroquinolone antibiotic and highly effective treatment for respiratory diseases. Here we aimed to evaluate the ex vivo activity of marbofloxacin against Streptococcus suis in pig serum, as well as the optimal dosages scheme for avoiding the fluoroquinolone resistance development. A single dose of 8 mg/kg body weight (bw) was administrated orally to healthy pigs and serum samples were collected during the next 72 h. Serum marbofloxacin content was determined by high-performance liquid chromatography. We estimated the Cmax (6.28 μg/ml), AUC0-24 h (60.30 μg.h/ml), AUC0-∞ (88.94 μg.h/ml), T1/2ke, (12.48 h), Tmax (0.75 h) and Clb (0.104 L/h) of marbofloxacin in pigs, as well as the bioavailability of marbofloxacin (94.21%) after a single 8 mg/kg oral administration. We also determined the pharmacodynamic of marbofloxacin against 134 Streptococcus suis strains isolated from Chinese cities in TSB and serum. These isolated strains had a MIC90 of 1 μg/ml. HB2, a virulent, serotype 2 isolate of SS, was selected for having antibacterial activity in TSB and serum to marbofloxacin. We determined the minimum inhibitory concentration (MIC, 1 μg/ml in TSB, 2 μg/ml in serum), minimum bactericidal concentration (MBC, 4 μg/ml in TSB, 4 μg/ml in serum), and mutant prevention concentration (2.56 μg/ml in TSB) for marbofloxacin against Streptococcus suis (HB2). In serum, by inhibitory sigmoid Emax modeling, the AUC0-24h/MIC values for marbofloxacin against HB2 were 25.23 (bacteriostatic), 35.64 (bactericidal), and 39.71 (elimination) h. Based on Monte Carlo simulations, the predicted optimal oral doses of marbofloxacin curing Streptococcus suis were 5.88 (bacteriostatic), 8.34 (bactericidal), and 9.36 (elimination) mg/kg.bw for a 50% target attainment ratio, and 8.16 (bacteriostatic), 11.31 (bactericidal), and 12.35 (elimination) mg/kg.bw for a 90% target attainment ratio. The data presented here provides optimized dosage information for clinical use; however, these predicted dosages should also be validated in clinical practice

Combination Susceptibility Testing of Common Antimicrobials in Vitro and the Effects of Sub-MIC of Antimicrobials on Staphylococcus aureus Biofilm Formation

The current study was conducted to evaluate the antibacterial combination efficacies, and whether the sub-inhibitory concentrations (sub-MIC) of antibiotics can influent on the biofilm formation of S. aureus. The minimum inhibitory concentration (MIC) of common antibacterial drugs was determined in vitro against clinical isolates of Staphylococcus aureus (S. aureus), Escherichia coli (E. coli), and Pasteurella multocida (P. multocida) alone and in combination with each other by using the broth microdilution method and the checkerboard micro-dilution method analyzed with the fractional inhibitory concentration index (FICI), respectively. Regarding these results, antibacterial drug combinations were categorized as synergistic, interacting, antagonistic and indifferent, and most of the results were consistent with the previous reports. Additionally, the effects of sub-MIC of seven antimicrobials (kanamycin, acetylisovaleryltylosin tartrate, enrofloxacin, lincomycin, colistin sulfate, berberine, and clarithromycin) on S. aureus biofilm formation were determined via crystal violet staining, scanning electron microscopy (SEM) and real-time PCR. Our results demonstrate that all antibiotics, except acetylisovaleryltylosin tartrate, effectively reduced the S. aureus biofilm formation. In addition, real-time reverse transcriptase PCR was used to analyze the relative expression levels of S. aureus biofilm-related genes such as sarA, fnbA, rbf, lrgA, cidA, and eno after the treatment at sub-MIC with all of the six antimicrobials. All antibiotics significantly inhibited the expression of these biofilm-related genes except for acetylisovaleryltylosin tartrate, which efficiently up-regulated these transcripts. These results provide the theoretical parameters for the selection of effective antimicrobial combinations in clinical therapy and demonstrate how to correctly use antibiotics at sub-MIC as preventive drugs